What is Dystonia?

According to the occurrence site of dystonia, it can be divided into localized, segmental, leaning and generalized. In general, the earlier the age of onset, the more severe the symptoms and the more likely it is to affect other parts of the body. The older the onset, the more likely it is that dystonia will remain focal. Local dystonia refers to dystonia that affects only a part of the body, such as spastic torticollis, writing spasm, eyelid spasm, and oral-mandibular dystonia. Segment dystonia involves more than one adjacent site, such as Meige syndrome (eyes, mouth, and lower jaw), one upper limb plus the neck, and two lower limbs. When one side of the body is involved, it is called hemi-muscular dystonia, which is usually caused by a contralateral cerebral hemisphere lesion. General dystonia, involving at least one segment, plus more than one other site.

Wang Yuping	(Chief physician)	Department of Neurology, Xuanwu Hospital, Capital Medical University
Wei Hua	(Deputy Chief Physician)	Department of Neurology, Xuanwu Hospital, Capital Medical University

Dystonia is a dyskinesia syndrome that is characterized by abnormal movements and postures of dystonia caused by uncoordinated or excessive contraction of active and antagonist muscle contractions. It has involuntary and persistent characteristics. According to the etiology can be divided into primary and secondary. Primary dystonia is genetically related. Secondary dystonia includes a large group of diseases, some are genetic diseases (such as hepatolenticular degeneration, Huntington's disease, ganglioside disease, etc.), and some are caused by exogenous factors (such as perinatal injury , Infections, neuroleptics).

Western Medicine Name: Dystonia
English name: dystonia

Affiliated Department: Internal Medicine-Neurology
Main cause: genetic factors

Classification of Dystonia

Etiology and pathogenesis of dystonia

Primary dystonia is mostly sporadic, with a small family history showing autosomal dominant or recessive inheritance, or X-linked inheritance. It is most common in children or adolescents aged 7-15 years. Autosomal dominant inherited primary torsional spasms are mostly caused by mutations in the DYTl gene located at 9q32-34, with a penetrance of 30% to 50%. Dopa-responsive dystonia is also an autosomal dominant inheritance caused by mutations in the guanosine triphosphate cyclase-1 (GCH-1) gene. On the island of Paray, Philippines, there is a dystonia-Parkinson's syndrome that is X-linked recessive. Familial localized dystonia is usually autosomal dominant with incomplete penetrance.

Studies have shown that peripheral trauma can induce dystonia in carriers of primary dystonia genes, such as oral-mandibular dystonia, and a history of facial or tooth damage before the disease. In addition, dystonia can also be induced by excessively acting limbs. Such as various occupational dystonia, writing cramps, typist cramps, instrumentalists and athletes limb cramps, etc., their peripheral factors are often considered to be the main role. Therefore, it is speculated that the etiology is due to the reorganization of the spinal cord motor circuit or changes in motor sensory connections above the spinal cord level leading to changes in basal ganglia function.

Secondary (symptomatic) dystonia refers to any disease involving the new striatum, old striatum, thalamus, blue spots, brain stem reticular structure, etc., which can cause symptoms of dystonia, such as liver Beanoid degeneration, nuclear jaundice, gangliosideosis, paleoglobin substantia nigra degeneration, progressive supranuclear ophthalmoplegia, bilateral basal ganglia calcification, hypoparathyroidism, poisoning, cerebrovascular disease, brain Trauma, encephalitis, split brain deformity, drug-induced (L-DOPA, phenothiazines, butyrylbenzenes, metoclopramide, chemotherapy drugs), etc. It has been reported that blepharospasm can be caused by ischemia or demyelinating lesions on the dorsal side of the brainstem.

The pathogenesis is unknown, and abnormal concentrations of noradrenaline, dopamine, and serotonin have been reported in some areas of the brain, but the significance is unknown. Recent research suggests that local dystonia is caused by abnormalities in the basal ganglia because static imaging studies have not identified anomalies, and dynamic imaging studies using positron emission tomography (PET) have shown that the caudate nucleus, the bean-shaped nucleus, and The metabolic rate of the frontal lobe projection area of the medial dorsal nucleus of thalamus is reduced, so the dysfunction of basal ganglia and frontal lobe connection is considered to be the main cause of dystonia.

Clinical manifestations of dystonia

Dystonia reverses spasms

Torsion spasm was first named by Oppenheim H in 1911. It refers to torsional dystonia, also known as dystonia musculornm deformans. It is clinically used on the limbs, trunk and even the whole body. It is characterized by severe involuntary torsional movements and abnormal posture.

According to the cause can be divided into two types of primary and secondary. The onset is mostly between 5 and 15 years old, with family history, the second generation has an earlier onset age than the first generation. 60% of the patients were hereditary, with autosomal dominant and recessive inheritance each accounting for half; 40% of the patients were sporadic. Eastern European Jews have a higher incidence. Recent research indicates that the gene is located at 9q34, most of which are caused by the deletion of the 3 bp GAC. Low striatum dopamine levels may be associated with primary dystonia. An X-linked autosomal recessive dystonia was found on Panag Island in the Philippines. This type of disease develops in early adulthood at the age of 20, and symptoms can begin in the legs and feet, as well as in the upper body. Fifty percent of patients develop whole body.

Can occur at all ages. Children with childhood onset often have a positive family history. Symptoms often start on one or both lower limbs and gradually progress to extensive involuntary torsional movements and posture abnormalities, leading to severe dysfunction. Adult onset is mostly sporadic. Symptoms usually begin in the upper limbs or torso. About 20% of patients eventually develop systemic dystonia, which is generally not severely disabled.

In the early stages of onset, often the involuntary toe plantar flexion on one side of the foot occurs when walking, and the heel cannot touch the ground when walking, which is called "toe gait". In the early stages of the onset, this abnormal movement only affects some casual movements, such as walking forward, but does not affect movements in other directions, such as backward, or walking is normal when walking horizontally. There are also sudden flexion or reflex spasms of one lower extremity. After a few months or years, this involuntary abnormal movement will also occur at rest, and gradually spread to the limbs in the adjacent parts, and finally to the face, neck and even the whole body. Facial involvement is manifested as squeezing, crooking, grinning, etc. Tongue muscles and throats may have tongues that sometimes extend, sometimes retract, and molars, accompanied by articulation disorders and difficulty swallowing. Neck involvements have spastic torticollis, and the limbs appear as Straighten, flex, or pronation, supination. Involvement of the trunk and paraspinal muscles causes torsional or spiral movements throughout the body, so it is easy to cause muscle hypertrophy, lordosis, scoliosis, and pelvic tilt. Reversal spasms are aggravated during voluntary exercise or stress, and disappear completely after falling asleep. Muscle tonicity increases during torsion and returns to normal or decreased after torsional motion ceases, hence the name of deformable dystonia. Severe cases cannot engage in normal exercise, and advanced cases can cause skeletal deformities and muscle contractures, leading to severe disability. Dystonia with torsional component is called torsion spasm.

Family members of autosomal dominant inheritors may have multiple members with the same disease or have a combination of localized symptoms, such as eyelid spasm, torticollis, writing cramps, scoliosis and other symptoms, and most often start from the upper limbs Can be confined to the onset site for a long time, even if it progresses to systemic type, the symptoms are mild.

The diagnosis of torsion spasm is not difficult, and the diagnosis can be made based on strange involuntary movements such as the face, neck, trunk, limbs, and / or pelvis. If various causes that may cause this disease can be ruled out, it can be diagnosed as primary torsional spasm.

Dystonia spastic torticollis

Spasmodic torticollis (spasmodic torticollis) was first proposed by Dutch doctor Tulpius in 1652. It is more common in 30-50 years old and can also occur in children or elderly people. The ratio of male to female is 1: 2. The disease is caused by spasticity or tonic contraction of the neck muscles, causing the head to turn to one side of ankylosing. The dystonia of the neck causes abnormal posture of the head and neck, so it is also called internal neck dystonia or abnormal neck muscle tension.

There has been much debate about the etiology of this disease for a long time. Among them, 5% to 10% of patients often have mild dystonia in other parts of the body, so it can be considered as a manifestation of dystonia. Rare familial, can also be secondary to rheumatic fever, multiple sclerosis, neurosyphilis, malaria, CO poisoning, certain drugs, encephalitis, hyperthyroidism, Wilson disease, Hallervorden-Spatz disease and so on.

The typical clinical manifestations are intermittent or persistent deflections of the head when the head is rapidly turning and resting. Adult onset spastic torticollis, usually with a slow onset, begins to turn its head involuntarily, and after a few days or months, the frequency and amplitude of rotation will gradually increase and superimpose clonic beating spasms. Both the deep and shallow neck muscles can be affected, and the clinical manifestations are different due to the different muscle groups involved. However, abnormal contractions of the sternocleidomastoid muscle, trapezius, and cervical clevis are most easily manifested. Some patients show an involuntary nod or shake their heads before symptoms become apparent. In addition, the spasm time can be long, short, and pauses. In severe cases, the muscles are tonically contracted, the spasms are chaotic and violent, causing the head to tilt, twist, and the direction of the twist is variable. Hypertrophy can occur in the affected muscle. This involuntary movement can be aggravated by emotions, aggravated when walking and cycling, relieved when lying down, and completely disappear during sleep. Spastic torticollis with involuntary contraction can cause cervical nerve tenderness. In severe cases, it can radiate to the arm and even cause muscle tension headache. Spastic torticollis associated with pain is more common than other local dystonias. Severe and long-term conditions can cause neck muscle contracture and permanent deformation.

Acute spastic torticollis, which can suddenly start, is typically caused by drug reactions such as haloperidol and metoclopramide. After stopping medication or giving anticholinergics or benzodiazepines, it will gradually return to normal.

Meige Dystonia Meige Syndrome

First described by French doctor Henry Meige in 1910, the main manifestations are blepharospasm and oromandibular dystonia, which can be divided into three types: eyelid spasm; eyelid spasm with mouth-mandibular muscle tension Obstacles; Mouth-mandibular dystonia. Type II is the complete type of Meige syndrome; types I and III are incomplete. Clinically, it mainly affects the muscles of the eyes, mouth, and jaw. Eye muscle affected people show eyelid irritation, dry eyes, photophobia and frequent blinking, and then develop into involuntary eyelid closure, and the spasm can last for several seconds to several minutes. Most are binocular, and a few start from one eye, gradually spread to both eyes, affect reading, walking, and even cause functional "blindness." Eyelid spasms are often aggravated during mental stress, strong light exposure, reading, and gaze, relieved during speech, singing, mouth opening, chewing, and laughing, and disappear during sleep. Mouth and mandibular muscle involvement are manifested as mouth opening and closing, skimming, grinning, lip shrinking, tongue extension and tongue twisting, tooth decay, and gritting. In severe cases, the mandible can be dislocated, the teeth wear out and even fall off, tear the gums, bite off the tongue and lower lip, and affect vocalization and swallowing. Spasticity is often triggered by speech and chewing. It can be relieved by touching the chin and pressing the lower part of the chin, and it disappears during sleep.

Dystonia hand and foot asthma

Athletosis is also referred to as spasm or mobile spasm, which is a slow, curved, peristaltic, involuntary movement mainly at the distal end of the limb. When the lower extremities are involved, the thumb is often spontaneous dorsiflexion. When the facial muscles are involved, they frown and wink, posing as various "grimace". When the larynx and tongue muscles are affected, speech is unclear and dysphagia is difficult, and it may be accompanied by torsional spasm and spastic torticollis. Involuntary movements worsen during stress and disappear after falling asleep. Muscle tension increases when muscle spasms, normal when muscles relax, feels normal, and can diminish intelligence. The course of the disease can be years to decades. Extremely slow hand and foot movements cause abnormal postures similar to torsional spasm, which mainly invades the proximal limbs, neck muscles, and trunk muscles, and typically manifests with the trunk as the axis of torsion.

Dystonia writing cramps

Writer's cramp and other occupational cramps refer to dystonia and abnormal postures of the hands and forearms when performing professional actions such as writing, playing the piano, and typing. More men than women, male: female is about 2: 1. The average age of onset is about 39 years. Writing spasticity mainly occurs in the sharp hand. Because there are many right-handed people, most patients have writing spasticity in the right hand. Patients often have to replace with the other hand, and it is normal to do other unrelated actions. The patient had stiff arms when writing, holding a pen like a dagger, the elbow involuntarily lifted outward, the wrist and hand bent, the palm facing the side, and the pen and paper almost parallel. Due to the relationship between writing and occupation, some patients can only change to writing or working with non-hands. The disease may have a family history.

Diagnosis and differential diagnosis of dystonia

Dystonia diagnosis

Symptoms are usually not difficult to diagnose based on medical history, involuntary movements, and / or characteristics and locations of abnormal postures, but they need to be distinguished from other similar involuntary movement symptoms.

Differential diagnosis of dystonia

(1) Torsion spasm should be distinguished from chorea and stiff-man syndrome: The main points to distinguish between torsion spasm and chorea are involuntary movement of chorea, unpredictable movement patterns, and no persistent posture Abnormal and accompanied by decreased muscle tone, while involuntary movements to reverse the spasticity are slow, exercise patterns are relatively fixed, persistent posture abnormalities, and increased muscle tone. Stiff-man syndrome manifests as episodic trunk muscles (paraspinal muscles and abdominal muscles) and proximal muscles of the extremities are tense, stiff, and rigid, while facial and distal limb muscles are often unaffected, and stiffness can significantly limit patients' active movement , And often accompanied by pain, electromyography examination can occur during rest and muscle relaxation, continuous movement unit electrical activity, easy to distinguish from dystonia.

(2) Spastic torticollis needs to be distinguished from head tremor and congenital torticollis: Congenital torticollis is at an early age, can be caused by fibrosis of the sternocleidomastoid muscle hematoma, congenital absence or fusion of the cervical spine, Myositis, cervical lymphadenitis, and ophthalmoplegia (such as paralysis of the upper oblique muscle). Paroxysmal torticollis often results in paroxysmal involuntary spasms, similar to head tremor, which need to be distinguished from primary tremor and Parkinson's disease.

(3) Meige syndrome should be distinguished from subtemporal joint syndrome, mandibular misalignment, facial muscle spasm, and neurosis: facial muscle spasm is a convulsive appearance of the lateral muscles and eyelids, without the presence of mouth-mandibular Feel free to exercise.

(4) Try to find the cause after the diagnosis of dystonia: the primary dystonia is usually free of other positive neurological symptoms and signs except for tremors. At the onset, static dystonia, early onset of persistent posture abnormalities, early involvement of language function, sudden onset, rapid progress, and unilateral dystonia suggest that it is secondary, and the cause should be actively sought. Accompanied by other neurological symptoms and signs, such as muscle cramps, dementia, cerebellar symptoms, retinal changes, muscle atrophy, and sensory symptoms, etc., also suggest secondary dystonia.

Screening methods for secondary dystonia include: skull CT or MRI (excluding organic damage to the brain), neck MRI (excluding cervical dystonia due to spinal cord disease), blood cell smear (excluding nerve-spine Erythrocytosis), metabolic screening (excluding genetic metabolic diseases), copper metabolism measurement and slit lamp examination (excluding Wilson disease). Screening for mutations in the DYTl gene is also available for childhood onset of torsional spasms. ^[1]

Dystonia treatment

Treatment measures include drugs, local injection of botulinum toxin A and surgical treatment. For localized or segmental dystonia, local injection of botulinum toxin type A is preferred. For systemic dystonia, oral medication plus selective local injection of botulinum toxin A should be used. Severe cases in which the drug or botulinum toxin type A are ineffective can be considered surgical treatment.

Dystonia medication

(1) Antan: High-dose antan has more or less improvement in 50% of patients, but it must be slowly increased, generally 2-6 mg / day, and then increased by 2 mg every one to two weeks until the effect is satisfactory and poor The response is not obvious. Adverse reactions are mainly blurred vision, dry mouth, and constipation, but adverse reactions should not be used as an absolute contraindication for increasing drug dose. In severe adverse reactions, increasing the dose should be postponed for 1 to 2 weeks, and the dose can be increased after the adverse reactions are alleviated or completely disappeared. Generally, the average tolerated dose under the age of 18 is 30-40 mg / day, and the maximum tolerated dose is 80 mg / day.

(2) Drugs that fight dopamine function: Haloperidol is 0.5 mg once a day for the first time, and then gradually increased to 1 mg 3 times a day. If the symptoms are not well controlled, it can be increased to a positive effect and adverse reactions. Not obvious. Taibili 50 ~ 100mg, 2 ~ 3 times a day, gradually increase until the symptoms improve, but the adverse reactions are not obvious. Piperidine, chlorpromazine, tetrabenazine and the like can also be used.

(3) Benzodiazepines: 1 to 2 mg of clonazepam for adults, 3 times a day. Or available nitrazepam, diazepam and so on.

(4) Carbamazepine: 0.1 ~ 0.2g each time for adults, 3 times a day, and children should reduce it as appropriate. Can also be used with clonazepam or with haloperidol.

(5) Levodopa: Dramatic effect on dopa-responsive dystonia.

A Dystonia injection of botulinum toxin type A

(1) Eyelid spasm: a total of 5 to 6 injections, at the junction of the middle and inner 1/3 segments of the upper and lower eyelids and at the junction of the middle and outer 1/3 segments, the injection point is 2 to 3 mm from the eye margin, a total of 4 injection points, the fifth The injection points were the temporal orbicularis oris muscle of the iliac crest, and the injection point was 1 cm from the iliac crest. The median and significant improvement were about 90% after injection. The incubation period from injection to the onset of improvement was 4.2 days, and the duration of effect was 15.7 weeks on average.

(2) Mouth-mandibular dystonia: select masseter muscle, temporal muscle, medial and lateral wing muscles, and abdominal muscles. Each muscle is injected at 2 to 4 points. In severe cases, it can be injected at 5 points in the upper palate portion of the mouth. Inject the submental muscle. The effective rate of treatment is about 50 ~ 70%, and the curative effect lasts for 3 months, and individual patients reach one year. Adverse reactions were swallowing discomfort, dysarthria, and weak chewing, all of which were temporary.

(3) Spastic torticollis: Correct identification of the muscles and accurate injection points that cause abnormal postures and movements is the key to successful treatment. It is best to perform the EMG examination, but there are also reports that the EMG examination is not under the EMG examination. There was no difference in injection effect. The muscles usually injected are sternocleidomastoid muscle, trapezius muscle, head and neck cheek muscle, posterior cervical muscle and deep neck muscle if necessary. The effective rate of treatment is 53% ~ 90%, and the accompanying symptoms such as tremor and myalgia are also relieved. The effective period is 3 to 10 days, and usually lasts 3 to 6 months. Adverse reactions were cervical weakness and difficulty swallowing, accounting for about 14%, and usually disappeared within 2 weeks. Repeated injections are effective.

(4) Writing spasticity and other limited limb dystonia: When writing hand or forearm muscles for writing spasticity, because of its thin abdomen and overlapping muscles, if the injection point can be selected in the end plate area under the monitoring of an EMG instrument , The effect is higher. Adverse reaction was weakness. Dystonia of the forearm, toes, trunk, etc. can also be injected locally, and all have certain effects.

Dystonia Surgery

Electrophysiology and PET studies have found that dystonia is caused by the destruction of the paleosphere-thalamus-cortex projection system, which provides treatment for dystonia by blocking abnormal afferent impulses from the thalamus to the frontal motor cortex Theoretical basis.

(1) Thalamotomy: It is suitable for unilateral dystonia that is ineffective for drug treatment.

(2) Peripheral surgery: There are three types of peripheral surgery to treat cervical dystonia, namely epidural selective posterior spinal nerve amputation, epidural anterior root rhizotomy, and spinal accessory nerve microvascular decompression.

(3) Microelectrode guided destructive surgery: used to treat torsional spasm.

(4) Deep brain electrical stimulation treatment: Some studies have found that the implantation of a single electrode stereotactically on the ventral side of the pale ball, and long-term electrical stimulation of the deep brain can significantly improve symptoms. ^[2]

Prognosis of dystonia

The prognosis varies from type to type, and is generally a benign process that can last for decades. Symptoms of primary writing spasticity are fairly stable and there is very little tendency to spread. About one-third of patients may be disabled.

Prevention of dystonia

Prevention of diseases with genetic background is particularly important. Preventive measures include avoiding close relatives' marriages, implementing genetic counseling, carrier genetic testing and prenatal diagnosis. Early diagnosis, early treatment, and enhanced clinical care are of great significance for improving the quality of life of patients.