Tardive Dyskinesia

Overview

Definition

Tardive dyskinesia (TD) is a hyperkinetic, medication-induced, involuntary movement disorder.

Etiology

Causative agents include medications with 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 mechanisms of action:

• Antipsychotic Antipsychotic Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics medications: 1st generation (higher affinity for 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 receptors Receptors 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) > 2nd generation
• Certain antiemetics Antiemetics Antiemetics are medications used to treat and/or prevent nausea and vomiting. These drugs act on different target receptors. The main classes include benzodiazepines, corticosteroids, atypical antipsychotics, cannabinoids, and antagonists of the following receptors: serotonin, dopamine, and muscarinic and neurokinin receptors. Antiemetics, such as:
  • Metoclopramide Metoclopramide A dopamine d2 antagonist that is used as an antiemetic. Antiemetics
  • Prochlorperazine Prochlorperazine A phenothiazine antipsychotic used principally in the treatment of nausea; vomiting; and vertigo. It is more likely than chlorpromazine to cause extrapyramidal disorders. Antiemetics
  • Chlorpromazine Chlorpromazine The prototypical phenothiazine antipsychotic drug. Like the other drugs in this class chlorpromazine’s antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking dopamine receptors. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup. First-Generation Antipsychotics
• Rare causes: amoxapine Amoxapine The n-demethylated derivative of the antipsychotic agent loxapine that works by blocking the reuptake of norepinephrine, serotonin, or both; it also blocks dopamine receptors. Amoxapine is used for the treatment of depression. Tricyclic Antidepressants (tetracyclic antidepressant Antidepressant Antidepressants encompass several drug classes and are used to treat individuals with depression, anxiety, and psychiatric conditions, as well as those with chronic pain and symptoms of menopause. Antidepressants include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and many other drugs in a class of their own. Serotonin Reuptake Inhibitors and Similar Antidepressants)

Risk factors

• Use of causative agents, including:
  • Higher doses
  • Long-term exposure
  • Development of early extrapyramidal symptoms Extrapyramidal Symptoms Ataxia-telangiectasia (EPS), including:
    • Dystonia Dystonia Dystonia is a hyperkinetic movement disorder characterized by the involuntary contraction of muscles, resulting in abnormal postures or twisting and repetitive movements. Dystonia can present in various ways as may affect many different skeletal muscle groups. Dystonia
    • Akathisia
    • Parkinsonism Parkinsonism West Nile Virus
• Certain patient characteristics also influence risk, particularly:
  • Age: > 55 years
  • Sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria: women > men
• Associated comorbidities Comorbidities The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. St. Louis Encephalitis Virus:
  • Psychotic disorders
  • Intellectual 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
  • Substance use (e.g., tobacco, alcohol)
  • Dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders
  • Diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus
  • Preexisting mood disorders
  • Prior electroconvulsive therapy Electroconvulsive therapy Electrically induced convulsions primarily used in the treatment of severe affective disorders and schizophrenia. Major Depressive Disorder

Pathophysiology

The underlying pathophysiology of hyperkinetic movement in TD is not fully understood, but may be related to structural and biochemical disturbances in 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 of 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, which are primarily responsible for motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology control and require the appropriate release of 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 at their input nuclei for their effective operation: 

• Blocking D2 receptors Receptors 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 results in:
  • ↑↑ D1-receptor-mediated striatopallidal output
  • Altered firing patterns in 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
  • ↑ Release of the excitatory neurotransmitter 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 in the striatum Striatum Striped gray matter and white matter consisting of the neostriatum and paleostriatum (globus pallidus). It is located in front of and lateral to the thalamus in each cerebral hemisphere. The gray substance is made up of the caudate nucleus and the lentiform nucleus (the latter consisting of the globus pallidus and putamen). The white matter is the internal capsule. Basal Ganglia: Anatomy → excitotoxic destruction of GABA-containing 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 → ↓ inhibitory output
• Chronic 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 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 blockade → upregulation of striatal 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 receptors Receptors 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 
• Potential changes in other 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 systems that provide feedback to the nigrostriatal 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

Clinical Presentation

The clinical presentation of TD 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, and can involve different body regions and types of involuntary movements. Symptoms may be insidious in onset, particularly with 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 movements. The repetitive movements characteristic of TD can be either intermittent or continuous, contributing to the complexity of the disorder.

Common types of movements

Head (most common):

• Facial grimacing
• 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 protrusion
• Lip smacking
• Mouth puckering
• Excessive or rapid blinking

Trunk:

• Shoulder shrugging
• Rocking or swaying
• Hip thrusting or rotary movements

Extremities:

• Writhing movements
• Foot Foot The foot is the terminal portion of the lower limb, whose primary function is to bear weight and facilitate locomotion. The foot comprises 26 bones, including the tarsal bones, metatarsal bones, and phalanges. The bones of the foot form longitudinal and transverse arches and are supported by various muscles, ligaments, and tendons. Foot: Anatomy tapping
• Finger movements:
  • “Piano-playing”-like
  • Spreading
  • Twisting
• Ballistic movements

Tardive dystonia Dystonia Dystonia is a hyperkinetic movement disorder characterized by the involuntary contraction of muscles, resulting in abnormal postures or twisting and repetitive movements. Dystonia can present in various ways as may affect many different skeletal muscle groups. Dystonia

This is a subtype of TD where dystonic characteristics predominate.

• Manifests as contraction of muscle groups which:
  • May be sustained or repetitive
  • Result in twisting or abnormal movements
  • Can cause abnormal fixed postures
• Examples:
  • Retrocollis: muscle contractions result in neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess extension Extension Examination of the Upper Limbs
  • 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: muscle contractions result in head turned to 1 side
  • Opishthotonus: backward arching of the head, neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess, and spine Spine The human spine, or vertebral column, is the most important anatomical and functional axis of the human body. It consists of 7 cervical vertebrae, 12 thoracic vertebrae, and 5 lumbar vertebrae and is limited cranially by the skull and caudally by the sacrum. Vertebral Column: Anatomy
  • Shoulder dystonia Dystonia Dystonia is a hyperkinetic movement disorder characterized by the involuntary contraction of muscles, resulting in abnormal postures or twisting and repetitive movements. Dystonia can present in various ways as may affect many different skeletal muscle groups. Dystonia: abnormal movement or posture of the shoulder
  • Blepharospasm: spasm of the eyelids Eyelids Each of the upper and lower folds of skin which cover the eye when closed. Blepharitis
  • 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 dystonia Dystonia Dystonia is a hyperkinetic movement disorder characterized by the involuntary contraction of muscles, resulting in abnormal postures or twisting and repetitive movements. Dystonia can present in various ways as may affect many different skeletal muscle groups. Dystonia: clenching or grinding of the 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
  • Leg Leg The lower leg, or just “leg” in anatomical terms, is the part of the lower limb between the knee and the ankle joint. The bony structure is composed of the tibia and fibula bones, and the muscles of the leg are grouped into the anterior, lateral, and posterior compartments by extensions of fascia. Leg: Anatomy or 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 hyperextension

Diagnosis

The diagnosis of TD is clinical and should be suspected if:

• Typical, involuntary movements are present.
• ≥  3 months of current or previous exposure to a 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 agent (1 month if additional risk factors, such as older age)
• Other potential causes are excluded or unlikely.

Physical examination

A physical examination should be performed to evaluate for signs of an alternative diagnosis.

• Full neurological examination Neurological examination A neurological exam is a systematic assessment of cognitive, sensory, and motor responses to identify pathologies of the nervous system. A neurological exam allows for the localization of neurologic lesions to narrow the differential diagnosis and focus on subsequent laboratory and imaging examinations. The exam should include assessments of the subject’s mental status, speech, cranial nerves, motor system, deep tendon reflexes, sensation, balance, and coordination. Neurological Examination to ensure no focal deficits, including:
  • Muscle strength Muscle strength The amount of force generated by muscle contraction. Muscle strength can be measured during isometric, isotonic, or isokinetic contraction, either manually or using a device such as a muscle strength dynamometer. Neurological Examination and tone
  • Sensation
  • Gait Gait Manner or style of walking. Neurological Examination
  • Coordination Coordination Cerebellar Disorders
• Cognitive examination to rule out dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders

Additional studies

Testing is not necessary for the diagnosis of TD, but may be useful to rule out other causes of the patient’s symptoms, particularly if the diagnosis is unclear. An evaluation may include:

• 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 → chronic 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 disease
• Ceruloplasmin Ceruloplasmin A multi-copper blood ferroxidase involved in iron and copper homeostasis and inflammation. Wilson Disease → 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
• Calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes → hyperparathyroidism Hyperparathyroidism Hyperparathyroidism is a condition associated with elevated blood levels of parathyroid hormone (PTH). Depending on the pathogenesis of this condition, hyperparathyroidism can be defined as primary, secondary or tertiary. Hyperparathyroidism
• Thyroid-stimulating hormone Thyroid-stimulating hormone A glycoprotein hormone secreted by the adenohypophysis. Thyrotropin stimulates thyroid gland by increasing the iodide transport, synthesis and release of thyroid hormones (thyroxine and triiodothyronine). Thyroid Hormones → hyperthyroidism Hyperthyroidism Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. Thyrotoxicosis and Hyperthyroidism
• Antiphospholipid antibody → lupus 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
• 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 MRI → if intracranial pathology is suspected

Management

There are no curative treatments for TD. Thus, prevention is paramount.

Prevention

• Consider effective alternative drug classes, when possible.
• If an antipsychotic Antipsychotic Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics is necessary, preference 2nd-generation medications over 1st-generation.
• Avoid prolonged use of causative agents.
• Use the lowest effective dose.
• Monitor regularly for signs of EPS.
• Take particular care in medication selection Selection Lymphocyte activation by a specific antigen thus triggering clonal expansion of lymphocytes already capable of mounting an immune response to the antigen. B cells: Types and Functions and use in high-risk groups (e.g., older adults).
• Although used for other EPS, 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 drug prophylaxis Prophylaxis Cephalosporins does not prevent TD and is not recommended.

Treatment

Discontinue the offending medication at the first signs of TD, if possible:

• To avoid withdrawal (which can worsen TD), be sure to taper antipsychotics.
• Monitor the patient’s psychiatric symptoms closely.

Medical therapy:

• Symptom management may be necessary for symptoms that are:
  • Moderate to severe in 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
  • Negatively affecting 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
  • Disabling
• Vesicular monoamine transporter type 2 (VMAT2) inhibitors:
  • 1st-line symptomatic therapy
  • Have shown benefit in reducing motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology symptoms
  • Possible mechanism:
    • Not exactly known 
    • VMAT2 is a transporter responsible for regulating the uptake of monoamines (e.g., 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, serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS, norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS) from the cytoplasm into synaptic vesicles Vesicles Female Genitourinary Examination for storage and subsequent release.
    • Reversible inhibition → depletion of 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 storage in presynaptic vesicles Vesicles Female Genitourinary Examination → reduces excessive dopaminergic activity
  • Examples:
    • 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
    • Valbenazine
    • Deutetrabenazine
  • Common side effects:
    • Fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia
    • Somnolence
    • Depression
    • Anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder
• Benzodiazepines Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines
  • Used commonly in TD management prior to the advent of VMAT2 inhibitors
  • Limited evidence of efficacy
  • Example: clonazepam Clonazepam An anticonvulsant used for several types of seizures, including myotonic or atonic seizures, photosensitive epilepsy, and absence seizures, although tolerance may develop. It is seldom effective in generalized tonic-clonic or partial seizures. The mechanism of action appears to involve the enhancement of gamma-aminobutyric acid receptor responses. Benzodiazepines
• Other medications have insufficient evidence to support their use.

Other therapies:

• 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:
  • An option for persistent, refractory TD despite medical therapy
  • Requires referral to movement disorder clinic/specialist
  • Limited data on effectiveness
• 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 injections: an option for tardive dystonia Dystonia Dystonia is a hyperkinetic movement disorder characterized by the involuntary contraction of muscles, resulting in abnormal postures or twisting and repetitive movements. Dystonia can present in various ways as may affect many different skeletal muscle groups. Dystonia

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

• Remission Remission A spontaneous diminution or abatement of a disease over time, without formal treatment. Cluster Headaches:
  • If identified early with prompt withdrawal of offending medication → 50–90% remission Remission A spontaneous diminution or abatement of a disease over time, without formal treatment. Cluster Headaches rate
  • May take several months to years
• Once chronic, TD does not worsen if continued drug exposure is necessary for mental health treatment.

Differential Diagnosis

• 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 caused by cytosine-adenine-guanine (CAG) trinucleotide repeats in the huntingtin 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 ( HTT HTT Huntington Disease). 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: abrupt, involuntary movements of the face, trunk, and limbs. Psychiatric and cognitive features are also characteristic. The diagnosis is primarily clinical, often with a positive family history Family History Adult Health Maintenance followed by genetic confirmation. Management involves an interdisciplinary team and is supportive, with the goal of maintaining 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.
• Idiopathic Idiopathic Dermatomyositis dystonia Dystonia Dystonia is a hyperkinetic movement disorder characterized by the involuntary contraction of muscles, resulting in abnormal postures or twisting and repetitive movements. Dystonia can present in various ways as may affect many different skeletal muscle groups. Dystonia: a neurological movement disorder characterized by involuntary muscle contractions, leading to abnormal postures and repetitive movements. The etiology is unknown, but it is believed to be multifactorial, involving a combination of genetic and environmental factors. Diagnosis primarily relies on clinical evaluation and ruling out other causes, as there are no specific tests. Management includes medications like 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, dopaminergic agents, VMAT2 inhibitors, 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 injections, and in some cases, 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.
• 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 neurological disorder that emerges in childhood, characterized by repetitive, stereotyped, involuntary movements and vocalizations, called 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. The etiology is complex, involving genetic and environmental factors, but the exact cause is still not fully understood. Diagnosis is primarily clinical, based on the history and observation of 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 for ≥ 1 year, with onset before the age of 18. Management often includes behavioral therapy and medications for 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 (e.g., 2nd-generation antipsychotics).