**1. Introduction**

#### **1.1. Background**

Neurocysticercosis (NCC) is a preventable and potentially eradicable neurological disease caused by the larva form of tapeworm *Taenia solium* which primarily affects people living in the developing world. Seizures are widely reported to be the most common symptom, occurring in 70–90% of patients [1]. Most patients respond to praziquantel, if cystic lesions are located in the parenchymal tissue, and albendazole when parasites are located in the ventricular system and subarachnoid space, including patients with an associated HIV infection [2]. A well-designed clinical trial about treatment response in subarachnoid neurocysticercosis (SNCC) has not been published; however, some authors have reported the effectiveness of these drugs in SNCC [3–5], while others have found that parasites remain alive at the subarachnoid space even after high dose of albendazole/praziquantel/prednisone was administered [6–10].

Several case reports about cerebral infarction related to cysticercosis have been published,

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In our region, there are other infectious diseases causing infective vasculitis leading to ischaemic stroke such as HIV/AIDS, tuberculosis, INCC and neurosyphilis, but Chagas disease, malaria, haemorrhagic fever, infective endocarditis and mucormycosis are also reported in

In 2001, Rocha et al. [30] reported three cases of stroke secondary to NCC. The first one was a 36-year-old man with bilateral middle cerebral artery occlusions presenting an acute right hemiparesis and expressive aphasia. MRI demonstrated several enhancing subarachnoid cysts surrounding the occluded vessels, a right parietal racemose cyst and a left temporal large infarction area. Angiographic study showed total occlusion of left middle cerebral artery and a subtotal occlusion of right middle cerebral artery. The second one was a 42-year-old man with vasculitis of small cortical vessels presenting headache, seizures and focal neurological deficit. CT scan demonstrated several calcifications and a left temporal infarct. Cerebral angiographic study was normal. The third case was a woman, 53 years old, with a past history of six stroke events, behaviour disturbance and seizures. MRI scan demonstrated several cortical and sub-cortical infarcts and cisternal cystic lesions, and angiographic study showed diffuse arteritis of basilar and carotid arterial system. In all three cases, CSF study

Aditya et al. [31] in 2004 reported two autopsied cases of chronic cysticercal basal arachnoiditis causing large arterial territory infarcts and, in the second case, a hypothalamic mass. Both patients were diagnosed and managed, clinically and by neuroimaging, as stroke and neurotuberculosis, respectively. The diagnosis was established only at autopsy, which revealed NCC causing basal arachnoiditis, major vessel vasculitis and infarcts. Histologically, one case showed degenerating racemose cysticercal cyst within the thick basal exudates. In the second case, remnants of the degenerated cysticercal cyst in the form of hooklets and calcareous corpuscles were identified within the giant cell inciting a granulomatous response to form a hypothalamic mass lesion mimicking tuberculoma. They highlighted the importance of considering the non-tuberculous aetiology of chronic basal arachnoiditis like SNCC before initi-

ating therapy, especially in countries where both NCC and tuberculosis are endemic.

study is to explore these inquiries and propose new hypotheses for future study.

Conspicuously absent in the case reports available in the current medical literature are the following research questions: What is the prevalence of SNCC in patients living with neurocysticercosis (PLWNCC)? Is SNCC a risk factor for ischaemic stroke? Does HIV comorbidity increases the stroke frequency in epileptic patients infected with NCC? The main aim of this

We performed a non-published cross-sectional study of epileptic patients diagnosed with NCC from January 1999 to December 2003 at Umtata General Hospital and from January 2004 to January 2010 at Nelson Mandela Academic Hospital from the rural areas of Mthatha, South Africa. Selected patients for a case–control study under the project: 'Neurocysticercosis' were

showed linfomonocitic pleocytosis and positive ELISA for cysticercosis.

including angiographic abnormalities [21–27].

the medical literature [28, 29].

**1.2. Our study**

taken for this research.

In 1977, Gubbay and Matz [11] reported two cases presenting with intracranial hypertension (ICH) and hydrocephalus in association with chronic meningitis; the authors confirmed that repeated CSF analysis may result in diagnostic confirmation of SNCC causing ICH with hemiparesis, partial seizures, and other neurological signs. Currently, it is well known that SNCC in the basal cisterns may cause inflammatory reaction; the leptomeninges become fibrotic at the base of the brain.

According to Takayanagui and Odashima [12], in approximately 60% of the cases, there is an obstruction of the CSF circulation, resulting in hydrocephalus and raised intracranial pressure. When hydrocephalus secondary to cysticercoid meningitis is present, the mortality rate is high (50%) and most patients die within 2 years after CSF shunting; therefore, ventricular and basal cisternal locations are considered to be malignant forms of NCC. In 2001, Bannur and Rajshekhar [13] reported a case as an example of difficulty in confirming diagnosis: this patient had a hypodense non-enhancing mass on CT scan in the regions of quadrigeminal cistern causing obstructive hydrocephalus. He was initially diagnosed with an epidermoid mass but subsequent MRI evaluation and surgery resulted in the diagnosis of a racemose cysticercus cyst. Authors concluded that clinical features of NCC largely depend on the number, type, size, localisation and stage of development of cysticerci, as well as on the host immune response against the parasite [13].

Typical of South Africa, high incidence and prevalence of NCC is found at the former Transkei, currently region C and D of Eastern Cape Province, which is the most disadvantaged region countrywide [14–18].

Many people in the world who suffer a fatal stroke live in developing countries where NCC is endemic. However, prevalence of several tropical diseases, including NCC, is likely to increase in Western, industrialised nations as a result of demographic changes due to migratory flows. It is very well known that stroke is the third most cause of death and the principal cause of adult disability worldwide. Cerebrovascular complications of NCC include transient ischaemic attacks, ischaemic strokes due to infective vasculitis and intraparenchymal haemorrhage [19, 20].

Several case reports about cerebral infarction related to cysticercosis have been published, including angiographic abnormalities [21–27].

In our region, there are other infectious diseases causing infective vasculitis leading to ischaemic stroke such as HIV/AIDS, tuberculosis, INCC and neurosyphilis, but Chagas disease, malaria, haemorrhagic fever, infective endocarditis and mucormycosis are also reported in the medical literature [28, 29].

In 2001, Rocha et al. [30] reported three cases of stroke secondary to NCC. The first one was a 36-year-old man with bilateral middle cerebral artery occlusions presenting an acute right hemiparesis and expressive aphasia. MRI demonstrated several enhancing subarachnoid cysts surrounding the occluded vessels, a right parietal racemose cyst and a left temporal large infarction area. Angiographic study showed total occlusion of left middle cerebral artery and a subtotal occlusion of right middle cerebral artery. The second one was a 42-year-old man with vasculitis of small cortical vessels presenting headache, seizures and focal neurological deficit. CT scan demonstrated several calcifications and a left temporal infarct. Cerebral angiographic study was normal. The third case was a woman, 53 years old, with a past history of six stroke events, behaviour disturbance and seizures. MRI scan demonstrated several cortical and sub-cortical infarcts and cisternal cystic lesions, and angiographic study showed diffuse arteritis of basilar and carotid arterial system. In all three cases, CSF study showed linfomonocitic pleocytosis and positive ELISA for cysticercosis.

Aditya et al. [31] in 2004 reported two autopsied cases of chronic cysticercal basal arachnoiditis causing large arterial territory infarcts and, in the second case, a hypothalamic mass. Both patients were diagnosed and managed, clinically and by neuroimaging, as stroke and neurotuberculosis, respectively. The diagnosis was established only at autopsy, which revealed NCC causing basal arachnoiditis, major vessel vasculitis and infarcts. Histologically, one case showed degenerating racemose cysticercal cyst within the thick basal exudates. In the second case, remnants of the degenerated cysticercal cyst in the form of hooklets and calcareous corpuscles were identified within the giant cell inciting a granulomatous response to form a hypothalamic mass lesion mimicking tuberculoma. They highlighted the importance of considering the non-tuberculous aetiology of chronic basal arachnoiditis like SNCC before initiating therapy, especially in countries where both NCC and tuberculosis are endemic.

Conspicuously absent in the case reports available in the current medical literature are the following research questions: What is the prevalence of SNCC in patients living with neurocysticercosis (PLWNCC)? Is SNCC a risk factor for ischaemic stroke? Does HIV comorbidity increases the stroke frequency in epileptic patients infected with NCC? The main aim of this study is to explore these inquiries and propose new hypotheses for future study.

#### **1.2. Our study**

**1. Introduction**

154 Seizures

**1.1. Background**

tered [6–10].

fibrotic at the base of the brain.

response against the parasite [13].

countrywide [14–18].

rhage [19, 20].

Neurocysticercosis (NCC) is a preventable and potentially eradicable neurological disease caused by the larva form of tapeworm *Taenia solium* which primarily affects people living in the developing world. Seizures are widely reported to be the most common symptom, occurring in 70–90% of patients [1]. Most patients respond to praziquantel, if cystic lesions are located in the parenchymal tissue, and albendazole when parasites are located in the ventricular system and subarachnoid space, including patients with an associated HIV infection [2]. A well-designed clinical trial about treatment response in subarachnoid neurocysticercosis (SNCC) has not been published; however, some authors have reported the effectiveness of these drugs in SNCC [3–5], while others have found that parasites remain alive at the subarachnoid space even after high dose of albendazole/praziquantel/prednisone was adminis-

In 1977, Gubbay and Matz [11] reported two cases presenting with intracranial hypertension (ICH) and hydrocephalus in association with chronic meningitis; the authors confirmed that repeated CSF analysis may result in diagnostic confirmation of SNCC causing ICH with hemiparesis, partial seizures, and other neurological signs. Currently, it is well known that SNCC in the basal cisterns may cause inflammatory reaction; the leptomeninges become

According to Takayanagui and Odashima [12], in approximately 60% of the cases, there is an obstruction of the CSF circulation, resulting in hydrocephalus and raised intracranial pressure. When hydrocephalus secondary to cysticercoid meningitis is present, the mortality rate is high (50%) and most patients die within 2 years after CSF shunting; therefore, ventricular and basal cisternal locations are considered to be malignant forms of NCC. In 2001, Bannur and Rajshekhar [13] reported a case as an example of difficulty in confirming diagnosis: this patient had a hypodense non-enhancing mass on CT scan in the regions of quadrigeminal cistern causing obstructive hydrocephalus. He was initially diagnosed with an epidermoid mass but subsequent MRI evaluation and surgery resulted in the diagnosis of a racemose cysticercus cyst. Authors concluded that clinical features of NCC largely depend on the number, type, size, localisation and stage of development of cysticerci, as well as on the host immune

Typical of South Africa, high incidence and prevalence of NCC is found at the former Transkei, currently region C and D of Eastern Cape Province, which is the most disadvantaged region

Many people in the world who suffer a fatal stroke live in developing countries where NCC is endemic. However, prevalence of several tropical diseases, including NCC, is likely to increase in Western, industrialised nations as a result of demographic changes due to migratory flows. It is very well known that stroke is the third most cause of death and the principal cause of adult disability worldwide. Cerebrovascular complications of NCC include transient ischaemic attacks, ischaemic strokes due to infective vasculitis and intraparenchymal haemor-

We performed a non-published cross-sectional study of epileptic patients diagnosed with NCC from January 1999 to December 2003 at Umtata General Hospital and from January 2004 to January 2010 at Nelson Mandela Academic Hospital from the rural areas of Mthatha, South Africa. Selected patients for a case–control study under the project: 'Neurocysticercosis' were taken for this research.

All patients were classified into one of the three respective sample groups according to presence and type of NCC or not, collected in groups A, B and C. All patients from Group A met the following selection criteria (inclusion criteria): a positive serology ELISA test for cysticercosis, CT scan of the brain with intravenous contrast enhancement consistent with definitive evidence of cystic lesion (isolate or racemose) in the subarachnoid space without hydrocephalus and suitable to evaluate: (1) focal arachnoiditis when there was contrast enhancement in only one cerebral basal cistern; (2) bilateral cystic lesions with diffuse arachnoiditis, in which contrast enhancement involved several basal cisterns; and (3) ischaemic infarction, in which the number and location of cerebral lesions were analysed and classified as superficial, deep no lacunar (>16 mm), and deep lacunar (<15 mm) at the basal ganglia, without an associated cardiac disease. Demographic and associated stroke were analysed in accordance with the presence of SNCC, and ELISA test for HIV when it was done.

right to intimacy, anonymity, confidentiality, withdrawal and information. Due to the large proportion of low literacy among the patient population, oral consent was observed and confirmed by an impartial witness in many cases where necessary. For patients selected between

Subarachnoid Cysticercosis and Ischaemic Stroke in Epileptic Patients

http://dx.doi.org/10.5772/intechopen.70697

157

All investigators completed CITI training course on the protection of human research. All are sworn to the Hippocratic Oath and committed to respecting the norms of good clinical prac-

Methods for patient selection and information processing were approved by clinical governance at Umtata General Hospital, and the research protocol was evaluated and approved by Mthatha Umtata General Hospital, University of Transkei and Walter Sisulu University IRB and the respective Ethical Committees (UGH:0001/99, UNITRA:0018/05 and WSU:0068/009). Out of 459 eligible epileptic patients asked to participate, five initially refused to participate for the baseline evaluation. Four out of the five patients agreed to participate during their

The proportion of SNCC without hydrocephalus in PLWNCC (Groups A and B) was 4.77%. Group A (n = 144) and B (n = 153) showed no remarkable differences between age, gender and HIV status. The control group C (n = 161) consisted of 35.1-year-old-mean age (SD 15.4), 43.5% were males (n = 70) and 56.5% were female (n = 91) and the frequency of HIV positive

In total, 243 serial CT scans with at least one scan (range = 1–2) per subject were available in Group A, 201 CT scans in Group B and 162 CT scans in Group C, over the 10-year study period. **Table 2** shows the frequencies of ischaemic stroke events in SNCC and INCC (Groups A and B)

**Table 2** shows the frequency and odds ratio of IS events in each NCC group (as previously discussed) now stratified by HIV seropositive status. HIV-positive patients in Groups A and B had greater odds of IS compared to the HIV-positive patients without NCC co-infection as expected. However, the increased odds were more pronounced in those HIV patients with SNCC (OR: 2.66, 95% CI). The risk of IS in HIV-negative patients followed similar trend with the greatest odds occurring in SNCC group patients comparatively. The risk of developing stroke was 2.82 times more probable in Group A compared with Group B. (**Table 2** and **Figure 1**). This suggests that although co-infection with HIV increases risk of IS, the location of NCC in the brain is a

**Mean (SD) Male Female + − Unknown**

A (144) 38.2 (16.9) 52.1 47.9 13.9 31.2 54.9 B (153) 36.9 (15.3) 47.7 52.3 15.7 28.8 55.6 C (161) 35.1 (15.4) 43.5 56.5 11.2 28.0 60.9

1999 and 2002 only oral consent was taken.

tice, as well as the requirements of the Helsinki Declaration.

follow-up appointment and their data are included here.

(stage I–II, 11.2%) almost similar to Groups A and B (**Table 1**).

**Groups Age Gender (%) HIV (%)**

**Table 1.** Patient characteristics by sample group.

and the reference sample (Group C) without considering HIV status.

From the large number of epileptic patients with NCC-HIV co-infection in our database, we selected only a few number of epileptic cases for Group B similar to Group A, regarding age and gender to assure a better statistical analysis and under an absolute diagnosis of intraparenchymal NCC (both active and calcified at the same time) with or without ischaemic stroke. The ELISA test for NCC and HIV were both positive. Patients in Group C had no NCC in any presentation and, ELISA test for NCC was negative and HIV test was positive.

Exclusion criteria: All patients with gross modifiable risk factors for stroke such as uncontrolled hypertension and diabetes mellitus, heavy drinkers or smokers, familial hyperlipidaemia, thrombophilia, bleeding disorders and other haematological disorders were excluded. We also excluded patients with heart problems, diagnosis of infective vasculitis apart from those associated with NCC/HIV, suspicion of primary or secondary arterial disease, cognitive or sensory deterioration, patients who have not had check-ups for their NCC/SNCC and stroke for more than 11 months, patients with intraventricular NCC and/or associated hydrocephalus; patients with terminal illnesses, serious psychological illnesses, active addictions to psychoactive substances; patients younger than 13 years old; pregnant patients; patients living with HIV/AIDS in stage IV, patients who have lived more than 6 months outside of our region, the 'first or worst' headache, headaches with increasing frequency or severity, progressive headache, chronic daily headache, headaches always on the same side, headache not responding to treatment, new-onset headaches in patients who have cancer or who were tested positive for HIV infection and new-onset headaches after age 45.

All statistical analyses were conducted using Statistical Package for the Social Sciences (SPSS) version 16.0 for Windows (SPSS Inc., Chicago, Ill). Analyses were performed using an intention to treat bias. A descriptive analysis and an analysis of baseline comparability between the study groups were performed for all study variables. The main variables are INCC, SNCC, IS and headache. All patients were epileptic and HIV reactive. To investigate the potential associations between ischaemic stroke outcomes and the variables of NCC group type and HIV status, prevalence odds ratio and 95% confidence intervals were calculated.

Written consent forms were administered in the first contact with the eligible patients following verbal agreement for participation. For all patients, information on the study's purpose and procedures was provided in addition to ethical considerations, including the participant's right to intimacy, anonymity, confidentiality, withdrawal and information. Due to the large proportion of low literacy among the patient population, oral consent was observed and confirmed by an impartial witness in many cases where necessary. For patients selected between 1999 and 2002 only oral consent was taken.

All investigators completed CITI training course on the protection of human research. All are sworn to the Hippocratic Oath and committed to respecting the norms of good clinical practice, as well as the requirements of the Helsinki Declaration.

Methods for patient selection and information processing were approved by clinical governance at Umtata General Hospital, and the research protocol was evaluated and approved by Mthatha Umtata General Hospital, University of Transkei and Walter Sisulu University IRB and the respective Ethical Committees (UGH:0001/99, UNITRA:0018/05 and WSU:0068/009).

Out of 459 eligible epileptic patients asked to participate, five initially refused to participate for the baseline evaluation. Four out of the five patients agreed to participate during their follow-up appointment and their data are included here.

The proportion of SNCC without hydrocephalus in PLWNCC (Groups A and B) was 4.77%.

Group A (n = 144) and B (n = 153) showed no remarkable differences between age, gender and HIV status. The control group C (n = 161) consisted of 35.1-year-old-mean age (SD 15.4), 43.5% were males (n = 70) and 56.5% were female (n = 91) and the frequency of HIV positive (stage I–II, 11.2%) almost similar to Groups A and B (**Table 1**).

In total, 243 serial CT scans with at least one scan (range = 1–2) per subject were available in Group A, 201 CT scans in Group B and 162 CT scans in Group C, over the 10-year study period.

**Table 2** shows the frequencies of ischaemic stroke events in SNCC and INCC (Groups A and B) and the reference sample (Group C) without considering HIV status.

**Table 2** shows the frequency and odds ratio of IS events in each NCC group (as previously discussed) now stratified by HIV seropositive status. HIV-positive patients in Groups A and B had greater odds of IS compared to the HIV-positive patients without NCC co-infection as expected. However, the increased odds were more pronounced in those HIV patients with SNCC (OR: 2.66, 95% CI). The risk of IS in HIV-negative patients followed similar trend with the greatest odds occurring in SNCC group patients comparatively. The risk of developing stroke was 2.82 times more probable in Group A compared with Group B. (**Table 2** and **Figure 1**). This suggests that although co-infection with HIV increases risk of IS, the location of NCC in the brain is a


**Table 1.** Patient characteristics by sample group.

All patients were classified into one of the three respective sample groups according to presence and type of NCC or not, collected in groups A, B and C. All patients from Group A met the following selection criteria (inclusion criteria): a positive serology ELISA test for cysticercosis, CT scan of the brain with intravenous contrast enhancement consistent with definitive evidence of cystic lesion (isolate or racemose) in the subarachnoid space without hydrocephalus and suitable to evaluate: (1) focal arachnoiditis when there was contrast enhancement in only one cerebral basal cistern; (2) bilateral cystic lesions with diffuse arachnoiditis, in which contrast enhancement involved several basal cisterns; and (3) ischaemic infarction, in which the number and location of cerebral lesions were analysed and classified as superficial, deep no lacunar (>16 mm), and deep lacunar (<15 mm) at the basal ganglia, without an associated cardiac disease. Demographic and associated stroke were analysed in accordance with the

From the large number of epileptic patients with NCC-HIV co-infection in our database, we selected only a few number of epileptic cases for Group B similar to Group A, regarding age and gender to assure a better statistical analysis and under an absolute diagnosis of intraparenchymal NCC (both active and calcified at the same time) with or without ischaemic stroke. The ELISA test for NCC and HIV were both positive. Patients in Group C had no NCC in any

Exclusion criteria: All patients with gross modifiable risk factors for stroke such as uncontrolled hypertension and diabetes mellitus, heavy drinkers or smokers, familial hyperlipidaemia, thrombophilia, bleeding disorders and other haematological disorders were excluded. We also excluded patients with heart problems, diagnosis of infective vasculitis apart from those associated with NCC/HIV, suspicion of primary or secondary arterial disease, cognitive or sensory deterioration, patients who have not had check-ups for their NCC/SNCC and stroke for more than 11 months, patients with intraventricular NCC and/or associated hydrocephalus; patients with terminal illnesses, serious psychological illnesses, active addictions to psychoactive substances; patients younger than 13 years old; pregnant patients; patients living with HIV/AIDS in stage IV, patients who have lived more than 6 months outside of our region, the 'first or worst' headache, headaches with increasing frequency or severity, progressive headache, chronic daily headache, headaches always on the same side, headache not responding to treatment, new-onset headaches in patients who have cancer or who were

All statistical analyses were conducted using Statistical Package for the Social Sciences (SPSS) version 16.0 for Windows (SPSS Inc., Chicago, Ill). Analyses were performed using an intention to treat bias. A descriptive analysis and an analysis of baseline comparability between the study groups were performed for all study variables. The main variables are INCC, SNCC, IS and headache. All patients were epileptic and HIV reactive. To investigate the potential associations between ischaemic stroke outcomes and the variables of NCC group type and HIV

Written consent forms were administered in the first contact with the eligible patients following verbal agreement for participation. For all patients, information on the study's purpose and procedures was provided in addition to ethical considerations, including the participant's

presentation and, ELISA test for NCC was negative and HIV test was positive.

tested positive for HIV infection and new-onset headaches after age 45.

status, prevalence odds ratio and 95% confidence intervals were calculated.

presence of SNCC, and ELISA test for HIV when it was done.

156 Seizures


**Table 2.** Frequency of stroke by groups.

better predictor of IS risk than comorbidity status. This is also evident in a similar difference in odds ratio for HIV- compared HIV+ were exhibited in Groups A and B. These results also suggest that the interactive effect of co-infection is generalised and do not vary significantly for one type of NCC.

Taking into consideration the HIV status of patients by groups, we found that 40% of patients presented ischaemic stroke (Group A) and the risk to develop an IS among Groups A and B is almost three times more.

After comparing all three groups with similar age, gender and HIV-positive status, the risk of developing an IS increases to more than seven times in patients presenting SNCC over the control group and almost four times in patients presenting intraparenchymal NCC, as shown in **Table 4**.

Concurrent infection with *T. solium* and HIV was expected to occur more frequently because of the increasing frequency of HIV infection in endemic areas of cysticercosis like our region. However, little is known about the influence of HIV infection on the frequency and the clinical course of cysticercosis. Delobel et al. [32] established that giant cysts and racemose forms of neurocysticercosis seem to be more frequent in HIV-infected patients and may be secondary to an uncontrolled parasitic growth because of an impaired cell-mediated immune response.

**(95% CI)**

**A vs. B**

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**HIV status Groups Stroke (%) OR**

B 11.4 (n = 139) C 6.7 (n = 157)

**Table 3.** Proportion of patients with IS events by groups and HIV status.

A vs. C 7.46 2.51 22.1 A vs. B 1.88 1.33 3.82 B vs. C 3.95 1.27 12.2

− A 20.0 (n = 121)

**Groups OR IC 95%**

**Table 4.** Odds ratio after comparing different groups.

+ A 40.0 (n = 20) 2.66 (n = 23) 2.82 B 25.0 (n = 24) 2.60 (n = 14) C 5.6 (n = 18) 0.82 (n = 4)

Prevalence on SNCC in patients LWNCC is not as higher as we expected but can represent the frequency of this problem, while the prevalence of HIV is increasing in countries where NCC is also endemic. Therefore, sooner or later SNCC will be highest, if adequate measures are not taken to eradicate NCC at due time. Other co-infection rates are expected to raise it but unfortunately no systematic reviews of the subject are available in the medical literature.

In spite of the variety of ways used by the parasite to modify host immune response, their mechanism of excretory/secretory product fail and its anti-immune properties are weaker, paradoxically these pathologic changes on the parasite membrane and the surrounding tissue (without remarkable oedema) can be seen in HIV patients with CD4 count around 350 cells/

 and viral load around 55,000 copies/ml or even in window period. Therefore, we have had hypothesised that at the colloid stage, there is an increased microglial activation, associated oligodendrocyte, astroglial changes and subsequent damage of the axonal functions and blood–brain barrier, which can explain the well-known mechanism of *pathological concentration of macrophage histocompatibility complex, interleukin-1 and -6 and tumour necrosis factor-alpha* 

mm3

**Figure 1.** Shows prevalence of stroke by groups and HIV status. *Source*: **Table 3**.


**Table 3.** Proportion of patients with IS events by groups and HIV status.


**Table 4.** Odds ratio after comparing different groups.

better predictor of IS risk than comorbidity status. This is also evident in a similar difference in odds ratio for HIV- compared HIV+ were exhibited in Groups A and B. These results also suggest that the interactive effect of co-infection is generalised and do not vary significantly for

Taking into consideration the HIV status of patients by groups, we found that 40% of patients presented ischaemic stroke (Group A) and the risk to develop an IS among Groups A and B is

After comparing all three groups with similar age, gender and HIV-positive status, the risk of developing an IS increases to more than seven times in patients presenting SNCC over the control group and almost four times in patients presenting intraparenchymal NCC, as shown in **Table 4**.

one type of NCC.

158 Seizures

almost three times more.

**Table 2.** Frequency of stroke by groups.

**Groups Stroke Total**

A 23(15.97%) 121(84.02%) 144 B 14(9.15%) 139(90.84%) 153 C 4(2.48%) 157(97.51%) 161

**Figure 1.** Shows prevalence of stroke by groups and HIV status. *Source*: **Table 3**.

**Yes No**

Concurrent infection with *T. solium* and HIV was expected to occur more frequently because of the increasing frequency of HIV infection in endemic areas of cysticercosis like our region. However, little is known about the influence of HIV infection on the frequency and the clinical course of cysticercosis. Delobel et al. [32] established that giant cysts and racemose forms of neurocysticercosis seem to be more frequent in HIV-infected patients and may be secondary to an uncontrolled parasitic growth because of an impaired cell-mediated immune response.

Prevalence on SNCC in patients LWNCC is not as higher as we expected but can represent the frequency of this problem, while the prevalence of HIV is increasing in countries where NCC is also endemic. Therefore, sooner or later SNCC will be highest, if adequate measures are not taken to eradicate NCC at due time. Other co-infection rates are expected to raise it but unfortunately no systematic reviews of the subject are available in the medical literature.

In spite of the variety of ways used by the parasite to modify host immune response, their mechanism of excretory/secretory product fail and its anti-immune properties are weaker, paradoxically these pathologic changes on the parasite membrane and the surrounding tissue (without remarkable oedema) can be seen in HIV patients with CD4 count around 350 cells/ mm3 and viral load around 55,000 copies/ml or even in window period. Therefore, we have had hypothesised that at the colloid stage, there is an increased microglial activation, associated oligodendrocyte, astroglial changes and subsequent damage of the axonal functions and blood–brain barrier, which can explain the well-known mechanism of *pathological concentration of macrophage histocompatibility complex, interleukin-1 and -6 and tumour necrosis factor-alpha*  *among other neurotoxins causing neurovascular lesions, accompanied by increased concentration of pro-inflammatory molecules from meningeal macrophages, choroids plexus macrophages, perivascular macrophages, multinucleated giant cells, according to the number and location of the cysticercus as previously described* [33]*. At the present moment, we believe that toxins released by the T. solium cysticercus cause inflammatory changes on the perforating arteries (toxic vasculitis?) at the subarachnoid space rather than a direct effect on the cluster of parasites (mechanical compression). However, the differential of infective vasculitis should be preserved because pathological source is the presence of intracranial cysticercosis.*

**2. Racemose neurocysticercosis**

mass effect in cases of very large cysts [44, 45].

mas, cavernous malformations and echinococcal cysts.

at the subarachnoid space.

SNCC.

Racemose neurocysticercosis (RC) also known as SNCC refers to a very uncommon form of NCC, with the cyst localised mainly in the subarachnoid space and basal cisterns. Usually, the scolex is absent and multiple complex small cysts may form (cluster of grapes), filling the basal cisterns, determining mass effect and distortion of adjacent structures, namely sulci, brainstem and cranial nerves [43–45], these authors consider that in racemose NCC, there is a presence of abnormally large growths of many cystic membranes without a scolex, normally without enhancement, in subarachnoid space and basal cisterns and they found on imagenology that the cysts have a thin wall without a scolex; their signal is isointense or slightly different from CSF, hypointense on T1-weighted images (T1-WIs) and fluid-attenuated inversion recovery (FLAIR), hyperintense on T2-WI, without diffusion restriction, and after contrast there is no wall enhancement. A three-dimensional balanced steady-state free precession sequence (constructive interference in steady state (CISS)), driven equilibrium (DRIVE) or contrast-enhanced MR cisternography helps to detect the underlying cysts [46]. Pamplona et al. [46] reported a case of a *43-year-old woman from Cabo Verde, with an eight-month history of right frontotemporal headaches (without releasing or aggravating factors), ataxia and loss of vision, without significant past medical history of note and no history of head trauma. Home hospital computed tomography (CT) disclosed a large intraventricular cyst, without enhancement after ionic contrast administration, distorting lateral and third ventricles, with obliterations of Monro foramina, determining non-communicating hydrocephalus, with enlargement of occipital and temporal horns of lateral ventricles and ependimary transudation.* They established that *racemose neurocysticercosis (INCC) refers to cysts in the subarachnoid space and is characterised by proliferative lobulated cysts without a scolex.* We also agree with such definition if the presence of scolex is not excluded from the definition, as discussed later. These cysts may vary in size, from 2 to 3 mm in subarachnoid space and basal cisterns, to a few centimetres when intraventricular. Intracranial hypertension and hydrocephalus are two complications that happen when there is a flow obstruction due to intraventricular cysts, arachnoiditis, ependymitis secondary to inflammatory response or

Subarachnoid Cysticercosis and Ischaemic Stroke in Epileptic Patients

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It is known that in the next several months to years, there is degeneration of the cyst, with associated inflammatory response and peripheral oedema, leading to clinical symptoms and manifestations that may vary according to localisation and mass effect [43–45]. The final stage (calcified) with or without associated oedema is seen in the intraparenchymal presentation and is the main cause of epilepsy in this series; obviously, associated oedema never happens

The differential diagnosis depends on where the cysts are localised; if in the subarachnoid space and basal cysterns, the differential diagnoses are arachnoid cysts, neuroglial cysts, glio-

Detection of cysticercal antigens by monoclonal antibody-based enzyme-linked immunosorbent assay (ELISA) in the CSF of clinically suspected patients supports the diagnosis of active

In our series, we did not identify any case presenting immune reconstitution inflammatory syndrome, probably because we selected patients from stage I to III of AIDS not on HAART. It is interesting to know that in the brain of patients with ischaemic stroke-associated deaths, there are abundant CD3+, CD8+ and CD68+ cells in the postmortem autopsy [34]. In our study, only one patient died from Group A. We believe that low mortality rate may be related to the exclusion of patients with subarachnoid cysticercosis growing to giant size causing mass effect and obstructive hydrocephalus with mechanical compression, as already discussed [33]. The disease course in SNCC is often long in duration and cysticerci continue to grow and proliferate through tissue. This increase in volume and mechanical resistance from the brain parenchymal may cause osmotic exchange with the CSF and this one factor that may lead to a poor prognosis [35]. Obviously, selecting patients before this stage can help to investigate the effect of the SNCC on the blood vessels without an effect of associated mechanical compression.

Evidence of carotid occlusion in cysticercosis [23, 36, 37], transient ischaemic attack of the vertebrobasilar territory [38] even in children [39] has been reported as anecdotic cases.

The most common affected vascular territory in our series was middle cerebral artery followed by posterior cerebral artery. We did not confirm any patients with SNCC and ischaemic infarct on the anterior cerebral artery territory and only one case has been reported in the medical literature [40].

Haemorrhagic stroke (intracerebral or subarachnoid) associated with NCC and HIV was not selected in our series and some cases reported in the medical literature are not certain [41, 42]. We will investigate the association of haemorrhagic stroke and SNCC in a forthcoming research. Strengths of our study include the large sample size, geographically distinct locations of the participating clinics from the former Transkei in rural South Africa, and potential feasibility of its replication in similar regions worldwide.

Weaknesses of this study include the exclusion of a number of variables that may have contributed to the analysis, such as patient's response to anti-parasitic treatment and the degree of immune compromise. Better reporting of HIV status is also necessary, as over half of the patients selected were HIV-status unknown. In our study, the prevalence of SNCC without hydrocephalus in patients living with NCC is 4.77%.

Risk for ischaemic stroke in patients with subarachnoid NCC is almost three times more for patients with intraparenchymal NCC. Comorbidity of subarachnoid NCC in HIV-positive patients increases up to 7.6-fold.
