RU2380111C2 - Method of treating aphasias - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention concerns medicine, neurology section and can find application in neurologic and neural rehabilitation clinic in treating the patients with aphasia. That is ensured by administration of acatinol memantin according to certain schedule with underlying logopedic lessons. Within the first week of therapy, the dose is 5 mg/day in the morning at mealtime. Within the second week, the dose is 10 mg/days, with 5 mg in the morning and in the evening. Within the third week, the dose is increased to 15 mg/days, with 10 mg in the morning and 5 mg in the evening. Within the fourth week, the dose is increased to 20 mg/days. And the maintenance dose makes 20 mg/days.

EFFECT: method provides effective treatment of apparent rough aphasia caused by disordered cerebral blood flow.

1 ex, 2 tbl

Description

The invention relates to medicine, to the section of neurology and can find application in a neurological and neurorehabilitation clinic in the treatment of patients in need of speech restoration - aphasia that occurs after a stroke or traumatic brain injury.

Neurorehabilitation is a branch of medicine related to the restoration and compensation of impaired higher mental functions (HF), including speech, in patients with focal brain lesions of various origins. Neurorehabilitation is a multi-level, comprehensive system of rehabilitation measures, which also include drug therapy, physiotherapy, psycho- and occupational therapy, methods of social and psychological adaptation to the environment.

Aphasias are speech disorders that occur during local lesions of the brain, mainly of the left hemisphere in right-handers, and are systemic disorders of various forms of speech activity - independent, dialogic and narrative speech, nominative and reflected speech, grammatical structure of speech and its understanding, written speech . The location and size of the lesion, as well as the mechanisms underlying this or that speech pathology, determine the variability of systemic speech disorders, i.e. forms of aphasia, on the basis of which various classifications of aphasia are created. In this work, we used the classification of A.R. Luria (Luria A.R. Traumatic aphasia. M., ed. AMSSSR, 1947).

Patients in need of speech neurorehabilitation receive basic care from speech therapists and neuropsychologist-rehabilitologists. Depending on the form and severity of aphasia, various methods and techniques of logotherapy and rehabilitation training are used. To increase the effectiveness of the logotherapeutic effect on patients with speech disorders and other HMF, pharmacological agents of directed action are used.

The first experiments of such drug exposure have been known since the Second World War and the post-war period. In order to restore normal synaptic conduction and activate temporarily inhibited functions, anticholinesterase drugs began to be used: proserin, eserin, dibazole. The use of prozerin in the observations of Perelman (1947), cited in the monograph by A.R. Luria, had a positive effect on tactile and pain sensitivity, as well as on motor function in paretic limbs, but did not improve gnostic, practical, and speech functions. The positive effect of anticholinesterase substances (proserin, galantamine, amipiridine) on the efferent part of speech activity in motor aphasia was noted by other authors (for example, NK Gogitidze. Dynamics of neuropsychological syndromes under the influence of various neurotropic drugs in patients with traumatic brain injury. Abstract. Dis. Candidate of Medical Sciences. M., 1990, p.14-16).

Muscle-relaxing drugs (midocal, elatin, melliktin) in the drug therapy of patients with aphasia had a positive effect on the latent response periods of patients in the dialogue (Krylova N.A., Alyakrinsky V.V. Neuropathology and Psychiatry named after S.S. Korsakov ". 1996, v.66, in Asp. 12; Markov G. On the treatment of aphasia and dysarthria with psychophorin (tofranil) and midcalm." Zhurn. Neuropathology and Psychiatry named after S.S. Korsakova ". 1973, v. 73, vos. 4, p. 512-513).

A known method of treating aphasia with drugs with a nootropic and stimulating effect (instenon, compliance, encephabol, piracetam, picamilon, gammalon). The use of instenon in patients with motor aphasia had a positive effect on the dynamics of speech and the emotional-volitional sphere of patients (Popova L.T., Pylaeva N.M., Tsvetkova L.S., Shovskaya N.Yu. On the issue of directed pharmacological effect in the process of restorative education of patients with aphasia in the post-stroke period. Problems of aphasia and restorative education. M., ed. MSU, 1975, p.206-214).

Experiments with the use of gamalon for the treatment of 48 post-stroke patients with aphasia showed that they had increased general and speech activity, improved reflected and nominative speech, reading and writing.

The use of all these drugs for the treatment of patients with motor aphasia in most cases was carried out without taking into account the form, severity, prescription of the disease, without assessing the dynamics of individual symptoms. In addition, pharmacotherapy in the treatment of aphasia was not always selective and often caused side effects in the form of disorders of the cardiovascular, respiratory system (anticholinesterase, nootropic drugs, muscle relaxants).

The closest in technical essence and the achieved result to the proposed method is a method of treating aphasia by administering to a patient a pharmacological preparation (RU, patent No. 2123858, class A61K 38/11, 1994).

The neuropeptide-vasopressin analogue of arginine-vasopressin (DDAVP) was used as a pharmacological preparation. 45 patients received treatment (44 post-stroke and 1 after traumatic brain injury) with various forms of aphasia. Each patient underwent a thorough examination with an assessment of each speech symptom. The use of this method reduced the severity of speech disorders, improved the expressive and impressive speech of patients with various forms of aphasia (except for afferent motor aphasia), optimized the attention and performance of patients, and improved the quality of speech therapy.

A disadvantage of the known method for the treatment of aphasia is its low efficiency.

The interest in targeted medical support for patients with aphasia contributed to the search for new, more effective drugs that help improve speech in the process of traditional rehabilitation.

The technical result, the achievement of which the present invention is directed, is to increase the effectiveness of treatment. The specified technical result is achieved by the fact that in the method of treating aphasia by administering to a patient a pharmacological preparation according to the invention, akatinol memantine is used as a preparation according to the following scheme: during the first week of therapy, a dose of 5 mg / day (in the morning with meals); during the second week - a dose of 10 mg / day (5 mg in the morning and evening); during the third week, increase the dose to 15 mg / day (10 mg in the morning and 5 mg in the evening); in the fourth week, the dose is increased to 20 mg / day, while the maintenance dose is 20 mg / day.

In addition, treatment with akatinol memantine can be carried out against the background of speech therapy.

The treatment with akatinol memantine of various forms of dementia carried out at the V.M.Bekhterev Institute at the present time, including at the stage when, in addition to intellectual-mnestic disorders, agnostic-apractic and aphatic disorders appear, has allowed for some time to stabilize the state of cognitive functions in these patients.

This made it possible to check the effect of akatinol on post-stroke patients suffering from various forms of aphasia in combination, in some cases, with the pathology of other HFM.

Akatinol, the active component of which is memantine, is a non-competitive antagonist of NMDA-H-methyl-D-aspartate receptors, which has a modulating effect on the glutamatergic system. Glutamate is the most important excitatory neurotransmitter in the central nervous system, controlling 70% of the exciting neurons. Glutamatergic transmission is responsible for the physiological processes of memory formation, long-term potentiation and synaptic plasticity. Disorders in the glutamatergic system of neurotransmission associated with a pathologically prolonged influx of calcium into postsynoptic cortical and subcortical neurons contribute to a chronic increase in the concentration of glutamate and lead to loss of function and death of the neuron. Clinically, this may manifest as signs of progressive dementia. Akatinol memantine, possessing fast receptive kinetics, prevents the pathological activation of NMDA receptors caused by chronically high concentrations of glutamate, improves the transmission of nerve impulses, replenishes cognitive and functional deficits, improves memory processes, learning ability, and increases daily activity.

With a violation of cerebral circulation, an increase in the concentration of glutamate occurs. Akatinol, blocking the excess of the ion-calcium channel, remains attached to the receptor even in the presence of an increased concentration of glutamate. It improves the functioning of neurons located on the periphery of the lesion, normalizes the membrane potential of surviving neurons, improves and accelerates the transmission of nerve impulses, strengthening and expanding synaptic connections. This mechanism of action of akatinol is, according to the authors, the basis of the positive effect of its use - speech restoration in aphasia. In clinical studies, the safety and tolerability of akatinol memantine was evaluated as good to very good. The total number of side effects did not differ from that in the placebo group. Memantine does not interact with other substances that are necessary for post-stroke patients.

The use of akatinol memantine in the study group of patients was carried out according to the following scheme: during the 1st week of therapy, a dose of 5 mg per day (in the morning with meals), during the 2nd week - at a dose of 10 mg per day (5 mg in the morning and in the evening), during the 3rd week - the dose increased to 15 mg (10 mg - 1 tablet in the morning and 5 mg - half a tablet in the evening). At week 4, the dose increased to 20 mg per day (10 mg in the morning and 10 mg in the evening). The maintenance dose remained 20 mg per day.

Akatinol memantine has no analogue in chemical composition and pharmacological action. To compare the results of treatment with akatinol in comparison with other drugs directed drug treatment of aphasia, we settled on DDAVP (1-desamino-8-D-arginine-vasopressin). The argument in favor of this decision was that the research process and processing of the results obtained by the authors earlier on vasopressin was identical to the study on akatinol. The study was conducted in the clinic NIPNI im.VM.Bekhtereva at the Department of rehabilitation of neurological patients. A detailed neuropsychological examination of patients with aphasia was carried out according to the program adopted at the institute, the severity of symptoms was evaluated according to the four-point system we developed: from 0 - normal or minimal disturbances, up to 3 points - deep decay of the evaluated function (Wasserman L.I. (red) Standardized set of diagnostic neuropsychological techniques. L., 1987; and Wasserman L.I., Dorofeeva S.A., Meerson Y.A. Methods of neuropsychological diagnosis. St. Petersburg, 1997, ed. The state of speech and writing was scored. Nine speech functions were evaluated by 84 indicators: expressive speech - by 9, reflected speech (repetition) - by 15, pronunciation features of speech - by 4, paraphase (word distortion) - by 3, nominative speech (naming) - by 4, speech understanding - by 14, letter - by 5, phonemic analysis of words - by 6, reading - by 13, retention of speech by ear - by 1 indicator. In addition, during a neuropsychological examination in aphasia syndrome, the state of non-speech HFF was determined: visual and auditory gnosis, various types of praxis: motor, ideamotor, ideator, dynamic, constructive, oral. The orientation in space, in the geographical map, in the right-left, in the "body diagram" was investigated; determined the safety of counting operations.

The state of non-verbal higher mental functions was evaluated by their presence or absence. 0 - no violations, 1 - there are violations. The results of the examination were recorded in the form of a protocol, and the assessment of each symptom was put down in the patient's individual questionnaire twice: before treatment with akatinol and at discharge. With repeated admission, the assessment of the patient's speech capabilities was put in dynamics.

Treatment with akatinol was carried out against the background of speech therapy sessions.

The drug was used in 30 patients with different forms and with varying severity of aphasia.

The result of using the drug is illustrated by an example.

Example

Patient Ezd-va A., 69 years old, before retiring worked as chief accountant. She became acutely ill on 09/20/06, when speech was suddenly disturbed, right-sided hemiparesis developed. She was hospitalized in a city hospital with a diagnosis of acute ischemic cerebrovascular accident in the pool of the left middle cerebral artery with mild right-sided hemiparesis and aphasia. Against the background of treatment, after 2 days (09/22/06) she suffered a repeated violation with increased right-sided hemiparesis and worsening symptoms of aphasia. CT data: ischemic stroke in the pool of the left middle cerebral artery, cyst in the pool of the left posterior cerebral artery. After a course of treatment with a slight improvement, 16/11/06 was admitted to the department of rehabilitation of neurological patients at the V.M. Bekhterev NIPNI for a course of rehabilitation treatment.

On admission: complaints of speech disorders, restriction of movements in the right limbs.

Neurologically determined deep right-sided hemiparesis, more pronounced in the hand, hypesthesia in the right half of the body, areflexia in the right limbs. Pathological reflexes were absent. Sick right handed.

Clinical diagnosis: grade III hypertension, cerebral arteriosclerosis, consequences of repeated cerebrovascular disorders in the left middle cerebral artery pool with right-sided hemiparesis and aphasia.

For the first time, a neuropsychological examination of the state of higher speech and non-speech functions was performed at the department. The survey data are shown in the table. Severe amnestic (parietal) aphasia was diagnosed in combination with apraxic agraphia and severe parietal symptoms (Gerstman syndrome) with localization of the lesion in the left parietal-temporal, occipital region.

During the examination: spontaneous and dialogical phrasal speech, without distinct agrammatism, lexically impoverished, replete with multiple verbal substitutions (paraphases), which make the patient’s speech often incomprehensible. Constantly repeats the words of the question or task. Speech disorders are not present. Oral and symbolic oral praxis are normal. Automated speech is inferior. Narrative is not available. When drawing up proposals for a single-story picture, he gives a lengthy description consisting of verbal replacements that have nothing to do with the plot. Reflected speech was practically unaffected. Difficulties arose in the reproduction of complex words, complex and polysyllabic sentences. Gross violations were revealed in the study of the nominative function of speech. The naming difficulties were manifested in two versions: by replacing the nomination with verbal paraphase, which had nothing to do with the semantics of the word, or attempts to describe the purpose of the subject, which also did not reflect its meaning. Understanding everyday and situational speech was possible. Poorly understood the meanings of individual words. Pronounced violations were revealed during the study of the understanding of complex logical and grammatical constructions. Gross violations in the study of written speech: reading, writing, sound-letter analysis of words. Reading aloud and to myself was absent. Signatures - the words to the subject pictures were not correctly placed. Writing and copying (with the left hand) was not available. When trying to write off individual letters or her surname, she drew several short lines with intersecting circles that did not resemble graphemes. The letter system - generalized ideas about the letter (classification) were not affected.

In the study of parietal (non-verbal) symptoms, gross structural apraxia, acalculia, and digital agnosia (Gerstman's syndrome) were revealed.

In addition to antihypertensive therapy, the patient was prescribed akatinol memantine according to the scheme recommended by the manufacturer: 1 week - 5 mg - in the morning, 2 weeks 5 mg - 2 times a day, 3 weeks 10 mg - morning, 5 mg - in the evening, 4 weeks and then 10 mg - 2 times a day.

From the first days, rehabilitation speech therapy classes were held. During the treatment, the general condition improved, the patient became more active, and interest in speech therapy increased. Positive dynamics was noted in expressive (spontaneous and dialogical) speech. Adequate words appeared, understanding of individual words improved. The global (ideogram) reading began to recover.

The patient was discharged after three weeks, and a month later was admitted for re-treatment. The outpatient continued to take antihypertensive therapy, akatinol memantine at a dose of 10 mg - 2 times a day. I did not deal with a speech therapist during this period.

A repeated neuropsychological examination revealed significant positive dynamics in speech and other higher mental functions (table, column 3). Spontaneous and especially dialogic speech has improved. It became clearer, the number of verbal substitutions decreased, perseveration occurred much less frequently - the patient practically stopped repeating the words of the question in her answers. Narrative and monologue speech became possible. So, the patient was able to coherently tell her biography, make a proposal or a story based on the plot picture. The understanding of the meanings of words, the ability to complete simple tasks was restored, the volume of speech and hearing memory increased. The understanding of complex logical-grammatical constructions has significantly improved. The nominative function of speech began to recover. Verbal paraphases during nomination became closer to the conceptual semantics of the word. The description of the subject in cases where the nomination was absent became more adequate.

The dynamics of writing and parietal symptoms were particularly effective. Now you can read aloud to yourself. The nature of reading has changed. If at first the process of putting words under the corresponding subject pictures was guessing, i.e. It was carried out according to the type of ideogram “grasping”, now the patient, although often using syllables with slight paralexes, read the word and only then found the corresponding pictures. The restoration of analytical reading contributed to an improvement in reading comprehension, both when reading aloud and when reading to oneself. It became possible to understand written instructions in silent reading. The restoration of constructive praxis — copying, sketching, and, in part, self-drawing — contributed to the restoration of aprastic agraphy, the mechanism of which was closely associated with the collapse of constructive praxis. Not only the process of cheating was restored, but it became possible to write letters, syllables, words and phrases under dictation. When writing, there were rare literary paragraphs (according to the type of substitution of one grapheme for another (Pskov-Tskov, courage-outrage), and mirror spelling of some letters (I-R, I-N)). The syllabic and alphabetic composition of the words was preserved. Other parietal symptoms recovered: digital gnosis, counting within the first ten and, partly, with passage through a dozen, orientation in the right-left and in the geographical map.

Table 1 shows the changes in individual speech functions during treatment with akatinol memantine in a patient with amnestic (parietal) aphasia.

Table 2 shows the changes in individual non-verbal higher mental functions during treatment with akatinol memantine in a patient with amnestic (parietal) aphasia.

Side effects when taking akatinol memontin were not observed.

The proposed method for the treatment of aphasia in comparison with the treatment of DDAVP has the following advantages.

1. More effective in the treatment of all forms of aphasia (motor, sensory, "parietal"), including gross afferent motor aphasia with the collapse of articulatory structures, the treatment of which DDADP does not give results or gives a slight improvement in speech not in the articulatory link.

2. More effective in the treatment of all types of disorders of expressive, impressive written language.

3. Particularly effective in complex exposure - a combination of pharmacotherapy with akatinol memantine with logotherapy.

4. Affects the process of logotherapy, shortening the time of the appearance of positive dynamics and improving results.

5. Improves speech function in a shorter period.

6. Positive dynamics does not depend on the duration of the disease.

7. The continuous use of the drug contributes to the progressive improvement of speech function without logotherapy.

8. Restores or improves the condition of non-speech HFF.

9. It has a more significant therapeutic effect on such mental states of patients as working capacity, speech activity, emotional-volitional sphere.

10. Restores the dynamics of the speech process itself: readiness and ability to independently engage in speech, strengthening the ability to verbal communication, along with the restoration of the speech process itself.

Table 1
Changes in individual speech functions during treatment with akatinol memantine in a patient with amnestic (parietal) aphasia No. p / p Separate speech functions and indicators characterizing them Example 1 before after treatment 1.0 Expressive speech: 3 2+ 1.1 overall rating 1.2 Spontaneous speech 3 2+ 1.3 Dialogue 2 1+ 1.4 Narrative 3 2+ 1.5 Compilation 3 2+ picture suggestions 1.6 Writing a story by 3 2+ 2.0 the picture 2.1 Automated: 2.2 a) score from 1 to 10 one 0+ 2.3 b) days of the week 2 0+ 2.4 c) naming of months 3 0+ 2.5 Reflected Speech: General 0 0 2.6 assessment 2.7 Repetition of consonants 0 0 2.8 Vowel repetition 0 0 Repetition of simple words 0 0 2.9 2.10 Syllable repetition 0 0 2.11 Repetition of complex 2 1+ 2.12 words 2.13 Repetition of foreign 2 1+ 2.14 words 3.0 Pseudoword repetition 2 1+ Repetition of a series of vowels 0 0 3.1 Repeating a series of syllables one 0+ 3.2 Reiteration 0 0 3.3 sentences of 2-3 words 4.0 Reiteration 2 1+ 4.1 sentences of 4-7 words 4.2
5.0 Repeating a series of words one 0+ 5.1 Reiteration 0 0 5.2 opposition syllables 5.3 Reiteration 0 0 6.0 opposition words 6.1 Pronouncing 0 0 6.2
6.3 features 6.4 overall rating: Effort, tension, 0 0 memorization Pronunciation 0 0 sounds Prosody 0 0 Paraphase: General 2 2 assessment Paraphase literal 0 0 Paraphase verbal 2 1+ Name: general 3 2+ assessment of subjects 3 2+ action 3 2+ at the same time several 3 3 items 7.0 understanding: general assessment 0 0 7.1 7.2 situational speech 0 0 7.3 single words 2 0+ 7.4 simple tasks 0 0 8.0 complex grammar 3 1+ 8.1 designs: a) relationships one 0+ 8.2 expressed by one 8.3 pretext 8.4 b) - "- two pretexts 2 1+ 8.5 c) inflectional 2 1+ 9.0 relations 9.1 9.2 d) - "- inverted constructions 2 1+ 9.3 e) passive voice 9.4
9.5 f) Head samples 2 1+ 9.6 g) temporary 2 1+ 9.7
9.8 constructions one 0+ 9.9 h) designs 9.10 genitive 2 1+ 9.11 i) sensitized 9.12 samples 2 2 j) speech retention rows by ear 3 2+ Letter: general assessment Cheating 3 1+ writing words under 3 0+ dictation 3 1+ writing phrases under dictation 3 1+ independent writing phonemic analysis: 3 2+ overall rating 3 1+ quantification letters in a word 3 2+ determining the number of letters in 3 2+ a recalled word - "- determination of the number of syllables in a word 0 0 - "- the first letter in the word 2 1+ - "- last -" - 3 1+ Reading: overall rating 3 1+ Attaching captions to pictures 3 1+ Captions for plot pictures 3 1+ Reading 3 1+ automated ideograms Reading single letters 3 1+ Reading individual syllables 3 1+ Reading simple words 3 1+ Reading compound words 3 1+ Reading offers 3 1+ Reading text out loud 3 1+ Reading written instructions to yourself 3 1+ Reading to oneself and understanding the text 3 2+ Reading pseudoword 3 2+ Legend: + performance improvements

table 2
Change in individual non-verbal higher mental functions during treatment with akatinol memantine in a patient with amnestic (parietal) aphasia Before treatment After treatment 10.0 10.0 study of movements and actions 10.1 spatial praxis - one-handed hand tests 0 0 10.2 two-handed - hand - hand 0 0 10.3 Head Samples: Unilateral 0 0 10.4 Head Samples: Cross one one 11.0 dynamic praxis: 11.1 with the right hand 0 0 11.2 left handed one 0 12. Reciprocal coordination 0 0 13. constructive praxis 13.1 copy one 0 13.2 flipping one 0 13.3 independent painting one 0 13.4 sketching one 0 13.5 circle one 0 14.0 praxis 14.1. articulatory praxis 0 0 14.2 oral praxis 0 0 14.3 symbolic oral praxis 0 0 14.4 motor praxis 0 0 14.5 ideator praxis 0 0 14.6 ideomotor praxis 0 0 15.0 account system research 15.1 prime reading one 0 15.2 reading complex numbers one one 16.3 writing complex numbers one one 17.0 simple counting operations 17.1 addition within the first ten one 0 17.2 subtraction within the first ten one one 17.3 addition with the transition through a dozen one one 17.4 subtraction with going over a dozen one one 17.5 repetition of the multiplication table one one 17.6 execution of a serial count one one 18.0 study of somatosensory gnosis 18.1 digital gnosis 0 0 18.2 finger pose one 0 18.3 stereo prediction 0 0

Claims (1)

A method of treating severe, severe aphasia due to cerebrovascular accident, characterized in that, against the background of speech therapy sessions, akatinol memantine is administered according to the following scheme: during the first week of therapy at a dose of 5 mg / day in the morning with meals; during the second week at a dose of 10 mg / day, 5 mg in the morning and evening; during the third week, increase the dose to 15 mg / day, introducing 10 mg in the morning and 5 mg in the evening; in the fourth week, the dose is increased to 20 mg / day, while the maintenance dose is 20 mg / day.