Extrapyramidal disorders. Guide to diagnosis and treatment
Ed. Shtok V.N., Ivanova-Smolenskaya I.A., Levin O.S. M.: MEDpress-inform, 2002. 608 p.
The publication is the first domestic guide to extrapyramidal disorders. The guide provides data on the prevalence, etiology, pathogenesis, and clinical manifestations of the main extrapyramidal syndromes and diseases. The diagnostic features and modern approaches to the treatment of extrapyramidal disorders are discussed in detail. In order to improve diagnostics and formulate a diagnosis, recommendations are given for coding the diagnosis according to the International Classification of Diseases, 10th revision. The manual is intended for neurologists, psychiatrists, neurosurgeons, neuroimaging specialists, doctors of other specialties, and medical students.
CONTENT
Preface
Section I. General problems of extrapyramidal disorders Chapter 1. Neurotransmitter organization of the basal ganglia (V.P. Barkhatova) Chapter 2. The mechanism of movement regulation and pathogenesis of the main extrapyramidal syndromes (O.S. Levin) Chapter 3. Classification of extrapyramidal disorders (V.N. Shtok, O.S. Levin) Chapter 4. Mental disorders in extrapyramidal diseases (Zh.M. Glozman, O.S. Levin)
Section II. Parkinsonism Chapter 5. Parkinson's disease (V.N. Shtok, N.V. Fedorova) Chapter 6. Mental disorders in Parkinson's disease and their correction (O.S. Levin) Chapter 7. Juvenile parkinsonism (S.N. Illarioshkin) Chapter 8. Secondary parkinsonism (O.S. Levin, S.N. Illarioshkin) Chapter 9. Progressive supranuclear palsy (Steele-Richardson-Olszewski disease) (O.S. Levin) Chapter 10. Multiple system atrophy (O.S. Levin) Chapter 11. Corticobasal degeneration (O.S. Levin) Chapter 12. Diffuse Lewy body disease (dementia with Lewy bodies) (O.S. Levin) Chapter 13. Parkinsonism in hereditary multisystem degenerations of the central nervous system (S.N. Illarioshkin)
Section III. Trembling hyperkinesis (I.A. Ivanova-Smolenskaya)
Chapter 14. Trembling hyperkinesis: phenomenology, classification, diagnosis Chapter 15. Essential tremor
Section IV. Dystonic hyperkinesis Chapter 16. Dystonic hyperkinesis: phenomenology, classification, generalized forms (E.D. Markova) Chapter 17. Focal and segmental forms of dystonia (V.L. Golubev)
Section V. Choreic hyperkinesis (S.N. Illarioshkin) Chapter 18. Choreic hyperkinesis: phenomenology, classification, diagnosis Chapter 19. Huntington’s disease
Section VI. Ticotic hyperkinesis (O.S. Levin)
Chapter 20. Tic hyperkinesis: phenomenology, classification, diagnosis Chapter 21. Tourette's syndrome
Section VII. Other hyperkinesis and movement disorders Chapter 22. Ballism (S.N. Illarioshkin) Chapter 23. Athetosis (S.N. Illarioshkin) Chapter 24. Myoclonic hyperkinesis (S.N. Illarioshkin) Chapter 25. Paroxysmal dyskinesia (O.S. Levin) ) Chapter 26. Hyperekplexia (O.S. Levin) Chapter 27. Drug-induced dyskinesias (O.S. Levin) Chapter 28. Restless legs syndrome (O.S. Levin) Chapter 29. Rigid person syndrome (O.S. Levin) Chapter 30. Hyperkinesis induced by peripheral actors (O.S. Levin) Chapter 31. Stereotypes (O.S. Levin) Chapter 32. Psychogenic hyperkinesis (V.L. Golubev) Chapter 33. Walking disorders: mechanisms, classification, principles of diagnosis and treatment (O.S. Levin)
Section VIII. Extrapyramidal syndromes in diseases of various etiologies Chapter 34. Hepatolenticular degeneration (I.A. Ivanova-Smolenskaya) Chapter 35. Extrapyramidal syndromes in cerebrovascular diseases (O.S. Levin) Chapter 36. Extrapyramidal syndromes in infectious and parasitic diseases of the central nervous system (O.S. Levin) Chapter 37. Extrapyramidal syndromes in chronic hepatic encephalopathy (O.S. Levin) Chapter 38. Extrapyramidal syndromes in rheumatism, antiphospholipid syndrome, diffuse connective tissue diseases and vasculitis (O.S. Levin)
Section IX. Special methods for the treatment of extrapyramidal disorders Chapter 39. Neurosurgical treatment of extrapyramidal disorders (V.A. Shabalov) Chapter 40. Treatment of extrapyramidal disorders with botulinum toxin (S.L. Timerbaeva, I.A. Ivanova-Smolenskaya, E.D. Markova, O.S. Levin)
Appendices Appendix 1. Formulation of the diagnosis of extrapyramidal disease and its coding in accordance with the International Classification of Diseases, 10th revision Appendix 2. Data on incidence and prevalence for major extrapyramidal diseases Appendix 3. Extrapyramidal diseases with established genetic markers Appendix 4. Diagnosis criteria for multiple system atrophy
Subject index Index of medicines
Extrapyramidal disorders in cerebrovascular diseases
The article discusses the most common post-stroke extrapyramidal disorders. Using the example of the drug Ceraxon®, the possibilities of neuroprotective therapy in the treatment of post-stroke extrapyramidal disorders are discussed.
Cerebrovascular diseases are the most important medical and social problem. The prevalence of cerebral stroke remains high throughout the world: 16.9 million strokes were registered in 2015, with an average incidence of 258 cases per 100 thousand population [1]. Every year, 5.9 million people die from stroke worldwide. The incidence of stroke in Russia is significantly higher than in Western European countries, amounting to 300–350 cases per 100 thousand population. In Moscow alone in 2014, over 35 thousand strokes occurred. The increase in the number of strokes among young people is also alarming. Extrapyramidal symptoms, which are characterized by great diversity, involvement of various structures in the pathological process, heterogeneity of treatment approaches and prognosis, are not among the frequent manifestations of acute stroke. However, the resulting disorders can be persistent and cause significant disability. Meanwhile, doctors are much less aware of post-stroke extrapyramidal disorders than of other focal symptoms.
Extrapyramidal disorders: epidemiology and pathogenesis
According to epidemiological data, extrapyramidal disorders are observed in 1–4% of patients who have had a stroke, in approximately equal proportions in men and women [2]. It is possible that the prevalence of post-stroke extrapyramidal disorders is greatly underestimated, since they can develop delayed (after several years), which makes it difficult to take them into account in epidemiological studies.
The main role of the basal ganglia in the system of organizing voluntary movements is to regulate the motor activity of the cortex, prepare for movement, regulate muscle tone and control the sequence of activation of various muscle groups. A kind of “exit gate” of the basal ganglia is the internal segment of the globus pallidus and the reticular part of the substantia nigra. The total vector of activity of the direct and indirect dopaminergic pathways is realized on these structures. Normally, inhibition of the globus pallidus and the reticular part of the substantia nigra occurs, and thalamocortical projections are disinhibited, which leads to facilitation of the movement initiated by the cortex. At the same time, the cortex, through direct corticostriatal and corticosubthalamic pathways, has a regulatory effect on the basal ganglia. In addition, there are numerous activating and inhibitory connections between individual structures of the basal ganglia. In a simplified way, the development of hypokinetic syndrome can be explained by increased activity of the indirect pathway, hyperkinetic disorders - by the direct pathway.
Despite the fact that the basal ganglia play a huge role in the control of voluntary movements, severe damage to the basal ganglia due to stroke is not always accompanied by motor impairment. According to the Lausanne Stroke Registry, out of 2500 patients, only 29 (1%) had post-stroke extrapyramidal disorders [3]. Today, the question of why morphological damage to the basal ganglia in some cases is not accompanied by clinical symptoms remains open. Probably, such factors as individual sensitivity to ischemia of neuronal subcortical structures, the possibility of plasticity of brain tissue, and the inclusion of compensatory mechanisms have an influence. In addition, apparently, for the disruption of the basal ganglia, it is not so much a single, lacunar lesion that is important, but rather the dysfunction of a number of interneuronal connections [4, 5]. Indeed, in the mechanisms of development of akinetic-rigid syndrome in Parkinson's disease, not only dysfunction of the direct and indirect dopaminergic pathways due to disruption of dopamine production by neurons of the substantia nigra plays a role, but also changes in the functional activity of cortical and stem structures. Thus, according to positron emission tomography with fluorodeoxyglucose, there is a decrease in the activity of metabolic processes in the premotor and supplementary motor cortex, as well as in the associative zones of the temporal lobe [6].
Post-stroke extrapyramidal disorders
Post-stroke extrapyramidal disorders are represented, as a rule, by unilateral disorders contralateral to the stroke focus (83% of cases), but bilateral symptoms are also possible [3]. In addition, stroke in the brainstem or cerebellum may result in unilateral ipsilateral symptoms.
The most common extrapyramidal syndromes associated with stroke include hemichorea (with or without hemiballismus), dystonia, tremor, parkinsonism, or myoclonus [3, 7]. Post-stroke extrapyramidal disorders can develop acutely, along with other focal manifestations of stroke, and delayed (after several weeks, months and even years), and also progress over time [2]. Options for the transformation of hyperkinesis from hemiballismus in the acute period to hemichorea and later to hemidystonia have been described [8].
There is a relationship between the timing of the formation of extrapyramidal symptoms and their nature [9–11]. Thus, chorea appears much earlier than the symptoms of parkinsonism. In a study by F. Alarcón et al., the average time to develop hemichorea was 4.3 days, parkinsonism was 117.5 days (p
A correlation was found between the time of development of hyperkinesis, its nature and the age of the patients. BL Scott and J. Jankovic found that at a young age, extrapyramidal symptoms do not appear immediately [11]. Thus, in two patients (average age 28.7 years) with ischemic infarctions, hemidystonia on the side of hemiparesis debuted after 42.8 years. In elderly patients, the latent period for the development of symptoms was one to four years. In addition, young patients are characterized by a tendency toward generalized hyperkinesis, while older patients have focal or segmental forms of dystonia [11].
According to F. Alarcón et al., dystonia is more common in young people with stroke, and chorea is more common in older age groups [7].
The pathophysiology of delayed onset of extrapyramidal disorders is not entirely clear. This phenomenon is characteristic not only of stroke, but also of traumatic brain injury. The hypothesis that explains it is the role of synaptic plasticity, which leads to the gradual formation of new functional connections in the system of subcortical-cortical circles, changes in the balance of activating and inhibitory influences and, as a result, the formation of abnormal motor patterns [2].
Extrapyramidal symptoms are most often caused by focal changes in the striatum/pallidum (44%) and thalamus [3]. There is no clear correlation between the localization of the stroke focus and the nature of hyperkinesis. Moreover, damage to the same formations can lead to different extrapyramidal symptoms. Thus, the cause of hemiballismus can be damage not only to the subthalamic nucleus, but also to the striatum and thalamus. Hemidystonia, hemichorea, and hemiathetosis occur due to damage to both the lentiform and caudate nuclei [3]. After a stroke, chorea, athetosis, or dystonia may develop in the thalamus. Extrapyramidal syndromes most often occur due to small deep infarctions against the background of microangiopathy [3, 7, 11]. However, cases of hyperkinesis have been described after cardioembolic or atherothrombotic stroke, as well as after parenchymal or subarachnoid hemorrhage [4].
Vascular chorea
Chorea is the most common post-stroke hyperkinesis. It is observed in 0.4–1.3% of patients who have suffered acute cerebrovascular accident, mainly in elderly people [11]. Choreic hyperkinesis debuts acutely in the first four days after the stroke [3, 11]. Hyperkinesis is most often represented by hemichorea or in the case of bilateral vascular lesions it can be generalized. In most patients it is accompanied by muscle weakness on the same side. Cases without paresis are less common. In addition, several cases of simultaneous presence of contralateral hemichorea and hemiparesis on the opposite side have been described [3, 13]. Choreic hyperkinesis, despite the restoration of muscle strength in the limbs, can persist and become chronic. In severe cases, chorea can be combined with throwing movements, that is, it can develop into hemiballismus. The latter, unlike chorea, involves not only a large range of movements, but also the mandatory involvement of the proximal limbs.
Vascular chorea develops as a result of ischemic or hemorrhagic damage to the thalamus, lentiform nuclei, and less commonly, the subthalamic nucleus (the area of blood supply to the lateral lenticulostriate or thalamoperforating arteries - the basin of the middle and posterior cerebral arteries) [12, 13]. Several studies have shown that vascular chorea can be caused by damage to the frontal, temporal or parietal lobes. Hyperkinesis in this case is the result of a decrease in the activating influence of the cortex on the subcortical ganglia and the functional inactivation of the latter. Another explanation is the presence of small lesions in the basal ganglia not identified by structural neuroimaging. Thus, N. Mizushima et al. described a patient with a right temporal lobe infarction and contralateral hemichorea who showed reduced perfusion in the right basal ganglia only using single-photon emission computed tomography [14]. A case of hemichorea was also observed in stenosis of the extracranial part of the internal carotid artery, with hypoperfusion in the small arteries of the basal ganglia, detected by functional neuroimaging, and a reduction in hyperkinesis after revascularization.
The development of hemiballismus is associated with predominant damage to the subthalamic nucleus (according to clinicopathological studies, damage to at least 20% of the substance of the subthalamic nucleus). Hemiballismus may be a consequence of a hemorrhagic focus in the striatum.
Spontaneous regression of choreic hyperkinesis against the background of acute stroke is observed in 50% of cases. In some patients, hyperkinesis may be persistent. Observations show that the prognosis is better in patients with cortical strokes compared to those who suffered subcortical infarctions. This is consistent with the assumption that chorea in cortical strokes is a consequence of transient hypoperfusion of the subcortical-thalamic pathways or their functional inactivation. In the case of hemiballismus, the same pattern is observed - the prognosis is better in the case of a cortical lesion.
The management strategy for patients with vascular chorea is the same as for patients with acute stroke - vasoactive, metabolic, antiplatelet therapy. However, if hyperkinesis becomes pronounced and is accompanied by a large range of movements (chorea and hemiballismus), it is necessary to prescribe symptomatic therapy aimed at blocking dopamine receptors. For treatment, typical antipsychotics (haloperidol, sulpiride, pimozide) are used in low doses. The duration of their use should be limited to two weeks with gradual withdrawal [15]. The effectiveness of atypical antipsychotics, such as risperidone, quetiapine, olanzapine, clozapine, has been confirmed in a number of studies [16]. Good results have been observed with tetrabenazine, an atypical antipsychotic that depletes the pool of presynaptic dopamine and is widely used throughout the world for the treatment of Huntington's chorea.
In addition to neuroleptics, benzodiazepines (clonazepam, diazepam), valproic acid preparations, gabapentin, trihexyphenidyl are prescribed as symptomatic treatment for vascular chorea. There are isolated reports of the effectiveness of the use of amantadines. Several randomized placebo-controlled studies showed that intravenous administration of 400 mg/day amantadine led to a significant reduction in the severity of hyperkinesis [17].
Surgical treatment of vascular chorea is not widespread. However, in a number of severe cases of hemichorea/ballisma (lasting more than one year), stereotactic operations on the thalamus or posteroventral pallidotomy had a positive effect [18]. Deep brain stimulation (thalamus, internal segment of the globus pallidus) is currently also considered as a way to correct choreic hyperkinesis. Some studies have demonstrated at least a three-year improvement in well-being [19].
Dystonia
Dystonia is the second most common (after chorea) hyperkinesis. Occurs several weeks or months after the stroke (on average nine months). Post-stroke dystonia is formed contralateral to the lesion located in the putamen or thalamus, less often in the globus pallidus [2, 4]. Cases of isolated hand dystonia as a result of a stroke in the parietal lobe have been described.
Dystonia is most often focal, but can be segmental or generalized (hemidystonia). Post-stroke hemidystonia in childhood is often combined with hemiatrophy [8]. Typically, the development of a dystonic position of the hand with flexion in the area of the metacarpophalangeal joints and extension of the interphalangeal joints, adduction and flexion of the elbow. With muscle dystonia in the leg, an equinovarus position of the foot is formed with or without an extension position of the big toe (similar to Babinsky’s symptom). Cases have been described where dystonia of the hand is joined after a few months by dystonia of the foot [8]. Cranial dystonia (blepharospasm, oromandibular dystonia) is extremely rare (damage to the brainstem-diencephalic projections or thalamus) [21]. Cervical dystonia may be a consequence of an ischemic or hemorrhagic lesion in the cerebellar hemisphere, pons, or tegmentum [22].
Treatment of post-stroke dystonia requires an integrated approach with the prescription of anticholinergics, clonazepam, carbamazepine, valproate, and a baclofen pump. For focal dystonia, botulinum toxin injections are used. In severe cases, surgical intervention is recommended - destruction of the globus pallidus or thalamic nuclei, as well as deep brain stimulation.
Vascular parkinsonism
The concept of vascular parkinsonism was first put forward in 1929 by M. Critchley [23]. He described the clinical manifestations of parkinsonism that developed against the background of cerebrovascular disease in elderly patients and proposed the term “atherosclerotic parkinsonism.” He listed rigidity, a mask-like face, and a shuffling gait as the main symptoms of atherosclerotic parkinsonism. Depending on additional symptoms (pseudobulbar palsy, dementia and urinary incontinence, pyramidal symptoms, cerebellar insufficiency), M. Critchley identified six types of the disease [23]. M. Critchley's concept came under serious criticism in subsequent years, since clinically Parkinson's disease and parkinsonism due to cerebrovascular disease are difficult to differentiate. Many patients with Parkinson's disease have vascular risk factors. Moreover, the presence of a vascular component aggravates the course of the disease. Subsequently accumulated pathological data confirmed the correctness of M. Critchley's assumption about the probable vascular nature of the disease. However, even today, despite the capabilities of neuroimaging, problems often arise in making a diagnosis.
According to epidemiological data, vascular parkinsonism accounts for 3–12% of all cases of parkinsonism [24]. The prevalence of vascular parkinsonism, according to pathologically confirmed studies, ranges from 1–6% [24]. Thus, in the work of KA Jellenger, during an autopsy of 759 patients with parkinsonism, vascular etiology was confirmed in 3.4% of cases [25].
Vascular parkinsonism most often develops against the background of multiple lesions of the basal ganglia. Less commonly, parkinsonism results from single infarcts in the thalamus, lenticular nuclei, or pons. It should be emphasized that only a very small number of patients with vascular pathology and even those with vascular lesions show symptoms of parkinsonism [24]. I. Reider-Groswasser found that only 38% of patients with focal changes in the basal ganglia suffered from parkinsonism [26].
Lacunar infarctions are often combined with leukoaraiosis and damage to the white matter of the frontal lobes. In a study of 14 patients with vascular parkinsonism, the most characteristic neuroimaging finding was a combination of lacunar changes in the striatum and leukoaraiosis [2]. It is extremely rare that a focal lesion affects the substantia nigra, but in these cases the clinical picture of the disease is identical to Parkinson's disease.
The basis of lacunar lesions of the basal ganglia in vascular parkinsonism is most often microangiopathy associated with hypertension or diabetes mellitus [27]. Cases of vascular parkinsonism have been described in CADASIL syndrome and Moyamoya disease [2]. Another cause of lacunar changes in the basal ganglia is lipohyalinosis of small vessels, leading to microocclusion, ischemia and gliosis. Pathomorphological examination reveals proliferation of astrocytes, demyelination of axons, and expansion of perivascular spaces. As a result, multiple lacunar changes are formed in the basal ganglia, internal capsule, and center semiovale [24].
Based on the nature of development, two forms of vascular parkinsonism are distinguished:
- with an acute onset due to extensive lacunar infarction in the basal ganglia and stepwise progression of symptoms;
- gradual onset and slow progression against the background of diffuse damage to the subcortical white matter in combination with ischemic changes in the striatum, lenticular nuclei or pons. A similar variant of the course of vascular parkinsonism occurs in every second or third patient with vascular parkinsonism.
Classic variants of vascular parkinsonism include cases of parkinsonism of the “lower body” - with bilateral symmetrical symptoms in the form of bradykinesia, rigidity in the legs and gait disturbances (decreased length and height of step, wide base, shuffling, postural instability, tendency to fall). Often in patients with vascular parkinsonism there is a starting delay when walking and a tendency to propulsion. Unlike Parkinson's disease, acheirokinesis (lack of cooperative arm movements when walking) is not typical for vascular parkinsonism. The presence of a resting tremor of the “pill rolling” type with a frequency of 4–6 Hz excludes the diagnosis of vascular parkinsonism. Slight postural or kinetic tremor may occur. Rigidity of the “cogwheel” type is observed very rarely. A combination of rigidity and spasticity is more common, predominantly in the lower extremities. In almost all patients (80%) with vascular parkinsonism, pyramidal symptoms (increased tendon and periosteal reflexes, Babinski's symptom), cognitive impairment, urinary disorders, and symptoms of pseudobulbar palsy can be detected. However, there are cases of vascular parkinsonism with a less obvious picture. Thus, in an Italian multicenter cross-sectional study in patients with diagnosed vascular parkinsonism, an asymmetric onset occurred in 59% of cases [2]. Hemiparkinsonism usually develops in the first months after an acute cerebrovascular accident and is associated with a large lesion in the basal ganglia.
The diagnosis of vascular parkinsonism must be confirmed by neuroimaging data in the form of focal changes in the basal ganglia, thalamus, and frontal lobe. In most cases, the DAT scan does not reveal any disturbances in binding to the dopamine transporter. At the same time, in vascular parkinsonism, changes, according to functional neuroimaging, can occur, but, unlike Parkinson’s disease, they are symmetrical in nature [24]. An additional diagnostic test may be a test of olfactory function. Anosmia is characteristic of Parkinson's disease and diffuse Lewy body disease, but not of vascular parkinsonism.
Dopaminergic therapy is ineffective for vascular parkinsonism. Only 20–30% of patients experience a moderate short-term effect from taking levodopa, and, as a rule, high doses of levodopa are used – 750–1500 mg/day [28]. If positive dynamics are not achieved within four to six weeks, then there is no point in continuing treatment with levodopa. A number of studies have noted that patients with changes on the DAT scan respond better to levodopa [28]. To improve the walking pattern, it is recommended to use rhythmic sound signals (metronome, music), visual references in the form of transverse stripes drawn on the floor corresponding to the width of the step, and a cane with a transverse crossbar. Courses of vasoactive and metabolic therapy are of particular importance in accordance with the principles of treatment of chronic cerebrovascular insufficiency and post-stroke conditions.
Tremor
Isolated post-stroke tremor is extremely rare. Typically, this is a unilateral postural or kinetic tremor. Tremor is one of the delayed post-stroke hyperkinesis. Tremor does not occur as a symptom of the acute period of stroke [29]. The development of hyperkinesis is caused by damage to the thalamus or dentato-rubro-thalamic, cerebellar-thalamic or nigrostriatal pathways. Cases of isolated tremor when writing as a result of lacunar infarction of the frontal lobe have been described. Damage to the midbrain is associated with Holmes tremor - unilateral, predominantly involving the proximal parts of the limbs, occurring at rest, while maintaining a pose (postural) and intensifying with movement [30]. Post-stroke tremor is practically refractory to pharmacotherapy. Propranolol or primidone are rarely effective. In severe cases, deep brain stimulation with implantation of electrodes into the ventral nuclei of the thalamus is recommended [24].
Myoclonus
Myoclonus rarely develops after an acute stroke. There are no reports in the literature of generalized myoclonus manifested in the late period of acute cerebrovascular accident. There are isolated descriptions of asterixis (negative myoclonus) - a repeated rhythmic drop in muscle tone in the hands when trying to hold them in a horizontal position. Asterixis in these cases was unilateral (contralateral to the lesion) or bilateral in nature. The appearance of asterixis is associated with damage to the thalamus, possibly in combination with the subthalamic nucleus [31, 32].
The role of neuroprotective therapy in post-stroke extrapyramidal disorders
The treatment of extrapyramidal disorders as focal symptoms that develop in the acute period of stroke is based on the principles of pathogenetic therapy of ischemic or hemorrhagic stroke. One of the areas of therapy in the acute period is the use of neuroprotective drugs. Among them, preference should be given to drugs with a convincing evidence base, with a multimodal effect and a proven safety profile.
Citicoline (Ceraxon®) is widely used in clinical practice for both ischemic and hemorrhagic stroke. Administration of citicoline for stroke significantly reduces mortality rates and permanent disability. A number of studies using computed tomography and magnetic resonance imaging have shown that the administration of citicoline on the first day of ischemic stroke led to a decrease in the volume of the ischemic lesion. The effect of the drug was dose-dependent (dosages of 500, 1000, 2000 mg/day were used). The average increase in lesion volume during therapy with Ceraxon® at a dose of 2000 mg/day was only 1.8% [33]. A. Davalos et al. Four clinical trials examined the results of oral citicoline in 1372 patients with ischemic stroke [34]. Citicoline was prescribed starting from the first day of the disease for six weeks. By week 12, recovery was achieved in 25% of cases in the citicoline group and 20% in the placebo group (p
All clinical studies emphasize the good tolerability and safety of the drug [33–35]. Citicoline is included in European recommendations and Russian standards for the treatment of stroke [34, 36].
The neuroprotective properties of the drug are associated with a pronounced membrane-stabilizing effect. Citicoline is involved in the synthesis of the main phospholipids (phosphatidylcholine, sphingomyelin, cardiolipin) of cell membranes [37–40]. By providing a direct repair effect, citicoline prevents damage to the cell surface and mitochondrial membranes when exposed to ischemia/hypoxia factors, as well as in neurodegenerative diseases. By stabilizing membranes, citicoline prevents the breakdown of phospholipids into fatty acids and the formation of free radicals [37–40]. The additional protective effect may be explained by an increase in the expression in brain neurons of the most important factor of endogenous neuroprotection, the protein sirtuin 1. Citicoline has a multicomponent neurotransmitter effect, promoting the synthesis of acetylcholine, serotonin, and norepinephrine [41]. The ability of citicoline to influence glutamatergic and GABA receptors has been noted [41]. In a number of experimental models of parkinsonism, the drug increased the level of dopamine in the striatum, stimulating its release by increasing the activity of tyrosine hydroxylase [42, 43]. Another reason for increased dopamine levels is inhibition of dopamine reuptake, possibly related to the effect of citicoline on phospholipid synthesis [44].
The dopamine-stimulating effect of citicoline served as the basis for its inclusion in the complex therapy of Parkinson's disease. Several double-blind crossover studies have demonstrated that citicoline administered as an intravenous infusion at a dose of 500 mg/day for 10–20 days improved motor performance and reduced bradykinesia, rigidity, and tremor. Improvement was observed when citicoline was prescribed both in monotherapy and in combination with levodopa [45, 46].
In the study by J. Acosta, citicoline was prescribed at a dose of 500 mg/day (with a stable dose of levodopa) for ten days intravenously, and then for 14 days as an oral solution [47]. At the end of the course of therapy, 36% of patients showed a good effect, mainly in relation to bradykinesia and rigidity. No significant effect on tremor was noted. According to an analysis of effectiveness depending on the time of administration of citicoline, the best results were observed in patients who were on levodopa therapy for less than two years. In some patients, the addition of citicoline reduced the dose of levodopa by 25–30% [47]. These data were confirmed by R. Eberhardt et al., who concluded that the administration of citicoline can reduce the dose of levodopa and thereby reduce the risk of adverse reactions associated with its use [48].
In a multicenter, blind, placebo-controlled study, C. Loeb et al. During the administration of citicoline at a dose of 1000 mg/day intravenously, in addition to the ongoing therapy, not only a significant positive effect of the drug was noted in comparison with placebo, but also a deterioration in the condition of patients after discontinuation of citicoline. This demonstrates the effectiveness of citicoline as an adjuvant agent during levodopa therapy in patients with Parkinson's disease [49].
Taking into account the neuroprotective effect and neurotransmitter potential, Ceraxon® is also indicated in the acute period of stroke, accompanied by extrapyramidal symptoms. Ceraxon® may be effective in the complex treatment of vascular parkinsonism. Experimental studies have proven the trophic and neuroprotective effects of citicoline on nigrostriatal dopaminergic neurons. In particular, citicoline protects dopaminergic neurons from the toxic effects of methyl 4-phenylpyridine [50, 51] and glutamate [50]. The recommended doses of the drug Ceraxon® in the acute period of stroke are 1000 mg/day intravenously every 12 hours, starting from the first day, followed by switching to oral forms (packaged form of the drug with a drinking solution). It is important to emphasize that intravenous and oral forms of the drug Ceraxon® have the same bioavailability. Treatment with Ceraxon® should continue for at least six weeks.
EXTRAPYRAMIDAL HYPERKINESIS: SYNDROMES, NOSOLOGICAL FORMS, AREAS OF PHARMACOTHERAPY
The paper presents a classification and brief account of clinical manifestations of different extrapyramidal hyperkinesias: tremor, torsion dystonia, including paroxysmal (dyskinesia), choreic hyperkyneses, various tics, and hyperkinesias caused by the adverse effects of drugs. Emphasis is laid on the fact that extrapyramidal hyperkinesias may be displayed both by neurological diseases proper (a nosological entity) and lesions of the extrapyramidal nervous system in other diseases, as well as by the side effects of drugs. Main approaches to choosing a pharmacotherapy for different types of extrapyramidal hyperkineses are described.
Prof.
V.N. Stock Manager
Department of Neurology of the Russian Medical Academy of Postgraduate Education, Head of the Center for Extrapyramidal Diseases of the Nervous System of the Ministry of Health. Moscow Prof. VNShtok, Head, Department of Neurology, Russian Medical Academy of Postgraduate Training; Head, Center of Extrapyramidal Diseases of the Nervous System, Ministry of Health of the Russian Federation, Moscow
E
The extrapyramidal system includes the basal ganglia, the cerebellum, some parts of the motor cortex, the thalamus optic, a number of nuclear formations of the brainstem (red, reticular and substantia nigra), as well as the segmental motor apparatus of the spinal cord. The majority of the efferent impulses of the extrapyramidal system are sent through the optic thalamus (the main relay distribution “station”) to the motor cortex and then, as part of the corticospinal tract, to the motor neurons of the spinal cord (see figure). A minority of efferent impulses reach spinal motor neurons as part of the tecto-, reticulo-, rubro-, vestibulo- and olivospinal tracts (see figure). The function of the extrapyramidal system with its multineuronal loop structure is ensured by the balance of the dopaminergic, acetylcholinergic and GABAergic neurotransmitter systems. An imbalance in neurotransmitter systems due to damage to the basal ganglia by hereditary, congenital or acquired diseases is manifested, in particular, by extrapyramidal hyperkinesis. Therefore, pharmacotherapy of hyperkinesis is aimed at restoring the disturbed imbalance of neurotransmitter regulation.
Drawing. Scheme of neuronal connections of the basal ganglia and motor pathways to spinal motor neurons (according to W. Tatton et al., 1983). VA, VL, CM – thalamus nuclei; Pi and Pe – internal and external members of the globus pallidus; Sth – subthalamic nucleus; SNR – substantia nigra pars reticularis; SNс – compact part of the substantia nigra; SC – nuclei of the superior colliculus; TPC – pedunculopontine nucleus; Hab – core of the frenulum; Ret – nuclei of the reticular formation; SMA – sensorimotor area of the cortex. 1 – afferent pathways to the basal ganglia; 2 – efferent pathways from the basal ganglia; 3 – neural connections between the basal ganglia; 4 – descending tracts to spinal motor neurons.
Extrapyramidal hyperkinesis manifests itself in different clinical forms: tremor, various variants of dystonia and myoclonus.
Tremor (shaky hyperkinesis)
Tremor is a rhythmic, regular, oscillating shaking of the head, torso, limbs or parts thereof.
Physiological tremor occurs in a healthy person under the influence of emotions or physical activity. Variants of pathological tremor include: resting tremor - present in the distal parts of the extremities at rest, usually decreases with voluntary movements; postural and static-dynamic tremor, most pronounced when the trunk or limbs, respectively, take and maintain a certain position in space; intention tremor, which appears in a limb when moving in a certain direction and intensifies when approaching the target; “wing flapping” tremor is a large-amplitude tremor, predominantly expressed in the proximal muscles of the limbs.
Essential tremor
(idiopathic hereditary tremor)
is transmitted in an autosomal dominant manner and is often found in families of long-livers.
The disease can begin at 20–30 years of age. Tremor is characterized by trembling when holding a pose or objects, i.e. it is static-dynamic in nature. At rest, it manifests itself with nodding (“yes-yes”) and negative (“no-no”) head movements. It intensifies with excitement and physical stress, when taking sympathomimetic ionizing agents (coffee, tobacco), and sometimes decreases with the influence of alcohol. The disease progresses slowly, and there may be a prolonged stabilization of the severity of tremor or even a decrease in tremor for a certain period. With a long course, intention tremor and other extrapyramidal symptoms may occur. For treatment, drugs that reduce sympathetic activation are used: alpha-presynaptic receptor agonists - clonidine, beta blockers - propranolol, as well as antiepileptic drugs - primidone, phenobarbital. Rest tremor
is considered a characteristic symptom
of Parkinson's disease
(idiopathic parkinsonism) and in this case is relieved by taking antiparkinsonian drugs: anticholinergics (for example, trihexyphenidyl), amantadine, DOPA-containing drugs (levodopa, levodopa + carbidopa, levodopa + benserazide), monoamine oxidase B inhibitors (selegiline etc.), catechol-o-methyltransferase inhibitors (tolcapone, entacapone), as well as dopamine receptor agonists (peribedil, bromocriptine).
Any antiparkinsonian drug can be used as initial monotherapy, which, as the disease progresses, is usually replaced by one or another combination of these drugs. In secondary parkinsonism
(vascular toxic, postencephalitic, posttraumatic), rest tremor may be absent, mildly expressed, or combined with statokinetic or intention tremor. Especially often, different types of tremor are observed in patients with various hereditary and degenerative diseases of the nervous system, for example, with olivopontocerebellar atrophy, Huntington's chorea, hepatocerebral dystrophy (Wilson-Konovalov disease). At the same time, other symptoms of damage to the extrapyramidal system, as well as pyramidal and cerebellar symptoms, are noted. In these cases, antiparkinsonian drugs for the correction of tremor are ineffective; drugs that are used to treat essential tremor are recommended.
Dystonia
Dystonia is a type of involuntary violent movement caused by slow contraction of the muscles of the limbs, trunk, neck, and face.
Can be distal, proximal, generalized, unilateral and focal.
Damage to the putamen, the centromedian nucleus of the visual thalamus, causes torsion dystonia, spastic torticollis, and spasms of the facial muscles. When the striatum is damaged, athetosis and tonic forms of dystonia are observed. Disruption of the interaction of the caudate nucleus, putamen and motor cortex causes chorea and tics; damage to the subthalamic nucleus and its connections with the internal segment of the globus pallidus - ballism; disruption of interaction in the stem-cerebellar “triangle” (dentate nuclei of the cerebellum - red nuclei - olives of the medulla oblongata) - myoclonus. Torsion dystonia (idiopathic generalized dystonia, deforming muscular dystonia)
is transmitted in an autosomal dominant and autosomal recessive manner.
Most often begins during puberty, but later onset is also possible. In the first stages it can manifest itself in a local form - blepharospasm, or a segmental form - spastic torticollis. During the course of the disease there may be spontaneous remissions. There are two clinical variants: in the hyperkinetic-dystonic form,
the increase in plastic tone is not constant, intensifies with voluntary movements, in a standing position and when walking (especially dystonia of the trunk muscles - torsion);
dystonia improves when lying down. In the rigid-hypokinetic form,
an increase in plastic tone, which varies in individual muscle groups, leads to pathological posture settings (deforming dystonia). The second form is associated with congenital slowly progressive dystonia, combined with signs of parkinsonism and pronounced fluctuation of symptoms during the day (Segawa syndrome, juvenile dystonic parkinsonism). For the rigid-hypokinetic form, DOPA-containing drugs are used, which are especially effective in juvenile dystonic parkinsonism. For the hyperkinetic-dystonic form, the following sequence of drug administration can be recommended: 1) anticholinergics (trihexyphenidyl); 2) baclofen; 3) carbamazepine; 4) clonazepam; 5) reserpine, which depletes dopamine reserves in presynaptic depots; 6) neuroleptics – dopamine receptor blockers (haloperidol); 7) a combination of the more effective listed means. Symptomatic (acquired) torsion dystonia is usually a manifestation of cerebral palsy. Pharmacotherapeutic approaches are the same as for torsion dystonia.
Spasmodic torticollis
It is a segmental (focal) form of dystonia. There are tonic, clonic and clonic-tonic forms, and depending on the direction of head rotation - anterior, posterior and lateral forms (antero-, retro- and laterocollis). In the absence of generalization of dystonia over a number of years, spastic torticollis can be considered an independent nosological form. There is a pronounced influence of cervical-tonic reflexes on the degree of clinical manifestations. Thus, torticollis decreases or goes away when the patient is lying down, and intensifies when standing up and walking; Significant relief from corrective gestures is also characteristic - supporting (or simply touching) the head with a hand, often in a very pretentious pose. The tonic form may be accompanied by pain in the neck and shoulder girdle. Torticollis may be the result of irritation of the cervical roots of the motor spinal nerves by pathologically tortuous vessels, arachnoid adhesions, etc. (peripheral form). These pathological processes can be identified using computed tomography, magnetic resonance imaging, angiography and myelography. When choosing individually effective pharmacotherapy, the following drugs are sequentially prescribed: 1) anticholinergics; 2) baclofen; 3) carbamazepine; 4) clonazepam; 5) reserpine; 6) neuroleptics – dopamine receptor blockers. Stereotactic operations on the basal ganglia, peripheral denervation, and the injection of botulinum toxin into the affected neck muscles (usually the sternocleidomastoid muscle) are less common. When a trigger substrate for peripheral spastic torticollis is identified, surgical removal of the irritating factor is resorted to. A rare, painful atlantoaxial torticollis (Grisel syndrome) is described as an independent form, when, with congenital weakness of the capsule of the atlantoaxial joint against the background of inflammatory processes (tonsillitis, acute respiratory infections), the ligamentous apparatus of the joint relaxes, soreness of the neck muscles and rotational positioning of the head appear. X-rays reveal displacement in the area of the atlantoaxial joint. Treatment includes anti-inflammatory drugs and orthopedic correction methods.
Athetosis
It is a slow dystonic hyperkinesis, the “creeping” spread of which in the distal parts of the limbs gives the involuntary movements a worm-like character, and in the proximal ones a snake-like character. When the muscles of the limbs, trunk and face are involved, it resembles writhing. As an independent clinical form, it is described under the name “double athetosis,” which occurs when the brain is damaged in the perinatal period: infections, trauma, hypoxia, hemorrhage, intoxication, with hemolytic jaundice due to Rh incompatibility of mother and fetus. As a symptom, it is observed in hereditary diseases with damage to the extrapyramidal nervous system (torsion dystonia, Huntington's chorea, hepatocerebral dystrophy), as well as in cases of damage to the basal ganglia of various etiologies (trauma, infections, intoxication). There is no effective treatment. Attempts to use the drugs used in the treatment of torsion dystonia are justified.
Local (focal) dystonia
In most cases, local dystonia is caused by congenital insufficiency of the basal ganglia, which manifests itself only under the influence of other diseases or exogenous factors in adulthood. Symptomatic local dystonia can be caused by local irritative factors and be based on a reflex mechanism. Blepharospasm
manifested by tonic (squinting) or clonic-tonic hyperkinesis of the orbicularis oculi muscle.
The predominance of the clonic component brings its shape closer to a tic (forced blinking). As an independent nosological form of damage to the extrapyramidal system, it can have a remitting, stationary or progressive course. In other cases, it acts as the initial manifestation of generalized torsion dystonia. It may be a manifestation of damage to the nervous system during exacerbation of autoimmune diseases such as systemic lupus erythematosus, Sjogren's syndrome. In chronic eye diseases, especially those accompanied by irritation of the mucous membrane and a pain component, blepharospasm develops as a reflex form of hyperkinesis. Facial hemispasm
(Brissot's spasm) is manifested by paroxysmal clonic or clonic-tonic contraction of the muscles of half the face.
The cause of hemispasm is often irritation or compression of the facial nerve trunk by adhesions or adjacent vessels. In these cases, microsurgical decompression of the nerve is necessary; pharmacotherapy is ineffective. Facial paraspasm
(bilateral facial hemispasm, Meige syndrome, Bruegel syndrome) is an idiopathic symmetrical focal dystonia of the facial muscles, in which blepharospasm and orofacial dystonia are combined.
The severity of episodes of tonic hyperkinesis varies significantly throughout the day (and from day to day). At night the hyperkinesis goes away. Provoking factors can be a rapid change in the direction of gaze, walking, psycho-emotional stress. A connection with changes in the psyche is indicated by a depressive mood background, clinically pronounced or maneuvered (hidden) depression, manic-depressive psychosis. The manifestations of hyperkinesis and mental disorders are often in an inverse relationship: hyperkinesis appears or intensifies during remission and depression and vice versa. The sequence of prescribing medications is as follows: anticholinergics, antipsychotics, benzodiazepine drugs, among which clonazepam is somewhat more effective. Idiopathic orofacial dystonia
(OFD, synonym – orobuccofacial dystonia) is manifested by complex, predominantly choreoathetoid hyperkinesis of facial muscles and tongue.
The movements resemble chewing. Sometimes described as oromandibular dyskinesia. Unlike facial paraspasm, there is no blepharospasm with OFD. OFD noticeably increases with excitement or under the influence of other external factors. Idipathic OFD affects older people and is sometimes described as “tardive dystonia.” Unfortunately, the same name is used to describe OPD, which develops after long-term treatment (hence, also “late”) with psychotropic drugs, especially antipsychotics, as well as antiparkinsonian drugs, especially DOPA-containing ones. To avoid confusion, spontaneously occurring OPD should be defined as idiopathic, and drug-induced hyperkinesis as drug-induced OPD. Rauwalfia, benzodiazepine and GABAergic drugs are used to treat idiopathic APD. Anticholinergics are prescribed with caution in low doses, since the latter sometimes enhance OPD. Drug-induced OPD can be stopped if the rules for prescribing, taking and discontinuing psychotropic drugs are observed. Writer's cramp
is a local form of painless kinesigenic hyperkinesis (action dystonia) with damage to the extrapyramidal system.
The possibility of its occurrence due to chronic hand fatigue and psycho-emotional stress cannot be ruled out. Treatment is the same as for other forms of central dystonia. Professional spasms
of the arm muscles in musicians, typists, hairdressers, jewelers, watchmakers, as well as in athletes (tennis players, golfers, billiard players) are usually caused by tenosynovitis due to chronic overstrain of the musculo-articular system. The main difference between professional dystonia and local forms of central dystonia is the pronounced pain component that accompanies muscle spasm. It is necessary to prevent the action of factors that cause spasms. Treatment by an orthopedist and arthrologist, in addition to medications, exercise therapy, acupuncture, and physiotherapy are used.
Chorea
Choreic hyperkinesis is involuntary violent irregular movements performed at a fast pace. The pattern of choreic hyperkinesis is determined by the number of muscles of the face, trunk, and limbs participating in hyperkinesis. At the same time, these sometimes complex hyperkinesis never develop into purposeful coordinated actions, although outwardly they sometimes resemble deliberate grimaces, antics and deliberate antics.
Huntington's chorea
A progressive hereditary disease of the nervous system, transmitted in an autosomal dominant manner. It begins most often in the 4th decade of life and progresses slowly. The morphological substrate is atrophy of the frontal and parietal cortex, basal ganglia (especially the striatum). The biochemical substrate is a decrease in the level of GABA and the enzyme that synthesizes it - glutamate decarboxylase, an increase in the content of dopamine and an increase in the activity of tyrosine hydroxylase, and as the disease progresses - a decrease in the activity of cholinergic systems. Choreic hyperkinesis gradually becomes generalized and develops against the background of decreased muscle tone. As the disease progresses, dementia develops, turning into dementia-like euphoria. In the juvenile form, akinetic-rigid syndrome may come to the fore, which complicates differential diagnosis (torsion dystonia, parkinsonism, hepatocerebral dystrophy). For treatment, neuroleptics, rauwolfia preparations, D2 receptor agonists (bromocriptine) are used, and for akinetic-rigid forms and a pronounced tonic component of choroathetoid hyperkinesis, small doses of DOPA-containing agents are used. To correct depression, tricyclic antidepressants (but not monoamine oxidase inhibitors) are prescribed.
Symptomatic forms of chorea (hemichorrhea)
They are observed in various diseases accompanied by damage to the striatum: rheumatism, systemic lupus erythematosus, discirculatory encephalopathy, traumatic brain injury, encephalitis, central nervous system intoxication, during treatment with DOPA-containing drugs and antipsychotics. The following are described as independent forms: congenital chorea with damage to the subcortical nodes in the perinatal period, Sydenham's minor chorea in children as a cerebral complication of rheumatism, chorea of pregnant women in the second or third trimester (toxicosis? unrecognized rheumatism?) and senile chorea. Senile chorea occurs in old age due to discirculatory encephalopathy. The difference from Huntington's chorea is the lack of data on the hereditary nature of the disease and information about the steady, slowly progressive increase of both chorea and dementia. For the symptomatic treatment of chorea, benzodiszepine drugs (diazepam, clonazepam), valproic acid drugs, and GABAergic drugs (baclofen, picamilon) are used.
Ballism
It is a large-scale hyperkinesis involving the muscles of the arms of the proximal limbs, most often the arms. Caused by damage to the subthalamic nucleus and striatum as a result of vascular disorders, including rheumatism and systemic lupus erythematosus. It may manifest itself in the form of hemiballismus. Perphenazine (etaperazine), haloperidol, and reserpine are used for treatment.
Tiki
They represent a fast, “selective”, repeated movement in individual muscle groups as a result of brief simultaneous activation of agonists and antagonists. Motor tics, according to the structure of hyperkinesis, are divided into simple and complex, and according to localization - into generalized and focal (in the muscles of the face, head, limbs, torso). Generalized complex tics may superficially resemble a goal-directed motor act. In addition to motor ones, there are also phonic tics: simple - with elementary vocalization and complex, when the patient shouts out whole words, sometimes curses (coprolalia).
Gilles de la Tourette syndrome (disease)
(generalized tic)
A hereditary disease, transmitted in an autosomal dominant manner, most often begins at the age of 7–10 years. In the advanced form of the disease, a generalized motor tic is combined with a phonic tic, as well as psychomotor (obsessive stereotypical actions), psycho-emotional (susceptibility, anxiety, fear) and personality changes (withdrawal, shyness, self-doubt). The course of the disease is extremely variable: with periodic improvement and deterioration, with long-term remissions, with a slow progression of hyperkinesis. There are cases of spontaneous disappearance of hyperkinesis. For treatment, small doses of D2 receptor antagonists are used - antipsychotics: haloperidol, sulpiride, tiapride; agonists of presynaptic D2 receptors (bromocriptine); agonists of presynaptic a2 receptors – clonidine; in the presence of paroxysmal activity on the electroencephalogram - anticonvulsants. Symptomatic tics can be a manifestation of damage to the extrapyramidal system due to encephalitis, traumatic brain injury, dyscirculatory encephalopathy, and intoxication. The treatment is the same.
Paroxysmal forms of dystonia (dyskinesia)
These rare forms of hyperkinesis have a number of common features: hereditary nature with varying degrees of penetrance of the pathological gene; multivariate external manifestations with a frequent combination of different forms of hyperkinesis: chorea, tics, ballism, etc.; paroxysmal occurrence of hyperkinesis; the relative short duration of the episode – seconds or minutes (rarely hours); difference in the mechanism of occurrence - either without visible provoking moments, or after emotional stress or a certain physical activity, targeted action (kinesigenic forms of paroxysmal hyperkinesis). The features of the different options are reflected in their name: familial paroxysmal dystonic choreoathetosis of Mount-Rebeck (kinesigenic and non-kinesigenic forms); kinesigenic paroxysmal dyskinesia (Rülf's intentional spasm, most often observed in the hands); paroxysmal stereotypic hyperexpression (a complex involuntary psychomotor act in response to external irritation, as a rule, amnesia after passing); nocturnal paroxysmal dystonia (episodes of hyperkinesis occur during sleep - outside the phase of rapid eye movements, last from several minutes to an hour and are represented by a combination of different forms of hyperkinesis - most often choreathetosis, ballism or torsion dystonia). The so-called symptomatic paroxysmal dystonias, which occur after injuries, neuroinfections, intoxications, have with these factors, apparently, only an external, temporary connection and occur only in persons who have a hereditary or congenital predisposition in the form of a predetermined defect of the extrapyramidal nervous system. To treat paroxysmal forms of dystonia, anticonvulsants, tranquilizers and sedatives are used.
Myoclonus
They are lightning-fast involuntary contractions of individual muscles and muscle groups. The external picture of myoclonic hyperkinesis depends on the frequency, rhythm, amplitude and localization of muscle contractions. Therefore, when characterizing the clinical forms of myoclonus, they distinguish: local and generalized, unilateral or bilateral, synchronous and asynchronous, rhythmic and nonrhythmic. As mentioned above, the occurrence of myoclonus is associated with a violation of the functional interaction in the stem-cerebellar “triangle” (dentate nuclei of the cerebellum - red nuclei - olives of the medulla oblongata). Hereditary degenerative diseases, in the clinical picture of which myoclonus is the leading symptom, include: Davidenkov's familial myoclonus, Tkachev's familial localized myoclonus, Lenoble-Obino familial nystagmus-myoclonus, Friedreich's multiple paramyoclonus. Rhythmic myoclonus (myorhythmia) is described as a special local form of myoclonus, characterized by stereotypicality and rhythm. Hyperkinesis is limited to the involvement of the soft palate (velopalatine myoclonus, velopalatine “nystagmus”), individual muscles of the face, tongue, neck, and less often the limbs. The nature of myorhythmias is unclear. Most authors classify local myoclonus as symptomatic. Symptomatic forms of myoclonus occur with neuroinfections, with traumatic, toxic, dysmetabolic damage to the brain. Thus, with neuroinfections, “electric” chorea of Dubini, convulsive chorea of Morphan, posthypoxic intentional myoclonus (Lance-Adams syndrome) occur. It is possible that a necessary prerequisite for the occurrence of symptomatic myoclonus is hereditary (or congenital) insufficiency of the extrapyramidal system in the structures of the “triangle”.
Myoclonus-epilepsy
In two hereditary progressive diseases, myoclonic hyperkinesis and other cerebellar disorders are either rarely (Hunt's cerebellar myoclonic dyssynergia) or usually (Unferricht-Lundborg myoclonic epilepsy) combined with epileptic seizures. The form of seizures can be different: generalized convulsive, absence seizures. There are no effective treatments for myoclonus. Sodium valproate, clonazepam, piracetam, tiapride are used. There are isolated reports of the effectiveness of treatment with the precursor of serotonitis, 5-hydroxytryptophan. To treat diseases in which myoclonus is combined with epilepsy, anticonvulsants are used.
Drug hyperkinesis
Antiparkinsonian DOPA-containing drugs (levodopa, etc.), as well as D2-receptor agonists, in individual overdoses, cause both generalized and local dystonias, which are manifested by choreoathetoid hyperkinesis, tonic forms of dystonia in the muscles of the limbs and trunk. Local hyperkinesis in the facial muscles takes the form of orofacial dystonia, in the foot - tonic hyperkinesis, in which the outer edge of the foot deviates downward and inward, and sometimes isolated tonic extension of the big toe occurs. Any forms of these hyperkinesis decrease or disappear when the dose of DOPA-containing drugs is reduced, especially when they are discontinued. Focal dystonia can sometimes be reduced with injections of the anticholinergic drug Tremblex. Neuroleptics - often butyrophenone derivatives (haloperidol), less often phenothiazine derivatives (aminazine) - also cause extrapyramidal disorders, which are manifested either by akinetic-rigid syndrome or hyperkinesis. The latter often take the form of an OFD. If OFD appears at the beginning of treatment with antipsychotics, it is called “early”, if after months and years (or when long-term treatment with antipsychotics is discontinued) it is called “late”. Early OPD can also occur when metoclopramide is prescribed. In the case of early OPD, one antipsychotic drug should be replaced by another, and if such replacement is ineffective, treatment with antipsychotics should be discontinued. The same tactics are used when OPD occurs during long-term treatment with antipsychotics. If OPD occurs when long-term treatment with antipsychotics is suddenly discontinued, then it is advisable to resume taking the drug at the previous dose for a while, and then begin a program of slow withdrawal of the antipsychotic. Hyperkinesis when prescribed psychostimulants and antidepressants manifests itself in the form of increased aimless motor activity (akathisia), chorea, focal or segmental dystonia, erratic muscle twitching, and, less commonly, tics. To stop these side effects, psychostimulants are canceled, tranquilizers and sedatives are prescribed.
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