COMPUTED TOMOGRAPHY I N NEUROCYSTICERCOSIS
A 1 0 - Y E A R L O N G E V O L U T I O N A N A L Y S I S O F 100 P A T I E N T S W I T H A N A P P R A I S A L O F A N E W C L A S S I F I C A T I O N
L. R. MACHADO * — J. P. S. NOBREGA * — N. G. BARROS * J. A. LIVRAMENTO * — L. A. BACHESCHI * — A. SPINA -FRANÇA **
S U M M A R Y — T h r e e hundred land fifty seven computed tomography ( C T ) from 100 different patients with neurocysticercosis ( N C ) w e r e studied between 1979 and 1988. A l l patients were treated with praziquantel ( P Z Q ) . A n e w classification attempting to recognize the C T evolution profile in N C as well as assigning a possible link between C T findings a n d biological conditions of cysts is evaluated. I t was possible to conclude that: intact cysts remain unchanged in consecutive C T s b y 11 months and exhibit signs of degeneration in about 18 months after P Z Q d r u g therapy; degenerating cysts can be detected b y 10.5 months, disappear in 11 months and become nodular calcifications in about 25 months. Therefore, a time period of at least 36 months can be estimated for the complete evolution profile of cysts in the brain parenchyma.
Tomografia computadorizada na neurocisticercose: análise d a evolução em 100 pacientes durante 10 anos e avaliação de nova classificação.
R E S U M O — F o r a m estudados 357 exames por tomografia computadorizada do crânio ( T C ) de 100 pacientes com neurocisticercose, tratados com praziquantel ( P Z Q ) entre 1979 e 1988. Foi utilizada nova classificação tomográfica, procurando estabelecer vincule entre as imagens observadas à T C e a evolução biológica dos cisticercos. Considerando-se como estimador o valor das medianas em meses após o tratamento com P Z Q , foi possível concluir q u e : vesículas íntegras permanecem inalteradas em exames consecutivos por período de 11 meses; apresen-tam sinais radiológicos sugestivos de processo inflamatório, geralmente associados à degene¬ ração de cisticercos, em período de 1S meses; estas vesículas em degenerarão podem ser detectadas durante 10,5 meses, desaparecem em 11 meses e evoluem para calcificações nodu¬ lares simples em 25 meses. D e acordo com este critério, pode ser estimado período mínimo de 36 meses p a r a o perfil de evolução de cisticercos no parênquima cerebral em pacientes tratados com P Z Q .
A d v a n c e s in the study of neurocysticercosis ( N C ) have been favoured in the last decade by the current use of computed t o m o g r a p h y brain scan ( C T ) . Cysts and calcifications w e r e r e c o g n i z e d as the t w o most common and important types of C T images suggesting the presence of the cysticerci in the brain parenchyma 9. In this same period drug therapy for the aetilogical agent through praziquantel ( P Z Q ) has been introduced, favouring interest on the study of C T images in N C . In fact, c o m -parison a m o n g C T images before and after P Z Q therapy has been often referred to evaluate the effectiveness of the drug 6,12,14. H o w e v e r , such an interpretation may be hazardous since it is possible to admit that the disappearance of cysts might not be
N e u r o l o g y Investigation Center, N e u r o l o g y Department, São P a u l o University Medicine School: * Assistant P r o f e s s o r ; ** F u l l Professor. This study w a s partly supported b y F I N E P (4.2.0904.00).
necessarily caused by the drug therapy 5
. A coincidence o w i n g to the natural evolution of cysts should also be considered. Clinical studies shedding some light on this issue are subjected to several constraints. In the first place it is clearly unethical to maintain selection of paired control group with no P Z Q therapy because first results strongly suggested an effectiveness of the treatment, mainly in the more severe forms of N C w i t h no other alternative therapy 1,15.16. in the second place, it is hard to determine, at least in an estimative fashion, the approximate time of central neurvous system ( C N S ) infection. Indeed, in Brazil for instance, nearly all patients studied are o r i g i n a l l y from endemic areas and s h o w signs of multiple as well as not a l w a y s simultaneous infection. A different number of classifications has been proposed for the study of C T in N C 2,6,9,10. One of the most commonly cited classi-fication w a s put f o r w a r d by Sotelo et al.13; N C is divided into active and non-active forms. Based on the evolutive study of e v e r y individual cystic C T images in N C patients with a long follow-up our research group has proposed a new C T classi-fication 4. T h i s classiclassi-fication endeavours to r e c o g n i z e the evolution profile of C T in N C as well as to assign a possible link between C T findings and the biological conditions of cysts within the C N S . T h i s classification o b b e y s the natural biological evolution of N C .
In this paper are reported the results of an investigation endeavoured to determine the evolution profile of C T images in N C patients submitted to P Z Q therapy, taking into account the analysis of clinical and C S F findings for each indi-vidual C T performed 17.
M A T E R I A L A N D M E T H O D S
Three hundred and fifty seven C T from 100 different patients with N C were studied in the period between 1979 and 1988. A l l patients were treated with P Z Q . T h e protocol included an initial C T before therapy. After therapy, consecutive C T evaluations were performed. Time medians of 3, 6, 12, 18, 24, 36, 48 and 72 months were considered. The third month evaluation w a s possible only in 17 patients. The other subsequent C T evaluations were performed in a number of patients ranging from 29 to 39.
Changes of cerebral parenchyma and those of ventricular system were studied separa-t e l y , according separa-to separa-the classificasepara-tion previously reporsepara-ted 4. Parenchymal changes were classified into 4 different types corresponding to C T images of cysticerci. T y p e I C T images displayed no parenchymal changes and the diagnosis of N C w a s made possible through C S F analysis 3,4. T y p e I I C T images showed cysts with regular morphology, with no signs of either edema or inflammatory changes. T y p e I I I C T images showed parenchymal cysts associated to inflammatory signs a n d / o r presence of cyst signs of degeneration: loss of sharpness, annular enhancement, nodular enhancement or localized edema a r e observed ( F i g . 1). T y p e I V C T images showed single or multiple nodular calcifications. Changes of the ventricular system w e r e considered separately and could b e present in any of the 4 types described. Ventricular dilatation, asymmetry and deformity of ventricular system w e r e considered. I n view of epidemiologic and immunobiological characteristics of N C and con-sidering the nature of the study, median values w e r e regarded for all results and estimatives.
R E S U L T S
T a b l e 1 contains a brief descriptive summary of C T findings in cerebral parenchyma. In the course of the study, 621 type I I C T images were carefully accompanied: 269 vesicles previously reported were not seen in the next C T (median time of 18 months after treatment); 239 cysts remained unchanged in consecutive C T s (median time: 11 months); 113 cysts with regular morphology changed to type I I I C T images (median time: 17.5 months). T h e r e w a s no follow-up in 271 type I I vesicles. I n the same w a y , 287 type I I I C T images w e r e analysed: 106 cysts previously reported were not seen in subsequent C T s (median time: 11 months); 20 have remained unchanged (median time: 10.5 m o n t h s ) ; 161 have changed to nodular calcifications (median time: 25 months). I n 198 type I I I C T images there w a s no follow-up. Concerning type I V C T images, the emergence, of n e w calcifications has been demonstrated in many patients, with a frequency histogram reaching a. maximum at 26.5 months after treatment (median time: 20 months).
Ventricular alterations w e r e reported in 59.7% of CTs, dilatation (51.3%) a n d asymmetry (20.7%) corresponding to the most usual abnormalities observed. Changes in the ventricular system have shown signs of improvement only in 26.7% of C T images.
C O M M E N T S
T h e Sotelo et al.13 active T C forms in N C comprise: arachnoiditis; hydroce-phalus secondary to meningeal inflammation; parenchymal cysts; brain infarction secondary to vasculitis; mass effect due to a large cyst or cyst clumps; intraventricular cysts; spinal cysts. T h e inactive forms a r e : parenchymal calcifications; hydrocephalus secondary to meningeal fibrosis. Cases studied in the present investigation may be included among Sotelo active forms, as shown in table 1. Patients with one single or few calcifications or ventricular dilatation but with no inflammatory C S F reaction w e r e excluded. Cysts lodged in basal cisterns or in the ventricular system w e r e not considered in this evaluation: it is rather difficult to identify cysts in C S F system by C T , particularly in an evolutive fashion.
T h e accuracy of classification adopted in this investigation concerning biological evolution of cysts w a s double-checked against clinical and C S F results. Signs of incre-ased intracranial hypertension or unexpected escape to anti-epileptic drug therapy often occurred particularly when previous sharp C T cystic images ( t y p e II C T i m a g e s ) changed to images of nodular or annular enhancement or localized edema. Other than that, significative clinical improvement w a s detected when C T cysts associated to inflammatory changes disappeared. T h i s clinical and C T behaviour w a s often accompained by increase in the inflammatory changes in the C S F analysis, thus parelling clinical and C T evaluation 17. In fact, many authors attempt to assign a link between C S F inflammatory changes exacerbation, clinical N C activity and d e g e
-neration of cysts in the C N S , as previously reviewed 2
>3
.
degeneration signs. In v i e w of these difficulties, the present study employs metho-d o l o g y that atempt to metho-determine not the time lost by cysticerci up to metho-degenerate, but how much time each vesicle remains unchanged in consecutive C T s . Intact cysts remained unchanged at about 11 months; signs of degeneration w e r e detected at about 18 months after treatment. D e g e n e r a t i n g cysts remained by 10.5 months; they have disappeared in C T s performed after 11 months and w e r e replaced by nodular calci-fications in C T s evaluated about 25 months. T h e r e f o r e , by this study and b y these methods, a time span of at least 36 months can be assumed for all the evolution profile of cysts in the brain for patients treated with P Z Q ( T a b l e 2 ) .
T h e evolution study of type III C T images ( c y s t s in d e g e n e r a t i o n ) brings par-ticularly interesting data. A c c e p t i n g that usual time spent for evolution of this particular type is about 10.5 to 11 months, and accepting that calcifications corres-ponding to these cysts became evident only in 25 months, there is an estimated period of 14 months with neither cysts nor definite calcifications. In this phase, C T often can be illusorily evaluated as normal or can exhibit incipient signs of calcification not a l w a y s detectable in consecutive C T s .
It is rather important to emphasize that C T classification used a l l o w s one to diagnose the evolution phase of each individual cyst l o d g e d in the brain parenchyma. T h e s e results are considerably different from those referred b y several authors reg ar din g the evaluation of effectiveness of drug therapy 8,n-i4) particularly considered
by C T criteria. T h e s e results are due possibly to the m e t h o d o l o g y e m p l o y e d , espe-cially in C T evaluation paired with C S F and clinical l o n g term evolution analysis.
R E F E R E N C E S
1. Botero D , Castafio S — Cisticercosis: tratamiento com praziquantel. T r i b u n a Médica (Colombia) 63:31, 1981.
2. Enzmann D R — I m a g i n g of infections and inflammations of the central nervous system: computed tomography, ultrasound, and nuclear magnetic resonance. Raven Press, N e w York, 1984, pg 103.
3. Livramento J A — Sindrome d o liqüido cefalorraqueano na neurocisticercose: estudo crítico sobre a evolugão d a imunidade humoral. A r q N e u r o - P s i q u i a t (São P a u l o ) 45:261, 1987.
4. Machado L R — L i q ü i d o cefalorraqueano e neurocisticercose: aspectos evolutivos da resposta inflamatória celular. A r q N e u r o - P s i q u i a t (São P a u l o ) 45:353, 1987.
5. Miller B L , Grinnell V , G o l d b e r g M A , H e i n e r D — Spontaneous radiographic dissappearance of cerebral cysticercosis: three cases. N e u r o l o g y 33:1377, 1983.
6. Minguetti G, F e r r e i r a M V C — Computed tomography in neurocysticercosis. J Neurol N e u r o s u r g Psychiat 46:936, 1983.
7. N a s h T E , N e v a F A — Recent advances in the diagnosis and treatment of cerebral cysticercosis. N E n g l J M e d 311:1492, 1984.
8. Ortiz C P , R i v a r a C A , Schmidt-Dommerque F — Cisticercosis del sistema nervioso: una evaluation a corto plazo del tratamiento con praziquantel. R e v N e u r o - P s i q u i a t ( L i m a ) 47:127, 1984.
9. R o d r i g u e z - C a r b a j a l J, Palácios E, A z a r - K i a B , Churchil R — Radiology of cysticercosis of the central nervous system including computed tomography. Radiology 125:127, 1977. 10. R o d r i g u e z - C a r b a j a l J, Palácios E , Zee C — N e u r o r a d i o l o g y of cysticercosis of the central nervous system. I n Palácios E , R o d r i g u e z - C a r b a j a l J, Taveras J M ( e d s ) : Cysticercosis of the Central Nervous System. Charles C Thomas, Springfield, 1983, p g 101.
11. Sotelo J — Neurocysticercosis. I n K e n n e d y P G E , Johnson R T ( e d s ) : Infections of the Nervous System. Butteworths, London, 1987, p g 145.
12. Sotelo J, Escobedo F, R o d r i g u e z - C a r b a j a l J, Torres B , Rubio-Donnadieu F — Therapy of parenchymal brain cysticercosis with praziquantel. N E n g l J M e d 310:1001, 1984. 13. Sotelo J, G u e r r e r o V , R u b i o F — Neurocysticercosis: a n e w classification based in
active and inactive forms. A study of 753 cases. A r c h Intern M e d 145:442, 1985. 14. Sotelo J, Torres B , R u b i o - D o n a d i e u F , Escobedo F , R o d r i g u e z - C a r b a j a l J — Praziquantel
in the treatment of neurocysticercosis: long-term follow-up. N e u r o l o g y 35:752, 1985. 15. Spina-França A , N ó b r e g a J P S — Neurocisticercose e praziquantel. R e v Paulista M e d
95:34, 1980.
16. Spina-Franga A , N ó b r e g a J P S , Livramento J A , Machado L R — Administration of pra-ziquantel in neurocysticercosis. Tropenmed Parasit 33:1, 1982.
17. SpinaFrança A , N ó b r e g a J P S , Machado L R , Livramento A — Neurocisticercose e p r a -ziquantel: evolução a longo prazo de 100 pacientes. A r q N e u r o - P s i q u i a t (São P a u l o ) 47:444, 1989.
R E F E R E N C E S
1. Botero D , Castaño S — Cisticercosis: tratamiento com praziquantel. T r i b u n a Médica (Colombia) 63:31, 1981.
2. Enzmann D R — I m a g i n g of infections and inflammations of the central nervous system: computed tomography, ultrasound, and nuclear magnetic resonance. Raven Press, N e w York, 1984, pg 103.
3. Livramento J A — Sindrome d o liqüido cefalorraqueano na neurocisticercose: estudo crítico sobre a evolugão d a imunidade humoral. A r q N e u r o - P s i q u i a t (São P a u l o ) 45:261, 1987.
4. Machado L R — L i q ü i d o cefalorraqueano e neurocisticercose: aspectos evolutivos da resposta inflamatória celular. A r q N e u r o - P s i q u i a t (São P a u l o ) 45:353, 1987.
5. Miller B L , Grinnell V , G o l d b e r g M A , H e i n e r D — Spontaneous radiographic dissappearance of cerebral cysticercosis: three cases. N e u r o l o g y 33:1377, 1983.
6. Minguetti G, F e r r e i r a M V C — Computed tomography in neurocysticercosis. J Neurol N e u r o s u r g Psychiat 46:936, 1983.
7. N a s h T E , N e v a F A — Recent advances in the diagnosis and treatment of cerebral cysticercosis. N E n g l J M e d 311:1492, 1984.
8. Ortiz C P , R i v a r a C A , Schmidt-Dommerque F — Cisticercosis del sistema nervioso: una evaluation a corto plazo del tratamiento con praziquantel. R e v N e u r o - P s i q u i a t ( L i m a ) 47:127, 1984.
9. R o d r i g u e z - C a r b a j a l J, Palácios E, A z a r - K i a B , Churchil R — Radiology of cysticercosis of the central nervous system including computed tomography. Radiology 125:127, 1977. 10. R o d r i g u e z - C a r b a j a l J, Palácios E , Zee C — N e u r o r a d i o l o g y of cysticercosis of the central nervous system. I n Palácios E , R o d r i g u e z - C a r b a j a l J, Taveras J M ( e d s ) : Cysticercosis of the Central Nervous System. Charles C Thomas, Springfield, 1983, p g 101.
11. Sotelo J — Neurocysticercosis. I n K e n n e d y P G E , Johnson R T ( e d s ) : Infections of the Nervous System. Butteworths, London, 1987, p g 145.
12. Sotelo J, Escobedo F, R o d r i g u e z - C a r b a j a l J, Torres B , Rubio-Donnadieu F — Therapy of parenchymal brain cysticercosis with praziquantel. N E n g l J M e d 310:1001, 1984. 13. Sotelo J, G u e r r e r o V , R u b i o F — Neurocysticercosis: a n e w classification based in
active and inactive forms. A study of 753 cases. A r c h Intern M e d 145:442, 1985. 14. Sotelo J, Torres B , R u b i o - D o n a d i e u F , Escobedo F , R o d r i g u e z - C a r b a j a l J — Praziquantel
in the treatment of neurocysticercosis: long-term follow-up. N e u r o l o g y 35:752, 1985. 15. Spina-França A , N ó b r e g a J P S — Neurocisticercose e praziquantel. R e v Paulista M e d
95:34, 1980.
16. Spina-França A , N ó b r e g a J P S , Livramento J A , Machado L R — Administration of pra-ziquantel in neurocysticercosis. Tropenmed Parasit 33:1, 1982.
