Dystonia

Overview

Definition

Dystonia is a group of movement disorders characterized by involuntary muscle contractions that cause abnormal control of movement and posture. Dystonia is a focal or generalized hyperkinetic disorder that presents with an excessive muscle-contraction response.

Epidemiology

• High prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency among movement disorders
• An estimated 500,000 adults and children are affected in North America.
• Heterogeneous disorder with variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency:
  • Focal dystonia is more prevalent than generalized dystonia.
  • Cervical dystonia is the most common form of focal dystonia.
• Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency of primary dystonia: approximately 16 in 100,000 cases
• Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency of gene Gene A 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 carriers Carriers The Cell: Cell Membrane: approximately 20 in 100,000 cases with variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables penetrance Penetrance The percent frequency with which a dominant or homozygous recessive gene or gene combination manifests itself in the phenotype of the carriers. Familial Juvenile Polyposis

Etiology

• Primary (isolated) dystonia:
  • Related to known genetic mutations Genetic Mutations Carcinogenesis:
    • DYT-TOR1A is the most common and most studied gene mutation Gene Mutation Myotonic Dystrophies.
    • Other causative DYT variants have been identified.
  • Must not have other known causes (aside from known genetic mutations Genetic Mutations Carcinogenesis)
  • Presents without other neurologic findings, except for tremors or myoclonus Myoclonus Involuntary 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
• Secondary (acquired) dystonia:
  • Caused by foreign insult or trauma:
    • Perinatal brain Brain The 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 injury
    • Traumatic brain injury Traumatic brain injury A form of acquired brain injury which occurs when a sudden trauma causes damage to the brain. Le Fort Fractures
    • Hypoxic brain Brain The 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 injury
    • Antidopaminergic drugs
    • Anti-N-methyl-D-aspartate (NMDA) receptor Receptor Receptors 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 encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis
  • Encompasses diverse causes including drug-induced, degenerative, and metabolic disorders
• Idiopathic Idiopathic Dermatomyositis dystonias:
  • No identifiable genetic or acquired etiology
  • The majority of adults with focal or segmental dystonia have an idiopathic Idiopathic Dermatomyositis etiology.
• Dystonia-plus syndromes:
  • No identifiable genetic or acquired etiology
  • Presents with dystonia AND other neurologic symptoms

Pathophysiology

• No consistent findings on pathological examination in primary dystonia
• No evidence of cellular degeneration on pathological examination
• No consistent neurotransmitter defects in primary dystonia
• Functional imaging findings are variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables among individuals affected with dystonia. Involved regions include:
  • Motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology cortex
  • Basal ganglia Basal Ganglia Basal ganglia are a group of subcortical nuclear agglomerations involved in movement, and are located deep to the cerebral hemispheres. Basal ganglia include the striatum (caudate nucleus and putamen), globus pallidus, substantia nigra, and subthalamic nucleus. Basal Ganglia: Anatomy
  • Brainstem
  • Cerebellum Cerebellum The cerebellum, Latin for “little brain,” is located in the posterior cranial fossa, dorsal to the pons and midbrain, and its principal role is in the coordination of movements. The cerebellum consists of 3 lobes on either side of its 2 hemispheres and is connected in the middle by the vermis. Cerebellum: Anatomy
• Mechanisms likely to be involved include:
  • Changes in neural circuitry:
    • Disturbance in neurotransmitter communication Communication The exchange or transmission of ideas, attitudes, or beliefs between individuals or groups. Decision-making Capacity and Legal Competence of striatal dopaminergic and cholinergic systems
    • Loss of GABA-mediated inhibition
  • Based on animal and imaging models
• Neurotransmitters likely to be involved:
  • Dopamine Dopamine One 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
  • Acetylcholine Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS
  • GABA GABA The most common inhibitory neurotransmitter in the central nervous system. Receptors and Neurotransmitters of the CNS
  • Glutamate Glutamate Derivatives of glutamic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure. Synthesis of Nonessential Amino Acids
• Primary dystonias:
  • Appear to be neurofunctional disorders without neuron loss
  • Strong hereditary component
  • Varying age range in terms of onset
• Secondary dystonias:
  • Symptoms thought to result from damage to the brain Brain The 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, specifically to the basal ganglia Basal Ganglia Basal ganglia are a group of subcortical nuclear agglomerations involved in movement, and are located deep to the cerebral hemispheres. Basal ganglia include the striatum (caudate nucleus and putamen), globus pallidus, substantia nigra, and subthalamic nucleus. Basal Ganglia: Anatomy
  • Sensorimotor circuitry can be disrupted further by toxic compounds and physiological stress, among other causes.
  • Secondary stressors combine to shift selected brain Brain The 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 regions into dystonia.

Classification

Body distribution

• Focal: affects 1 body region:
  • Periocular muscles → blepharospasm
  • Jaw Jaw The 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 and tongue Tongue The 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 → oromandibular dystonia
  • Laryngeal dystonia → dysphagia Dysphagia Dysphagia 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
  • Brachial dystonia → “writer’s cramp”
  • Cervical dystonia → spasmodic torticollis Torticollis A symptom, not a disease, of a twisted neck. In most instances, the head is tipped toward one side and the chin rotated toward the other. The involuntary muscle contractions in the neck region of patients with torticollis can be due to congenital defects, trauma, inflammation, tumors, and neurological or other factors. Cranial Nerve Palsies
• Segmental: affects ≥ 2 adjacent body regions:
  • Periocular + oromandibular
  • Cervical + brachial
• Generalized: affects the trunk and ≥ 2 other sites:
  • Trunk involvement → abnormal posture
  • Limb involvement is variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables.
• Multifocal Multifocal Retinoblastoma:
  • Affects ≥ 2 nonadjacent body regions
  • Does not meet the criteria for generalized dystonia
  • Most commonly observed in early-onset dystonia
• Hemidystonia:
  • Affects multiple body regions on the same side of the body
  • Most commonly a manifestation of contralateral insult (acquired dystonia) to the basal ganglia Basal Ganglia Basal ganglia are a group of subcortical nuclear agglomerations involved in movement, and are located deep to the cerebral hemispheres. Basal ganglia include the striatum (caudate nucleus and putamen), globus pallidus, substantia nigra, and subthalamic nucleus. Basal Ganglia: Anatomy

Selected types of common dystonias

Clinical Presentation

Excessive and frequent muscle contractions leading to abnormal postures and/or repetitive movements are the hallmark of dystonia.

Examples of movement abnormalities

• Abnormal postures:
  • May be sustained
  • May be intermittent
• Repetitive movements
• Patterned movements
• Twisting movements
• Tremors

Features of movement abnormalities

Can affect any part of the body:

• Focal: affects 1 body region
• Segmental: affects ≥ 2 adjacent body regions
• Generalized: affects the trunk and ≥ 2 other sites
• Multifocal Multifocal Retinoblastoma: affects ≥ 2 nonadjacent body regions
• Hemidystonia: affects multiple body regions unilaterally

Worsened by voluntary action:

• Attempts to maintain normal posture
• Purposeful coordinated movements (e.g., writing → “writer’s cramp”)

Most often occurs in anatomically distinct sites:

• Neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess
• Limbs
• Face
• Trunk

May present early in life (early-onset dystonia):

• May begin in:
  • Infancy (0–2 years)
  • Childhood (3–12 years)
  • Adolescence (13–20 years)
• Most commonly begins as a focal lower limb dystonia
• More likely to progress to generalized dystonia
• Most often genetic or idiopathic Idiopathic Dermatomyositis etiologies

May present later in life (late-onset dystonia):

• May begin in:
  • Early adulthood (21–40 years)
  • Late adulthood (> 40 years)
• Most commonly begins as a focal or segmental upper body dystonia (e.g., cervical, facial, arm Arm The arm, or “upper arm” in common usage, is the region of the upper limb that extends from the shoulder to the elbow joint and connects inferiorly to the forearm through the cubital fossa. It is divided into 2 fascial compartments (anterior and posterior). Arm: Anatomy(s)):
  • Isolated generalized dystonia is rare in adults.
  • When present, exposure to antidopaminergics is the most common cause.
• Some initial focal sites of onset are more likely to spread than others.

May have temporal dominance:

• Fluctuations in frequency or intensity with circadian variation
• Worsens as the wakeful period progresses
• Improvement is observed after a period of rest.

May have dynamic features:

• Dystonia only manifests with task specificity (i.e., “writers cramp”).
• Overflow phenomenon:
  • May manifest with involuntary dystonic movement of an affected limb that “mirrors” voluntary movement of the contralateral limb
  • May manifest with involuntary dystonic movement of a nonadjacent or distant body region with voluntary movement of a limb or body region
• Sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology trick:
  • Sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology stimulation of a dystonic body part abates dystonic movements.
  • Observed in approximately 60% of individuals affected with dystonia
  • May be useful in the management of dystonia:
    • Affected individuals may be trained to self-administer sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology tricks.
    • Affected individuals may even be trained to “imagine” the sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology trick to stop dystonic movements.

May present with comorbid movement disorders:

• Examples:
  • Parkinsonism Parkinsonism West Nile Virus + dystonia
  • Myoclonus Myoclonus Involuntary 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 + parkinsonism Parkinsonism West Nile Virus
• Other neurologic findings may be present:
  • Ataxia Ataxia Impairment 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
  • Weakness
  • Cognitive impairment
  • Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures
  • Ocular palsies

Diagnosis

Dystonia is diagnosed clinically based on a thorough history and physical examination, with a particular focus on musculoskeletal and nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. Nervous System: Anatomy, Structure, and Classification examination findings.

History and physical

• Thorough history taking should distinguish primary versus secondary dystonia:
  • Age of onset
  • Anatomic distribution
  • Other neurologic symptoms
• History should rule out:
  • Trauma (especially head trauma Head trauma Head trauma occurs when external forces are directed to the skull and brain structures, resulting in damage to the skull, brain, and intracranial structures. Head injuries can be classified as open (penetrating) or closed (blunt), and primary (from the initial trauma) or secondary (indirect brain injury), and range from mild to severe and life-threatening. Head Trauma)
  • Medication exposure:
    • Antidopaminergic drugs ( dopamine Dopamine One 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 receptor-blocking agents)
    • Metoclopramide Metoclopramide A dopamine d2 antagonist that is used as an antiemetic. Antiemetics
    • 1st-generation antipsychotics
    • 2nd-generation antipsychotics
  • Toxic exposure
• Family history Family History Adult Health Maintenance of dystonia, especially, is an important factor.
• Detailed physical exam is key to diagnosing specific types of dystonia.
  • Presence of the following observable or palpable findings:
    • Muscle contractions
    • Abnormal movements
    • Abnormal posture
    • Tremors
    • Other neurologic findings
  • Note the anatomic distribution and laterality of findings.
• Absence of neurologic findings, besides dystonia and tremor Tremor Cyclical 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, should separate primary from secondary dystonias.
• AIMS score:
  • Acronym for Abnormal Involuntary Movement Scale Scale Dermatologic Examination
  • Used to determine baseline score before commencing dopamine-blocking agents, such as antipsychotics

Levodopa Levodopa The 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 trial

• Recommended for individuals with early-onset dystonia of unknown etiology
• Should also be considered in adults presenting with dystonia of unknown etiology
• Helps identify affected individuals who may benefit from dopamine-agonist therapy

Laboratory evaluation

• No specific routine laboratory markers are available that are diagnostic of dystonia.
• Laboratory analysis helps exclude other etiologies that may present similarly, and in identifying comorbid and contributing conditions.
• Workup includes:
  • CBC
  • Electrolytes Electrolytes Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions. Electrolytes
  • Renal and liver function tests Liver function tests Liver function tests, also known as hepatic function panels, are one of the most commonly performed screening blood tests. Such tests are also used to detect, evaluate, and monitor acute and chronic liver diseases. Liver Function Tests
  • Antinuclear antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions
  • Serum ceruloplasmin Ceruloplasmin A multi-copper blood ferroxidase involved in iron and copper homeostasis and inflammation. Wilson Disease
  • Copper Copper A heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55. Trace Elements levels
  • 24-hour urinary copper Copper A heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55. Trace Elements
  • Lysosomal screen
  • Erythrocyte sedimentation rate Erythrocyte Sedimentation Rate Soft Tissue Abscess
  • Rapid plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products reagin

Neuroimaging Neuroimaging Non-invasive methods of visualizing the central nervous system, especially the brain, by various imaging modalities. Febrile Infant

• Brain Brain The 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 CT and/or MRI
• Evaluate for lesions of the basal ganglia Basal Ganglia Basal ganglia are a group of subcortical nuclear agglomerations involved in movement, and are located deep to the cerebral hemispheres. Basal ganglia include the striatum (caudate nucleus and putamen), globus pallidus, substantia nigra, and subthalamic nucleus. Basal Ganglia: Anatomy.

Genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies

• Indicated in primary dystonia, especially in individuals with a strong family history Family History Adult Health Maintenance or in cases with onset < 26 years of age
• Mutations at the DYT1 locus Locus Specific 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 is often associated with hereditary dystonia:
  • Specific panels are available to test for DYT variants.
  • Genetic counseling Genetic Counseling An educational process that provides information and advice to individuals or families about a genetic condition that may affect them. The purpose is to help individuals make informed decisions about marriage, reproduction, and other health management issues based on information about the genetic disease, the available diagnostic tests, and management programs. Psychosocial support is usually offered. Myotonic Dystrophies for affected individuals and their families is recommended.

Management

Treatment is largely symptomatic as there is no cure for dystonia.

Pharmacotherapy

• Aim to address impairments in the dopaminergic and cholinergic neurotransmitter circuitry and/or GABA-mediated inhibition.
• Drug classes include:
  • Anticholinergics Anticholinergics Anticholinergic drugs block the effect of the neurotransmitter acetylcholine at the muscarinic receptors in the central and peripheral nervous systems. Anticholinergic agents inhibit the parasympathetic nervous system, resulting in effects on the smooth muscle in the respiratory tract, vascular system, urinary tract, GI tract, and pupils of the eyes. Anticholinergic Drugs ( trihexyphenidyl Trihexyphenidyl One of the centrally acting muscarinic antagonists used for treatment of parkinsonian disorders and drug-induced extrapyramidal movement disorders and as an antispasmodic. Anticholinergic Drugs)
  • Dopaminergic agents (carbidopa/ levodopa Levodopa The 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)
  • GABA GABA The most common inhibitory neurotransmitter in the central nervous system. Receptors and Neurotransmitters of the CNS agonists (high-dose baclofen Baclofen A gamma-aminobutyric acid derivative that is a specific agonist of gaba-b receptors. It is used in the treatment of muscle spasticity, especially that due to spinal cord injuries. Its therapeutic effects result from actions at spinal and supraspinal sites, generally the reduction of excitatory transmission. Spasmolytics)
  • Vesicular monoamine transporter type 2 Type 2 Spinal Muscular Atrophy (VMAT2) inhibitors ( tetrabenazine Tetrabenazine A drug formerly used as an antipsychotic and treatment of various movement disorders. Tetrabenazine blocks neurotransmitter uptake into adrenergic storage vesicles and has been used as a high affinity label for the vesicle transport system. Huntington Disease):
    • Combination of anticholinergic Anticholinergic Anticholinergic drugs block the effect of the neurotransmitter acetylcholine at the muscarinic receptors in the central and peripheral nervous systems. Anticholinergic agents inhibit the parasympathetic nervous system, resulting in effects on the smooth muscle in the respiratory tract, vascular system, urinary tract, GI tract, and pupils of the eyes. Anticholinergic Drugs and antidopaminergic properties
    • Limited use due to side effects

Botulinum toxin Botulinum toxin Toxic proteins produced from the species Clostridium botulinum. The toxins are synthesized as a single peptide chain which is processed into a mature protein consisting of a heavy chain and light chain joined via a disulfide bond. The botulinum toxin light chain is a zinc-dependent protease which is released from the heavy chain upon endocytosis into presynaptic nerve endings. Once inside the cell the botulinum toxin light chain cleaves specific snare proteins which are essential for secretion of acetylcholine by synaptic vesicles. This inhibition of acetylcholine release results in muscular paralysis. Botulism

• Treatment of choice for isolated cervical dystonia
• Blocks acetylcholine Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS release from motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology neurons Neurons The 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
• Administered as IM injections to the affected areas
• Aimed at reducing dystonic symptoms via neuromuscular blockade Neuromuscular Blockade The intentional interruption of transmission at the neuromuscular junction by external agents, usually neuromuscular blocking agents. It is distinguished from nerve block in which nerve conduction (neural conduction) is interrupted rather than neuromuscular transmission. Neuromuscular blockade is commonly used to produce muscle relaxation as an adjunct to anesthesia during surgery and other medical procedures. It is also often used as an experimental manipulation in basic research. It is not strictly speaking anesthesia but is grouped here with anesthetic techniques. The failure of neuromuscular transmission as a result of pathological processes is not included here. Aminoglycosides only to the affected area
• Widespread use is not feasible due to the potential for systemic toxicity Toxicity Dosage Calculation ( iatrogenic botulism Iatrogenic Botulism Botulism).
• Some recipients lose responsiveness to botulinum toxin Botulinum toxin Toxic proteins produced from the species Clostridium botulinum. The toxins are synthesized as a single peptide chain which is processed into a mature protein consisting of a heavy chain and light chain joined via a disulfide bond. The botulinum toxin light chain is a zinc-dependent protease which is released from the heavy chain upon endocytosis into presynaptic nerve endings. Once inside the cell the botulinum toxin light chain cleaves specific snare proteins which are essential for secretion of acetylcholine by synaptic vesicles. This inhibition of acetylcholine release results in muscular paralysis. Botulism over time:
  • May need dose adjustments
  • May need more anatomically precise injections
  • May need adjunctive PT
• Some recipients develop autoantibodies Autoantibodies Antibodies that react with self-antigens (autoantigens) of the organism that produced them. Blotting Techniques against botulinum toxin Botulinum toxin Toxic proteins produced from the species Clostridium botulinum. The toxins are synthesized as a single peptide chain which is processed into a mature protein consisting of a heavy chain and light chain joined via a disulfide bond. The botulinum toxin light chain is a zinc-dependent protease which is released from the heavy chain upon endocytosis into presynaptic nerve endings. Once inside the cell the botulinum toxin light chain cleaves specific snare proteins which are essential for secretion of acetylcholine by synaptic vesicles. This inhibition of acetylcholine release results in muscular paralysis. Botulism, leading to its inefficacy.

Surgery

• Deep brain Brain The 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:
  • Targets the globus pallidus Globus pallidus The representation of the phylogenetically oldest part of the corpus striatum called the paleostriatum. It forms the smaller, more medial part of the lentiform nucleus. Basal Ganglia: Anatomy
  • Mixed evidence for efficacy and uncertain for use in secondary dystonia
• Lesional surgeries were used in the past but discontinued due to severe side effects.

Rehabilitative therapy

• PT for individuals whose gait Gait Manner or style of walking. Neurological Examination or writing, among other actions, are affected
• Speech therapy Speech Therapy Treatment for individuals with speech defects and disorders that involves counseling and use of various exercises and AIDS to help the development of new speech habits. Myotonic Dystrophies for individuals in whom dystonia has affected speech or swallowing Swallowing The act of taking solids and liquids into the gastrointestinal tract through the mouth and throat. Gastrointestinal Motility

Differential Diagnosis

• Parkinson disease Parkinson disease Parkinson’s disease (PD) is a chronic, progressive neurodegenerative disorder. Although the cause is unknown, several genetic and environmental risk factors are currently being studied. Individuals present clinically with resting tremor, bradykinesia, rigidity, and postural instability. Parkinson’s Disease: a chronic, progressive, neurodegenerative disorder. Affected individuals present clinically with resting tremor Resting Tremor Parkinson’s Disease, bradykinesia Bradykinesia Parkinson’s Disease, rigidity Rigidity Continuous 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 postural instability. Parkinson disease Parkinson disease Parkinson’s disease (PD) is a chronic, progressive neurodegenerative disorder. Although the cause is unknown, several genetic and environmental risk factors are currently being studied. Individuals present clinically with resting tremor, bradykinesia, rigidity, and postural instability. Parkinson’s Disease is diagnosed clinically based on its characteristic signs and symptoms. Treatment includes supportive physical and emotional care plus medications such as levodopa Levodopa The 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, monoamine oxidase type B inhibitors Monoamine Oxidase Type B Inhibitors Parkinson’s Disease, and dopamine Dopamine One 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.
• Cerebral palsy Palsy paralysis of an area of the body, thus incapable of voluntary movement Cranial Nerve Palsies: a group of conditions that limits physical activity and results in motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology impairment, affecting tone and posture. Cerebral palsy Palsy paralysis of an area of the body, thus incapable of voluntary movement Cranial Nerve Palsies is caused by a nonprogressive CNS injury to the fetal or infant brain Brain The 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. Cerebral palsy Palsy paralysis of an area of the body, thus incapable of voluntary movement Cranial Nerve Palsies is classified according to muscle tone Muscle tone The state of activity or tension of a muscle beyond that related to its physical properties, that is, its active resistance to stretch. In skeletal muscle, tonus is dependent upon efferent innervation. Skeletal Muscle Contraction, its distribution, and the presumed time of injury. Diagnosis is based on a detailed history, physical exam, and MRI to confirm the CNS insult. Interventions are multidisciplinary and the prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas depends on the degree of disability Disability Determination of the degree of a physical, mental, or emotional handicap. The diagnosis is applied to legal qualification for benefits and income under disability insurance and to eligibility for social security and workman’s compensation benefits. ABCDE Assessment.
• Tourette syndrome Tourette Syndrome A neuropsychological disorder related to alterations in dopamine metabolism and neurotransmission involving frontal-subcortical neuronal circuits. Both multiple motor and one or more vocal tics need to be present with tics occurring many times a day, nearly daily, over a period of more than one year. The onset is before age 18 and the disturbance is not due to direct physiological effects of a substance or another medical condition. The disturbance causes marked distress or significant impairment in social, occupational, or other important areas of functioning. Tics and Tourette Syndrome: a severe form of neurobehavioral disorder of childhood characterized by sudden, repeated, nonrhythmic, stereotyped muscle movements sometimes accompanied by sounds or vocalizations. Tourette syndrome Tourette Syndrome A neuropsychological disorder related to alterations in dopamine metabolism and neurotransmission involving frontal-subcortical neuronal circuits. Both multiple motor and one or more vocal tics need to be present with tics occurring many times a day, nearly daily, over a period of more than one year. The onset is before age 18 and the disturbance is not due to direct physiological effects of a substance or another medical condition. The disturbance causes marked distress or significant impairment in social, occupational, or other important areas of functioning. Tics and Tourette Syndrome is clinically diagnosed, and the treatment involves behavioral therapy, antipsychotics, and addressing comorbid conditions. A majority of children outgrow their symptoms in adulthood, although a minority of adults will continue to demonstrate severe tics Tics Habitual, repeated, rapid contraction of certain muscles, resulting in stereotyped individualized actions that can be voluntarily suppressed for only brief periods. They often involve the face, vocal cords, neck, and less often the extremities. Examples include repetitive throat clearing, vocalizations, sniffing, pursing the lips, and excessive blinking. Tics tend to be aggravated by emotional stress. When frequent they may interfere with speech and interpersonal relations. Conditions which feature frequent and prominent tics as a primary manifestation of disease are referred to as tic disorders. Tics and Tourette Syndrome.
• Huntington disease Huntington disease Huntington disease (HD) is a progressive neurodegenerative disorder with an autosomal dominant mode of inheritance and poor prognosis. It is caused by cytosine-adenine-guanine (CAG) trinucleotide repeats in the huntingtin gene (HTT). The most common clinical presentation in adulthood is a movement disorder known as chorea: abrupt, involuntary movements of the face, trunk, and limbs. Huntington Disease: a progressive neurodegenerative disorder with an autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance mode of inheritance and poor prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas. The most common clinical presentation in adulthood is a movement disorder known as chorea Chorea Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of chorea as a primary manifestation of disease are referred to as choreatic disorders. Chorea is also a frequent manifestation of basal ganglia diseases. Huntington Disease, which is characterized by abrupt, involuntary movements of the face, trunk, and limbs. Psychiatric and cognitive features are also common. The diagnosis is primarily clinical, often with a positive family history Family History Adult Health Maintenance followed by genetic confirmation. Management is supportive and involves an interdisciplinary team working toward the goal of maintaining the quality Quality Activities 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.
• Wilson disease Wilson disease Wilson disease (hepatolenticular degeneration) is an autosomal recessive disorder caused by various mutations in the ATP7B gene, which regulates copper transport within hepatocytes. Dysfunction of this transport mechanism leads to abnormal copper accumulations in the liver, brain, eyes, and other organs, with consequent major and variably expressed hepatic, neurologic, and psychiatric disturbances. Wilson Disease: an autosomal recessive Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant Inheritance disorder characterized by abnormal copper Copper A heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55. Trace Elements metabolism resulting from mutations in the ATP7B gene Gene A 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. Copper Copper A heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55. Trace Elements accumulates in the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy and CNS leading to progressive organ dysfunction. Neurologic symptoms are almost always limited to the motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology system and include dystonia, tremor Tremor Cyclical 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, ataxia Ataxia Impairment 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, and loss of motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology control. The diagnosis is based on laboratory findings, including reduced serum ceruloplasmin Ceruloplasmin A multi-copper blood ferroxidase involved in iron and copper homeostasis and inflammation. Wilson Disease and elevated copper Copper A heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55. Trace Elements levels. Treatment consists of a diet low in copper Copper A heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55. Trace Elements and the use of copper-chelating agents.
• Tardive dyskinesia: an extrapyramidal syndrome secondary to the long-term use of drugs, such as neuroleptics, which block dopamine-receptor activity. Tardive dyskinesia presents with focal dystonia, especially torticollis Torticollis A symptom, not a disease, of a twisted neck. In most instances, the head is tipped toward one side and the chin rotated toward the other. The involuntary muscle contractions in the neck region of patients with torticollis can be due to congenital defects, trauma, inflammation, tumors, and neurological or other factors. Cranial Nerve Palsies or blepharospasm. The onset is latent and occurs anywhere from days to years following the use of dopamine-blocking agents. Management involves early detection and discontinuation/change of the offending drug. Newer drugs such as VMAT2 inhibitors show promise.