**2. Defining the human tremor**

Tremor is the most common movement disorder characterized by repetitive and stereotyped movements [1]. The human tremor is a clinical manifestation characterized by an

involuntary, rhythmic, oscillatory movement of a body part that can be classified in many ways, depending on its etiology, phenomenology, frequency, location and pharmacological response [2; 3].

Human Tremor: Origins, Detection and Quantification 5

amplitude with movement. Instead, the cerebellar tremor appears while performing a movement, therefore, is considered an action tremor, predominantly kinetic. In mesencephalic and Holmes' tremor it can be found a mixture of resting, postural and kinetic

Regarding the frequency of tremor, or rather, according to number of oscillations of the affected segment in a unit time, tremor can be classified into three main types: low frequency tremor (less than four cycles per second or Hertz); middle frequency tremor (between 4 and 7 Hz) and high-frequency tremor (more than 7 Hz) [4]. Physiological tremor usually presents high frequency (8-12 Hz) and low amplitude. Essential tremor reaches frequencies between 6-12 Hz while tremor from Parkinson`s disease usually has frequencies between 4 and 6 Hz. The cerebellar tremor is also a low frequency tremor (less than 5 Hz), such as the mesencephalic tremor (2-5 Hz). However, the frequency range for tremor can

Regarding to the location, it is possible to observe that tremor can occur in any part of the body; however the limb segments and the head are the most affected. There may be involvement of other body parts, such as the trunk, but this situation is not common [4].

According to drug response, beta-adrenergic blockers are commonly used in physiological tremor treatment. Alcohol, which can be used as therapeutic method, may be employed in patients with essential tremor. Tremor can also be reduced by relaxation, concentration,

About two thirds of patients with essential tremor show considerable reduction of tremor for 45 to 60 minutes after the ingestion of alcohol; however alcohol cannot be used over a long period of time because in the course of time larger quantities will be required to produce similar effects, which can cause chronic alcoholism. Furthermore, when the effect of alcohol is over, tremor gets worse. The treatment of essential tremor is done with primidone or beta-blockers, another alternative is the use of the botulinum toxin direct in the affected muscles. Besides this, alprazolam has effect in the treatment of essential tremor. When this

The parkinsonian tremor can be reduced or controlled by the use of drugs with dopaminergic effects and with anticholinergics; in certain cases, a thalamotomy able to reach the thalamic nucleus, specially the lower ventral medial nucleus, is used in the case of unilateral Parkinson's disease. The constant thalamic high frequency stimulation is related with good results in essential and parkinsonian tremor. The deep thalamic cerebral stimulation is safer and more effective than thalamotomy, which requires the permanent placement of an electrode in the brain. Side effects of deep brain stimulation are reversible

The cerebellar tremor does not respond well to treatments. Usually substances that increase the gabaergic activity, like valproic acid, clonazepam and isoniazid, are used. The mesencephalic tremor does not respond well to some drugs either, especially its postural component. However, the resting component can improve with anticholinergics. The

pathology is clinically intractable, a contralateral thalamotomy surgery is indicated.

with the manipulation of the stimulation parameters.

vary depending on the patient condition and the type of treatment he is receiving.

voluntary suppression and the increase of load on the affected extremity.

tremor with high amplitude and intensity.

The rhythmic characteristic of tremor around a balanced position, as the regular rhythm, amplitude and frequency make easier the identification and also the differential diagnosis of tremor, distinguishing it from other involuntary movements.

The movement caused by tremor can be associated to many factors such as neurological disorders and natural processes. The latter is often referred to as physiological tremor and is present in greater or lesser degree, in all humans [2; 4]. The presence of severe tremor disorders causes many difficulties, and can also indicate the presence of diseases related to the central nervous system (CNS). However, the dividing landmark between physiological tremor and that resultant of dysfunctions is tenuous and has not been precisely established, since the changes in the CNS control that causes it can be associated to many factors. Some examples of pathological tremor, i.e. associated to neurological disorder factors, are the cerebellar, essential and parkinsonian tremor [5], and others, such as in psychogenic, orthostatic and neuropathic tremor, which are considered relatively rare in the medical literature [6].

According to phenomenology, or better, according to the circumstances in which tremor manifests it can be classified in two main types: resting tremor and action tremor [4]. The resting tremor can be observed when the body part in which it appears is not suffering the effects of gravity and the muscles are not contracted [4]. Usually, the resting tremor has the characteristic of adduction-abduction or flexion-extension. The main example of resting tremor is the parkinsonian tremor.

The action tremor appears during a voluntary muscle contraction [4]. The action tremor encompasses postural, kinetic, intentional, task-specific and isometric tremor.

The postural tremor can be observed when maintaining a voluntary position against the effect of gravity [4]. Some examples of postural tremor are the essential, cephalic, axial cerebellar and primary orthostatic tremor. The kinetic tremor can be observed while performing a voluntary movement [4], whereas the intentional tremor occurs during a movement, but specifically when there is the intention to hit a target, like in the test of finger-nose, while writing, speaking and handling objects. The cerebellar, essential and mesencephalic tremor are examples of intentional tremor.

The task-specific tremor is manifested almost exclusively during a specific motor movement, such as the activities of writing, drawing or playing a musical instrument [4]. Finally, the isometric tremor occurs when the affected segment is contracted without the occurrence of the displacement of the body segment [4]. Generally it can be observed in isometric muscle contraction, which occurs when force is exerted against a steady object, like in the act of pushing a wall or flexing the wrist on a surface.

Usually, the essential tremor and the enhanced physiological tremor are classified as postural tremor. The parkinsonian tremor is typically a resting tremor and decreases its amplitude with movement. Instead, the cerebellar tremor appears while performing a movement, therefore, is considered an action tremor, predominantly kinetic. In mesencephalic and Holmes' tremor it can be found a mixture of resting, postural and kinetic tremor with high amplitude and intensity.

4 Practical Applications in Biomedical Engineering

tremor is the parkinsonian tremor.

tremor, distinguishing it from other involuntary movements.

tremor, which are considered relatively rare in the medical literature [6].

response [2; 3].

involuntary, rhythmic, oscillatory movement of a body part that can be classified in many ways, depending on its etiology, phenomenology, frequency, location and pharmacological

The rhythmic characteristic of tremor around a balanced position, as the regular rhythm, amplitude and frequency make easier the identification and also the differential diagnosis of

The movement caused by tremor can be associated to many factors such as neurological disorders and natural processes. The latter is often referred to as physiological tremor and is present in greater or lesser degree, in all humans [2; 4]. The presence of severe tremor disorders causes many difficulties, and can also indicate the presence of diseases related to the central nervous system (CNS). However, the dividing landmark between physiological tremor and that resultant of dysfunctions is tenuous and has not been precisely established, since the changes in the CNS control that causes it can be associated to many factors. Some examples of pathological tremor, i.e. associated to neurological disorder factors, are the cerebellar, essential and parkinsonian tremor [5], and others, such as in psychogenic, orthostatic and neuropathic

According to phenomenology, or better, according to the circumstances in which tremor manifests it can be classified in two main types: resting tremor and action tremor [4]. The resting tremor can be observed when the body part in which it appears is not suffering the effects of gravity and the muscles are not contracted [4]. Usually, the resting tremor has the characteristic of adduction-abduction or flexion-extension. The main example of resting

The action tremor appears during a voluntary muscle contraction [4]. The action tremor

The postural tremor can be observed when maintaining a voluntary position against the effect of gravity [4]. Some examples of postural tremor are the essential, cephalic, axial cerebellar and primary orthostatic tremor. The kinetic tremor can be observed while performing a voluntary movement [4], whereas the intentional tremor occurs during a movement, but specifically when there is the intention to hit a target, like in the test of finger-nose, while writing, speaking and handling objects. The cerebellar, essential and

The task-specific tremor is manifested almost exclusively during a specific motor movement, such as the activities of writing, drawing or playing a musical instrument [4]. Finally, the isometric tremor occurs when the affected segment is contracted without the occurrence of the displacement of the body segment [4]. Generally it can be observed in isometric muscle contraction, which occurs when force is exerted against a steady object,

Usually, the essential tremor and the enhanced physiological tremor are classified as postural tremor. The parkinsonian tremor is typically a resting tremor and decreases its

encompasses postural, kinetic, intentional, task-specific and isometric tremor.

mesencephalic tremor are examples of intentional tremor.

like in the act of pushing a wall or flexing the wrist on a surface.

Regarding the frequency of tremor, or rather, according to number of oscillations of the affected segment in a unit time, tremor can be classified into three main types: low frequency tremor (less than four cycles per second or Hertz); middle frequency tremor (between 4 and 7 Hz) and high-frequency tremor (more than 7 Hz) [4]. Physiological tremor usually presents high frequency (8-12 Hz) and low amplitude. Essential tremor reaches frequencies between 6-12 Hz while tremor from Parkinson`s disease usually has frequencies between 4 and 6 Hz. The cerebellar tremor is also a low frequency tremor (less than 5 Hz), such as the mesencephalic tremor (2-5 Hz). However, the frequency range for tremor can vary depending on the patient condition and the type of treatment he is receiving.

Regarding to the location, it is possible to observe that tremor can occur in any part of the body; however the limb segments and the head are the most affected. There may be involvement of other body parts, such as the trunk, but this situation is not common [4].

According to drug response, beta-adrenergic blockers are commonly used in physiological tremor treatment. Alcohol, which can be used as therapeutic method, may be employed in patients with essential tremor. Tremor can also be reduced by relaxation, concentration, voluntary suppression and the increase of load on the affected extremity.

About two thirds of patients with essential tremor show considerable reduction of tremor for 45 to 60 minutes after the ingestion of alcohol; however alcohol cannot be used over a long period of time because in the course of time larger quantities will be required to produce similar effects, which can cause chronic alcoholism. Furthermore, when the effect of alcohol is over, tremor gets worse. The treatment of essential tremor is done with primidone or beta-blockers, another alternative is the use of the botulinum toxin direct in the affected muscles. Besides this, alprazolam has effect in the treatment of essential tremor. When this pathology is clinically intractable, a contralateral thalamotomy surgery is indicated.

The parkinsonian tremor can be reduced or controlled by the use of drugs with dopaminergic effects and with anticholinergics; in certain cases, a thalamotomy able to reach the thalamic nucleus, specially the lower ventral medial nucleus, is used in the case of unilateral Parkinson's disease. The constant thalamic high frequency stimulation is related with good results in essential and parkinsonian tremor. The deep thalamic cerebral stimulation is safer and more effective than thalamotomy, which requires the permanent placement of an electrode in the brain. Side effects of deep brain stimulation are reversible with the manipulation of the stimulation parameters.

The cerebellar tremor does not respond well to treatments. Usually substances that increase the gabaergic activity, like valproic acid, clonazepam and isoniazid, are used. The mesencephalic tremor does not respond well to some drugs either, especially its postural component. However, the resting component can improve with anticholinergics. The

stereotactic surgery on the ventral medial nucleus of thalamus can control the postural component.

Human Tremor: Origins, Detection and Quantification 7

Regarding to the study of tremor's origins only relatively recently such ideas have received

The movement caused by tremor can be associated to factors such as neurological disorders and natural processes. [2; 11; 12] The former is called pathological tremor whereas the latter

There are several hypotheses to explain the appearance of physiological tremor (PT). One explanation for the existence of physiological tremor is the effect of ballistocardiogram, i.e., the passive vibration of the body tissues produced by the mechanical activity of the heart [13], i.e., a result of mechanical reflexes of the heartbeat and also of neural reflexes [14]. Another hypothesis is that physiological tremor is induced by mechanical properties of

It is also believed that the physiological tremor is a peripheral manifestation of neural oscillatory activity in the central nervous system (CNS) and that some types of pathological

According to Hallett (1998), the sources of tremor can be summarized into three groups:

The first source is the mechanical oscillations, in which joints and muscle movements satisfy the laws of physics and the complex joint-muscle-tendon system can be compared to masses and springs. Therefore, the oscillations can be interpreted as the movements of masses and

The second source of tremor is the reflex oscillations that are reported in the central and peripheral circuits. On the peripheral circuit the path occurs from muscles to the spinal cord and from the spinal cord to the muscles. On the central circuit the path occurs from peripheral to the spinal cord and supraspinal segments including the brain, cerebellum,

The third and last source of tremor is central oscillations that can be observed since the first recordings of the electroencephalography (EEG). The neural activity follows rhythmic behavior. Therefore, the cerebral cortex, the basal ganglia, the cerebellum and the brainstem

Detailed analysis of oscillations in the CNS are imprecise due to the difficulty in performing measurements directly in the human brain [8]. As these neural oscillations can directly influence motor control and indicate the status of the CNS, the interest in the study of various types of tremor, as peripheral manifestations of central oscillations, has grown in recent years. We still do not have a precise definition of the origin of tremor in humans. It is believed that it is a product of several factors. Thus, the tremor is considered a peripheral oscillation that may also have, in addition to contributions of neural activities, activities originating from

Moreover, the pathological tremor can be associated with several factors, such as

tremors are resultant of distortions and amplifications of these central oscillations [8].

great interest [8].

springs [10].

is often referred to as physiological tremor.

mechanical, reflex and central oscillations [9].

basal ganglia and cerebral cortex [10].

neurological disorders [2].

nucleus are all involved in the genesis of tremor [10].

the motor units and from the resonances of reflex arcs [8].

limbs and motor neurons firings.

Thousands of people each year begin to present some type of motor dysfunction, which interferes in their daily activities and reduces significantly the quality of life of these individuals. A number of studies and governmental statistics have shown that the elderly population is the most affected by tremor and its consequences, which are responsible for physical limitations of these individuals [1].

The manifestation of the tremor can cause considerable functional incapacity leading to social isolation by interference in the activities of daily living (ADLs) and instrumental activities of daily living (IADL) such as eating, writing, dressing and maintaining some personal care [7].

Moreover, recent researches from the Brazilian Ministry of Health (available on www.saude.gov.br) suggest that signs like tremor and loss of balance do not always mean the presence of neurological diseases such as Parkinson's disease, which affects mainly the population with age over 50 years old. According to this Ministry about 25% of patients who exhibit signs of Parkinson do not have the disease. The imprecise diagnosis of these diseases and the consequent use of unnecessary or inappropriate drugs also results in waste of public resources.

Generally, current therapies are limited because they relieve symptoms more than cure. The most commonly used drugs are: propranolol, primidone, gabapentin, topiramate and others to be considered comprise in the second row like alprazolam, atenolol, sotalol and clonazepam and, in the third line: clozapine, nadolol, nimodipine, being the botulinum toxin the first line for hands, head and voice tremors, in cases of essential tremor.

Some studies have suggested that moderate tremor, which accompanies the natural aging process can be diagnosed as pathological tremor. It is also possible that the pathological tremor is wrongly diagnosed as physiological tremor [5].

The human tremor is a public health problem faced all over the world. Costs related to medical and social aspects, necessary for diagnosis and treatment of tremor, have grown constantly in past decades and currently reach billions of dollars in many countries. A treatment that seeks to mitigate the symptoms and create the possibility of a person with tremor accomplish everyday tasks constitute an important intervention. In this context, studies that contribute to the understanding of tremor are of paramount importance.
