Tremor

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Tremor 

Tremor
Writing by a person with Parkinson's disease
Pronunciation	/ˈtrɛmər/
Specialty	Neurology

A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, face, head, vocal folds, trunk, and legs. Most tremors occur in the hands. In some people, a tremor is a symptom of another neurological disorder. A very common tremor is the teeth chattering, usually induced by cold temperatures or by fear.

Causes

Tremor can be a symptom associated with disorders in those parts of the brain that control muscles throughout the body or in particular areas, such as the hands. Neurological disorders or conditions that can produce tremor include multiple sclerosis, stroke, traumatic brain injury, chronic kidney disease and a number of neurodegenerative diseases that damage or destroy parts of the brainstem or the cerebellum, Parkinson's disease being the one most often associated with tremor. Other causes include the use of drugs (such as amphetamines, cocaine, caffeine, corticosteroids, SSRIs) or alcohol, mercury poisoning, or the withdrawal of drugs such as alcohol or benzodiazepine. Tremors can also be seen in infants with phenylketonuria (PKU), overactive thyroid or liver failure. Tremors can be an indication of hypoglycemia, along with palpitations, sweating and anxiety. Tremor can also be caused by lack of sleep, lack of vitamins, or increased stress. Deficiencies of magnesium and thiamine have also been known to cause tremor or shaking, which resolves when the deficiency is corrected. Tremors in animals can also be caused by some spider bites, e.g. the redback spider of Australia.

Types

Tremor is most commonly classified by clinical features and cause or origin. Some of the better-known forms of tremor, with their symptoms, include the following:

• Cerebellar tremor (also known as intention tremor) is a slow, broad tremor of the extremities that occurs at the end of a purposeful movement, such as trying to press a button or touching a finger to the tip of one's nose. Cerebellar tremor is caused by lesions in or damage to the cerebellum resulting from stroke, tumor, or disease such as multiple sclerosis or some inherited degenerative disorder. It can also result from chronic alcoholism or overuse of some medicines. In classic cerebellar tremor, a lesion on one side of the brain produces a tremor in that same side of the body that worsens with directed movement. Cerebellar damage can also produce a “wing-beating” type of tremor called rubral or Holmes’ tremor — a combination of rest, action, and postural tremors. The tremor is often most prominent when the affected person is active or is maintaining a particular posture. Cerebellar tremor may be accompanied by other manifestations of ataxia, including dysarthria (speech problems), nystagmus (rapid, involuntary rolling of the eyes), gait problems and postural tremor of the trunk and neck. Titubation is tremor of the head and is of cerebellar origin.
• Dystonic tremor occurs in individuals of all ages who are affected by dystonia, a movement disorder in which sustained involuntary muscle contractions cause twisting and repetitive motions or painful and abnormal postures or positions. Dystonic tremor may affect any muscle in the body and is seen most often when the patient is in a certain position or moves a certain way. The pattern of dystonic tremor may differ from essential tremor. Dystonic tremors occur irregularly and can often be relieved by complete rest. Touching the affected body part or muscle may reduce tremor severity (a geste antagoniste). The tremor may be the initial sign of dystonia localized to a particular part of the body. The dystonic tremor has usually a frequency of about 7 Hz.^[6]
• Essential tremor (sometimes inaccurately called benign essential tremor) is the most common of the more than 20 types of tremor. Although the tremor may be mild and nonprogressive in some people, in others, the tremor is slowly progressive, starting on one side of the body but affecting both sides within 3 years. The hands are most often affected but the head, voice, tongue, legs, and trunk may also be involved. Head tremor may be seen as a vertical or horizontal motion. Essential tremor may be accompanied by mild gait disturbance. Tremor frequency may decrease as the person ages, but the severity may increase, affecting the person's ability to perform certain tasks or activities of daily living. Heightened emotion, stress, fever, physical exhaustion, or low blood sugar may trigger tremors or increase their severity. Onset is most common after age 40, although symptoms can appear at any age. It may occur in more than one family member. Children of a parent who has essential tremor have a 50 percent chance of inheriting the condition. Essential tremor is not associated with any known pathology. Its frequency is between 4 and 8 Hz.
• Orthostatic tremor is characterized by fast (>12 Hz) rhythmic muscle contractions that occur in the legs and trunk immediately after standing up. Cramps are felt in the thighs and legs and the patient may shake uncontrollably when asked to stand in one spot. No other clinical signs or symptoms are present and the shaking ceases when the patient sits or is lifted off the ground. The high frequency of the tremor often makes the tremor look like rippling of leg muscles while standing. Orthostatic tremor may also occur in patients who have essential tremor, and there might be an overlap between these categories of tremor.
• Parkinsonian tremor is caused by damage to structures within the brain that control movement. This resting tremor, which can occur as an isolated symptom or be seen in other disorders, is often a precursor to Parkinson's disease (more than 25 percent of patients with Parkinson's disease have an associated action tremor). The tremor, which is classically seen as a "pill-rolling" action of the hands that may also affect the chin, lips, legs, and trunk, can be markedly increased by stress or emotion. Onset is generally after age 60. Movement starts in one limb or on one side of the body and usually progresses to include the other side. The tremor's frequency is between 4 and 6 Hz.
• Physiological tremor occurs in every normal individual and has no clinical significance. It is rarely visible and may be heightened by strong emotion (such as anxiety or fear), physical exhaustion, hypoglycemia, hyperthyroidism, heavy metal poisoning, stimulants, alcohol withdrawal or fever. It can be seen in all voluntary muscle groups and can be detected by extending the arms and placing a piece of paper on top of the hands. Enhanced physiological tremor is a strengthening of physiological tremor to more visible levels. It is generally not caused by a neurological disease but by reaction to certain drugs, alcohol withdrawal, or medical conditions including an overactive thyroid and hypoglycemia. It is usually reversible once the cause is corrected. This tremor classically has a frequency of about 10 Hz.
• Psychogenic tremor (also called hysterical tremor) can occur at rest or during postural or kinetic movement. The characteristics of this kind of tremor may vary but generally include sudden onset and remission, increased incidence with stress, change in tremor direction or body part affected, and greatly decreased or disappearing tremor activity when the patient is distracted. Many patients with psychogenic tremor have a conversion disorder (see Posttraumatic stress disorder) or another psychiatric disease.
• Rubral tremor is characterized by coarse slow tremor which is present at rest, at posture and with intention. This tremor is associated with conditions which affect the red nucleus in the midbrain, classically unusual strokes.

Tremor can result from other conditions as well

• Alcoholism, excessive alcohol consumption, or alcohol withdrawal can kill certain nerve cells, resulting in a tremor known as asterixis. Conversely, small amounts of alcohol may help to decrease familial and essential tremor, but the mechanism behind it is unknown. Alcohol potentiates GABAergic transmission and might act at the level of the inferior olive.
• Tremor in peripheral neuropathy may occur when the nerves that supply the body's muscles are traumatized by injury, disease, abnormality in the central nervous system, or as the result of systemic illnesses. Peripheral neuropathy can affect the whole body or certain areas, such as the hands, and may be progressive. Resulting sensory loss may be seen as a tremor or ataxia (inability to coordinate voluntary muscle movement) of the affected limbs and problems with gait and balance. Clinical characteristics may be similar to those seen in patients with essential tremor.
• Tobacco withdrawal symptoms include tremor.
• Most of the symptoms can also occur randomly when panicked.

Diagnosis

During a physical exam, a doctor can determine whether the tremor occurs primarily during action or at rest. The doctor will also check for tremor symmetry, any sensory loss, weakness or muscle atrophy, or decreased reflexes. A detailed family history may indicate if the tremor is inherited. Blood or urine tests can detect thyroid malfunction, other metabolic causes, and abnormal levels of certain chemicals that can cause tremor. These tests may also help to identify contributing causes, such as drug interaction, chronic alcoholism, or another condition or disease. Diagnostic imaging using CT or MRI imaging may help determine if the tremor is the result of a structural defect or degeneration of the brain.

The doctor will perform a neurological examination to assess nerve function and motor and sensory skills. The tests are designed to determine any functional limitations, such as difficulty with handwriting or the ability to hold a utensil or cup. The patient may be asked to place a finger on the tip of her or his nose, draw a spiral, or perform other tasks or exercises.

The doctor may order an electromyogram to diagnose muscle or nerve problems. This test measures involuntary muscle activity and muscle response to nerve stimulation. The selection of the sensors used is important. In addition to studies of muscle activity, tremor can be assessed with accuracy using accelerometers .

Categories

The degree of tremor should be assessed in four positions. The tremor can then be classified by which position most accentuates the tremor:

Position	Name	Description
At rest	Resting tremors	Tremors that are worse at rest include Parkinsonian syndromes and essential tremor if severe. This includes drug-induced tremors from blockers of dopamine receptors such as haloperidol and other antipsychotic drugs.
During contraction (e.g. a tight fist while the arm is resting and supported)	Contraction tremors	Tremors that are worse during supported contraction include essential tremor and also cerebellar and exaggerated physiological tremors such as a hyperadrenergic state or hyperthyroidism. Drugs such as adrenergics, anticholinergics, and xanthines (such as caffeine) can exaggerate physiological tremor.
During posture (e.g. with the arms elevated against gravity such as in a 'bird-wing' position)	Posture tremors	Tremors that are worse with posture against gravity include essential tremor and exaggerated physiological tremors.
During intention (e.g. finger to nose test)	Intention tremors	Intention tremors are tremors that are worse during intention, e.g. as the patient's finger approaches a target, including cerebellar disorders. The terminology of "intention" is currently less used, to the profit of "kinetic".

Treatment

There is no cure for most tremors. The appropriate treatment depends on accurate diagnosis of the cause. Some tremors respond to treatment of the underlying condition. For example, in some cases of psychogenic tremor, treating the patient's underlying psychological problem may cause the tremor to disappear. A few medications can help relieve symptoms temporarily.

Medications

Medications remain the basis of therapy in many cases. Symptomatic drug therapy is available for several forms of tremor:

• Parkinsonian tremor drug treatment involves L-DOPA or dopamine-like drugs such as pergolide, bromocriptine and ropinirole; They can be dangerous, however, as they may cause symptoms such as tardive dyskinesia, akathisia, clonus, and in rare instances tardive (late developing) psychosis. Other drugs used to lessen parkinsonian tremor include amantadine and anticholinergic drugs like benztropine
• Essential tremor may be treated with beta blockers (such as propranolol and nadolol) or primidone, an anticonvulsant
• Cerebellar tremor symptoms may decrease with the application of alcohol (ethanol) or benzodiazepine medications, both of which carry some risk of dependence or addiction
• Rubral tremor patients may receive some relief using L-DOPA or anticholinergic drugs. Surgery may be helpful
• Dystonic tremor may respond to diazepam, anticholinergic drugs, and intramuscular injections of botulinum toxin. Botulinum toxin is also prescribed to treat voice and head tremors and several movement disorders
• Primary orthostatic tremor sometimes is treated with a combination of diazepam and primidone. Gabapentin provides relief in some cases
• Enhanced physiological tremor is usually reversible once the cause is corrected. If symptomatic treatment is needed, beta blockers can be used

Lifestyle

Eliminating tremor “triggers” such as caffeine and other stimulants from the diet is often recommended. Essential tremor may benefit from slight doses of ethanol, but the potential negative consequences of regular ethanol intake need to be taken into account. Beta blockers have been used as an alternative to alcohol in sports such as competitive dart playing and carry less potential for addiction.

Physical therapy and occupational therapy may help to reduce tremor and improve coordination and muscle control for some patients. A physical therapist or occupational therapist will evaluate the patient for tremor positioning, muscle control, muscle strength, and functional skills. Teaching the patient to brace the affected limb during the tremor or to hold an affected arm close to the body is sometimes useful in gaining motion control. Coordination and balancing exercises may help some patients. Some occupational therapists recommend the use of weights, splints, other adaptive equipment, and special plates and utensils for eating.

Surgery

Surgical intervention such as thalamotomy and deep brain stimulation may ease certain tremors. These surgeries are usually performed only when the tremor is severe and does not respond to drugs. Response can be excellent.

Thalamotomy, involving the creation of lesions in the brain region called the thalamus, is quite effective in treating patients with essential, cerebellar, or Parkinsonian tremor. This in-hospital procedure is performed under local anesthesia, with the patient awake. After the patient's head is secured in a metal frame, the surgeon maps the patient's brain to locate the thalamus. A small hole is drilled through the skull and a temperature-controlled electrode is inserted into the thalamus. A low-frequency current is passed through the electrode to activate the tremor and to confirm proper placement. Once the site has been confirmed, the electrode is heated to create a temporary lesion. Testing is done to examine speech, language, coordination, and tremor activation, if any. If no problems occur, the probe is again heated to create a 3-mm permanent lesion. The probe, when cooled to body temperature, is withdrawn and the skull hole is covered. The lesion causes the tremor to permanently disappear without disrupting sensory or motor control.

Deep brain stimulation (DBS) uses implantable electrodes to send high-frequency electrical signals to the thalamus. The electrodes are implanted as described above. The patient uses a hand-held magnet to turn on and turn off a pulse generator that is surgically implanted under the skin. The electrical stimulation temporarily disables the tremor and can be “reversed,” if necessary, by turning off the implanted electrode. Batteries in the generator last about 5 years and can be replaced surgically. DBS is currently used to treat parkinsonian tremor and essential tremor. It is also applied successfully for other rare causes of tremor.

The most common side effects of tremor surgery include dysarthria (problems with motor control of speech), temporary or permanent cognitive impairment (including visual and learning difficulties), and problems with balance.

Biomechanical loading

As well as medication, rehabilitation programmes and surgical interventions, the application of biomechanical loading on tremor movement has been shown to be a technique that is able to suppress the effects of tremor on the human body. It has been established in the literature that most of the different types of tremor respond to biomechanical loading. In particular, it has been clinically tested that the increase of damping or inertia in the upper limb leads to a reduction of the tremorous motion. Biomechanical loading relies on an external device that either passively or actively acts mechanically in parallel to the upper limb to counteract tremor movement. This phenomenon gives rise to the possibility of an orthotic management of tremor.

Starting from this principle, the development of upper-limb non-invasive ambulatory robotic exoskeletons is presented as a promising solution for patients who cannot benefit from medication to suppress the tremor. In this area robotic exoskeletons have emerged, in the form of orthoses, to provide motor assistance and functional compensation to disabled people. An orthosis is a wearable device that acts in parallel to the affected limb. In the case of tremor management, the orthosis must apply a damping or inertial load to a selected set of limb articulations.

Recently, some studies demonstrated that exoskeletons could achieve a consistent 40% of tremor power reduction for all users, being able to attain a reduction ratio in the order of 80% tremor power in specific joints of users with severe tremor. In addition, the users reported that the exoskeleton did not affect their voluntary motion. These results indicate the feasibility of tremor suppression through biomechanical loading.

The main drawbacks of this mechanical management of tremor are (1) the resulting bulky solutions, (2) the inefficiency in transmitting loads from the exoskeleton to the human musculo-skeletal system and (3) technological limitations in terms of actuator technologies. In this regard, current trends in this field are focused on the evaluation of the concept of biomechanical loading of tremor through selective Functional Electrical Stimulation (FES) based on a (Brain-to-Computer Interaction) BCI-driven detection of involuntary (tremor) motor activity.

Neurological disorder

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Neurological_disorder 

 

Neurological disorder
Neurons in person with epilepsy, 40x magnified.
Specialty	Neurology

A neurological disorder is any disorder of the nervous system. Structural, biochemical or electrical abnormalities in the brain, spinal cord or other nerves can result in a range of symptoms. Examples of symptoms include paralysis, muscle weakness, poor coordination, loss of sensation, seizures, confusion, pain and altered levels of consciousness. There are many recognized neurological disorders, some relatively common, but many rare. They may be assessed by neurological examination, and studied and treated within the specialities of neurology and clinical neuropsychology.

Interventions for neurological disorders include preventive measures, lifestyle changes, physiotherapy or other therapy, neurorehabilitation, pain management, medication, operations performed by neurosurgeons or a specific diet. The World Health Organization estimated in 2006 that neurological disorders and their sequelae (direct consequences) affect as many as one billion people worldwide, and identified health inequalities and social stigma/discrimination as major factors contributing to the associated disability and suffering.

Causes

Part of the causal chain leading to Alzheimer's disease.

Although the brain and spinal cord are surrounded by tough membranes, enclosed in the bones of the skull and spinal vertebrae, and chemically isolated by the blood–brain barrier, they are very susceptible if compromised. Nerves tend to lie deep under the skin but can still become exposed to damage. Individual neurons, and the neural circuits and nerves into which they form, are susceptible to electrochemical and structural disruption. Neuroregeneration may occur in the peripheral nervous system and thus overcome or work around injuries to some extents, but it is thought to be rare in the brain and spinal cord.

The specific causes of neurological problems vary, but can include genetic disorders, congenital abnormalities or disorders, infections, lifestyle or environmental health problems including malnutrition, and brain injury, spinal cord injury, nerve injury and gluten sensitivity (with or without intestinal damage or digestive symptoms). Metal poisoning, where metals accumulate in the human body and disrupt biological processes, has been reported to induce neurological problems, at least in the case of lead. The neurological problem may start in another body system that interacts with the nervous system. For example, cerebrovascular disorders involve brain injury due to problems with the blood vessels (cardiovascular system) supplying the brain; autoimmune disorders involve damage caused by the body's own immune system; lysosomal storage diseases such as Niemann-Pick disease can lead to neurological deterioration. The National Institutes of Health recommend considering the evaluation of an underlying celiac disease in people with unexplained neurological symptoms, particularly peripheral neuropathy or ataxia.

In a substantial minority of cases of neurological symptoms, no neural cause can be identified using current testing procedures, and such "idiopathic" conditions can invite different theories about what is occurring.

Numerous examples have been described of neurological disorders that are associated with mutated DNA repair genes. Inadequate repair of DNA damages can lead directly to cell death and neuron depletion as well as disruptions in the pattern of epigenetic alterations required for normal neuronal function.

Classification

Deaths due to neurological conditions per million persons 2012

  18-52

  53-68

  69-84

  85-99

  100-131

  132-157

  158-186

  187-243

  244-477

  478-1,482

Neurological disorders can be categorized according to the primary location affected, the primary type of dysfunction involved, or the primary type of cause. The broadest division is between central nervous system disorders and peripheral nervous system disorders. The Merck Manual lists brain, spinal cord and nerve disorders in the following overlapping categories:

Nervous system
The Human Nervous System.
Identifiers
MeSH	D009422
Anatomical terminology

• Brain:
  • Brain damage according to cerebral lobe (see also 'lower' brain areas such as basal ganglia, cerebellum, brainstem):
    • Frontal lobe damage
    • Parietal lobe damage
    • Temporal lobe damage
    • Occipital lobe damage
  • Brain dysfunction according to type:
    • Aphasia (language)
    • Dysgraphia (writing)
    • Dysarthria (speech)
    • Apraxia (patterns or sequences of movements)
    • Agnosia (identifying things or people)
    • Amnesia (memory)
• Spinal cord disorders (see spinal pathology, injury, inflammation)
• Peripheral neuropathy and other Peripheral nervous system disorders
• Cranial nerve disorder such as Trigeminal neuralgia
• Autonomic nervous system disorders such as dysautonomia, multiple system atrophy
• Seizure disorders such as epilepsy
• Movement disorders of the central and peripheral nervous system such as Parkinson's disease, essential tremor, amyotrophic lateral sclerosis, Tourette's syndrome, multiple sclerosis and various types of peripheral neuropathy
• Sleep disorders such as narcolepsy
• Migraines and other types of headache such as cluster headache and tension headache
• Lower back and neck pain (see back pain)
• Central neuropathy (see neuropathic pain)
• Neuropsychiatric illnesses (diseases and/or disorders with psychiatric features associated with known nervous system injury, underdevelopment, biochemical, anatomical, or electrical malfunction, and/or disease pathology e.g. attention deficit hyperactivity disorder, autism, Asperger syndrome, Tourette's syndrome and some cases of obsessive compulsive disorder as well as the neurobehavioral associated symptoms of degeneratives of the nervous system such as Parkinson's disease, essential tremor, Huntington's disease, Alzheimer's disease, multiple sclerosis and organic psychosis.)

Many of the diseases and disorders listed above have neurosurgical treatments available (e.g. Tourette's syndrome, Parkinson's disease, essential tremor and obsessive compulsive disorder).

• Delirium and dementia such as Alzheimer's disease
• Dizziness and vertigo
• Stupor and coma
• Head injury
• Stroke (CVA, cerebrovascular attack)
• Tumors of the nervous system (e.g. cancer)
• Multiple sclerosis and other demyelinating diseases
• Infections of the brain or spinal cord (including meningitis)
• Prion diseases (a type of infectious agent)
• Complex regional pain syndrome (a chronic pain condition)

Neurological disorders in non-human animals are treated by veterinarians.

Mental functioning

A neurological examination can, to some extent, assess the impact of neurological damage and disease on brain function in terms of behavior, memory or cognition. Behavioral neurology specializes in this area. In addition, clinical neuropsychology uses neuropsychological assessment to precisely identify and track problems in mental functioning, usually after some sort of brain injury or neurological impairment.

Alternatively, a condition might first be detected through the presence of abnormalities in mental functioning, and further assessment may indicate an underlying neurological disorder. There are sometimes unclear boundaries in the distinction between disorders treated within neurology, and mental disorders treated within the other medical specialty of psychiatry, or other mental health professions such as clinical psychology. In practice, cases may present as one type but be assessed as more appropriate to the other. Neuropsychiatry deals with mental disorders arising from specific identified diseases of the nervous system.

One area that can be contested is in cases of idiopathic neurological symptoms - conditions where the cause cannot be established. It can be decided in some cases, perhaps by exclusion of any accepted diagnosis, that higher-level brain/mental activity is causing symptoms, rather than the symptoms originating in the area of the nervous system from which they may appear to originate. Classic examples are "functional" seizures, sensory numbness, "functional" limb weakness and functional neurological deficit ("functional" in this context is usually contrasted with the old term "organic disease"). Such cases may be contentiously interpreted as being "psychological" rather than "neurological". Some cases may be classified as mental disorders, for example as conversion disorder, if the symptoms appear to be causally linked to emotional states or responses to social stress or social contexts.

On the other hand, dissociation refers to partial or complete disruption of the integration of a person's conscious functioning, such that a person may feel detached from one's emotions, body and/or immediate surroundings. At one extreme this may be diagnosed as depersonalization disorder. There are also conditions viewed as neurological where a person appears to consciously register neurological stimuli that cannot possibly be coming from the part of the nervous system to which they would normally be attributed, such as phantom pain or synesthesia, or where limbs act without conscious direction, as in alien hand syndrome. Theories and assumptions about consciousness, free will, moral responsibility and social stigma can play a part in this, whether from the perspective of the clinician or the patient.

Some of the fields that contribute to understanding mental functioning

Conditions that are classed as mental disorders, or learning disabilities and forms of intellectual disability, are not themselves usually dealt with as neurological disorders. Biological psychiatry seeks to understand mental disorders in terms of their basis in the nervous system, however. In clinical practice, mental disorders are usually indicated by a mental state examination, or other type of structured interview or questionnaire process. At the present time, neuroimaging (brain scans) alone cannot accurately diagnose a mental disorder or tell the risk of developing one; however, it can be used to rule out other medical conditions such as a brain tumor. In research, neuroimaging and other neurological tests can show correlations between reported and observed mental difficulties and certain aspects of neural function or differences in brain structure. In general, numerous fields intersect to try to understand the basic processes involved in mental functioning, many of which are brought together in cognitive science. The distinction between neurological and mental disorders can be a matter of some debate, either in regard to specific facts about the cause of a condition or in regard to the general understanding of brain and mind.

Moreover, the definition of disorder in medicine or psychology is sometimes contested in terms of what is considered abnormal, dysfunctional, harmful or unnatural in neurological, evolutionary, psychometric or social terms.

Essential tremor

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Essential_tremor 

 

Essential tremor
Other names	Idiopathic tremor
Archimedean spiral drawings from a man with a unilateral essential tremor. The spiral on the left was drawn by the subject using the left hand, and the one on the right using the right hand.
Specialty	Neurology
Usual onset	Any age, but typically after 40
Causes	Unknown
Risk factors	Family history, exposure to particular toxins
Diagnostic method	Based on symptoms
Differential diagnosis	Cerebellar tremor, dystonic tremor, multiple sclerosis, Parkinson's disease
Treatment	Medications, surgery
Medication	Beta blockers, primidone, anti-epileptics, topiramate, gabapentin, levetiracetam, benzodiazepines
Frequency	Annual incidence of 23.7 per 100,000 (2010)

Essential tremor (ET), also called benign tremor, familial tremor, and idiopathic tremor, is a medical condition characterized by involuntary rhythmic contractions and relaxations (oscillations or twitching movements) of certain muscle groups in one or more body parts of unknown cause. It typically is symmetrical, and affects the arms, hands, or fingers; but sometimes involves the head, vocal cords, or other body parts.  Essential tremor is either an action (intention) tremor—it intensifies when one tries to use the affected muscles during voluntary movements such as eating and writing—or it is a postural tremor, present with sustained muscle tone. This means that it is distinct from a resting tremor, such as that caused by Parkinson's disease, which is not correlated with movement.

Essential tremor is a progressive neurological disorder, and the most common movement disorder. Its onset is usually after age 40, but it can occur at any age. The cause is unknown. Diagnosis is by observing the typical pattern of the tremor coupled with the exclusion of known causes of such a tremor.

While essential tremor is distinct from Parkinson's disease, which causes a resting tremor, essential tremor is nevertheless sometimes misdiagnosed as Parkinson's disease. Some patients have been found to have both essential tremors and resting tremors.

Treatments for essential tremor include medications, typically given sequentially to determine which is most effective coupled with which has the least troublesome side effects. Clostridium botulinum toxin (Botox) injections and ultrasound are also sometimes used for cases refractory to medications.

Signs and symptoms

In mild cases, ET can manifest as the inability to stop the tongue or hands from shaking, the ability to sing only in vibrato, and difficulty doing small, precise tasks such as threading a needle. Even simple tasks such as cutting in a straight line or using a ruler can range from difficult to impossible, depending on the severity of the condition. In disabling cases, ET can interfere with a person's activities of daily living, including feeding, dressing, and taking care of personal hygiene. Essential tremor generally presents as a rhythmic tremor (4–12 Hz) that occurs only when the affected muscle is exerting effort. Any sort of physical or mental stress tends to make the tremor worse.

The tremor may also occur in the head (neck), jaw, and voice, as well as other body regions, with the general pattern being that the tremor begins in the arms and then spreads to these other regions in some people. Women are more likely to develop the head tremor than are men. Other types of tremor may also occur, including postural tremor of the outstretched arms, intention tremor of the arms, and rest tremor in the arms. Some people may have unsteadiness and problems with gait and balance.

ET-related tremors do not occur during sleep, but people with ET sometimes complain of an especially coarse tremor upon awakening that becomes noticeably less coarse within the first few minutes of wakefulness. Tremor and disease activity/intensity can worsen in response to fatigue, strong emotions, low blood sugar, cold and heat, caffeine, lithium salts, some antidepressants, and other factors. Typically, the tremor worsens in "performance" situations, such as when writing a cheque for payment at a store or giving a presentation.

Parkinson's disease and parkinsonism can also occur simultaneously with ET. The degree of tremor, rigidity, and functional disability did not differ from patients with idiopathic Parkinson's disease. Hand tremor predominated (as it did in Parkinson’s disease), and occurred in nearly all cases, followed by head tremor, voice tremor, neck, face, leg, tongue, and trunk tremor. Most other tremors occurred in association with hand tremor. More severe tremors, a lower sleep disorder frequency, and a similar prevalence of other non-motor symptoms also can occur.

Walking difficulties in essential tremor are common. About half of patients have associated dystonia, including cervical dystonia, writer's cramp, spasmodic dysphonia, and cranial dystonia, and 20% of the patients had associated parkinsonism. Olfactory dysfunction (loss of sense of smell) is common in Parkinson’s disease, and has also been reported to occur in patients with essential tremor. A number of patients with essential tremor also exhibit many of the same neuropsychiatric disturbances seen in idiopathic Parkinson's disease.

Essential tremor with tremor onset after the age of 65 has been associated with mild cognitive impairment, as well as dementia; although the link between these conditions, if any, is still not understood.

Essential tremor has two tremor components, central and peripheral. These two tremor components were identified by measuring the tremor of ET patients once with no weights on their hands and then with 1-lb weights on their hands. The addition of the weights resulted in a tremor spectrum with two peaks, one that maintained the same frequency (the central tremor) and one that decreased in frequency (the peripheral tremor). Only with the addition of the weights was the peripheral tremor distinguishable from the central tremor.

Cause

Genetic

The underlying cause of essential tremor is not clear, but many cases seem to be familial. About half of the cases are due to a genetic mutation and the pattern of inheritance is most consistent with autosomal dominant transmission. No genes have been identified yet, but genetic linkage has been established with several chromosomal regions.

Toxins

Some environmental factors, including toxins, are also under active investigation, as they may play a role in the disease's cause.

Pathophysiology

In terms of pathophysiology, clinical, physiological and imaging studies point to an involvement of the cerebellum and/or cerebellothalamocortical circuits. Changes in the cerebellum could also be mediated by alcoholic beverage consumption. Purkinje cells are especially susceptible to ethanol excitotoxicity. Impairment of Purkinje synapses is a component of cerebellar degradation that could underlie essential tremor. Some cases have Lewy bodies in the locus ceruleus. ET cases that progress to Parkinson's disease are less likely to have had cerebellar problems. Recent neuroimaging studies have suggested that the efficiency of the overall brain functional network in ET is disrupted.

Recent post mortem studies have evidenced alterations in (leucine-rich repeat and Ig domain containing 1 (LINGO1) gene and GABA receptors in the cerebellum of people with essential tremor. HAPT1 mutations have also been linked to ET, as well as to Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy.

In 2012, the National Toxicology Program concluded that sufficient evidence exists of an association between blood lead exposure at levels >10 μg/dl and essential tremor in adults, and limited evidence at blood lead levels >5 μg/dl.

Diagnosis

Usually, the diagnosis is established on clinical grounds. Tremors can start at any age, from birth through advanced ages (senile tremor). Any voluntary muscle in the body may be affected, although the tremor is most commonly seen in the hands and arms and slightly less commonly in the neck (causing the person's head to shake), tongue, and legs. A resting tremor of the hands is sometimes present. Tremor occurring in the legs might be diagnosable as orthostatic tremor.

ET occurs within multiple neurological disorders besides Parkinson's disease. This includes migraine disorders, where co-occurrences between ET and migraines have been examined.

Terminology

This type of tremor is often referred to as "kinetic tremor". Essential tremor has been known as "benign essential tremor", but the adjective "benign" has been removed in recognition of the sometimes disabling nature of the disorder.

Treatment

General measures

Not all individuals with ET require treatment, but many treatment options are available depending on symptom severity. Caffeine and stress should be avoided, and adequate good-quality sleep is recommended.

Oral medications

First-line

When symptoms are sufficiently troublesome to warrant treatment, the first medication choices are beta blockers such as propranolol or alternately, nadolol and timolol. Atenolol and pindolol are not effective for tremor. The anti-epileptic primidone may also be effective.

Propranolol and primidone only have tremor-reducing effects on about half of ET patients, and the effects are moderate.

Second-line

Second-line medications are the anti-epileptics topiramate, gabapentin (as monotherapy) or levetiracetam, or benzodiazepines such as alprazolam.

Third-line

Third-line medications are clonazepam and mirtazapine.

Fourth-line

Theophylline has been used by some practitioners to treat ET, though it may also induce tremor. However, its use is debated due to conflicting data on its efficacy. Some evidence shows that low doses may lead to improvement.

Ethanol has shown superior efficacy to those of benzodiazepines in small trials. It improves tremor in small doses and its effects are usually noticeable within 20 minutes for 3–5 hours, but occasionally appears in a rebound tremor augmentation later.

Some systematic reviews of medications for the treatment of ET have been conducted. A 2017 review of topiramate found limited data and low quality evidence to support its efficacy and the occurrence of treatment-limiting adverse effects, a 2017 review of zonisamide found insufficient information to assess efficacy and safety, and a 2016 review of pregabalin determined the effects to be uncertain due to the low quality of evidence.

Botulinum injection

When medications do not control the tremor or the person does not tolerate medication, C. botulinum toxin, deep brain stimulation, or occupational therapy can be helpful. The electrodes for deep brain stimulation are usually placed in the "tremor center" of the brain, the ventral intermediate nucleus of the thalamus.

Ultrasound

Additionally, MRI-guided high-intensity focused ultrasound is a nonsurgical treatment option for people with essential tremor who are medication refractory. MRI-guided high-intensity focused ultrasound does not achieve healing, but can improve the quality of life. While its long-term effects are not yet established, the improvement in tremor score from baseline was durable at 1 year and 2 years following the treatment. To date, reported adverse events and side effects have been mild to moderate. Possible adverse events include gait difficulties, balance disturbances, paresthesias, headache, skin burns with ulcerations, skin retraction, scars, and blood clots. This procedure is contraindicated in pregnant women, persons who have non-MRI compatible implanted metallic devices, allergy to MR contrast agents, cerebrovascular disease, abnormal bleeding, hemorrhage and/or blood clotting disorders, advanced kidney disease or on dialysis, heart conditions, severe hypertension, and ethanol or substance abuse, among others. The US Food and Drug Administration (FDA) approved Insightec’s Exablate Neuro system to treat essential tremor in 2016.

Another treatment for essential tremor is a surgical option; deep brain stimulation is used.

Prognosis

Although essential tremor is often mild, people with severe tremor have difficulty performing many of their routine activities of daily living. ET is generally progressive in most cases (sometimes rapidly, sometimes very slowly), and can be disabling in severe cases.

Epidemiology

ET is one of the most common neurological diseases, with a prevalence around 4% in persons age 40 and older and considerably higher among persons in their 60s, 70s, 80s, with an estimated 20% of individuals in their 90s and over. Aside from enhanced physiological tremor, it is the most common type of tremor and one of the most commonly observed movement disorders.

Society and culture

Actress Katharine Hepburn (1907–2003) had an essential tremor, which she inherited from her grandfather, that caused her head—and sometimes her hands—to shake. The tremor was noticeable by the time of her performance in the 1979 film The Corn is Green, when critics mentioned the "palsy that kept her head trembling". Hepburn's tremor worsened in her later life.

In 2010, musician Daryl Dragon of The Captain and Tennille was diagnosed with essential tremor, with the condition becoming so severe that Dragon was forced to retire from music.

Director-writer-producer-comedian Adam McKay was diagnosed with essential tremor.

Downton Abbey creator Julian Fellowes has the condition, as does the show's character Charlie Carson 

Research

Harmaline is a widely used model of essential tremor (ET) in rodents. Harmaline is thought to act primarily on neurons in the inferior olive. Olivocerebellar neurons exhibit rhythmic excitatory action when harmaline is applied locally. Harmane or harmaline has been implicated not only in essential tremors, but is also found in greater quantities in the brain fluid of Parkinson's disease sufferers as well as cancer. Higher levels of the neurotoxin are associated with greater severity of the tremors. Harmane is particularly abundant in meats, and certain cooking practices (e.g., long cooking times) increase its concentration, however, at least one study has shown that harmane blood concentrations do not go up after meat consumption in ET patients with already elevated harmane levels, where as the control group's harmane levels increase accordingly, suggesting that another factor, like a metabolic defect, may be responsible for the higher harmane levels in E.T. patients.

Caprylic acid is being researched as a possible treatment for essential tremor. It has currently been approved by the FDA and designated as GRAS, and is used as a food additive and has been studied as part of a ketogenic diet for treatment of epilepsy in children. Research on caprylic acid as a possible treatment for ET begun because researchers recognized that ethanol was effective in reducing tremor, and because of this, they looked into longer-chain alcohols reducing tremor. They discovered that 1-octanol reduced tremor and did not have the negative side effects of ethanol. Pharmacokinetic research on 1-octanol lead to the discovery that 1-octanol metabolized into caprylic acid in the body and that caprylic acid actually was the tremor-reducing agent. Many studies of the effects of caprylic acid on essential tremor have been done, including a dose-escalation study on ET patients and a study testing the effects of caprylic acid on central and peripheral tremor. The dose-escalation study examined doses of 8 mg/kg to 128 mg/kg and determined that these concentrations were safe with mild side effects. The maximum tolerated dose was not reached in this study. The study testing the effects of caprylic acid on central and peripheral tremors determined that caprylic acid reduced both.

Mesolimbic pathway

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Mesolimbic_pathway

The mesolimbic pathway, sometimes referred to as the reward pathway, is a dopaminergic pathway in the brain. The pathway connects the ventral tegmental area in the midbrain to the ventral striatum of the basal ganglia in the forebrain. The ventral striatum includes the nucleus accumbens and the olfactory tubercle.

The release of dopamine from the mesolimbic pathway into the nucleus accumbens regulates incentive salience (e.g. motivation and desire for rewarding stimuli) and facilitates reinforcement and reward-related motor function learning; it may also play a role in the subjective perception of pleasure. The dysregulation of the mesolimbic pathway and its output neurons in the nucleus accumbens plays a significant role in the development and maintenance of an addiction.

Anatomy

The mesolimbic pathway and its positioning in relation to the other dopaminergic pathways

The mesolimbic pathway is a collection of dopaminergic (i.e., dopamine-releasing) neurons that project from the ventral tegmental area (VTA) to the ventral striatum, which includes the nucleus accumbens (NAcc) and olfactory tubercle. It is one of the component pathways of the medial forebrain bundle, which is a set of neural pathways that mediate brain stimulation reward.

The VTA is located in the midbrain and consists of dopaminergic, GABAergic, and glutamatergic neurons. The dopaminergic neurons in this region receive stimuli from both cholinergic neurons in the pedunculopontine nucleus and the laterodorsal tegmental nucleus as well as glutamatergic neurons in other regions such as the prefrontal cortex. The nucleus accumbens and olfactory tubercle are located in the ventral striatum and are primarily composed of medium spiny neurons. The nucleus accumbens is subdivided into limbic and motor subregions known as the NAcc shell and NAcc core. The medium spiny neurons in the nucleus accumbens receive input from both the dopaminergic neurons of the VTA and the glutamatergic neurons of the hippocampus, amygdala, and medial prefrontal cortex. When they are activated by these inputs, the medium spiny neurons' projections release GABA onto the ventral pallidum.

Function

The mesolimbic pathway regulates incentive salience, motivation, reinforcement learning, and fear, among other cognitive processes.

The mesolimbic pathway is involved in motivation cognition. Depletion of dopamine in this pathway, or lesions at its site of origin, decrease the extent to which an animal is willing to go to obtain a reward (e.g. the number of lever presses for intravenous nicotine delivery in rats or time spent searching for food). Dopaminergic drugs are also able to increase the extent an animal is willing to go to obtain a reward. Moreover, the firing rate of neurons in the mesolimbic pathway increases during anticipation of reward, which may explain craving. Mesolimbic dopamine release was once thought to be the primary mediator of pleasure, but is now believed to have only a minor or secondary role in pleasure perception.

Clinical significance

Mechanisms of addiction

The mesolimbic pathway and a specific set of the pathway's output neurons (e.g. D1-type medium spiny neurons within the nucleus accumbens) play a central role in the neurobiology of addiction. Drug addiction is an illness caused by habitual substance abuse that induces chemical changes in the brain's circuitry. Commonly abused substances such as cocaine, alcohol, and nicotine have been shown to increase extracellular levels of dopamine within the mesolimbic pathway, preferentially within the nucleus accumbens. The mechanisms by which these drugs do so vary depending on the drug prototype. For example, cocaine precludes the re-uptake of synaptic dopamine through blocking the presynaptic dopamine transporter. Another stimulant, amphetamine, promotes increased dopamine from the synaptic vesicles. Non-stimulant drugs typically bind with ligand-gated channels or G protein-coupled receptors. Such drugs include alcohol, nicotine, and tetrahydrocannabinol (THC).

These dopaminergic activations of the mesolimbic pathway are accompanied by the perception of reward. This stimulus-reward association shows a resistance to extinction and creates an increased motivation to repeat that same behavior that caused it.

In relation, a 2017 study found that abusive (emotional, physical, and sexual) and adverse life events were associated with a heightened limbic response to cocaine. In other words, individuals who had previously suffered abuse were more likely to have a brain pathway primed for cocaine or drug use.

Relation to neurological and psychological disorders

The mesolimbic pathway is implicated in schizophrenia, depression, and Parkinson's disease. It is also theorized to be implicated in overuse of digital media. Each involves distinct structural changes within the mesolimbic pathway.