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Maksudova Laylo Bakhtiyarovna, neurologist of Department of emergency neurology № 1, seeker of doctoral degree, Republican Research Centre of Emergency Medicine, Tashkent, Uzbekistan E-mail: laylo26@mail.ru
Clinical-pathogenic analysis of brain arteriovenous malformation neurologic manifestations
Abstract: Retrospective analysis of 109 patients with arteriovenous malformations (AVM) of brain has been carried out. Men were 67 (61.4 %) and women were 42 (38.6 %). Brain AVM are detected two times frequently in men than in women and are appeared in them at younger age. Prevalence ofAVM small and big sizes with sinistrocerebral lateralization has been revealed at the analysis. The most frequent manifestation of AVM are cephalgic and epileptic syndromes.
Keywords: arteriovenous malformations, brain, sinistrocerebral lateralization, cephalgia, epilepsy.
Introduction
Vascular malformations (VM) of central nervous system (CNS) are local or extensive abnormalities of vascular system. For the first time VM of CNS were described by U. Gunter in 1757 who offered «malformation» term which means «defect of development» [7]. Brain AVM is not frequently occurred nosological form but capable to provoke severe neurologic disorders and even a death. In majority of cases brain AVM are manifested by intracranial hemorrhage, epileptic attacks and hard headache. Due to up-to-date diagnostic methods of CNS AVM are often diagnosed at pre-hospital stage, surgical treatment methods of patients with CNS AVM are significantly improved, facilities of malformations intravascular occlusion have been increased and radiologic surgery has been available.
Views on brain malformations have been changed for recent decades. Viewpoint stating absolutely congenital nature of disease is subject to be reviewed. Majority of facts pointing on possibility of AVM appearance in postembryonal period and evidences of AVM features significant changes within a period of time have appeared. Increased activity of mitogen of endothelial growth factor of vessels in malformations and surrounding brain endotheliocytes has been proved and it confirms continued neoangiogenesis in malformations, partially explains their slow growth and recurrence [21]. AVM refers to the more frequent variant of vascular angiomatous defect of nervous system development and is an effect of dysontogenetic metamorphosis initiated by unknown factors. The real frequency of vascular malformations, particularly AVM, in population is unknown. It is supposed that a carrier ofAVM can be up to 0.1 % of population [5]. By autopsy data, AVM are revealed in 1.4-4.3 % of autopsies [16], semeiotic ones makes 12.2 % ofthem [18; 22]. Clinical manifestation of AVM in population is rather stable and due to various data makes up 0.94-1.2 cases for 100 thousand ofpopulation a year [5; 6]. Characteristics ofAVM by sex is unspecific: ration of men and women varies from 1.09:1 to 1.91:1, at average 1.4:1 [17].
Long-term prognosis at conservative treatment of brain AVM is unfavorable: deep invalidism becomes in 48 % ofAVM carriers, and 23 % ofpatients die [20]. Survivability of patients with AVM makes up 85 % during first 10 years, 65 % — during 30 years from the time of diagnosis confirmation. Active treatment tactics promotes
decrease of annual mortality from 3.4 % at conservative treatment up to 1.2 % at radical intervention [14].
Mostly symptomatology of vascular malformations is observed at young and middle age — from 20 to 40 years but it can manifest itself practically at any age. If a pathology has been detected by chance at elderly age, there is a chance that it will not be manifested. In women vascular malformation's course can be worsened during pregnancy. In majority of cases AVM is manifested by hemorrhages (~50 % patients) and convulsive attacks (25 %), rarely patients complain on headache (15 %), increasing neurologic deficiency (5 %), pulsatile noise and etc. [12]. Hemorrhages origins at AVM are mostly strictly very thin, varicose vessels in the structure of malformation's glome. Due to AVM glome localization and its structure, the form of hemorrhage can be different: combined ones (31 %) and subarachnoidal (30 %) occur more frequent, rarely — parenchymatous (23 %) and ventricular (16 %) hemorrhages [13].
Key points of pathogenesis of formation primary epileptic nidus connected with brain AVM is cortical localization of AVM; blood supply with medial cerebral artery (MCA) branches, afferents from cortical arteries, varicose-draining vein, aneurisms absence in malformation glome [23]. The nature of attacks can indirectly point on AVM localization.
AVM clinical presentation, as a rule, can be manifested in two types of the disease's course: torpid and hemorrhagic ones. Torpid or pseudotumorous type ofAVM course is characterized by convulsive syndrome's début, cluster headaches, semiotics of progressing neurologic deficiency. Symptomatic convulsive attacks are mostly observed (up to 67 % patients with AVM), which in 87.9 % patients remains as the first manifestation till the age of 30 years. Simple partial attacks are observed in 10 % patients, complex partial ones — in 4.3 %, partial ones with secondary generalization — in 22.4 %, generalized — in 63.3 % patients.
From other symptoms there are observed progressive neurologic disorders (19.6 %), headache (11.8 %). In 27.5 % observations torpid course is complicated by hemorrhages which stipulate the following development of convulsive syndrome in 18 % patients. Torpid course is more typical for big AVM of the 4th and the 5th category by Spetzler-Martin.
Clinical-pathogenic analysis of brain arteriovenous malformation neurologic manifestations
It is explained by more possible involvement of cortex as a source of convulsive activity at bigger malformations. Pulsatile glome of vascular malformation probably has stimulating effect on cortex and it together with cicatrical-atrophic changes along AVM perimeter, can explain pathogenic mechanisms of convulsive syndrome formation and progressing neurologic deficiency [1-4; 25].
Lethality from the first hemorrhage varies from 10 to 30 %, invalidism reaches 50 % [19]. At the same time, there are some data about more favorable functional outcomes. So, by A. Hartmann et al. (1998), 85 % patients from survived ones had minimal clinical manifestations, 13 % had medium invalidism, rough one — 2 % patients. Patients who had parenchymatous hemorrhage (52 %) were prone on invalidism [13]. More favorable prognosis of outcomes for hemorrhages from AVM unlike aneurismal or hypertensive ones is explained by relatively not high blood pressure in malformation vessels; favorable conditions for thrombosing; rare development of vascular spasm. The risk of repeated hemorrhage, especially within one year is higher and by various data, varies from 6 to 32.9 % [9-11; 15] with further reducing up to primary level.
By H. J. Svien et al. (1965) data, repeated hemorrhage occurs in 34 % patients survived after the first and among survived ones after the second hemorrhage 36 % suffer from the third one. Hemorrhages in the following years were observed in 20 % patients from the quantity of ones with unruptured AVM. Lethality at repeated hemorrhages makes up from 13 to 29 % vs 10-13 % at primary ones [8; 24]. Cephalgic syndrome is rare variant of disease first manifestation. By different authors data, headache is connected with enchancement of cerebral blood flow in the zone of AVM localization. The frequency and intensity of headache are varied. It
can be both constant intractable by analgesics and short-time, yielding to medicamental treatment. Regardless of début variants, AVM must be considered as potential source of lethal or incapacitating hemorrhage. Prophylaxis of AVM complications is possible subject to the total stoppage of malformation blood supply.
Objective
To work-out the most optimal approaches to treatment tactics choice of patients with AVM on the base of retrospective and prospective analysis results of clinical-semiologic and pathogenic features of brain AVM.
Investigation tasks: the following tasks had to be solved for achieving the objective of investigation:
1. To study the semiology of the disease and its dynamics on the base of estimation results of retrospective and prospective analysis of brain AVM clinical cases.
2. To detect the most typical clinical syndromes of AVM.
3. To determine syndromes value in treatment tactics choice of patients with AVM.
Materials and methods
109 patients with brain AVM (67 men and 42 women) were observed in the department of neurology, neurosurgery and ICU of RRCEM in 2009-2014. The mean age of men — 25.9 ± 5.6 years, women — 30.3 ± 9.3 years. Diagnosis has been verified on the base of EEG, CT and MRI of brain, MSCT-angiography of intracranial vessels and also traditional cerebral angiography. AVM of right-brain localization has been diagnosed in 40 patients, left-brain localization — in 69 ones. All patients were delivered to the hospital with the signs of urgent neurologic condition. Patient group was selected by the principle of random choice (table 1).
Table 1. - Clinical manifestation of brain AVM, abs. ( %)
Criterion Right-brain, n = 40 Left-brain, n = 69 Total, n = 109
men, n = 21 women, n = 19 men, n = 46 women, n = 23
Age, years 20 ± 14 29.3 ± 8.6 31.8 ± 9.9 31.4 ± 10.0
Size of AVM (a) small 6 (28.6) 11 (57.9) 23 (50) 10 (43.5) 50 (45.9)
big 14 (66.7) 7 (36.9) 20 (43.5) 10 (43.5) 51 (46.8)
giant 1 (4.7) 1 (5.2) 3 (6.5) 3 (13 %) 8 (7.3)
Convulsions (b) 18 (85.8) 14 (73.7) 38 (82.6) 20 (87) 90 (82.6)
Hemorrhages 2 (9.5) 5 (26.3) 5 (10.9) 2 (8.7) 14 (12.8)
Convulsions + Hemorrhages 1 (4.7) - 3 (6.5) 1 (4.3) 5 (4.6)
Results
As it is seen from the table, the patients quantity with left-brain localization of AVM was 30 % more than right-brain one. These differences were more evident among men. So, location of AVM in the left-brain in men has been observed two times more frequent than in women (46 and 23 respectively). Such strict inter-hemispheric dominance at AVM location in the right-brain has not been observed (in 21 men and in 19 women). Left-brain localization ofAVM in men was two times more frequent than right-brain one (46 and 21 patients respectively).
Comparative analysis ofAVM lateralization subject to patients age and sex presents special interest. So, patients-men with left-brain location were 11 years elder than men with right-brain location (31.8 ± 9.9 and 20 ± 14 years respectively). At the same time, age difference among patient-women with different hemispheric AVM lateralization made up only 2 years (29.3 ± 8.6 and 31.4 ± 10 years respectively).
While studying sizes and AVM lateralization subject to patients sex we got the following results. As it is seen from the table, AVM of small (45.9 %) and medium (46.8 %) sizes were detected more often and they in aggregate were diagnosed in 101 (92.7 %) patients.
Giant AVM were detected only in 8 (8.3 %) investigated patients with equal frequency among both men and women. The third part of giant AVM had left-brain lateralization.
Small sized AVM which were diagnosed in 50 (45.9 %) patients also two times more frequent were located in the left-brain (from the right — in 17, from the left — in 33). Gender peculiarities in the small sized AVM structure were manifested by well-defined dominance ofleft-brain localization among men, small sized AVM in women had equal interhemispheric extension.
As it is presented in the table, big sized AVM were detected more frequent and they were located predominately in the left brain — in 51 (46.8 %) patients among whom men were two times more than women (34 and 17 relatively).
Clinical semiology also depended from AVM lateralization and had gender differences. So, epileptic syndrome as partial attack with secondary generalization significantly more frequent has been observed at left brain lesion. In the pattern of epileptic attack partial convulsive tonic were dominated, in the single cases — non-convulsive, pseudoabsance attacks. Attacks frequency varied from 1-2 cases a month up to single attacks during a year. Attacks also were repeated on the background of taking antiepileptic drugs.
Cephalgia syndrome which was manifested in 80 % patients had migrainous and in 20 % — trigeminal nature. Unlike migraine, headache attacks at brain AVM are not followed by specific phases and have strict locality without hemicrany lateralization.
Hemorrhage into brain was in 14 (12.8 %) patients and AVM in the right and left hemispheres were located with equal frequency. In 11 patients hemorrhage was subarachnoidal and in the rest 3 ones — parenchymatous-subarachnoidal.
Convulsive syndrome combined with hemorrhage into the brain can be regarded as the most severe clinical manifestation of AVM. Such combination of symptoms was in 5 patients, 4 of them had AVM of left-brain localization.
Conclusion
So, study of AVM sizes and its semiology subject to AVM lateralization has shown:
In majority of cases AVM are located in the left carotid system, predominately in the vessels of medial and anterior cerebral arteries;
Brain AVM two time more frequent occur in men and are detected in them at younger age. Small and big sized AVM with the left-brain lateralization dominate by pathomorphology structure. The most frequent manifestation of AVM is cephalgic syndrome on which all patients complain. The pains have vascular and\or trigeminal origin. Epileptic syndrome is more often manifested in men, especially at left-brain localization of AVM. Epileptic syndrome has partial nature with secondary generalization, rarely pseudoabsance one is noted. Antiepileptic drugs have significant favorable effect at brain AVM. Isolated hemorrhage into brain and combination of epileptic syndrome with hemorrhage is not often observed (in 17.4 % patients), but this combination is the most severe clinical manifestation of brain AVM.
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