RU2651767C1 - Method for the treatment of trigeminal neuralgia - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: present invention relates to medicine, namely to neurology, and relates to the treatment of trigeminal neuralgia. To do this, in addition to the therapy, which stimulates the process of remyelination (SPR), L-arginine is administered. L-arginine is administered orally on the 2nd and 4th days of treatment at a dose of 500 mg once a day, on the 6th and 8th days – 500 mg in the morning and in the evening. Beginning from the 10th day of treatment, SPR therapy is canceled. L-arginine is continued to be administered daily to the patient according to the following schedule: in a dose of 1,000 mg in the morning and in the evening until the 19th day of treatment, inclusive, from the 20th day of treatment, 500 mg 3 times a day. Therapeutic course makes 30 days.

EFFECT: such empirically selected mode of administration of drugs provides an increase in the period of remission of the disease by about one and a half times.

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Description

The present invention relates to medicine, namely to neurology, and can be used to treat patients with trigeminal neuralgia.

Trigeminal neuralgia (NTN) is a chronic recurrent disease that manifests itself in sudden, intense, shooting pain in the innervation zones of the third, second and, very rarely, the first branches of the trigeminal nerve, with a predominance on the right side of the face (Reveguk EA, Karpov S .M. The urgency of the problem of trigeminal neuralgia in neurology // Successes in modern natural sciences. - 2013. - No. 9. - P. 127-128).

The disease is characterized by severe bouts of excruciating pains in the face resulting from irritation of trigger points during conversation, eating, shaving, washing, etc. (Eller JL Stubhang A. Trigeminal neuralgia: definition and classification. // Neuro-surg. Focus. - 2005 Vol. 18, N5. - P. 63).

The intensity and frequency of seizures, often reaching 100 or more per day, drives patients to despair, sometimes even to suicide attempts. The intensity of pain and the lack of effective methods of treating NTN deprive the patient of the joy of life, disability, locking all his interests on this excruciating pain (Irasek A., Surgery of pain // Czechoslovakia: Atria, 1958, pp. 13-15; Grachev Yu.V. Pathogenetic mechanisms and clinical features of trigeminal facial pain // Neurologist and Psychiatrist named after S.S. Korsakov, 1999. - T. 99, No. 8. - P. 38-42 .; Love S. Trigeminal neuralgia: pathology and pathogenesis / Brain. - 2002. - Vol. 125, N 3. - P. 687). Therefore, the development of new, effective methods of treating trigeminal neuralgia is an urgent problem of modern medicine.

Studies on the medical, scientific and patent literature have revealed various methods of treating trigeminal neuralgia.

In the work of Karlov V.A. and Savitskaya O.N. (Trigeminal neuralgia // M .: Medicine, 1980, pp. 96-97) describes a method for the treatment of trigeminal neuralgia by prescribing dibenzoazepine drugs to the patient: finlepsin, carbamazepine, tegretol.

The disadvantage of this method is that taking these drugs leads to short-term remission of the disease. With each subsequent exacerbation of the disease, the effectiveness of these drugs, and hence the effectiveness of NTN treatment, is progressively decreasing, and the number of side effects is steadily increasing (Savitskaya O.N. Trigeminal neuralgia: peripheral and central mechanisms of pathogenesis, clinical and treatment issues // Abstract. Diss. Doct. Medical Sciences. M., 1976).

USSR author's certificate No. 1114423 (1984, BI No. 35) protected "A method for the treatment of trigeminal neuralgia." Along with prescribing antiepileptic drugs, histamine liberalizers are administered locally to the infraorbital, infraorbital or chin openings, depending on the branch of the trigeminal nerve affected by neuralgia, and calcium, ascorbic acid, and antihistamines are prescribed.

The disadvantages of the method are the lack of effectiveness of the treatment, since blockades are performed far from the focus of demyelination, short periods of remission and frequent exacerbations, requiring continued administration of antiepileptic drugs in relatively large doses and after the course of treatment.

USSR author's certificate No. 1822775 (1993, BI No. 23) protected the "Method for the treatment of trigeminal neuralgia", which includes the introduction of a 4% solution of novocaine in the region of large trigeminal trunks, which is administered by ten injections every other day, 2 ml into the first day, 3 ml in the second, 4 ml in the third and 5 ml from the 4th to the 10th day of drug administration, after 2 weeks the course is repeated.

The disadvantages of the method are the short duration of the analgesic effect, the presence of a wide range of side effects of the drug and contraindications, as well as the need for long-term treatment.

RF patent No. 2020972 (1994, BI No. 19) protected the "Method for the treatment of trigeminal neuralgia", which provides for anticonvulsant therapy with a single hemosorption of the venous-venous circuit at a speed of 50 ml / min with perfusion of at least one volume of circulating blood.

The disadvantages of the method are the technical complexity of the method, requiring complex expensive equipment, sorbents, as well as the risk of complications during hemosorption, such as pulmonary embolism, erythrocyte hemolysis, anemia, shock.

In the patent of the Russian Federation No. 2202349 (2003, BIPM No. 10), a "Method for the treatment of trigeminal neuralgia" is described. The patient is prescribed a complex of drugs, which includes small doses of anticonvulsants, for example, finlepsin 50 mg three times a day, and neurovasoactive drugs daily, imigran every other day, stol during the first two days. Once a week, 20 ml of a 1% solution of novocaine are introduced into the stellate node on the affected side.

The disadvantages of this method are its lack of effectiveness, since the effectiveness of anticonvulsants with each subsequent exacerbation decreases, and the number of side effects increases; in addition, an anesthetic solution injected into an area distant from the trigeminal nerve does not directly affect the affected nerve.

RF patent No. 2227028 (2004, BIPM No. 11) protected "A method for the treatment of trigeminal neuralgia." The method provides for oral administration of glycerol to the patient in the morning at 0.5 mg per 1 kg of the patient’s body weight, as well as the implementation of drug therapy that stimulates the remyelination process. Directly to the site of demyelination of the second and third branches of the trigeminal nerve, a complex of medicines, collected in one syringe, is introduced into the region of the round and oval openings, as a part of the kenalog, i.e. triamcinolone - 40 mg, vitamin B12 - 500 mcg and 2% lidocaine solution - 4.0 ml. Blockades are performed every other day in an amount of 3 to 5, depending on the onset of remission. Berlition is administered intravenously in a dose of 300 mg twice a day with an interval of 10-12 hours for 5 days. Over the next 5 days, berlition at the same dose is administered orally twice a day. Milgamma is administered 2.0 ml intramuscularly every other day, alternating with blockages, in an amount of 3 to 5 injections.

The disadvantages of the method are the lack of effectiveness of treatment, since pain paroxysms in the interval between the blockades, especially in the first days of treatment, remain, the complexity of the method of performing blockades in the region of the round and oval openings, due to the proximity of the carotid artery and the risk of damage, the occurrence of side effects, such as violation of the water-electrolyte balance, nausea, vomiting after applying glycerin - a dehydration drug of osmotic effect.

In the patent of the Russian Federation No. 2349313 (2009, BIPM No. 8), the “Method for the medical treatment of trigeminal neuralgia” is described. The patient is given applications of the projection area of the output of the affected branches of the trigeminal nerve on the face skin with tissues moistened and moderately squeezed in a solution consisting of a 98% solution of dimethyl sulfoxide and a 2% solution of anesthetic - novocaine or lidocaine in a volume ratio of 1: 9, or 1 : 5, or 3:10 for 20-30 minutes 2-3 times a day for 10-15 days.

The disadvantage of this method is its lack of effectiveness, since applications are performed on the area where the trigeminal nerve branches exit onto the face, and at present most neurologists and neurosurgeons consider the neurovascular conflict between the root of the trigeminal nerve and one or more loops of cerebellar arteries as the cause of trigeminal neuralgia (Jannetta PJ Trigeminal neuralgia Eds. RS Rovit et al. Baltimore, 1990, p. 201-222; L. La Mantia, Role Microvascular decompression in Trigeminal neuralgia and multiple sclerosis (letter). // Lancet, 1999, vol. 354, No. 9193, p . 1878-1879).

RF patent No. 2438657 protected "Method for the treatment of trigeminal neuralgia" (2012, BIPM No. 1). The method provides for drug therapy that stimulates the remyelination process in the composition: daily intravenous administration of berlition and blockade of the second and third branches of the trigeminal nerve, alternating every other day with intramuscular injection of milgamma. Berlition is administered at 300 mg twice a day with an interval of 10-12 hours, blockades are performed with drugs taken in the same syringe: Kenalog (Depo-Medrol) - 40 mg, vitamin B12 - 500 μg and 2% lidocaine solution - 4, 0 ml, every other day in an amount of 3 to 5 blockades. Milgamma is administered to the patient intramuscularly at a dose of 2.0 ml once a day. Blockades of the second and third branches of the trigeminal nerve are performed in the region of the round and oval openings. Glycerin is also orally administered to the patient in the morning at a dose of 0.5 mg per 1 kg of the patient's body weight. Every day, every 3-4 hours, 4-5 times a day, on the zones of the trigger points of the patient’s face, applications are made for 30-45 minutes with napkins moistened in a solution consisting of a mixture of drugs, with the following volume ratio of components,%: 98% dimethyl sulfoxide solution - 20, 2% lidocaine solution - 40, 2% alcohol anestezin solution - 40. The course of treatment is 7-10 days.

The disadvantages of this method are the lack of effectiveness of the treatment, due to the duration of treatment and a short period of remission, the complexity of the method of performing blockades in the area of the round and oval openings, due to the proximity of the carotid artery and the risk of damage, the occurrence of side effects, such as a violation of the water-electrolyte balance, nausea , vomiting after the use of glycerol - an osmotic dehydration drug.

RF patent No. 2551228 (2015, BIPM No. 14) protected "A method for the treatment of neuralgia and trigeminal neuritis." The method involves the action of electric current on the projection area of the Gasser node, on the upper edges of the eye sockets in the foramen supraorbitale region, on the lower edges of the eye sockets in the foramen infraorbitale region, on the lower end of the jaw in the foramen mentale region and on the areas of the anterior abdomen of the double-abdominal muscle and chewing muscles, effects of low-intensity a pulsed magnetic field in the same areas, on the neck and upper third of the chest, as well as the imposition of mud applications on the collar area.

The disadvantages of this method are the lack of effectiveness of treatment, since the method is used during the remission of the disease, in addition, the method has a limited scope, since physiotherapeutic treatment is contraindicated in patients with tumor processes, systemic blood diseases, diseases of the cardiovascular system in the decompensation stage, infectious diseases in acute stage, etc.

The closest technical solution adopted for the prototype is protected by RF patent No. 2612936 "Method for the treatment of trigeminal neuralgia" (2017, BIPM No. 8). The method involves conducting therapy that stimulates the process of remyelination (SBP): berlition, Depot-Medrol, vitamin B12 (cyanocobalamin), lidocaine, milgamma, L-lysine escinate. Berlition is administered daily to the patient and blockades of the second and third branches of the trigeminal nerve are performed, alternating every other day with intramuscular administration of milgamma. Berlition is administered 300 mg twice a day with an interval of 10-12 hours. Blockades of the second and third branches of the trigeminal nerve are performed on the lesion side in the area of the infraorbital and mandibular openings with drugs drawn into one syringe: Depo-Medrol - 40 mg, vitamin B12 (Cyanocobalamin) - 500 μg and 2% solution of lidocaine 4.0 ml , in an amount of 3 to 5 blockades, depending on the onset of complete remission. Milgamma is administered in a dose of 2.0 ml once a day. From the first day, the patient is injected intravenously once a day with the preparation of L-lysine escinate at a dose of 10 mg diluted in 100 ml of 0.9% sodium chloride solution. The course of treatment is 5-9 days.

The disadvantages of the prototype are the lack of effectiveness of treatment due to the short term of remission, which according to the authors of the prototype is from 18 to 20 months.

The task of the invention is to develop a highly effective method of treating patients with trigeminal neuralgia.

The technical result manifested by the implementation of this method is to increase the period of remission of trigeminal neuralgia.

The technical result is achieved by the fact that a patient with trigeminal neuralgia is given therapy that stimulates the process of remyelination (SPR). The course of treatment also includes the biologically active supplement L-arginine, which is administered to the patient per os, on the 2nd and 4th days of treatment at a dose of 500 mg once a day, on the 6th and 8th days - 500 mg each morning and evening. Starting from the 10th day of treatment, the ABP therapy is canceled, and L-arginine is continued to be administered to the patient per os daily according to the scheme: at a dose of 1000 mg in the morning and evening until the 19th day of treatment, 500 from the 20th day of treatment - 500 mg 3 times a day. The course of treatment is 30 days.

L - arginine (registration number: FS - 000651) - is a biologically active additive. It is an amino acid whose action is aimed at maintaining a sufficient concentration of cholesterol in the blood, which, in turn, has a positive effect on the physiological properties of the cardiovascular system. The use of L-arginine leads to a decrease in the tension of the smooth muscles of the arteries, increases their elasticity, maintains blood pressure within the physiological norm, prevents the development of atherosclerosis, helps maintain normal blood vessel patency and ensures proper blood circulation (Voloshin P.V., Malakhov V. A., Zavgorodnaya AN Endothelial dysfunction in cerebrovascular pathology. - Kharkov, 2006. - 93 p.).

The practical feasibility of the proposed method for the treatment of trigeminal neuralgia is illustrated by examples from clinical practice.

Example 1: patient L., 65 years old, was admitted to the clinic of neurology and neurosurgery of the Rostov State Medical University (Rostov State Medical University) for a course of conservative therapy with complaints of strong, sharp shooting attacks of pain in the right half of the face in the lower jaw provoked by conversation, chewing, toilet of the oral cavity. He considers himself to be a patient of 10 years, when the first attack of pain lasting up to 3 seconds arose sharply for no apparent reason. The pain zone is the third branch of the right trigeminal nerve. The last exacerbation lasted up to 2 months, the attacks of pain did not stop. Neurological examination revealed hyperesthesia in the innervation zone of the third branch of the right trigeminal nerve. Trigger zone - lower lip, chin. Quantification of pain on a visual analogue scale (VAS) was 10 points.

Patient L. was performed magnetic resonance imaging (MRI) of the brain. Conclusion: volumetric formations in the posterior cranial fossa were not found.

Patient L. was diagnosed with classic neuralgia of the right trigeminal nerve with localization of pain in the innervation zone of the third branch, the stage of exacerbation.

Patient L. was treated according to the claimed method.

From the first day of admission to the hospital, patient L. underwent therapy stimulating the process of remyelination (SBP): berlition, Depo-Medrol, vitamin B12 (cyanocobalamin), lidocaine, milgamma, L-lysine escinate. The patient was daily injected with berlition, L-lysine escinate and blockade of the third branch of the trigeminal nerve, alternating every other day with intramuscular injection of milgamma, was performed. Berlition was administered 300 mg twice a day with an interval of 10 hours. L-lysine escinate was administered to the patient once a day intravenously at a dose of 10 mg, diluted in 100 ml of 0.9% sodium chloride solution. Blockages of the third branch of the trigeminal nerve were performed on the lesion side in the area of the infraorbital and mandibular openings with drugs drawn into one syringe: Depo-Medrol - 40 mg, vitamin B12 (Cyanocobalamin) - 500 μg and 2% solution of lidocaine 4.0 ml. Milgamma was administered at a dose of 2.0 ml once a day. The treatment course additionally included the biologically active supplement L-arginine, which was administered to the patient per os, on the 2nd and 4th days of treatment at a dose of 500 mg once a day, on the 6th and 8th days - 500 mg morning and evening. On the 9th day after SPR therapy, the patient was discharged with recommendations to continue taking L-arginine according to the treatment schedule we had planned: taking L-arginine per os daily 2 times a day in a dose of 1000 mg in the morning and evening until the 19th day of treatment inclusively, from the 20th to the 30th day of treatment inclusively - 500 mg 3 times a day.

Patient L. was recommended to start a journal in which she had to follow daily notes about taking L-arginine according to the above scheme during the 21st day. Patient L. performed the recommendations of the attending physician, which was recorded by the attending physician at the follow-up examination on the 31st day from the start of treatment.

The term of remission in patient L. was 27 months.

Example 2: patient V., 62 years old, was admitted to the clinic of neurology and neurosurgery of Rostov State Medical University with complaints of severe bouts of shooting pain in the left half of the face in the upper and lower jaw provoked by conversation, food intake, and an oral toilet. He considers himself a patient of 9 years, when after hypothermia, the first pain paroxysm arose lasting up to 15 seconds. The pain zone is the second and third branches of the left trigeminal nerve. Conducted drug therapy provided short-term remissions of 6 months. Neurological examination of the symptoms of loss of neurological functions did not reveal. The trigger zone is the wing of the nose on the left, upper lip, lower lip. The quantitative assessment of pain by YOUR was 10 points.

Patient V. was performed an MRI of the brain. Conclusion: volumetric formations in the posterior cranial fossa were not found.

Patient V. was diagnosed with classic neuralgia of the left trigeminal nerve with localization of pain in the innervation zone of the second and third branches, the stage of exacerbation.

Patient C. was treated according to the claimed method.

From the first day of admission to the hospital, patient V. underwent therapy, Doc: Berlition, Depot-Medrol, vitamin B12 (Cyanocobalamin), lidocaine, milgamma, L-lysine escinate. The patient was daily injected with berlition, L-lysine escinate and blockade of the second and third branches of the trigeminal nerve, alternating every other day with intramuscular injection of milgamma, was performed. Berlition was administered 300 mg twice a day with an interval of 10 hours. L-lysine escinate was administered to the patient once a day intravenously at a dose of 10 mg, diluted in 100 ml of 0.9% sodium chloride solution. Blockade of the second and third branches of the trigeminal nerve was performed on the lesion side in the infraorbital and mandibular foramen with the drugs drawn into one syringe: Depo-Medrol - 40 mg, vitamin B12 (Cyanocobalamin) - 500 μg and 2% solution of 4.0 ml lidocaine . Milgamma was administered at a dose of 2.0 ml once a day. The treatment course additionally included the biologically active supplement L-arginine, which was administered to the patient per os, on the 2nd and 4th days of treatment at a dose of 500 mg once a day, on the 6th and 8th days - 500 mg morning and evening. On the 9th day after SPR therapy, the patient was discharged with recommendations to continue taking L-arginine according to the treatment schedule we had planned: taking L-arginine per os daily 2 times a day in a dose of 1000 mg in the morning and evening until the 19th day of treatment inclusively, from the 20th to the 30th day of treatment inclusively - 500 mg 3 times a day.

Patient V. was recommended to start a journal in which for 21 days she had to carry out daily marks on taking L-arginine according to the above scheme. Patient V. carried out the recommendations of the attending physician, which was recorded by the attending physician at the follow-up examination on the 31st day from the start of treatment.

The term of remission in patient B. was 29 months.

Example 3: patient I., 70 years old, was admitted to the clinic of neurology and neurosurgery of Rostov State Medical University with complaints of severe shooting pains like an electric shock in the right half of the face, provoked by talking, using a face toilet, eating more than 50 times a day and lasting up to 10 seconds. He considers himself a patient of 15 years, when for the first time after hypothermia, paroxysmal pain appeared in the right half of the face. Remissions during the first 10 years of the disease ranged from 4 to 6 months. The last exacerbation lasted up to 3 months, the attacks of pain did not stop, and the patient was admitted to the clinic for a course of conservative therapy. Neurological examination of the symptoms of loss of nervous system function was not revealed. Trigger zone - nose wing on the right, upper lip, lower lip, chin. Your pain intensity was 10 points.

Patient I. was performed magnetic resonance imaging (MRI) of the brain. Conclusion: volumetric formations in the posterior cranial fossa were not found.

Patient I. was diagnosed with classical neuralgia of the right trigeminal nerve with localization of pain in the innervation zone of the second and third branches, the stage of exacerbation.

Patient I. was treated according to the claimed method.

From the first day of admission to the hospital, patient I. underwent therapy, DST: berlition, Depot-Medrol, vitamin B12 (cyanocobalamin), lidocaine, milgamma, L-lysine escinate. The patient was daily injected with berlition, L-lysine escinate and blockade of the second and third branches of the trigeminal nerve, alternating every other day with intramuscular injection of milgamma, was performed. Berlition was administered 300 mg twice a day with an interval of 10 hours. L-lysine escinate was administered to the patient once a day intravenously at a dose of 10 mg, diluted in 100 ml of 0.9% sodium chloride solution. Blockages of the second and third branches of the trigeminal nerve were performed on the lesion side in the infraorbital and mandibular foramen with the drugs drawn into one syringe: Depo-Medrol -40 mg, vitamin B12 (Cyanocobalamin) - 500 μg and 2% solution of lidocaine 4.0 ml . Milgamma was administered at a dose of 2.0 ml once a day. The treatment course additionally included the biologically active supplement L-arginine, which was administered to the patient per os, on the 2nd and 4th days of treatment at a dose of 500 mg once a day, on the 6th and 8th days - 500 mg morning and evening. On the 9th day after SPR therapy, the patient was discharged with recommendations to continue taking L-arginine according to the treatment schedule we had planned: taking L-arginine per os daily 2 times a day in a dose of 1000 mg in the morning and evening until the 19th day of treatment inclusively, from the 20th to the 30th day of treatment inclusively - 500 mg 3 times a day.

Patient I. was recommended to start a journal in which for 21 days she had to daily follow the notes on taking L-arginine according to the above scheme. Patient I. performed the recommendations of the attending physician, which was recorded by the attending physician at the follow-up examination on the 31st day from the start of treatment.

The term of remission in patient I. was 30 months.

Using the proposed method in the clinic of neurology and neurosurgery, Rostov State Medical University (9 days - hospital, 21 - outpatient), 14 NTN patients aged 54 to 75 years were treated, 10 of them women, 4 men. Remission periods for these patients were from 27 to 30 months.

Thus, the proposed method in comparison with the prototype increases the effectiveness of the treatment of NTN and increases the duration of remission of approximately 1.5 times.

Claims (1)

A method of treating trigeminal neuralgia, including conducting therapy that stimulates the process of remyelination (SBP), characterized in that the course of treatment further includes a biologically active supplement L-arginine, which is administered to the patient per os, on the 2nd and 4th days of treatment a dose of 500 mg once a day, on the 6th and 8th days - 500 mg in the morning and evening; starting from the 10th day of treatment, the ABP therapy is canceled, and L-arginine is continued to be administered to the patient per os daily according to the scheme: at a dose of 1000 mg in the morning and evening until the 19th day of treatment, 500 from the 20th day of treatment mg 3 times a day; the course of treatment is 30 days.