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Cerebral cysticercosis
Journal of the Neurological Sciences, 1978, 35:365-374 © Elsevier/North-Holland Biomedical Press
365
C E R E B R A L CYSTICERCOSIS
G. K. AHUJA, S. ROY, G. KAMLA and V. VIRMANI Department of Neurology and Pathology, All India Institute of Medical Sciences, New Delhi-110016 (India)
(Received 3 August, 1977)
SUMMARY Twenty cases of cysticercosis involving the central nervous system were seen during a 6-year period. Twelve patients presented with symptom and signs of raised intracranial pressure, 6 with seizures and 1 each with subacute meningitis and psychosis. The diagnosis of cerebral cysticercosis was established by brain biopsy in 8 patients, at autopsy in 3, and by biopsy of a subcutaneous nodule in 7. It was presumed on the basis of typical intracranial calcification in 1 case and soft tissue calcification in another. The protean clinical manifestations of this condition and the diagnostic difficulties it raises are discussed.
INTRODUCTION Infestation of the central nervous system by cysticerci was mentioned by Paranoli as early as 1550 and by Rumler in 1588 (Olive and Angulo Rivero 1962). This was followed by Virchow's description of racemose cysticercosis of the basal meninges. Evidence that intracranial cysticercosis is causally related to symptoms such as epilepsy is usually indirect, i.e., based on the biopsy of subcutaneous nodules (McArthur 1934; Dixon and Hargreaves 1944; Singh and Jolly 1957; Dixon and Lipscomb 1961; Singh, Singh and Sham 1963; Dinaker, Mathai and Chandy 1970; Mani, Ramesh, Ahuja and Mani 1974) or upon the suggestive neuroradiological features elicited in contrast studies of suspect cases (Arana and Asenju 1945; Natarajan and Balakrishan 1970). Though known to occur in all parts of the world the greatest number of verified cases of cerebral cysticercosis have been reported from Mexico, Central and South America, Spain and Eastern Europe (Stepien and Chorobski 1949; Tolosa 1954; Arseni and Samitca 1957; Stepien 1962; Arseni and Cristesca 1972). From India the largest verified series of intracranial cysticercosis was reported by Dinaker et al. in 1970. Sixteen of their 25 cases were confirmed histopathologically. Showramma and
366 Reddy (1963) and Bhaskaran (1973) reported cases of asymptomatic cerebral cysticercosis in their autopsies of subjects dying of urelated causes. We are reporting here our experience of cysticercosis of the nervous system. MATERIAL AND OBSERVATIONS During the past 6 years (from January 1971 to December 1976), 20 cases of neurocysticercosis presenting in a variety of ways were seen at the AIIMS Hospital, New Delhi. The clinical examination included special attention to the presence or absence of palpable subcutaneous nodules. Investigations included haemogram, erythrocyte sedimentation rate, urinalysis, fasting blood sugar, urea, electrolytes and repeated stool examinations in all of the cases, X-rays of the chest, skull (antero-posterior and lateral views) and soft tissues when indicated, and neuroradiological investigations with contrast media as and when needed.
Fig. 1. Calcified soft tissue cysts.
367 Twelve cases presented with symptoms and signs of increased intracranial pressure. All 12 had papilloedema, 10 had headache and vomiting, 8 had seizures. The visual acuity was diminished in 6. Abducens palsies were seen in 6 cases. An ocular cysticercus was seen in I patient. In addition, 3 exhibited states of altered consciousness. A paralysis of upward gaze was seen in 1 patient. Only 2 patients had palpable subcutaneous nodules. The diagnosis of intracranial cysticercosis was confirmed at autopsy in 2 cases and by biopsy in 8. In the other 2 cases, the diagnosis was based on subcutaneous nodule biopsy. Six cases presented with seizures only. The presumptive diagnosis of cerebral cysticercosis was based upon the findings on subcutaneous nodule biopsy in 4, and on the presence of widespread intracranial and soft tissue calcification in 2 (Fig. 1). One case presented as psychosis and 1 as subacute meningitis. The erythrocyte sedimentation rate (Westergren's method) was moderately elevated in 3 cases and normal in others. A raised total leucocyte count (17,000/m 3) was found in I case with extensive subcutaneous and intramuscular nodules. One case had a total leucocyte count of 14,000/m 3 with an eosinophilia of 30 ~/oo-This was the solitary case which showed eosinophilia. He had presented with seizures and papilloedema. Stool examination did not show proglottids or ova in any case. One patient gave a history of passing tapeworm segments on 2 occasions, 18 years earlier. The cerebrospinal fluid (CSF) was not examined as a routine, as a diagnosis of space-occupying lesion was considered possible in most of the cases. Of the 8 cases where the CSF was
.
o5"-
F~g. 2, Sagittal section of the brain showing cysticerci cysts spread over both cerebral and cerebellar hemispheres, basal ganglia, internal capsule and brain stem.
368 studied, the b i o c h e m i s t r y o f the fluid was n o r m a l m 5, its protein content was elevated in 2 and the globulin was increased in b o t h o f these. One patient presenting as subacute meningitis h a d a m a r k e d pleocytosis in the fluid. Elevated total protein and globulin were f o u n d on several occasions. The sugar content o f the C S F was n o r m a l in all 8 cases. Three cases came to a u t o p s y and 8 were d i a g n o s e d on brain biopsy. A notable feature o f these cases was the absence o f p a l p a b l e subcutaneous nodules.
Fig. 3. (a) Cyst containing viable parasite with practically no inflammatory reaction in the wall. H and E..< 50. (b) High power of (a). H and E 160.
369 CASE HISTORIES
Case 1 A 26-year-old male was admitted for headache and vomiting of 6 months duration and right focal setzures of 4 months duration. For 6 weeks vision had been impaired. Examination revealed gross bilateral papilloedema with markedly reduced visual acuity and bilateral 6th nerve palsies. Ventriculography showed small ventricles without a shift of midline structures. Bilateral subtemporal decompression was carried out. The patient died within 48 hr. On removing the skin flaps at autopsy both the parietal bones were found to be separated from the rest of the skull. Both parietal lobes were herniating and were intensely congested. The brain was oedematous. Multiple pale, greyish-white cystic areas were seen scattered over the brain surface. They varied in size from 2 to 3 m m in diameter. Some contained clear watery fluid. No areas of necrosis were seen. Uncal herniation was present on both sides in the form of well-demarcated grooves. On sectioning many cystic areas of similar size were seen in the cerebral and cerebellar hemispheres, mostly in the grey matter. A few were also seen in the white matter (Fig. 2). A few cysts were also present in the brain stem.
Case 2 An I 1-year-old boy presented with classical features of a subacute meningitis with clouding of consciousness and seizures of focal onset which proved intractable to anti-convulsant therapy. Hm EEG showed periodic lateralised epileptiform discharges. He was treated for suspected tuberculous meningitis but deteriorated and died. Macroscopically the brain was slightly oedematous. There were multiple small translucent cysts spread throughout the entire brain. Some of these contained whitish granules. On sectioning the brain, numerous small cysts measuring 3-6 m m in diameter were seen in all areas including both cerebral and cerebellar hemispheres, basal ganglia, thalami, brain stem and corpus callosum. The meninges showed mild focal thickening in areas overlying the cysts. There was no hydrocephalus. This case has been separately reported (Virmani, Roy and Kamla 1977).
Case 3 A 40-year-old woman who was admitted in coma with a history of headache and vomiting of 12 years duration, worse in the last 6 years, during which time she had developed left focal seizures which tended to become generalised. On examination she was found to have bilateral papilloedema and bilateral extensor plantar responses. She did not improve despite supportive therapy and expired 4 hr after admission. The brain before fixation weighed 1100 g. The external surface was normal. On sectioning, small cysts were seen diffusely distributed throughout both cerebral hemispheres. The cortex was more severely involved than the white matter. The basal ganglia on both sides were spared. These cysts varied in size from 2 to 10 m m in diameter. Their walls were thin and were filled with clear fluid. In the cavity of the cyst pearly-white structures were seen, attached to one side of the cyst wall. A few cysts were also present on the right side of the ports and in both cerebellar hemispheres. The cerebellum, however, was affected less severely than the cerebral hemispheres. The mid-brain and the medulla oblongata were normal. The circle of Willis and the meninges did not reveal any abnormality. The cysts were confirmed to be cysticerci on microscopic examination in all 3 cases.
Microscopic appearances o f cysts in autopsy and brain biopsy material The appearance varied not only from case to case but also in different cysts from t h e s a m e case. T h e cysts c o n t a i n i n g v i a b l e p a r a s i t e s g e n e r a l l y s h o w e d little o r n o inflammatory reaction around them. Occasionally, such cysts were surrounded by a mild to moderate degree of inflammatory reaction consisting mainly of lymphocytes and plasma
cells a d m i x e d
with a few polymorphonuclear
leucocytes and eosinophils
( F i g . 3). O t h e r cysts c o n t a i n e d n e c r o t i c p a r a s i t e s . M a n y s u c h cysts c o n t a i n e d p o l y m o r p h s a n d n e c r o t i c d e b r i s ( F i g . 4). T h e i n f l a m m a t o r y r e a c t i o n a r o u n d s u c h c y s t s w a s g e n e r a l l y v e r y m a r k e d , c o n s i s t i n g m o s t l y o f l y m p h o c y t e s a n d p l a s m a cells a d m i x e d
370
Fig. 4. The cyst containing necrotic parasite with dense inflammatory exudate in the lumen as well as the cyst wall. H and E. ," 50
Fig. 5. Brain tissue adjacent to the cyst showing perivascular infiltratLon with lymphocytes and plasma cells H and E. "-" 160.
with small n u m b e r s o f p o l y m o r p h o n u c l e a r cells, eosmophils, histiocytes a n d multinucleated giant cells. A variable degree o f fibrosis was also seen. There were still o t h e r cysts which a p p e a r e d to be collapsed c o n t a i n i n g either no parasite in the cavity or having hyalinised m a t e r i a l representing hyalinisation o f the d e a d parasite. I n the wall o f such cysts, i n f l a m m a t o r y infiltration was generally m i l d e r b u t the fibrosis a r o u n d t h e m was very m a r k e d . The b r a i n tissue in the i m m e d i a t e vicinity o f cysts c o n t a i n i n g viable parasites showed very little change or a few reactive astrocytes while the tissue a r o u n d necrotic parasites showed a mild to m o d e r a t e degree o f o e d e m a a n d reactive astrocytosis. The pearly-white structures a t t a c h e d to the side o f the cyst wall represent the scolices. H o o k l e t s are clearly seen in some o f the scolices. However, the cysticercus
371
Fig. 6. Brain tissue away from the cyst showing oedema and reactive astrocytic proliferation. H and E_ x 160.
Fig. 7. Section showing inflammatory cellular infiltration of the meninges and reactwe astrocytosls of the molecular layer. H and E. x 160.
o f taenia solium cannot be differentiated from that o f taenia saginata. Calcification is usually seen in the cyst wall but it was at times noted within the cyst containing a necrotic parasite. A few vessels in some cases showed mild perivascular infiltration with lymphocytes and plasma cells (Fig. 5). In some areas with marked inflammatory reaction endarteritis as described by A d a m s (1976) was noted but was not a significant feature. The brain tissue away from the cysts showed varying degrees of oedema and reactive astrocytic proliferation (Fig. 6). In some cases where the cysts were superficially placed under the pia, the leptomeninges showed a mild to moderate inflamm a t o r y reaction consisting of lymphocytes and plasma cells (Fig. 7).
372 DISCUSSION Cerebral cysticercosis has always presented a diagnostic challenge. The presence of subcutaneous nodules and of soft tissue calcification does not always imply intracranial cysticercosis nor does the absence of subcutaneous nodules exclude the possibility of such a diagnosis. Cerebral cysticercosis may be entirely asymptomatic, being a chance finding at autopsy (Showramma and Reddy 1963; Bhaskaran 1973). The viable cysts produce very little reaction in the surrouding tissues (Menon and Veliath 1940; Showramma and Reddy 1963) and consequently few symptoms; it is the dead or dying parasites which produce marked tissue changes and give rise to symptoms. This was evident in both the autopsy and biopsy material of the present series. In cases of epilepsy the role of cysticercosis is difficult to assess. The condition may never have been thought of in the absence of subcutaneous nodules. When the latter are present in patients with epilepsy, the causative relationship may be difficult to establish without confirmation of the presence of intracranial cysticercosis. A definitive diagnosis can only be made during craniotomy which is seldom performed for conditions such as headache and epilepsy. Even when symptoms are severe enough to warrant an intracranial exploration, the site of involvement may be missed by a localised biopsy if the lesions are not diffuse. Ventriculography may be normal. When filling defects are seen, they may provide supportive but not confirmatory evidence. The high prevalence of cysticercosis in the developing countries is due to poor socio-economic conditions and hygienic habits. If man ingests inadequately cooked ('measly') pork containing the cysticerci of taenia solium he will develop the adult tapeworm (not cysticercosis). Man is the only definitive host of this parasite. Cysticercosis develops when man consumes tapeworm ova. The ova are usually ingested on unwashed, faecally contaminated vegetables. Antiperistaltic regurgitation of gravid proglottids is a theoretical method of contamination, the frequency of which is impossible to assess. Ova may also be carried from anus to mouth through bad hygienic habits. The paucity of cases of human cysticercosis found to be harbouring the adult tapeworm is, however, noteworthy. Whatever the mode of infestation the shell of the egg is digested with the liberation of the larval forms, which burrow into the stomach wall and enter the circulation from whence they are disseminated into the tissues including the central nervous system. The clinical presentation of neurocysticercosis depends on the size, site and number of parasites and on the tissue reaction to the infestation. Cerebral cysticercosis can mimic many psychiatrical and neurological conditions. Patients may present with features of idiopathic raised intracranial tension of acute or subacute onset, as intracranial space-occupying lesions, as focal neurological deficits, or with epilepsy, headache, subacute meningitis, acute or subacute encephaJopathy, obstructive hydrocephalus, or personality or behavioural disorders. Minor or even extensive involvement of the brain with cysts may remain clinically silent, as reported by Showramma and Reddy (1963) and Bhaskaran (1973). Allergic reaction to the cysts may be responsible for the varying degrees of white matter oedema. In the absence of subcutaneous nodules, the suspicion of cysticercosis may not be entertained.
373 D i n a k a r et al. (1970) f o u n d s u b c u t a n e o u s cystic nodules in 7 of their 25 cases. I n Stepien's (1962) large series only 4.5 ~ of cases showed i n t r a c r a n i a l calcification. I n the present series only 2 of the 12 cases which presented with increased i n t r a c r a n i a l pressure had s u b c u t a n e o u s nodules. I n the 3 cases coming to autopsy a n d in 8 in w h o m the diagnosis was established by b r a i n biopsy, n o s u b c u t a n e o u s nodules were seen. Of the 6 cases with epilepsy, 4 were diagnosed o n the basis of s u b c u t a n e o u s nodules a n d 1 had i n t r a c r a n i a l a n d soft tissue calcification. One patient presented as a psychiatric p r o b l e m a n d only later developed seizures a n d a s u b c u t a n e o u s nodule. The e x a m i n a t i o n of C S F offers no help in diagnosis. Mild to moderate elevation of the protein c o n t e n t of the C S F is non-specific. The C S F sugar was n o r m a l in all 8 cases. Pleocytosis m a y lead to an erroneous diagnosis of meningitis as in 1 case in this series. The n o r m a l sugar value does n o t distinguish between the 2 since tuberculous meningitis is well k n o w n to exist with pleocytosis a n d n o r m a l sugar (Virmani, R a n g a n a n d Shriniwas 1975). The serological diagnosis of cysticercosis is still at an experimental stage. The h a e m a g g l u t i n a t i o n test is more reliable t h a n the c o m p l e m e n t fixation test ( M a h a j a n a n d C h o p r a 1975). The frequency of false-positive and falsenegative reactions as reported by these authors is too high to be of definitive value.
REFERENCES Adams, J. H. (1976) Parasitic and fungal infections of the nervous system. In: W. Blackwood and J. Corsellis (Eds_), Greenfield's Neuropathology, Edward Arnold, London, p. 277. Arana, R. and A. Asenju (1945) Ventriculographic diagnosis of cysticercosis of the posterior fossa, J. Neurosurg., 2: 181-190. Arseni, C. and A. Cristesca (1972) Epilepsy due to cerebral cysticercosis, Epilepsia (Amst.), 13: 253-258. Arseni, C. and D. C. Samitca (1957) Cysticercosis of the brain, Brit. reed. J., 2: 494-497. Bhaskaran, C. S. (1973) Cerebral cysticercosis as a cause of unnatural deaths, Indian J. reed. Sci., 27 : 545-547. Dinakar, J., K. V. Mathai and J. Chandy (1970) Cysticercosis of the brain, Neurology (Bombay), 18: 165-169. Dixon, H. B. F. and W. H. Hargreaves (1944) Cysticercosis (taenia solium). A further then years clinical study covering 284 cases, Quart. J. Med., 13: 107-121. Dixon, H. B. F. and F. M. Lipscomb (1961) Cysticercosis, an Analysis and Follow-up of 450 Cases, M.R.C. Spec. Rep. Ser. No. 299. MacArthur, W. P. (1934) Cysticercosis as seen in the British Army with special reference to the production of epilepsy, Trans. roy. Soc. trop. Med. Hyg., 27: 343. Mahajan, R. C. and J. S. Chopra (1975) Cysticercosis amongst cases of epilepsy and intracranial space occupying lesions. In: Proc. Nat. Sem_ on Epilepsy, lndia, pp. 95-97. Mani, A. J_, C. K. Ramesh, G. K. Ahuja and K_ S. Mani (1974) Cerebral cysticercosis presenting as epilepsy, Neurology (Bombay), 22: 30-34. Menon, T. B. and G. D. Veliath (1940) Tissue reactions to cysticercus celhdosae in man, Trans. roy. Soc. trop. Med. Hyg., 33: 537-544. Natarajan, M. and D. Balakrishnan (1970) Cysticercosis of the brain, Neurology (Bombay), 18: 171-175. Olive, J. I. and P. Angulo Rivero (1962) Introduction and general aspects. Panel discussion. Cysticercosis of the nervous system, J. Neurosurg_, 19: 632-634. Showramma, A. and D. B. Reddy (1963) Silent cysticereosis of the brain (An analysis of five cases with special reference to histopathology), Indian J. Path. Bact_, 6: 142-147.
374 Singh, A. and S. S. Jolly (1957) Cysticercosis case report, lndtan J_ reed. Sci., I 1 : 98-101. Singh, H., A. Singh and R. Sham (1963) Cerebral cysticercosis, J. Indian Med., 41: 196-199 Steplen, L. (1962) Cerebral cysticercosis m Poland, J. Neuroaurg., 19 : 503 513. Stepien, L. and J. Chorobski (1949) Cysticercosls cerebri and its operative treatment, Arch. NeuroL Psychiat. (Chic.), 61 : 499 527. Tolosa, E. (1954) Cysticercose cer6brale - - aspects climques et possibdites th6rapeutlques, Rev. neurol., 90 : 187-208. VJrmani, V_, G. Rangan and G. Shriniwas (I 975) A study ofcerebrospinal fluid in atypical presentation of tuberculous meningitis, J. neurol. Sci., 26" 587 592. Virmani, V., S. Roy and G. Kamla (1977) Pseudo lateralised epileptiform discharges in a case of diffuse cerebral cysticercosis, Neurop6diatrie, 8: 196-203.
365
C E R E B R A L CYSTICERCOSIS
G. K. AHUJA, S. ROY, G. KAMLA and V. VIRMANI Department of Neurology and Pathology, All India Institute of Medical Sciences, New Delhi-110016 (India)
(Received 3 August, 1977)
SUMMARY Twenty cases of cysticercosis involving the central nervous system were seen during a 6-year period. Twelve patients presented with symptom and signs of raised intracranial pressure, 6 with seizures and 1 each with subacute meningitis and psychosis. The diagnosis of cerebral cysticercosis was established by brain biopsy in 8 patients, at autopsy in 3, and by biopsy of a subcutaneous nodule in 7. It was presumed on the basis of typical intracranial calcification in 1 case and soft tissue calcification in another. The protean clinical manifestations of this condition and the diagnostic difficulties it raises are discussed.
INTRODUCTION Infestation of the central nervous system by cysticerci was mentioned by Paranoli as early as 1550 and by Rumler in 1588 (Olive and Angulo Rivero 1962). This was followed by Virchow's description of racemose cysticercosis of the basal meninges. Evidence that intracranial cysticercosis is causally related to symptoms such as epilepsy is usually indirect, i.e., based on the biopsy of subcutaneous nodules (McArthur 1934; Dixon and Hargreaves 1944; Singh and Jolly 1957; Dixon and Lipscomb 1961; Singh, Singh and Sham 1963; Dinaker, Mathai and Chandy 1970; Mani, Ramesh, Ahuja and Mani 1974) or upon the suggestive neuroradiological features elicited in contrast studies of suspect cases (Arana and Asenju 1945; Natarajan and Balakrishan 1970). Though known to occur in all parts of the world the greatest number of verified cases of cerebral cysticercosis have been reported from Mexico, Central and South America, Spain and Eastern Europe (Stepien and Chorobski 1949; Tolosa 1954; Arseni and Samitca 1957; Stepien 1962; Arseni and Cristesca 1972). From India the largest verified series of intracranial cysticercosis was reported by Dinaker et al. in 1970. Sixteen of their 25 cases were confirmed histopathologically. Showramma and
366 Reddy (1963) and Bhaskaran (1973) reported cases of asymptomatic cerebral cysticercosis in their autopsies of subjects dying of urelated causes. We are reporting here our experience of cysticercosis of the nervous system. MATERIAL AND OBSERVATIONS During the past 6 years (from January 1971 to December 1976), 20 cases of neurocysticercosis presenting in a variety of ways were seen at the AIIMS Hospital, New Delhi. The clinical examination included special attention to the presence or absence of palpable subcutaneous nodules. Investigations included haemogram, erythrocyte sedimentation rate, urinalysis, fasting blood sugar, urea, electrolytes and repeated stool examinations in all of the cases, X-rays of the chest, skull (antero-posterior and lateral views) and soft tissues when indicated, and neuroradiological investigations with contrast media as and when needed.
Fig. 1. Calcified soft tissue cysts.
367 Twelve cases presented with symptoms and signs of increased intracranial pressure. All 12 had papilloedema, 10 had headache and vomiting, 8 had seizures. The visual acuity was diminished in 6. Abducens palsies were seen in 6 cases. An ocular cysticercus was seen in I patient. In addition, 3 exhibited states of altered consciousness. A paralysis of upward gaze was seen in 1 patient. Only 2 patients had palpable subcutaneous nodules. The diagnosis of intracranial cysticercosis was confirmed at autopsy in 2 cases and by biopsy in 8. In the other 2 cases, the diagnosis was based on subcutaneous nodule biopsy. Six cases presented with seizures only. The presumptive diagnosis of cerebral cysticercosis was based upon the findings on subcutaneous nodule biopsy in 4, and on the presence of widespread intracranial and soft tissue calcification in 2 (Fig. 1). One case presented as psychosis and 1 as subacute meningitis. The erythrocyte sedimentation rate (Westergren's method) was moderately elevated in 3 cases and normal in others. A raised total leucocyte count (17,000/m 3) was found in I case with extensive subcutaneous and intramuscular nodules. One case had a total leucocyte count of 14,000/m 3 with an eosinophilia of 30 ~/oo-This was the solitary case which showed eosinophilia. He had presented with seizures and papilloedema. Stool examination did not show proglottids or ova in any case. One patient gave a history of passing tapeworm segments on 2 occasions, 18 years earlier. The cerebrospinal fluid (CSF) was not examined as a routine, as a diagnosis of space-occupying lesion was considered possible in most of the cases. Of the 8 cases where the CSF was
.
o5"-
F~g. 2, Sagittal section of the brain showing cysticerci cysts spread over both cerebral and cerebellar hemispheres, basal ganglia, internal capsule and brain stem.
368 studied, the b i o c h e m i s t r y o f the fluid was n o r m a l m 5, its protein content was elevated in 2 and the globulin was increased in b o t h o f these. One patient presenting as subacute meningitis h a d a m a r k e d pleocytosis in the fluid. Elevated total protein and globulin were f o u n d on several occasions. The sugar content o f the C S F was n o r m a l in all 8 cases. Three cases came to a u t o p s y and 8 were d i a g n o s e d on brain biopsy. A notable feature o f these cases was the absence o f p a l p a b l e subcutaneous nodules.
Fig. 3. (a) Cyst containing viable parasite with practically no inflammatory reaction in the wall. H and E..< 50. (b) High power of (a). H and E 160.
369 CASE HISTORIES
Case 1 A 26-year-old male was admitted for headache and vomiting of 6 months duration and right focal setzures of 4 months duration. For 6 weeks vision had been impaired. Examination revealed gross bilateral papilloedema with markedly reduced visual acuity and bilateral 6th nerve palsies. Ventriculography showed small ventricles without a shift of midline structures. Bilateral subtemporal decompression was carried out. The patient died within 48 hr. On removing the skin flaps at autopsy both the parietal bones were found to be separated from the rest of the skull. Both parietal lobes were herniating and were intensely congested. The brain was oedematous. Multiple pale, greyish-white cystic areas were seen scattered over the brain surface. They varied in size from 2 to 3 m m in diameter. Some contained clear watery fluid. No areas of necrosis were seen. Uncal herniation was present on both sides in the form of well-demarcated grooves. On sectioning many cystic areas of similar size were seen in the cerebral and cerebellar hemispheres, mostly in the grey matter. A few were also seen in the white matter (Fig. 2). A few cysts were also present in the brain stem.
Case 2 An I 1-year-old boy presented with classical features of a subacute meningitis with clouding of consciousness and seizures of focal onset which proved intractable to anti-convulsant therapy. Hm EEG showed periodic lateralised epileptiform discharges. He was treated for suspected tuberculous meningitis but deteriorated and died. Macroscopically the brain was slightly oedematous. There were multiple small translucent cysts spread throughout the entire brain. Some of these contained whitish granules. On sectioning the brain, numerous small cysts measuring 3-6 m m in diameter were seen in all areas including both cerebral and cerebellar hemispheres, basal ganglia, thalami, brain stem and corpus callosum. The meninges showed mild focal thickening in areas overlying the cysts. There was no hydrocephalus. This case has been separately reported (Virmani, Roy and Kamla 1977).
Case 3 A 40-year-old woman who was admitted in coma with a history of headache and vomiting of 12 years duration, worse in the last 6 years, during which time she had developed left focal seizures which tended to become generalised. On examination she was found to have bilateral papilloedema and bilateral extensor plantar responses. She did not improve despite supportive therapy and expired 4 hr after admission. The brain before fixation weighed 1100 g. The external surface was normal. On sectioning, small cysts were seen diffusely distributed throughout both cerebral hemispheres. The cortex was more severely involved than the white matter. The basal ganglia on both sides were spared. These cysts varied in size from 2 to 10 m m in diameter. Their walls were thin and were filled with clear fluid. In the cavity of the cyst pearly-white structures were seen, attached to one side of the cyst wall. A few cysts were also present on the right side of the ports and in both cerebellar hemispheres. The cerebellum, however, was affected less severely than the cerebral hemispheres. The mid-brain and the medulla oblongata were normal. The circle of Willis and the meninges did not reveal any abnormality. The cysts were confirmed to be cysticerci on microscopic examination in all 3 cases.
Microscopic appearances o f cysts in autopsy and brain biopsy material The appearance varied not only from case to case but also in different cysts from t h e s a m e case. T h e cysts c o n t a i n i n g v i a b l e p a r a s i t e s g e n e r a l l y s h o w e d little o r n o inflammatory reaction around them. Occasionally, such cysts were surrounded by a mild to moderate degree of inflammatory reaction consisting mainly of lymphocytes and plasma
cells a d m i x e d
with a few polymorphonuclear
leucocytes and eosinophils
( F i g . 3). O t h e r cysts c o n t a i n e d n e c r o t i c p a r a s i t e s . M a n y s u c h cysts c o n t a i n e d p o l y m o r p h s a n d n e c r o t i c d e b r i s ( F i g . 4). T h e i n f l a m m a t o r y r e a c t i o n a r o u n d s u c h c y s t s w a s g e n e r a l l y v e r y m a r k e d , c o n s i s t i n g m o s t l y o f l y m p h o c y t e s a n d p l a s m a cells a d m i x e d
370
Fig. 4. The cyst containing necrotic parasite with dense inflammatory exudate in the lumen as well as the cyst wall. H and E. ," 50
Fig. 5. Brain tissue adjacent to the cyst showing perivascular infiltratLon with lymphocytes and plasma cells H and E. "-" 160.
with small n u m b e r s o f p o l y m o r p h o n u c l e a r cells, eosmophils, histiocytes a n d multinucleated giant cells. A variable degree o f fibrosis was also seen. There were still o t h e r cysts which a p p e a r e d to be collapsed c o n t a i n i n g either no parasite in the cavity or having hyalinised m a t e r i a l representing hyalinisation o f the d e a d parasite. I n the wall o f such cysts, i n f l a m m a t o r y infiltration was generally m i l d e r b u t the fibrosis a r o u n d t h e m was very m a r k e d . The b r a i n tissue in the i m m e d i a t e vicinity o f cysts c o n t a i n i n g viable parasites showed very little change or a few reactive astrocytes while the tissue a r o u n d necrotic parasites showed a mild to m o d e r a t e degree o f o e d e m a a n d reactive astrocytosis. The pearly-white structures a t t a c h e d to the side o f the cyst wall represent the scolices. H o o k l e t s are clearly seen in some o f the scolices. However, the cysticercus
371
Fig. 6. Brain tissue away from the cyst showing oedema and reactive astrocytic proliferation. H and E_ x 160.
Fig. 7. Section showing inflammatory cellular infiltration of the meninges and reactwe astrocytosls of the molecular layer. H and E. x 160.
o f taenia solium cannot be differentiated from that o f taenia saginata. Calcification is usually seen in the cyst wall but it was at times noted within the cyst containing a necrotic parasite. A few vessels in some cases showed mild perivascular infiltration with lymphocytes and plasma cells (Fig. 5). In some areas with marked inflammatory reaction endarteritis as described by A d a m s (1976) was noted but was not a significant feature. The brain tissue away from the cysts showed varying degrees of oedema and reactive astrocytic proliferation (Fig. 6). In some cases where the cysts were superficially placed under the pia, the leptomeninges showed a mild to moderate inflamm a t o r y reaction consisting of lymphocytes and plasma cells (Fig. 7).
372 DISCUSSION Cerebral cysticercosis has always presented a diagnostic challenge. The presence of subcutaneous nodules and of soft tissue calcification does not always imply intracranial cysticercosis nor does the absence of subcutaneous nodules exclude the possibility of such a diagnosis. Cerebral cysticercosis may be entirely asymptomatic, being a chance finding at autopsy (Showramma and Reddy 1963; Bhaskaran 1973). The viable cysts produce very little reaction in the surrouding tissues (Menon and Veliath 1940; Showramma and Reddy 1963) and consequently few symptoms; it is the dead or dying parasites which produce marked tissue changes and give rise to symptoms. This was evident in both the autopsy and biopsy material of the present series. In cases of epilepsy the role of cysticercosis is difficult to assess. The condition may never have been thought of in the absence of subcutaneous nodules. When the latter are present in patients with epilepsy, the causative relationship may be difficult to establish without confirmation of the presence of intracranial cysticercosis. A definitive diagnosis can only be made during craniotomy which is seldom performed for conditions such as headache and epilepsy. Even when symptoms are severe enough to warrant an intracranial exploration, the site of involvement may be missed by a localised biopsy if the lesions are not diffuse. Ventriculography may be normal. When filling defects are seen, they may provide supportive but not confirmatory evidence. The high prevalence of cysticercosis in the developing countries is due to poor socio-economic conditions and hygienic habits. If man ingests inadequately cooked ('measly') pork containing the cysticerci of taenia solium he will develop the adult tapeworm (not cysticercosis). Man is the only definitive host of this parasite. Cysticercosis develops when man consumes tapeworm ova. The ova are usually ingested on unwashed, faecally contaminated vegetables. Antiperistaltic regurgitation of gravid proglottids is a theoretical method of contamination, the frequency of which is impossible to assess. Ova may also be carried from anus to mouth through bad hygienic habits. The paucity of cases of human cysticercosis found to be harbouring the adult tapeworm is, however, noteworthy. Whatever the mode of infestation the shell of the egg is digested with the liberation of the larval forms, which burrow into the stomach wall and enter the circulation from whence they are disseminated into the tissues including the central nervous system. The clinical presentation of neurocysticercosis depends on the size, site and number of parasites and on the tissue reaction to the infestation. Cerebral cysticercosis can mimic many psychiatrical and neurological conditions. Patients may present with features of idiopathic raised intracranial tension of acute or subacute onset, as intracranial space-occupying lesions, as focal neurological deficits, or with epilepsy, headache, subacute meningitis, acute or subacute encephaJopathy, obstructive hydrocephalus, or personality or behavioural disorders. Minor or even extensive involvement of the brain with cysts may remain clinically silent, as reported by Showramma and Reddy (1963) and Bhaskaran (1973). Allergic reaction to the cysts may be responsible for the varying degrees of white matter oedema. In the absence of subcutaneous nodules, the suspicion of cysticercosis may not be entertained.
373 D i n a k a r et al. (1970) f o u n d s u b c u t a n e o u s cystic nodules in 7 of their 25 cases. I n Stepien's (1962) large series only 4.5 ~ of cases showed i n t r a c r a n i a l calcification. I n the present series only 2 of the 12 cases which presented with increased i n t r a c r a n i a l pressure had s u b c u t a n e o u s nodules. I n the 3 cases coming to autopsy a n d in 8 in w h o m the diagnosis was established by b r a i n biopsy, n o s u b c u t a n e o u s nodules were seen. Of the 6 cases with epilepsy, 4 were diagnosed o n the basis of s u b c u t a n e o u s nodules a n d 1 had i n t r a c r a n i a l a n d soft tissue calcification. One patient presented as a psychiatric p r o b l e m a n d only later developed seizures a n d a s u b c u t a n e o u s nodule. The e x a m i n a t i o n of C S F offers no help in diagnosis. Mild to moderate elevation of the protein c o n t e n t of the C S F is non-specific. The C S F sugar was n o r m a l in all 8 cases. Pleocytosis m a y lead to an erroneous diagnosis of meningitis as in 1 case in this series. The n o r m a l sugar value does n o t distinguish between the 2 since tuberculous meningitis is well k n o w n to exist with pleocytosis a n d n o r m a l sugar (Virmani, R a n g a n a n d Shriniwas 1975). The serological diagnosis of cysticercosis is still at an experimental stage. The h a e m a g g l u t i n a t i o n test is more reliable t h a n the c o m p l e m e n t fixation test ( M a h a j a n a n d C h o p r a 1975). The frequency of false-positive and falsenegative reactions as reported by these authors is too high to be of definitive value.
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