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УДК 616.98:578.828В1Л:616.831:576.31 https://doi.Org/10.26641/2307-0404.2018.1.124925
L.R. Shostakovych-Koretskaya*, MORPHOLOGICAL CHARACTERISTICS OF
KY Lytvyn * * BRAIN LESIONS IN HIV POSITIVE PATIENTS
Z.O. Chykarenko ,
T.V. Usenko ,
V.O. Logvinenko
SE «Dnipropetrovsk medical academy of Health Ministry of Ukraine» Department of Infectious Diseases
(Chief - MD, PhD, Professor L.R. Shostakovych-Koretskaya) V. Vernadsky str., 9, Dnipro, 49044, Ukraine e-mail: k-lytvyn@ukr.net
CE «Dnipropetrovsk Regional Children's Clinical Hospital»
Pathoanatomical Department
(Head Physician - O.L. Khytryk)
Kosmichna str., 31, Dnipro, 49100, Ukraine
CE «Dnipropetrovsk City Clinical Hospital N 21»
Pathoanatomical Department
(HeadPhysician -L.V. Tymofieieva)
Kanatna str., 17, Dnipro, 49006, Ukraine
ДЗ «Днтропетровська медична академiя МОЗ Укра!ни»
кафедра тфекцшних хвороб
(зав. - д. мед. н., проф. Л.Р. Шостакович-Корецька)
вул. В. Вернадського, 9, Днтро, 49044, Укра!на
КЗ «Днтропетровська обласна дитяча клiнiчна лжарня»
патологоанатомiчне вiддiлення
(голов. лiкар - О.Л. Хитрик)
вул. Космiчна, 13, Днтро, 49100, Украша
КЗ «Днтропетровська мкька клтчна лiкарня № 21 iM. професора С.Г. Попково!»
nатологоанатомiчне вiддiлення
(голов. лжар - Л.В. Тимофеева)
вул. Канатна,17, Днтро, 49006, Укра!на
Key words: HIV infection, pathology, morphology, brain, mortality
Ключовi слова: В1Л-1нфекщя, патологiя, морфологiя, головний мозок, летальнiсть
Abstract. Morphological characteristics of brain lesions in HIV infection. Shostakovych-Koretskaya L.R., Lytvyn K.Y., Chykarenko Z.O., Usenko T.V., Logvinenko V.O. Currently, diseases of the central nervous system are a common cause of death of patients with HIV infection. The article presents results of retrospective analysis of etiotropic structure of 186 lethal cases and typical pathological changes of brain tissue ofpatients aged 21 to 61 years who had confirmed diagnosis of HIV and died of diseases associated with CNS damage in the Municipal infectious hospital in the city of Dnepr (Ukraine) in the period from 2011 to 2016. The most common causes of death in patients with HIV infection and CNS infection were cerebral tuberculosis (75.0%) including co-infection (n = 35) and meningoencephalitis that developed as a result of yeast fungal (15.6%). In the study of neuropathological processes in the autopsy material of the brain tissue of patients with HIV, various multifocal and diffuse morphological changes have been identified that can be presented in this work in the form of 4 groups: 1) Multiple nonspecific changes associated with both direct action of HIV and co-factors: infection, inflammation, hypoxia, etc., 2) Viral-induced vasculitis with hemorrhages, 3) Subacute aseptic encephalitis, 4) HIV-associated opportunistic infections. General pathomorphological changes in brain tissue are revealed that can cause similarities of clinical manifestations, can complicate differential diagnosis of cerebral lesions of various etiologies, and lead to a divergence of pre and postmortal diagnoses.
Реферат. Морфолопчш характеристики ураження головного мозку у В1Л-позитивних пащенив. Шостакович-Корецька Л.Р., Литвин К.Ю., Чикаренко З.О., Усенко Т.В., Логвшенко В.О. На цей час за-
хворювання центральноI нервово'1' системи е частою причиною смерт1 пацieнтiв з ВШ-тфекщею. У роботi представленi результати ретроспективного аналiзу етiологiчноi структури 186 летальних випадюв i характерт патологiчнi змти тканини мозку пацieнтiв, у вiцi вiд 21 до 61 року, яю мали пiдтверджений дiагноз В1Л i померли вiд захворювань, пов'язаних з ураженням центрально'1' нервово'1' системи, в тфекцшнш лiкарнi мкта Днтро (Украша) в перюд з 2011 по 2016 ргк. Найбтьш поширеними причинами летальностi в цш грут
пацгентгв був церебральний туберкульоз (75,0%), у тому числг в складI когнфекцИ (п=35), I ментгоенцефалти, як виникли внаслгдок фунгемИ дргжджових грибгв (15,6%). При вивченнI нейропатологгчних процеаву мозковш тканинI виявлен р1зн1 мультифокальн й дифузнг морфолог1чн1 змти, як в роботI представленI у виглядг 4-х груп: 1) множиннI неспецифгчш змти, пов'язанг як з прямою д1ею В1Л, так I супуттх чинниюв: тфекцИ, запалення, ггпокая та т.; 2) в1рус-тдукован1 васкулгти з гемораггями; 3) пгдгострий асептичний енцефалт; 4) В1Л-асоцшован1 опортутстичнг ¡нфекцИ. Стльш патологгчнг морфолог1чн1 змти в тканинI головного мозку, як були виявлен при досл1джент, можуть бути причиною часто'1 схожост1 клгтчних проявгв та ускладнювати диференцгальну дгагностику церебральних уражень р1зно'1 етгологИ I призводити до розбгжностг пре- I постмортального д1агноз1в.
Despite some positive changes in recent years, the epidemiological situation regarding HIV in Ukraine remains complicated: there is a high rate of HIV infection increase, which is one of the largest in the Dnipropetrovsk region comparing to the whole Ukraine (95.1 per 100 thousand of population). Mortality from AIDS in the Dnipropetrovsk region in 2016 was estimated at the level of 31.0 per 100 thousand of population, which is much higher than the same index for Ukraine (7.6 per 100 thousand) [1].
According to the literature, neurological disorders as the first manifestation of symptomatic HIV-infection occur in 10-20% of patients and about 6070% of patients with advanced HIV infection; they have a clinical picture of neurological dysfunction and their development is associated with a significant increase in mortality risk [4, 5, 9].
The structure of HIV-associated brain lesions varies in different countries, but in common there is a high incidence of infectious diseases of the central nervous system such as tuberculosis, toxoplasmosis, cryptococcosis, progressive multifocal leukoen-cephalopathy [2, 4, 6, 8, 9]. Existing studies of the nervous tissue in patients who died from HIV / AIDS indicate presence of pathological changes in the brain tissue typical for slow neuroinfections such as focal demyelination. It is believed that these changes start to appear already in the early stages of the disease [3].
There is an assumption that a significant loss of neurons (brain neural weight is reduced to 18%) in patients with HIV may be the pathomorphological substrate for the development of dementia [7].
At the same time, there is not enough information about the structural changes of nervous system disorders that develop in patients with HIV infection. So, there are no explanations for frequent occurrence of focal demyelination, which is associated with the development of symptoms of HIV encephalopathy [6].Changes caused by both the virus itself and toxic or infectious factors are not delineated. Pathomorphological changes characterizing general clinical picture that exists in many different etiology cases of CNS lesions remain not completely defined.
All these issues require further investigation.
Objective: To analyze cases of CNS-related mortality and to characterize the main patho-morphological patterns of brain tissue lesions in patients with HIV-associated disorders of the central nervous system (CNS).
MATHERIALS AND METHODS
Retrospective data analysis with postmortem study of autopsied brain tissue of 186 patients aged 21 to 61 was conducted; the patients had laboratory confirmed diagnosis of HIV and died from CNS -related diseases in the Municipal Clinical Hospital of Infectious Diseases, city Dnipro (Ukraine), in the period 2011 - 2016.
RESULTS AND DISCUSSION
The most common diseases of the central nervous system among lethal cases in patients with HIV infection were cerebral tuberculosis (n = 125, 75.0%), including co-infection (dual and triple CNS infection, n=35) and meningoencephalitis, which developed as a consequence of systemic fungal infection of yeast fungi (n=29, 15.6%). The other lethal causes included EBV infection (n=23); cerebral toxoplasmosis (n = 18); secondary bacterial meningitis (n=11); progressive multifocal leu-coencephalopathy (PML) (n=10); encephalitis caused by the herpes simplex virus (HSV 1-2 types) and cytomegalovirus CMV (n=9); primary central nervous system lymphoma (n=4).
Evaluation of neuropathological processes in autopsy material of brain tissue of patients with HIV/AIDS in most cases (> 90%) revealed various multifocal and diffuse brain lesions that can be considered as HIV-induced brain damages and/or the result of other infections and opportunistic diseases.
All autopsy findings were presented in four patterns:
1st Pattern: nonspecific features that were related both to the direct effect of HIV and co-factors: infections, inflammation, toxicity with signs of edema, nucleus tigrolysis of large neurons; and the loss of their processes (Fig. 1, 2).
The presence of vacuolization zones and the edema of laminar myelin layer were observed in most patients (Fig. 3).
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,.■* * f: * „ * ». t %%! : V ■ * î' - ' ' i *•" « -v " Л 5л * " rj V • * * * 'í-r * ' V • , ^ . ь Л - . ; ¿ » -4 '
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Fig. 1. Brain tissue with edema, nuclei's tigrolysis of large neurons and the loss of their processes H & E x150
In all lethal cases, regardless of the diagnosis, there were pericellular and perivascular edema, hy-
Fig. 3. Vacuolization zones and laminar myelin layer edema H & E x150
2nd Pattern: Virus-induced vasculitis. Vasculitis in patients with HIV infection was a frequent phenomenon which included poor pig-
Fig. 5. Substancia nigra, focal depigmentation of dophamiergical neurones, clusters of lymphocytes around of capillaries H&E x150
Fig. 2. Cerebellum, edema, nuclei's tigrolysis of the pear-shaped neuron's with loss of processes H&E. x150
perchromatosis of neurons nuclei, astrocyte reaction and multiple foci of demyelination identified (Fig. 4).
Fig. 4. Multiple foci of demyelination H & E х150
mentation of the substantia nigra, formation of cysts, necrobiosis of neurons (Fig. 5, 6).
Fig. 6. Virus induced vasculitis in the form of clusters of lymphoid and glial cells, necrobiosis of large neurons H&E. x150
In some cases there was a suppurative ne- tissue (Fig.7), hemorrhages, brain tissue necrosis crotizing vasculitis and purulent melting of brain with the formation of cysts (Fig. 8).
Fig 7. Purulent melting of brain tissue H&E x 150
Fig. 8. Hemorrhagic focus with accumulation of hemosiderophages, areas of necrosis, hemorrhage and cyst formation zones H&E. x150
3rd Pattern: aseptic subacute encephalitis. In the cerebral cortex, white matter and other areas in patients with HIV-associated CNS lesions signs of
subacute aseptic encephalitis, lymphocyte and macrophage infiltration, brain tissue necrosis and proliferation of microglia were found (Fig. 9, 10).
Fig. 9. Meningitis features with the thickening of vascular walls, lymphoid infiltration (green arrow) in the background of the picture of subacute encephalitis (violet arrow) H&E. x150
Fig. 10. Subtotal brain tissue necrosis involving arterial vessels with changes typical for subacute encephalitis (upper right corner) H&E. x150
4th Pattern: specific changes related to certain HIV-associated CNS infections such as cerebral Tuberculosis, cerebral Toxoplasmosis and fungal infections.
Changes caused by M. tuberculosis were presented by exudative-necrotic encephalitis with a large area of caseous necrosis and proliferation of astrocytes (Fig. 11, 12).
Changes in brain caused by Cryptococcus were presented by clusters of yeast fungi Cryptococcus with necrosis of brain tissue, formation of cysts, the black substance focal depigmentation (Fig. 13). Pathological changes of brain in patients with To-xoplasmic encephalitis were presented by Tropho-zoites of toxoplasma in brain tissue, neuronophagia and edema (Fig. 14).
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Fig. 11. Exudative-necrotic encephalitis caused by M.tuberculosis with a large zone of caseous necrosis and macrophage-leukocyte infiltration, vasculitis H&E x150
Fig. 12. Central nervous system tuberculosis with proliferation of astrocytes H&E. x600
Fig 13. Diffuse vasculitis, angiomatosis, aggregations of Fig. 14. Trophozoites of toxoplasma (yellow arrows)
colonies of fungi spores (yellow arrows) in brain tissue, neuronophagia and edema
around arterial vessel H&Ex600 H&E x150
CONCLUSIONS
1. Neurological lesions are specific complications of HIV infection. This phenomenon is confirmed by analysis of autopsy series that show the presence of neuropathological changes
2. Neuropathological examination of post - mortem brain tissue of the HIV/ AIDS patients revealed the multifocal and diffuse brain tissue lesions in 90% of lethal cases and in 75% of them due to tuberculosis. Neurological manifestations of HIV infection in real practice are often non-specific, due to
the complex of comorbidities, including toxic factors, and not always correlating with the severity of morphological signs of CNS damage. Difficulties in differential diagnosis of CNS disorders in patients with HIV infection may lead to discordance between pre- and postmortem diagnosis.
3. Thus, further comprehensive studies for the advancement of our knowledge of neurological problems of HIV and improvement of diagnosis and treatment of patients with HIV/AIDS are required.
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Стаття надшшла до редакци 14.11.2017
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