Nervous diseases - movement disorders. Psychogenic movement disorders (diagnosis) Movement disorders in neurology

GRODNO STATE MEDICAL INSTITUTE

DEPARTMENT OF NEUROLOGY

LECTURE

Subject: MOVEMENT DISORDER SYNDROMES.

PERIPHERAL AND CENTRAL PARALYSIS.

Learning objective . Consider the organization of movements in the process of evolution of the nervous system, anatomy, physiology and topical diagnosis of movement disorders.

1
Contents of the lecture (2). 1. Evolution of the nervous system, definition and types of motor disorders. 2. Peripheral movement disorders. 3. Syndromes of central movement disorders. 4. Differential diagnosis of paralysis.

Grodno, 1997

Movement- one of the main manifestations of life, both in the most primitive creature and in a highly organized organism, which is man. To understand the complex motor functions of a person, it is necessary to briefly recall the stages of development that the nervous system went through in the process of evolution from the simplest forms to the most differentiated form in humans.

A primitive creature lacks differentiation into a receptor - perceiving irritation and an effector - reacting apparatus. With the appearance of a ganglion cell, it becomes possible to transmit information from the receptor organ to the muscle cell. At the initial stage of development of the central nervous system, the independence of the nervous apparatus continues to exist in its individual segments, each of which mainly relates to a specific metamer of the body. The ventrally located motor cell, which subsequently develops into the anterior horn cell, is initially in communication only with the peripheral centripetal, receptor and effector terminal apparatus of the same one segment.

The next stage of development is the emergence of intersegmental connections between the motor cell of the anterior horn and the receptor apparatus of not only adjacent but also distant segments of the spinal cord, this in turn leads to a complication of motor function. With further development of the brain, pathways are added that serve to regulate the function of the motor cells of the anterior horn from the higher parts of the nervous system. Thus, the organ of vision has a regulatory influence on the motor cell of the anterior horn through the tractus tecto-spinalis, the organ of balance through the tractus vestibulo-spinalis, the cerebellum - through the tractus rubro-spinalis and the subcortical formations - through the tractus reticulo-spinalis. Thus, the cell of the anterior horn is influenced by a number of systems important for movement and muscle tone, connected on the one hand with all the muscles, and on the other, through the optic tubercle and reticular substance with all the receptor apparatus.

During further phylogenetic development, the most important pathway arises - the tractus cortico-spinalis pyramidal, which originates mainly in the anterior central gyrus of the cerebral cortex and, unlike the paths listed above that contribute to the implementation of large mass movements, conducts impulses to the cells of the anterior horns for the most differentiated, voluntary movements.

Consequently, the cell of the anterior horn is like a pool into which many irritations flow, but from which only one stream of impulses flows to the muscle - this is the final motor path. The cells of the anterior horns of the spinal cord in the brain stem correspond to the cells of the nuclei of the motor cranial nerves.

It becomes obvious that these movement disorders are fundamentally different depending on whether the final motor pathway or any of the pathways that regulate it are affected.

Movement disorders can be divided into the following types:

paralysis due to damage to bulbar or spinal motor neurons;

paralysis due to damage to corticospinal, corticobulbar or stem descending (subcorticospinal) neurons;
coordination disorders (ataxia) as a result of lesions of the afferent and efferent fibers of the cerebellar system;
disturbances in movement and body position due to damage to the extrapyramidal system;
apraxia or non-paralytic disorders of goal-directed movements due to damage to certain areas of the brain.

This lecture discusses objective and subjective symptoms that develop as a result of damage to peripheral motor neurons, corticospinal and other conduction systems of the brain and spinal cord.

Definitions of movement disorders.
In everyday medical practice, the following terminology is used to characterize movement disorders:

paralysis (plegia) - complete absence of active movements due to interruption of one or more motor pathways going from the brain to the muscle fiber;
paresis - limitation of active movements due to decreased muscle strength.

In addition to weakness, an important functional deficiency is loss of smooth movements.

Peripheral movement disorders.
Peripheral motor neuron palsy is caused by physiological blockade or destruction of anterior horn cells or their axons in the anterior roots and nerves. The main clinical signs of peripheral motor neuron damage are:

hypo-areflexia - loss of tendon reflexes;
hypo-atonia - lethargy and loss of tone of the affected muscles;
degenerative atrophy, muscle (qualitative and quantitative), 70-80% of total muscle mass;
both muscle groups and individual muscles are affected;
plantar reflex, if evoked, is of the normal, flexion type;
fasciculations, electromyography shows a decrease in the number of motor units, fibrillation.

Objective and subjective symptoms of peripheral motor neuron damage vary depending on the location of the pathological process . A topical diagnosis is formed on the basis of knowledge of the symptoms characteristic of damage to various parts of the peripheral motor neuron (anterior horns of the spinal cord - motor roots - nerves).

Syndromes of damage to the anterior horns. They are characterized by the presence of peripheral motor disorders without sensory disturbances. Paralysis of muscles innervated by different nerves is observed. The asymmetrical distribution of paralysis is especially typical. With an unfinished pathological process, fibrillations with corresponding changes in the EMG are possible. Damage to the anterior horn cells rarely affects the entire length of the spinal cord. Usually the process is limited to one or another area, often characteristic of individual forms of the disease.

Syndrome of damage to cells of the anterior horns of the spinal cord is the leading one in the clinic polio, one of the serious and already common diseases of childhood. We are talking about an acute viral infection, the causative agent of which has a significant affinity for the cells of the anterior horns of the spinal cord and the motor nuclei of the trunk. After a relatively short acute general infectious period, peripheral paralysis develops, which at first is more widespread, and then concentrated in limited segments, where destructive changes in the cells of the anterior horns are especially strong.

The process is characterized by scattered localization at different levels. Often it is limited to one side and affects some of the muscles belonging to the same spinal segment. The distal ends of the limbs are affected less frequently. Much more often, paralysis is localized in the proximal sections: on the arms - in the deltoid muscle, in the shoulder muscles, on the legs - in the quadriceps, in the muscles of the pelvic girdle. With polio, not only the muscles atrophy, but also the growth of the bones of the corresponding affected limb is impaired. Characterized by persistent areflexia, according to the affected segments.

Damage to cells of the anterior horns of the spinal cord with localization in the cervical region is characteristic of another neuroviral infection - spring-summer tick-borne encephalitis. The disease occurs in the spring and summer months and develops acutely 10-15 days after the tick bite. Against the background of general infectious symptoms of the disease, already in the first days one can note the appearance of paralysis, initially widespread, involving the arms and shoulder girdle, later usually limited to the muscles of the neck, shoulder girdle and proximal arms. Atrophy develops early, often with fibrillary twitching. Paralysis of the muscles of the legs and trunk is rare.

Anterior horn syndrome is the main clinical sign Werdnig-Hoffmann spinal amyotrophy . The disease belongs to the hereditary group. The first symptoms appear in the second half of life. Flaccid paresis is initially localized in the legs, then quickly spreads to the muscles of the trunk and arms. Muscle tone and tendon reflexes fade away. Fasciculations and fibrillation of the tongue with the development of bulbar palsy are typical. Fatal outcome by 14-15 years.

Anterior horn lesion syndrome is part of the picture of a disease that is not limited to the peripheral neuron, but also extends to the central motor neuron - the pyramidal tract. A clinical picture emerges amyotrophic lateral sclerosis , characterized by amyotrophy and pyramidal symptoms with subsequent development of bulbar palsy.

In some cases, anterior horn syndrome is part of the clinical picture of diseases such as syringomyelia, intramedullary tumor of the spinal cord.

Anterior root lesion syndromes. Diseases of the anterior roots are characterized by atrophic paralysis, which is difficult to distinguish from paralysis caused by damage to the cells of the anterior horns of the spinal cord. It should be especially noted that purely radicular atrophies are never accompanied by fibrillary twitching. In this case, more coarse fascicular muscle twitching may be observed. Since the anterior roots are usually affected as a result of a disease of the spinal cord membranes or vertebrae, along with the anterior root syndrome, symptoms from the posterior roots, spine and spinal cord are almost always present.

Plexus lesion syndromes. The anterior and posterior roots of the spinal cord, united at the intervertebral foramen, form the spinal nerve, which, upon exiting the spine, is divided into anterior and posterior branches. The posterior branches of the spinal nerves go to the skin and muscles of the neck and back. The anterior branches, anastomosing among themselves, form plexuses in the cervical and lumbosacral regions.

Cervical plexus syndrome (C1-C4) is characterized by paralysis of the deep cervical muscles combined with paralysis or symptoms of phrenic nerve irritation. Occurs with tumors, enlarged lymph nodes, purulent and other processes in the area of the upper cervical vertebrae, lung cancer, aneurysms of the aorta and subclavian artery. Brachial plexus syndromes manifest as a combination of paralysis of individual muscles belonging to different nerves. When the entire brachial plexus is affected due to a dislocated shoulder or fracture of the clavicle, a gunshot wound or birth injury, all muscles, both the shoulder girdle and the upper limb, are affected.

According to the topographic division of the plexus into two parts, two main forms of brachial plexus palsy are clinically distinguished upper (Erb-Duchenne) And lower (Dezherina-Klumpke ). The upper type of plexus palsy develops when a specific area above the collarbone is damaged to a finger lateral to the sternocleidomastial muscle (Erb's point), where the 5th and 6th cervical nerves join to form a plexus. In this case, raising and abducting the arm and bending the elbow are impossible. With lower paralysis, which occurs much less frequently than upper paralysis, small muscles of the hand and individual muscles of the palmar surface of the forearm suffer.

Lumbosacral plexus syndrome is manifested by symptoms of damage to the femoral and sciatic nerves. Etiological factors are tumors and pelvic fractures, abscesses, and enlarged retroperitoneal nodes.

Syndromes of central movement disorders.
Central paralysis occurs due to damage to corticospinal, corticobulbar and subcorticospinal neurons. The corticospinal tract originates from the giant and small Betz cells of the anterior central gyrus, the premotor zone of the superior frontal and postcentral gyri and represents the only direct connection between the brain and the spinal cord. Fibers to the cranial nerve nuclei are separated at the level of the midbrain, where they cross the midline and are directed on the opposite side to the corresponding nuclei in the brainstem. The crossing of the corticospinal tract occurs at the border of the medulla oblongata and the spinal cord. Two thirds of the pyramidal path intersect. Subsequently, the fibers are directed to the motor cells of the anterior horns of the spinal cord. Central paralysis occurs when the cerebral cortex, subcortical white matter, internal capsule, brain stem or spinal cord is affected and is characterized by the following general clinical signs:

increased muscle tone according to the type of spasticity (the “jackknife” phenomenon);
hyperreflexia of deep and areflexia of superficial reflexes;
moderate quantitative muscle atrophy (from inactivity);
pathological symptoms of the extensor (Babinsky) and flexion (Rossolimo) type;
strengthening of protective reflexes;
the presence of pathological synkinesis (friendly movements);

When the corticospinal tract is damaged in humans, the distribution of paralysis will be different depending on the location of the lesion and the nature of the pathological process (acute, chronic). Thus, lesions of the anterior central gyrus are characterized by focal seizures and central paresis or paralysis of one limb on the opposite side; for the subcortical process - contralateral hemiparesis with a predominance in the arm or leg; for the internal capsule - hemiplegia with subsequent outcome in the Wernicke-Mann position; for the brain stem - hemiplegia with damage to the nuclei of the cranial nerves (alternating syndromes) and for the spinal cord - hemi-monoparesis - plegia (depending on the level of damage). The severity of movement disorders in each specific case varies widely and depends on many reasons.

Bilateral loss of corticobulbar function. pathways (from the cortex to the nuclei of the cranial nerves) gives a picture of pseudobulbar palsy with a disorder of chewing, swallowing, and dysarthria (speech impairment due to paralysis of the muscles involved in articulation). At the same time, the face is ammimmic, the mouth is half-open, and saliva flows out of it. Unlike bulbar palsy, the muscles of mastication and the muscles of the tongue are not atrophic, and there are no fibrillary twitches. All tendon reflexes of the face are increased. Characteristic are violent laughter and crying. Pseudobulbar palsy is caused by bilateral hemispheric lesions, often developing at different times. The combination of pseudobulbar palsy with tetraplegia can occur when the base of the pons is affected.

Damage to the central neuron of the motor pathway occurs in many diseases of the brain and spinal cord, in particular, in various types of vascular pathology (stroke), multiple sclerosis, amyotrophic lateral sclerosis, trauma, tumors, abscesses, and encephalitis.

Differential diagnosis of paralysis.

When diagnosing paralysis, the location and distribution of muscle weakness must be taken into account. The presence or absence of muscle atrophy in the paretic limb may be a diagnostic clue.

Monoplegia. It must be remembered that prolonged immobility of a limb can lead to its atrophy. However, in this case, atrophy usually does not reach the same degree of severity as occurs in diseases leading to muscle denervation. Tendon reflexes do not change. Electrical excitability and EMG differ little from the norm.

The most common cause of monoplegia without a decrease in muscle mass is damage to the cerebral cortex. When the corticospinal tract is damaged at the level of the capsule, trunk and spinal cord, monoplegia syndrome rarely occurs, since the fibers going to the upper and lower limbs in these sections are located compactly. The most common cause of monoplegia is damage to the vessels of the cerebral cortex. In addition, some injuries, tumors, and abscesses can cause similar symptoms. Weakness in one limb, especially the lower one, can develop with multiple sclerosis and spinal tumors, especially in the early stages of the disease.

Paralysis accompanied by muscle atrophy is characteristic of a pathological process in the spinal cord, roots or peripheral nerves. The level of damage can be determined by the nature of the distribution of weakness in the muscles, as well as using additional paraclinical diagnostic methods (CT, NMR and others). Atrophic brachial monoplegia can occur with brachial plexus injury, poliomyelitis, syringomyelia, and amyotrophic lateral sclerosis. Femoral monoplegia is more common and can be caused by damage to the thoracic and lumbar spinal cord due to trauma, tumor, myelitis, multiple sclerosis. Unilateral lower limb paralysis may result from compression of the lumbosacral plexus by a retroperitoneal tumor.

Hemiplegia. Most often, paralysis in humans is expressed in the appearance of unilateral weakness in the upper and lower limbs and half of the face. The localization of the lesion is usually determined by the corresponding neurological manifestations. Among the causes of hemiplegia, lesions of the cerebral and brainstem vessels (stroke) predominate. Less significant causes include trauma (brain contusion, epidural and subdural hematomas, brain tumor, abscess, encephalitis, demyelinating diseases, complications after meningitis).

Paraplegia. Paralysis of both lower extremities can develop due to lesions of the spinal cord, spinal roots and peripheral nerves. As a rule, with acute spinal cord injuries, paralysis of all muscles below this level occurs. In the case of extensive damage to the white matter, sensory disturbances often occur below the level of the lesion, and the function of the sphincters of the bladder and intestines is impaired. An intermittent spinal block (dynamic block, increased protein, or cytosis) often occurs. With an acute onset of the disease, difficulties sometimes arise in differential diagnosis from neural paralysis, since in any acute process spinal shock can lead to complete areflexia.

The most common causes of acute paraplegia (or tetraplegia) are spontaneous hematomyelia due to vascular malformations of the spinal cord, thrombosis of the anterior spinal artery with infarction, dissecting aortic aneurysm, occlusion of the spinal arteries with subsequent infarction (myelomalacia), spinal cord injuries and tumor metastases.

Subacute (rarely acute) development of paraplegia is observed in post-vaccination and post-infectious myelitis, acute demyelinating myelitis (Devik's disease), necrotizing myelitis, as well as epidural abscess with compression of the spinal cord.

Chronic paraplegia can develop with multiple sclerosis, spinal cord tumor, herniated intervertebral disc of the cervical spine, chronic epidural infectious processes, familial spastic paraplegia, syringomyelia. The source of chronic asymmetric paraplegia can be parasagittal meningioma.

Tetraplegia. Possible causes of tetraplegia are similar to those of paraplegia, except that this spinal cord lesion is most often located at the level of the cervical spinal cord.

Isolated paralysis. Paralysis of an isolated muscle group indicates damage to one or more peripheral nerves. Diagnosis of an individual peripheral nerve lesion is based on the presence of weakness or paralysis of a muscle or group of muscles and deterioration or loss of sensation in the area of innervation of the nerve of interest. EMG research is of significant diagnostic value.

To carry out a motor act, it is necessary that an impulse from the motor area of the cortex be unhindered to the muscle. If the cortico-muscular tract is damaged in any part of it (the motor zone of the cerebral cortex, the pyramidal tract, the motor cells of the spinal cord, the anterior root, the peripheral nerve), the conduction of the impulse becomes impossible, and the corresponding muscles can no longer take part in the movement - it becomes paralyzed. Thus, paralysis, or plegia, is the absence of movement in a muscle or muscle groups as a result of an interruption in the motor reflex pathway. Incomplete loss of movement (limitation of its volume and strength) is called paresis.

Depending on the prevalence of paralysis, there are monoplegia (paralysis of one limb), hemiplegia (paralysis of one half of the body), paraplegia (paralysis of both arms or legs), tetraplegia (paralysis of all four limbs). When the peripheral motor neuron and its connections to the muscle (peripheral nerve) are damaged, peripheral paralysis occurs. When the central motor neuron and its connection with the peripheral neuron are damaged, central paralysis develops. The qualitative characteristics of these paralysis are different (Table 1).

Table 1

Clinical characteristics of central and peripheral paralysis

Symptoms of paralysis	Central paralysis	Peripheral paralysis
Muscle tone
Reflexes	Tendon reflexes are increased, abdominal reflexes are decreased or lost	Tendon and skin reflexes are lost or reduced
Pathological reflexes		None
Friendly movements (syncinesia)		Absent
Muscle atrophy	Absent	Expressed
rebirth reaction	Absent

Peripheral paralysis

Peripheral paralysis is characterized by the following main symptoms: absence of reflexes or their decrease (hyporeflexia, areflexia), decrease or absence of muscle tone (atony or hypotonia), muscle atrophy. In addition, changes in electrical excitability, called the degeneration reaction, develop in paralyzed muscles and affected nerves. The depth of changes in electrical excitability allows one to judge the severity of the lesion in peripheral paralysis and the prognosis. Loss of reflexes and atony are explained by interruption of the reflex arc; such a break in the arc leads to loss of muscle tone. For the same reason, the corresponding reflex cannot be evoked. Muscle atrophy, or sudden weight loss, develops due to the disconnection of the muscle from the neurons of the spinal cord; From these neurons, impulses flow through the peripheral nerve to the muscle, stimulating normal metabolism in muscle tissue. With peripheral paralysis, fibrillar twitching may be observed in atrophied muscles in the form of rapid contractions of individual muscle fibers or bundles of muscle fibers (fascicular twitching). They are observed during chronic progressive pathological processes in the cells of peripheral motor neurons.

Damage to a peripheral nerve leads to peripheral paralysis of the muscles innervated by this nerve. In this case, sensory disturbances and autonomic disorders are also observed in the same area, since the peripheral nerve is mixed - motor and sensory fibers pass through it. As a result of damage to the anterior roots, peripheral paralysis of the muscles innervated by this root occurs. Damage to the anterior horns of the spinal cord causes peripheral paralysis of the muscles in the areas of innervation by this segment.

Thus, damage to the anterior horns of the spinal cord in the area of the cervical thickening (the fifth - eighth cervical segments and the first thoracic) leads to peripheral paralysis of the arm. Damage to the anterior horns of the spinal cord at the level of the lumbar enlargement (all lumbar and first and second sacral segments) causes peripheral paralysis of the leg. If the cervical or lumbar thickening on both sides is affected, then upper or lower paraplegia develops.

An example of peripheral paralysis of the limbs is the paralysis that occurs with polio, an acute infectious disease of the nervous system (see Chapter 7). With polio, paralysis of the legs, arms, and respiratory muscles can develop. When the cervical and thoracic segments of the spinal cord are affected, peripheral paralysis of the diaphragm and intercostal muscles is observed, leading to respiratory failure. Damage to the upper thickening of the spinal cord leads to peripheral paralysis of the arms, and the lower (lumbar thickening) leads to paralysis of the legs.

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MAIN SYMPTOMS and SYNDROMES IN DISEASES OF THE NERVOUS SYSTEM
Chapter 4
4.1. MOTOR DISORDERS

Voluntary movements of a person are carried out due to the contraction of one group of skeletal muscles and the relaxation of another group, which occur under the control of the nervous system. The regulation of movements is carried out by a complex system, including motor zones of the cerebral cortex, subcortical formations, cerebellum, spinal cord, and peripheral nerves. The correctness of movements is controlled by the central nervous system with the help of special sensory endings (proprioceptors) located in the muscles, tendons, joints, ligaments, as well as distant sensory organs (vision, vestibular apparatus), signaling to the brain about all changes in the position of the body and its individual parts . When these structures are damaged, various motor disorders can occur: paralysis, convulsions, ataxia, extrapyramidal disorders.

4.1.1. Paralysis

Paralysis is a disorder of voluntary movements caused by impaired innervation of muscles.
The terms paralysis and plegia usually mean a complete lack of active movement. With partial paralysis-paresis, voluntary movements are possible, but their volume and strength are significantly reduced. To characterize the distribution of paralysis (paresis), the following prefixes are used: “hemi” - means involvement of an arm and leg on one side, right or left, “para” - both upper limbs (upper paraparesis) or both lower limbs (lower paraparesis), “three” - three limbs, “tetra”, - all four limbs. Clinically and pathophysiologically, two types of paralysis are distinguished.
Central (pyramidal) paralysis is associated with damage to the central motor neurons, the bodies of which are located in the motor zone of the cortex, and the long processes follow as part of the pyramidal tract through the internal capsule, brain stem, lateral columns of the spinal cord to the anterior horns of the spinal cord (Fig. 4.1). The following symptoms are characteristic of central paralysis.

Rice. 4.1. Descending motor pathway from the cortex to the cranial nerve nuclei and spinal cord (pyramidal tract). *

* Increased tone (“spasm”) of paralyzed muscles - Spasticity. Spasticity is detected during passive movements as increased resistance of the muscle to its stretching, which is especially noticeable at the beginning of the movement, and is then overcome during subsequent movements. This resistance that disappears with movement is called the “jackknife” phenomenon, since it is similar to what happens when opening the blade of a jackknife. Usually it is most pronounced in the flexor muscles of the arm and extensor muscles of the leg, therefore, with spastic paralysis, a flexion contracture is formed in the arms, and an extensor contracture in the legs. Paralysis accompanied by increased muscle tone is called spastic.

Revitalization of tendon reflexes (hyperreflexia) in paralyzed limbs.
Clonus (repeating the rhythmic contractions of muscles that occur after rapid stretching; an example is clonus of the foot, observed after rapid dorsiflexion).
Pathological reflexes (foot reflexes of Babinsky, Oppenheim, Gordon, Rossolimo, carpal reflex of Hoffmann, etc. - see section 3.1.3). Pathological reflexes are normally observed in healthy children under 1 year of age, when the formation of the central parts of the motor system has not yet been completed; they disappear immediately after myelination of the pyramidal tracts.
Lack of rapid weight loss in paralyzed muscles.

Spasticity, hyperreflexia, clonus, and pathological foot reflexes arise due to the elimination of the inhibitory effect of the pyramidal tract on the segmental apparatus of the spinal cord. This leads to the disinhibition of reflexes that are closed through the spinal cord.
In the first days of acute neurological diseases, such as strokes or spinal cord injury, paralyzed muscles first develop a decrease in muscle tone (hypotonia), and sometimes a decrease in reflexes, and spasticity and hyperreflexia appear after a few days or weeks.
Peripheral paralysis is associated with damage to peripheral motor neurons, the bodies of which lie in the anterior horns of the spinal cord, and long processes follow as part of roots, plexuses, and nerves to the muscles with which they form neuromuscular synapses.
The following symptoms are characteristic of peripheral paralysis.

Decreased muscle tone (this is why peripheral paralysis is called flaccid paralysis).
Decreased tendon reflexes (hyporeflexia).
Absence of foot clonus and pathological reflexes.
Rapid weight loss (atrophy) of paralyzed muscles due to disruption of their trophism.
Fasciculations are muscle twitches (contractions of individual bundles of muscle fibers), indicating damage to the anterior horns of the spinal cord (for example, with amyotrophic lateral sclerosis).

The distinctive features of central and peripheral paralysis are summarized in table. 4.1.
Muscle weakness in primary muscle diseases (myopathies) and disorders of neuromuscular transmission (myasthenia gravis and myasthenic syndromes) approaches peripheral paralysis in its characteristics.
Table 4.1. Differential diagnosis of central (pyramidal) and peripheral paralysis

Sign	Central (pyramidal) palsy	Peripheral paralysis
Genoa muscle
Tendon reflexes	Promoted	Reduced or absent
	Often observed	None
Pathological reflexes	Called	None
	Moderately expressed, develops slowly	Sharply expressed, develops early
Fasciculations	None	Possible (if the anterior horns are affected)

Unlike neurogenic peripheral paralysis, muscle lesions are not characterized by severe atrophy, fasciculations, or early loss of reflexes. In some diseases (for example, amyotrophic lateral sclerosis), signs of central and peripheral paralysis can be combined (mixed paralysis).
Hemiparesis is usually central in nature and most often results from a unilateral lesion involving the opposite hemisphere of the brain or the opposite half of the brain stem (eg, stroke or tumor). As a result of the fact that muscle groups are involved to varying degrees, patients usually develop a pathological posture in which the arm is adducted to the body, bent at the elbow and rotated inward, and the leg is abducted at the hip joint and straightened at the knee and ankle joints (Wernicke's posture). Manna). Due to the redistribution of muscle tone and lengthening of the leg, the patient, when walking, is forced to lift the paralyzed leg to the side, describing it in a semicircle (Wernicke-Mann gait) (Fig. 4.2).
Hemiparesis is often accompanied by weakness of the muscles of the lower half of the face (for example, sagging cheeks, drooping and immobility of the corner of the mouth). The muscles of the upper half of the face are not involved, as they receive bilateral innervation.
Central paraparesis most often occurs when the thoracic spinal cord is damaged as a result of its compression by a tumor, abscess, hematoma, trauma, stroke or inflammation (myelitis).

Rice. 4.2. Wernicke-Mann gait in a patient with right-sided spastic hemiparesis.

The cause of flaccid lower paraparesis may be compression of the cauda equina by a herniated disc or tumor, as well as Guillain-Barré syndrome and other polyneuropathies.
Central tetraparesis may be a consequence of bilateral damage to the cerebral hemispheres, brain stem, or upper cervical spinal cord. Acute central tetraparesis is often a manifestation of stroke or trauma. Acute peripheral tetraparesis usually occurs due to polyneuropathy (eg, Guillain-Barré syndrome or diphtheria polyneuropathy). Mixed tetraparesis is caused by amyotrophic lateral sclerosis or compression of the cervical spinal cord by a herniated disc.
Monoparesis is often associated with damage to the peripheral nervous system; in this case, weakness is noted in the muscles innervated by a specific root, plexus or nerve. Less commonly, monoparesis is a manifestation of damage to the anterior horns (for example, with poliomyelitis) or central motor neurons (for example, with a small cerebral infarction or compression of the spinal cord).
Ophthalmoplegia is manifested by limited mobility of the eyeballs and may be associated with damage to the external muscles of the eye (for example, with myopathy or myositis), disruption of neuromuscular transmission (for example, with myasthenia gravis), damage to the cranial nerves and their nuclei in the brain stem or centers coordinating their work in the brain stem, basal ganglia, frontal lobes.
Damage to the oculomotor (III), trochlear (IV) and abducens (VI) nerves or their nuclei causes limited mobility of the eyeballs and paralytic strabismus, subjectively manifested by double vision.
Damage to the oculomotor (III) nerve causes divergent strabismus, limited movement of the eyeball up, down and inward, drooping of the upper eyelid (ptosis), dilation of the pupil and loss of its reaction.
Damage to the trochlear (IV) nerve is manifested by limited downward movement of the eyeball in its abduction position. It is usually accompanied by double vision when the patient looks down (for example, when reading or going down stairs). Double vision decreases when the head is tilted in the opposite direction, so when the trochlear nerve is damaged, a forced position of the head is often observed.
Damage to the abducens (VI) nerve causes convergent strabismus, restricting outward movement of the eyeball.
The causes of damage to the oculomotor nerves may be their compression by a tumor or aneurysm, impaired blood supply to the nerve, granulomatous inflammatory process at the base of the skull, increased intracranial pressure, inflammation of the meninges.
If the brain stem or frontal lobes, which control the nuclei of the oculomotor nerves, are damaged, gaze paralysis may occur - the absence of voluntary conjugate movements of both eyes in the horizontal or vertical plane.
Paralysis of horizontal gaze (to the right and/or left) may be caused by damage to the frontal lobe or pons of the brain due to stroke, trauma, tumor). With acute damage to the frontal lobe, a horizontal deviation of the eyeballs towards the lesion occurs (i.e. in the direction opposite to hemiparesis). When the pons of the brain is damaged, the eyeballs deviate in the direction opposite to the lesion (i.e., towards hemiparesis).
Vertical gaze palsy occurs when the midbrain or the pathways following it from the cortex and basal ganglia are damaged due to stroke, hydrocephalus, and degenerative diseases.
Paralysis of facial muscles. When the ovarian (VII) nerve or its nucleus is damaged, weakness of the facial muscles of the entire half of the face occurs. On the affected side, the patient is unable to close his eyes, raise his eyebrows, or bare his teeth. When you try to close your eyes, your eyes move upward (Bell's phenomenon) and due to the fact that the eyelids do not close completely, a diarrhea of the conjunctiva becomes visible between the iris and the lower eyelid. The cause of damage to the facial nerve may be compression of the nerve by a tumor in the cerebellopontine angle or compression in the bone canal of the temporal bone (due to inflammation, swelling, trauma, middle ear infection, etc.). Bilateral weakness of the facial muscles is possible not only with bilateral damage to the facial nerve (for example, with basal meningitis), but also with impaired neuromuscular transmission (myasthenia gravis) or primary muscle damage (myopathies).
With central paresis of the facial muscles, caused by damage to the cortical fibers following the nucleus of the facial nerve, only the muscles of the lower half of the face on the side opposite to the lesion are involved in the process, since the upper facial muscles (orbicularis oculi muscle, forehead muscles, etc.) have bilateral innervation. The cause of central paresis of the facial muscles is usually a stroke, tumor or injury.
Paralysis of the masticatory muscles. Weakness of the masticatory muscles can be observed with damage to the motor portion of the trigeminal nerve or the nerve nucleus, and occasionally with bilateral damage to the descending pathways from the motor cortex to the trigeminal nucleus. Rapid fatigue of the masticatory muscles is characteristic of myasthenia gravis.
Bulbar palsy. The combination of dysphagia, dysphonia, dysarthria, caused by weakness of the muscles innervated by the IX, X and XII cranial nerves, is usually referred to as bulbar palsy (the nuclei of these nerves lie in the medulla oblongata, which in Latin was previously called bulbus). The cause of bulbar palsy can be various diseases that cause damage to the motor nuclei of the trunk (trunk infarction, tumors, poliomyelitis) or the cranial nerves themselves (meningitis, tumors, aneurysm, polyneuritis), as well as a disorder of neuromuscular transmission (myasthenia gravis) or primary muscle damage ( myopathy). A rapid increase in signs of bulbar palsy in Guillain-Barré syndrome, brainstem encephalitis or stroke is the basis for transferring the patient to the intensive care unit. Paresis of the muscles of the pharynx and larynx impairs the airway and may require intubation and mechanical ventilation.
Bulbar palsy should be distinguished from pseudobulbar palsy, which also manifests as dysarthria, dysphagia, and tongue paresis, but is usually associated with bilateral damage to the corticobulbar tracts in diffuse or multifocal brain lesions (for example, in discirculatory encephalopathy, multiple sclerosis, trauma). In contrast to bulbar palsy, with pseudobulbar palsy the pharyngeal reflex is preserved, there is no atrophy of the tongue, reflexes of “oral automatism” (proboscis, sucking, palmar-chin), forced laughter and crying are detected.

Convulsions

Cramps are involuntary muscle contractions caused by increased excitability or irritation of motor neurons at various levels of the nervous system. According to the mechanism of development, they are divided into epileptic (caused by pathological synchronous discharge of a large group of neurons) or non-epileptic, according to duration - into faster clonic or slower and persistent - tonic.
Convulsive epileptic seizures can be partial (focal) and generalized. Partial seizures are manifested by muscle twitching in one or two limbs on one side of the body and occur against a background of preserved consciousness. They are associated with damage to a certain area of the motor cortex (for example, with a tumor, traumatic brain injury, stroke, etc.). Sometimes seizures sequentially involve one part of the limb after another, reflecting the spread of epileptic excitation along the motor cortex (Jacksonian march).
With generalized convulsive seizures occurring against the background of lost consciousness, epileptic excitation covers the motor zones of the cortex of both hemispheres; respectively, tonic and clonic spasms diffusely involve muscle groups on both sides of the body. The cause of generalized seizures can be infections, intoxications, metabolic disorders, and hereditary diseases.
Non-epileptic seizures may be associated with increased excitation or disinhibition of the motor nuclei of the brain stem, subcortical ganglia, anterior horns of the spinal cord, peripheral nerves, and increased muscle excitability.
Brainstem spasms usually have a paroxysmal tonic character. An example is hormetonia (from the Greek horme - attack, tonos - tension) - repeated topical spasms in the limbs that occur spontaneously or under the influence of external stimuli in patients in a coma with damage to the upper parts of the brain stem or hemorrhage in the ventricles.
Convulsions associated with irritation of peripheral motor neurons occur with tetanus and strychnine poisoning.
A decrease in calcium levels in the blood leads to increased excitability of motor fibers and the appearance of tonic spasms of the muscles of the forearm and hand, causing a characteristic positioning of the hand (“obstetrician’s hand”), as well as other muscle groups.

Motor (motor) disorders can occur due to pathological changes in the muscular, skeletal or nervous systems. When trying to classify motor disorders, it quickly becomes clear that any disorder can be sufficiently characterized only by describing it in several dimensions. According to the WHO proposal (WHO, 1980), pathophysiological signs (impairments) are used to describe any damage. Examples of this include paralysis or decreased sensitivity, particularly after a cerebral hemorrhage. A myriad of motor disorders have been described for CNS injuries alone (Freund, 1986; Kurlan, 1995). The traditional approach to organizing the variety of possible disorders is to distinguish between negative and positive symptoms. Negative symptoms are those in which normal function is lost, for example, loss of normal mobility due to paralysis or limited coordination of movements due to damage to the cerebellum. The concept of “positive symptoms” combines pathological movements such as hyperkinesis (pathologically increased motor skills, sometimes with involuntary movements), myoclonus (jerky contractions of individual muscles), tics (a sequence of coordinated movements, most often occurring involuntarily) or changes in muscle tone, for example with rigidity (pathologically increased muscle tension).

IN DSM-IV Lists some disorders in which motor disorders are a significant component. This is stuttering DSM-IV 307.0), hyperactivity ( DSM-IV 314.xx), Gilles de la Tourette disorder ( DSM-IV 307.23), vocal tic ( DSM-IV 307.22), transient tic ( DSM-IV 307.21), unspecified teak ( DSM-IV 307.20) and stereotypic movement disorder ( DSM-IV 307.3). These disorders, however, represent only a small and arbitrary part of the totality of motor disorders.

Data on pathophysiological signs in many cases only provide an approximate prediction of which motor functions can actually still be performed. Therefore, direct testing of functional abilities, such as the ability to walk or grasp, is mandatory. The loss or limitation of functional capabilities is called, according to WHO, disabilities. The difficulty of describing motor disorders in terms of functional limitations lies in the vast variety of possibilities for testing functions. There is currently no generally accepted taxonomy of motor functions. In cerebral motor disorders, attempts have often been made to infer some order of motor function from models of cerebral motor control (eg, Brooks, 1990, and Chapter 26).

In order to assess the limitation of a function, it is enough to compare specific capabilities with normal values. True, if it is necessary to describe the handicap of a particular person, then one has to take into account the conditions of his life. The main consequence of any movement disorder is an actual decrease in professional and daily activities, and this can only be recorded by observing the patient in his environment or using questionnaires. To allow interindividual comparisons, attempts have often been made to develop standardized daily tasks. For example, can a patient walk a distance of 10 m without assistance? Can the patient dress himself? Due to the wide variety of possible disorders, the choice of daily tasks tested is always arbitrary. Without data on the individual patient's functional limitations, the description of the motor disorder will be incomplete at best. Losing a little finger would not be a big deal for many people, but for a pianist it would mean the end of his professional career.

Motor disorders can be divided according to the type of their genesis into primary organic and psychogenic movement disorders. In primary organic movement disorders, pathological changes are observed in the muscular, skeletal or nervous systems; in psychogenic movement disorders, the presence of such changes cannot be proven. But the mere absence of such evidence of an organic disorder does not allow us to draw a conclusion about the mental cause of the movement disorder. To do this, it must be shown that the occurrence or severity of the movement disorder is significantly influenced by psychological or mental factors. Because even many organic movement disorders (eg, dystonia, essential tremor, Parkinson's disease) can only be diagnosed based on clinical presentation, clinical observation is particularly important in distinguishing between organic and psychogenic movement disorders (Factor et al., 1995; Marsden, 1995). 1995). Williams et al. (Williams et al., 1995) suggest that the psychogenic origin of a movement disorder should be considered proven only if the cure for this movement disorder is achieved through psychotherapy or this movement disorder changes in its course, the pattern of its manifestation is not comparable with a picture of the manifestation of known organic movement disorders and in addition to this there are signs of the presence of some kind of mental disorder (cf. Table 25.1.1).

Table 25.1.1. Clinical characteristics of psychogenic movement disorders

Sudden onset resulting from a uniquely identifiable event.

Simultaneous occurrence of several movement disorders.

Movement disorder symptoms vary and fluctuate even within the same assessment session.

The signs of a movement disorder do not correspond to the symptom complexes that are known for organically caused movement disorders.

Movement disorders are aggravated when the examiner focuses their attention on the affected part of the body.

Movement disorders improve or disappear when they are not the center of attention or when the patient performs tasks that require him to concentrate.

A particularly pronounced reaction of fear.

The severity of the movement disorder can be influenced by suggestion or placebo treatment.

- “Neurological loss” of patients is not consistent with neurological loss in known neurological diseases.

Patients also exhibit mental disorders.

There is no movement disorder when the patient is unaware that he is being monitored.

Movement disorder can be successfully treated with psychotherapy.

If several of the above characteristics are present, then this speaks in favor of a psychogenic movement disorder. This table is given in modified form by Williams, Ford, and Fahn (1995).

We also identify a third class of movement disorders, namely disorders arising from inadequate compensation (Mai, 1996). What is meant by this can be explained using the example of the occurrence of writer's cramp. Limitation of hand function, initially organically caused (for example, inflammation of the tendon sheath, decreased tactile sensitivity in the fingers), leads to the fact that movements when writing become less free and handwriting may become less legible. The patient reacts to this by starting to hold the pencil differently, changing the position of the hand and the entire arm. This makes handwriting more legible in the short term. However, after a longer period of time, the learned motor program, which was previously included in writing, is replaced by new and, most often, extremely unergonomic movements. Writing requires more and more effort and can eventually become completely impossible. If these acquired errors are corrected, dramatic improvements in writing function can often be achieved (Mai & Marquardt, 1994).

Inadequate compensations occur within the framework of many primarily organically caused movement disorders and can turn an initially mild limitation of function into a pronounced one. In addition, manifestations of inadequate compensation may continue even after the organic disease has already passed. Since their treatment is possible even if the underlying organic disease is unlikely to be curable (for example, writing impairment in patients with multiple sclerosis, cf. Schenk et al., in press), it makes sense to distinguish between aspects of movement disorders that are reduced to inadequate compensation, from organically caused disorders. In contrast to psychogenic disorders, movement disorders caused by inadequate compensation require correction of “non-ergonomic” postures and movements through a suitable training program; psychotherapy can be of little help here (Mai & Marquardt, 1995). In addition, inadequate compensation leads to movement disorders, the pattern of manifestation of which is characterized by high temporal density; Inadequate compensation, as a rule, is not accompanied by mental disorders.

These include tremor, dystonia, athetotic tics and ballism, dyskinesia and myoclonus.

Classification of causes, symptoms, signs of movement disorders

Movement disorder	Classification, causes, symptoms, signs
Tremor = rhythmic oscillating movements of a body part	Classification: resting tremor, intention tremor, essential tremor (usually postural and actional), orthostatic tremor Parkinsonism is characterized by resting tremor. Essential tremor often exists for many years before seeking medical attention and is usually bilateral; in addition, a positive family history is often noted. Intention and action tremor is often combined with damage to the cerebellum or efferent cerebellar pathways. Orthostatic tremor is expressed primarily by instability in a standing position and high-frequency trembling of the leg muscles. Causes of increased physiological tremor (according to the standard of the German Society of Neurology): hyperthyroidism, hyperparathyroidism, renal failure, vitamin B2 deficiency, emotions, stress, exhaustion, cold, drug/alcohol withdrawal syndrome Drug-induced tremor: neuroleptics, tetrabenazine, metoclopramide, antidepressants (mainly tricyclics), lithium drugs, sympathomimetics, theophylline, steroids, anti-arrhythmia drugs, valproic acid, thyroid hormones, cytostatics, immunosuppressive drugs, alcohol
Dystonia = long-lasting (or slow), stereotyped and involuntary muscle contraction, often with repeated twisting movements, unnatural postures and abnormal positions	Classification: idiopathic dystonia in adults is usually focal dystonia (for example, blepharospasm, torticollis, dystonic writer's cramp, laryngeal dystonia), segmental, multifocal, generalized dystonia and hemidystonia are also distinguished. Rarely, primary dystonias (autosomal dominant dystonias, e.g. dopa-sensitive dystonia) or dystonias as part of an underlying degenerative disease (e.g. Hallerforden-Spatz syndrome) occur. Secondary dystonias have also been described, for example, in Wilson's disease and syphilitic encephalitis. Rarely: dystonic status with respiratory failure, muscle weakness, hyperthermia and myoglobinuria.
Tics = involuntary, sudden, brief and often repetitive or stereotyped movements. Tics can often be suppressed for a period of time. Often there is an obsessive desire to perform a movement followed by relief.	Classification: motor tics (clonic, dystonic, tonic, e.g., blinking, grimacing, head nodding, complex movements, e.g., grasping, adjusting clothing, copropraxia) and phonic (vocal) tics (e.g., coughing, coughing, or complex tics → coprolalia, echolalia). Juvenile (primary) tics often develop in association with Tourette's syndrome. Causes of secondary tics: encephalitis, trauma, Wilson's disease, Huntington's disease, drugs (SSRIs, lamotrigine, carbamazepine)
Choreiform movement disorders = involuntary, undirected, sudden and brief, sometimes complex movements Athetosis = slow choreiform movement, accentuated in the distal areas, sometimes worm-shaped, writhing) Ballism/hemiballism=severe form with throwing motion, usually unilateral, affecting proximal limbs	Huntington's chorea is an autosomal dominant neurodegenerative disease that is typically accompanied by hyperkinetic and often choreiform movements (the lesion is in the striatum). Non-genetic causes of chorea: lupus erythematosus, chorea minor (Sydenham), chorea of pregnancy, hyperthyroidism, vasculitis, drugs (eg, levodopa overdose), metabolic disorders (eg, Wilson's disease). The causes of hemiballismus/ballismus are typical lesions of the contralateral subthalamic nucleus, but other subcortical lesions should also be considered. Most often we are talking about ischemic foci. Rarer causes are metastases, arteriovenous malformations, abscesses, lupus erythematosus and drugs.
Dyskinesia = involuntary, continuous, repetitive, purposeless, often ritualized movements	Classification: simple dyskinesias (eg, tongue thrusting, chewing) and complex dyskinesias (eg, stroking movements, repetitive leg crossing, marching movements). The term akathisia describes motor restlessness with complex stereotyped movements (“inability to sit still”), usually caused by antipsychotic therapy. Tardive dyskinesia (usually in the form of dyskinesia of the mouth, cheeks and tongue) occurs due to the use of antidopaminergic drugs (neuroleptics, antiemetics, for example, metoclopramide).
Myoclonus = sudden, involuntary, brief muscle jerks with a visible motor effect of varying degrees (from subtle muscle twitches to severe myoclonus affecting the muscles of the body and limbs)	Classification: Myoclonus can occur at the cortical, subcortical, reticular and spinal levels. They can be focal segmental, multifocal or generalized. Association with epilepsy (juvenile epilepsy with West syndrome, Lennox-Gastaut syndrome; progressive myoclonic epilepsy with Unferricht-Lundborg syndrome, Lafora body disease, MERRF syndrome) Essential causes (sporadic, hereditary myoclonus usually with early onset) Metabolic disorders: hepatic encephalopathy, renal failure (dialysis encephalopathy due to chronic aluminum intoxication), diabetic ketoacidosis, hypoglycemia, electrolyte imbalance, pH crises Intoxications: cocaine, LSD, marijuana, bismuth, organophosphates, heavy metals, drug overdose Drugs: penicillin, cephalosporin, levodopa drugs, MAO-B inhibitors, opiates, lithium drugs, tricyclic antidepressants, etomidate Storage diseases: lipofuscinosis, salidosis Trauma/hypoxia: Lance-Adams syndrome (post-hypoxic myoclonus syndrome) after cardiac arrest, respiratory failure, traumatic brain injury Paraneoplasia Infections: encephalitis (typical of subacute sclerosing panencephalitis after measles infection), meningitis, myelitis, Creutzfeldt-Jakob disease Neurodegenerative diseases: Huntington's chorea, Alzheimer's dementia, hereditary ataxias, parkinsonism

Diagnosis of movement disorders

Hyperkinetic movement disorder is initially diagnosed based on the clinical picture:

Rhythmic, such as tremor
Stereotypic (same repetitive movement), eg dystonia, tic
Irrhythmic and non-stereotypical, for example chorea, myoclonus.

Attention: drugs that were taken several months ago may also be responsible for the movement disorder!

Additionally, an MRI of the brain should be performed to differentiate between primary (eg, Huntington's disease, Wilson's disease) and secondary (eg, drug-induced) causes.

Routine laboratory tests should primarily include determination of electrolyte levels, liver and kidney function, and thyroid hormones.

In addition, it seems advisable to study the cerebrospinal fluid to exclude a (chronic) inflammatory process in the central nervous system.

In case of myoclonus, EEG, EMG and somatosensory evoked potentials are used to determine the topographic and etiological characteristics of the lesion.

Differential diagnosis of movement disorders

Psychogenic hyperkinesia: in principle, psychogenic movement disorders can imitate the entire spectrum of organic movement disorders listed in the table. Clinically, they appear as abnormal, involuntary and undirected movements, which are combined with disturbances in walking and speaking. Movement disorders usually begin acutely and progress rapidly. Movements, however, are most often heterogeneous and variable in severity or intensity (unlike organic movement disorders). It is not uncommon for multiple movement disorders to also appear. Patients can often be distracted and thus interrupted in their movements. Psychogenic movement disorders may increase if they are observed (“spectators”). Often, movement disorders are accompanied by “inorganic” paralysis, diffuse or anatomically difficult to classify sensitization disorders, as well as speech and walking disorders.
Myoclonus can also occur “physiologically” (=without an underlying disease causing it), such as sleep myoclonus, postsyncopal myoclonus, hiccups, or myoclonus after exercise.

Treatment of movement disorders

The basis of therapy is the elimination of provoking factors, such as stress in essential tremor or medications (dyskinesia). The following options are considered as options for specific treatment of various movement disorders:

For tremor (essential): beta-receptor blockers (propranolol), primidone, topiramate, gabapentin, benzodiazepine, botulinum toxin in case of insufficient effect of oral medications; in treatment-resistant cases with severe disability, deep brain stimulation is indicated.

Tremor in parkinsonism: initially, treatment of stupor and akinesis with dopaminergics, for persistent tremor, anticholinergics (caution: side effects, especially in elderly patients), propranolol, clozapine; for treatment-resistant tremor - deep brain stimulation if indicated

For dystonia, physiotherapy is generally also carried out, and orthoses are sometimes used
- for focal dystonias: trial therapy with botulinum toxin (serotype A), anticholinergics
- for generalized or segmental dystonia, first of all, drug therapy: anticholinergic drugs (trihexphenidyl, piperidene; attention: visual impairment, dry mouth, constipation, urinary retention, cognitive impairment, psychosyndrome), muscle relaxants: benzodiazepine, tizanidine, baclofen (in severe cases, sometimes intrathecal), tetrabenazine; in severe cases resistant to therapy, according to indications - deep brain stimulation (globus pallidus internus) or stereotactic surgery (thalamotomy, pallidotomy)
- children often have dopa-sensitive dystonia (often also reacts to dopamine agonists and anticholinergics)
- dystonic status: observation and treatment in the intensive care unit (sedation, anesthesia and mechanical ventilation if indicated, sometimes intrathecal baclofen)
For tics: explanation to the patient and relatives; drug therapy with risperidone, sulpiride, tiapiride, haloperidol (second choice due to unwanted side effects), aripiprazole, tetrabenazine or botulinum toxin for dystonic tics
For chorea: tetrabenazine, tiapride, clonazepam, atypical antipsychotics (olanzapine, clozapine) fluphenazine
For dyskinesias: discontinue provoking drugs, trial therapy with tetramenazine, for dystonias - botulinum toxin
For myoclonus (usually difficult to treat): clonazepam (4-10 mg/day), levetiracetam (up to 3000 mg/day), piracetam (8-24 mg/day), valproic acid (up to 2400 mg/day)