Медико-биологический
информационный портал
для специалистов
 
БИОМЕДИЦИНСКИЙ ЖУРНАЛ Medline.ru

СОДЕРЖАНИЕ ЖУРНАЛА:
Физико-химическая биология

Клиническая медицина

Профилактическая медицина

Медико-биологические науки


АРХИВ:

Фундаментальные исследования

Организация здравохраниения

История медицины и биологии



Последние публикации

Поиск публикаций

Articles

Архив :  2000 г.  2001 г.  2002 г. 
               2003 г.  2004 г.  2005 г. 
               2006 г.  2007 г.  2008 г. 
               2009 г.  2010 г.  2011 г. 
               2012 г.  2013 г.  2014 г. 
               2015 г.  2016 г. 

Редакционная информация:
        Опубликовать статью
        Наша статистика


 РЕДАКЦИЯ:
Главный редактор

Заместители главного редактора

Члены редколлегии
Специализированные редколлегии


 УЧРЕДИТЕЛИ:
Федеральное государственное бюджетное учреждение науки
"Институт токсикологии Федерального медико-биологического агентства"
(ФГБУН ИТ ФМБА России)

Институт теоретической и экспериментальной биофизики Российской академии наук.

ООО "ИЦ КОМКОН".




Адрес редакции и реквизиты

199406, Санкт-Петербург, ул.Гаванская, д. 49, корп.2

ISSN 1999-6314

Российская поисковая система
Искать: 


VOL 6, СТ. 2 (pp. 2-5) // февраль 2005г.

ELECTRONEIROMYOGRAPHIC CHANGES DURING THE LONG ANTICONVULSANT THERAPY

Voitenkov V., Borisova E
Institute of Experimental Medicine, St.-Petersburg. Neurology Clinic


Epilepsy is a chronic disease, characterized with a system influence not only on the brain, but also on the whole organism. Neurologist must use anticonvulsants in the therapy of this condition, and that medicaments have to be used long, often lifelong, sometimes in high dosage. That stimulate for a very careful choosing of a medicament, its daily dose and repetition, cause all of the known anticonvulsants have some side-effects. Spectrum of these side-effects is quite wide and strongly depends of pharmacological features of the medicaments and its daily doses. These side-effects usually have a reversible character and disappear with lowering of medicament's daily dose. However along with side-effects some therapy complications can occur, and these conditions need a special attention and specific therapy.

Taking into account an anticonvulsant's influence on the cytochrome P 450 system, all this medicaments can be divided on a two large groups: inductors and inhibitors of liver enzymes. For the inductors of cytochrome P 450 system (barbiturates, carbamazepine, phenytoin) shown its suppression of folic acid levels in blood and a possibility of causing some impairments of natrium metabolism. Cytochrome P 450 inhibitors, in its turn, cause calcium metabolism impairments and carnitine deficit [4, 15, 17], also they can cause an disammonemia.

Folic acid, as it is widely known, take its part in many aspects of metabolism, predominantly it involved in a hematosis process. Its deficit causes specific changes of peripheral blood. Impairments of natrium and calcium metabolism cause a wide spectrum of pathological changes, including a direct damage of neurons.

As for the assume side-effects of a long anticonvulsant therapy, in the view of neuronal transgression we have to mark a lot of observations about a hyperammoniemic encephalopathy, connected with a usage of valproates [5, 6, 7, 9, 10, 11, 12, 13, 16]. Also we found some accounts about an anticonvulsant hypersensitivity syndrome [8], including some neuronal damage aspects. As for the side-effects of anticonvulsants on the peripheral nervous system, we found some accounts [18, 19, 20, 21] about this medicaments as a cause of chronic and acute polineuropathy.

The amount of these accounts is quite limited, and it seems very important to prove the availability or absence of polineuropathy in patients with long courses of anticonvulsants therapy. Such works was done by Danner R, Lang H,, Yale C,1987 [2], who analyzed the ENMG changes in 23 patients with phenytoin and carbamazepine therapy's duration 22 months, and found no signs of polineuropathy. This research included patients with quite short duration of therapy. More sizeable research was made by Bono A, Beghi E, Bogliun G et all [3], they investigated 141 patients and besides a standard neurological examination used ENMG and neuronal biopsy. They found that polineuropatic changes appeared in 54% of investigated.

We did an investigation that was going to prove an idea that long anticonvulsant therapy cause a polineuropathy, and to verificate it, we did an electroneiromyography, studying the conduction nerve velocity, amplitudes of M-responses and the presence of polyphasic waves.

45 patients were studied, group of patients using anticonvulsants, age between 18 to 74 years old (average age 36,3 years old) - 19 females and 15 males, and control group including 11 patients.

To the control group we choose neurologically healthy persons (4 patients) and patients, not using anticonvulsants (7 persons). Most of them were patients with vertebral-basilar insufficiency. Choosing group members we excluded persons with: smoking, chronic alcohol intoxication, prolonged usage of any pharmacological medicaments, endocrinological pathology, hematological diseases, diseases with any metabolism shift, occupational diseases.

There were 11 persons totally, 6 females and 5 males. Age was between 18 and 65 years, average 35,4 years.

Carrying out an ENMG we analyzed: conduction nerve velocity through sensor and motor fibers of n.ulnaris and n.medianus on the both hands, form of the M-response (appearance of polyphasy), difference between the amplitudes of a distal and a proximal M-responses (higher than 25 %).

ENMG results for the control group:
Average conduction nerve velocity motor fibers n.ulnaris, mps63,9
Average conduction nerve velocity motor fibers n. medianus, mps65,3
Average conduction nerve velocity sensor fibers n.ulnaris, mps54,5
Average conduction nerve velocity sensor fibers n.medianus, mps54,1
Polyphasy appearance, 1 or 2 times, %80
Polyphasy appearance, more than 2 times, %0
Amplitudes difference higher than 25 %, %0


Thus, control group results is almost entirely conform the parameters of medical standards for ENMG.
Average age of control group is almost the same as in the group of patients using the anticonvulsants.

Group of patients using anticonvulsants consist of, as it was said earlier, 34 members. An overwhelming majority (90%) of them was epileptics with different forms of this disorder. All of them received anticonvulsants, in 70% it was a polytherapy, and 30% monotherapy. Duration of treatment vary between 1 month and 40 years, most of the patients (80%) received anticonvulsants longer than 2 years. Following medicaments were used: phenobarbital (20% of cases), carbamazepine (50 %), depakin-chrono (40 %) and phenytoin (2%).

For this group we excluded the same disutilities, as for the control group. Most of the patients (82%) didn't show any symptoms of polineuropathy during a neurological study. Parallel with a common neurological study all patients got an electroneiromyography investigation. ENMG results for this group:
Average conduction nerve velocity motor fibers n.ulnaris, mps62,8
Average conduction nerve velocity motor fibers n. medianus, mps66,1
Average conduction nerve velocity sensor fibers n.ulnaris, mps44,5
Average conduction nerve velocity sensor fibers n.medianus, mps44
Polyphasy appearance, 1 or 2 times, %77
Polyphasy appearance, more than 2 times, %13
Amplitudes difference higher than 25 %, %20


So we found that were no lowering of a CNV in the motoric fibers, but it decreased significantly (10 meters per second) in sensory fibers (p<0,05). Also were some significant difference between the groups in appearance of polyphasy responses in more than 2 cases and overfall of amplitudes.

Thus, according to the modern standards of diagnostic, these results can be interpreted as a signs of chronic demyelinizating polineuropathy.

There was a difference in findings according to a duration of a therapy: patients with a short duration of a therapy (less than 4 years) - 18% - had no EMG signs of a polyneuropathy, and those who had a long duration (more than 10 years) - had an EMG signs of a polineuropathy at 50% of all cases.

Obviously we wanted to find what group of medicaments caused less ENMG changes, so we excluded a group of patients who received only inductors of cytochrome P 450 system (16 persons). 56% of them received carbamazepine, 20% benzonal and 24% received a duotherapy.

ENMG results for this group:
Average conduction nerve velocity motor fibers n.ulnaris, mps63,2
Average conduction nerve velocity motor fibers n. medianus, mps66,7
Average conduction nerve velocity sensor fibers n.ulnaris, mps46,8
Average conduction nerve velocity sensor fibers n.medianus, mps46,2
Polyphasy appearance, 1 or 2 times, %50
Polyphasy appearance, more than 2 times, %7
Amplitudes difference higher than 25 %, %13


As we can see, ENMG results for this group somewhat better than those from the main group: average CNV through sensory fibers more on 2 meters per second, less cases of polyphasy and lesser the dispersion of M-response amplitudes.

Thus, analyzing the results of investigation, we can suppose that prolonged receiving of common anticonvulsants can cause a chronic demyelinizating polineuropathy. Exist some dependence between the duration of therapy and intensity of ENMG changes, also we can mark that this signs occur more seldom during the therapy by inductors of cytochrome P 450 comparing with therapy included valproates.

References:

1. Vaintrub M. Medicament side-effects during epilepsy. / Clin Psychofarm RMZH 1998 5.

2. DannerR,,Lang H.,Yale C. Prospective neurometric studies during the beginning of carbamazepine and phenytoin therapy //Acta Neurol Scand.-1984.- Apr;69(4):207-17.

3. Bono A, Beghi E, Bogliun G, Cavaletti G, CurtцЁ N, Marzorati L, Frattola L. Antiepileptic drugs and peripheral nerve function: a multicenter screening investigation of 141 patients with chronic treatment. Epilepsia. 1993 Mar-Apr;34(2):323-31.

4.Biomed Khim. 2004 Jul-Aug;50(4):384-9. Biochemical basis of valproic acid toxicity: role of oxidative stress and effects of L-carnitine.

5. Papp Z, TцTrцTk L. Anticonvulsant hypersensitivity syndrome. Orv Hetil. 2004 Aug 8;145(32):1665-8.

6. McCall M, Bourgeois JA. Valproic acid-induced hyperammonemia: a case report J Clin Psychopharmacol. 2004 Oct;24(5):521-6

7. Mallet L, Babin S, Morais JA. Valproic acid-induced hyperammonemia and thrombocytopenia in an elderly woman.

8. Durц¦n-Ferreras E, Mir-Mercader J, Morales-Martц-nez MD, Martц-nez-Parra. Anticonvulsant hypersensitivity syndrome with severe repercussions in the skin and kidneys due to carbamazepine

9. Elgudin L, Hall Y, Schubert D. Ammonia induced encephalopathy from valproic acid in a bipolar patient: case report.

10. Verrotti A, Trotta D, Morgese G, Chiarelli F. Valproate-induced hyperammonemic encephalopathy.

11. Sztajnkrycer MD. Valproic acid toxicity: overview and management.

12. Perucca E. Pharmacological and therapeutic properties of valproate: a summary after 35 years of clinical experience.

13. Ziyeh S, Thiel T, Spreer J, Klisch J, Schumacher M. Valproate-induced encephalopathy: assessment with MR imaging and 1H MR spectroscopy.

14. Barrueto F, Hack JB. Hyperammonemia and coma without hepatic dysfunction induced by valproate therapy.

15. Raskind JY, El-Chaar GM. The role of carnitine supplementation during valproic acid therapy.

16. Miyamoto T, Miyamoto M, Hirata K, Katayama S. A case report of valproate encephalopathy.

17. Verrotti A, Greco R, Morgese G, Chiarelli F. Carnitine deficiency and hyperammonemia in children receiving valproic acid with and without other anticonvulsant drugs.

18. Stefan H. Side effects of anticonvulsants on the peripheral nervous system and vestibulo-ocular functions. Fortschr Neurol Psychiatr. 1985 Jan;53(1):29-32.

19. Noring L. Carbamazepine as a cause of Guillain-Barre syndrome? Lakartidningen. 1985 May 8;82(19):1778, 1780.

20. Meienberg O, Bajc O. Acute polyneuropathy caused by diphenylhydantoin intoxication. Dtsch Med Wochenschr. 1975 Jul 18;100(29):1532-4, 1539.

21. Bauer G, Nowak H, Polaczek R. Polyneuropathy due to diphenylhydantoin overdosage.

Свидетельство о регистрации сетевого электронного научного издания N 077 от 29.11.2006
Журнал основан 16 ноября 2000г.
Выдано Министерством РФ по делам печати, телерадиовещания и средств массовых коммуникаций
(c) Перепечатка материалов сайта Medline.Ru возможна только с письменного разрешения редакции

Размещение рекламы

Rambler's Top100