**2. Zoonotic parasites**

Zoonotic parasites are separated into four categories, such as direct-zoonotic, meta-zoonotic, cyclo-zoonotic , and sapro-zoonotic parasites. Direct-zoonotic parasites, such as, *C. parvum*, *T. gondii,* and *P. carinii* have been prevalent in endemic areas and places where the prevalence of HIV/AIDS is increasing. Meta-zoonotic parasites can infect humans from invertebrate intermediate hosts, such as, *Babesia bovis, Babesia divergens, Plasmodium schwetzi, Clonorchis sinensis, Fasciola hepatica, Paragonimus westermani, Diphyllobothrium latum, Dipylidium caninum, Dirofilaria immitis, Brugia malayi, Onchocerca gibsoni,*and *Polymorphus boschadis* and some of them like *C. sinensis, H. nocens,M. yokogawai, P. westermanii,* and sparganum (*Spirometra* spp.), remain prevalent among people who consume raw freshwater fish or crabs in endemic areas. Cyclo-zoonotic parasites have vertebrate intermediate hosts, such as, *Taenia multiceps, Echinococcus granulosus, Taenia saginata, Taenia solium,* sparganum (*Spirometra* spp.), *Porrocaecum crassum, Contracaecum osculatum, Capillaria hepatica,* and *Gnathostoma spinigerum.* Cyclo-zoonotic parasites, such as, *T. saginata, T. solium,* and *T. asiatica,* are still prevalent in peoples who consumed raw cattle or pig meat and there is a tendency to increase and spread all over the world due to globalization. Sapro-zoonotic parasites mean that parasites can infect humans from soil or water, such as, *Ancylostoma caninum, Ascaris suum, Capillaria hepatica, Strongyloides stercoralis, Trichuris vulpis,* and *Hypoderma bovis.* 

Many of carnivorous parasites are zoonotic parasites because dogs and cats have lived with humans for a long period of time. On the other hand, anthroponotic parasites mean that the

Epilepsy Secondary to Parasitic Zoonoses of the Brain 311

Cryptosporidial infection can thus be transmitted from fecally contaminated food and water, from animal-person contact, and via person-person contact. The probability of transmission from just a small amount of contamination is fairly high, (DuPont, *et al*., 1995). Infection is by ingestion of infective oocysts (*Cryptosporidium*) from the environment or from

Climate change has the potential to alter survival rates for the cysts and oocysts (which are infective when voided by the hosts) and, because both parasites are found in surface water, shifts in local and regional hydrology may alter parasite distributions and the risks of human and animal exposure. In human settlements altered patterns of precipitation and extreme climatic events may disrupt the integrity of the infrastructure, particularly water supplies and sewage disposal, increasing the risk of human infection. Risk for epilepsy is not certain in most of the cases. In addition, these elements of the climate change may result in increased run-off and contamination of water with animal feces, and increased risk of

The most important zoonotic protozoa recently are *T. gondii, C. parvum,* and *Pneumocystis carinii (*Hong, 1991; Chai et al., 1996; Choi et al., 1997). The first one affects the nervous system more than others. Before AIDS, reactivation of neurotoxoplasmosis occurred most often in patients with hematologic malignancies. Because many of these patients receive immunosuppressive therapy, the relative contribution of immune dysfunction from malignancy versus immune suppression from drugs is difficult to define. (Dukes, 1997). neurotoxoplasmosis can also occur in patients receiving immunosuppressive chemotherapy after organ transplantation or for collagen vascular disorders. *Toxoplasma gondii* is a causal agent. *T.gondii* is an intracellular protozoan parasite. Most human infections with *T. gondii* are asymptomatic, but it can potentially cause four syndromes as can be seen in Table 3:

Meningoenchephalitis during primary infection of an

Epilepsy, intracerebral mass lesions or encephalitis in

Retinochoroiditis associated with primary infection or reactivation

Congenital toxoplasmosis, encephalitis, and retinochoroiditis as a

The only definitive host for T. gondii is domestic cats. Transmission of T. gondii to humans occurs commonly, usually by eating undercooked meat or by inadvertent ingestion of oocysts from cat feces. Systemic parasitemia occurs after the invasion of the gut lining by toxoplasma and it is certainly associated with seizures and it is one of the most common opportunistic infections in advanced stage of HIV infections, so cases of neurotoxoplasmosis have increased dramatically since 1981. Neurotoxoplasmosis is responsible for over one-

**2.1.2 Cryptosporidiasis** 

contaminated food or water.

zoonotic transmission. (Polley, 2010).

immunocompetent host

of an earlier infection

result of transplacental

Table 3. Clinical presentation of neurotoxoplasmosis

fetal infection. (McCabe et al., 1987)

immunocompromised hosts

**2.1.3 Neurotoxoplasmosis** 

parasites can be transmitted from humans to animals. Some examples of these are *E. histolytica, C. sinensis, D. latum,* and *Trichuris trichiura. (*Youn H, 2009). On the other hand, along with social, epidemiological and environmental changes, together with improvements in our ability to diagnose helminth infections, several neglected parasite species are now fast-becoming recognized as important zoonotic diseases of humans, e.g. anasakiasis, several fish-borne trematodiasis and fasciolosis.Direct zoonotic parasites infect humans directly from animals, such as:

### **2.1.1 Neuroamebiasis**

There is about 65,000 species of protozoan parasites worldwide. Unicellular organisms, almost all protozoa, live by holozoic nutrition. Protozoa are divided into 5 phyla, Sarcomastigophora, Apicomplexa, Microspora, Myxozoa, and Ciliophora. Sarcomastigophora have flagella or pseudopodia for locomotive organs, reproduce by binary fission, and include *Trichomonas* spp., *Giardia* spp., and amoeba (including *Endolimax nana, Entamoeba coli, E. histolytica,* and *Iodamoeba bu*\_*tschlii*). Amebae can invade the central nervous system, causing rare but fatal infections and seizures can complicate any of the amoeba-caused clinical syndromes.

Although, epidemiologic data are inadequate to comment on the seizure incidence and prevalence is well-known that intracranial infection by *Entamoeba histolytica* can cause brain abscess (Shah et al., 1994) with an associated focal neurological signs, and other signs due to raised intracranial pressure such as: abducens palsy which can be identified ipsilateral or contralateral of the infective mass. Some micro abscess located near to the cerebral cortex can cause partial, partial with secondary generalization or generalized motor seizures but no only *E histolytica* cause neurological manifestation as can be seen in the Table 2.


\*There are concerns that endemic infections and infestations, such as malaria and neurocysticercosis, could be responsible for the increased incidence of epilepsy in the developing world. (Sander & Perucca, 2003)

Table 2. Some protozoans than can infect cerebral hemispheres

#### **2.1.2 Cryptosporidiasis**

310 Novel Aspects on Epilepsy

parasites can be transmitted from humans to animals. Some examples of these are *E. histolytica, C. sinensis, D. latum,* and *Trichuris trichiura. (*Youn H, 2009). On the other hand, along with social, epidemiological and environmental changes, together with improvements in our ability to diagnose helminth infections, several neglected parasite species are now fast-becoming recognized as important zoonotic diseases of humans, e.g. anasakiasis, several fish-borne trematodiasis and fasciolosis.Direct zoonotic parasites infect humans

There is about 65,000 species of protozoan parasites worldwide. Unicellular organisms, almost all protozoa, live by holozoic nutrition. Protozoa are divided into 5 phyla, Sarcomastigophora, Apicomplexa, Microspora, Myxozoa, and Ciliophora. Sarcomastigophora have flagella or pseudopodia for locomotive organs, reproduce by binary fission, and include *Trichomonas* spp., *Giardia* spp., and amoeba (including *Endolimax nana, Entamoeba coli, E. histolytica,* and *Iodamoeba bu*\_*tschlii*). Amebae can invade the central nervous system, causing rare but fatal infections and seizures can complicate any of the

Although, epidemiologic data are inadequate to comment on the seizure incidence and prevalence is well-known that intracranial infection by *Entamoeba histolytica* can cause brain abscess (Shah et al., 1994) with an associated focal neurological signs, and other signs due to raised intracranial pressure such as: abducens palsy which can be identified ipsilateral or contralateral of the infective mass. Some micro abscess located near to the cerebral cortex can cause partial, partial with secondary generalization or generalized motor seizures but no

only *E histolytica* cause neurological manifestation as can be seen in the Table 2.

these)

of these)

Table 2. Some protozoans than can infect cerebral hemispheres

Primary amebic

Zoonotic protozoa Neurological complications Clinical features

meningoenchephalitis (acute meningoenchephalitis)

Granulomatous amebic encephalitis (resembles brain abscess, tumour, chronic meningitis, or a combination

\*There are concerns that endemic infections and infestations, such as malaria and neurocysticercosis, could be responsible for the increased incidence of epilepsy in the developing world. (Sander &

Amebic brain abscess (resembles brain abscess, tumours, chronic meningitis, or a combination of

Meningeal sings Focal signs Seizures

Meningeal signs

Meningeal signs

Seizures Stupor/coma

Seizures Focal deficits Stupor/coma

Cerebral malaria\* Epileptic seizures Coma

directly from animals, such as:

amoeba-caused clinical syndromes.

**2.1.1 Neuroamebiasis** 

*Entamoeba histolytica*

*Naegleria fowleri*

*Acanthamoeba or Hartmannella*

Perucca, 2003)

*Plasmodium falciparum.* (*P. malariae* and *P. vivax* are infrequent causes of CNS malaria.)????

Cryptosporidial infection can thus be transmitted from fecally contaminated food and water, from animal-person contact, and via person-person contact. The probability of transmission from just a small amount of contamination is fairly high, (DuPont, *et al*., 1995). Infection is by ingestion of infective oocysts (*Cryptosporidium*) from the environment or from contaminated food or water.

Climate change has the potential to alter survival rates for the cysts and oocysts (which are infective when voided by the hosts) and, because both parasites are found in surface water, shifts in local and regional hydrology may alter parasite distributions and the risks of human and animal exposure. In human settlements altered patterns of precipitation and extreme climatic events may disrupt the integrity of the infrastructure, particularly water supplies and sewage disposal, increasing the risk of human infection. Risk for epilepsy is not certain in most of the cases. In addition, these elements of the climate change may result in increased run-off and contamination of water with animal feces, and increased risk of zoonotic transmission. (Polley, 2010).

#### **2.1.3 Neurotoxoplasmosis**

The most important zoonotic protozoa recently are *T. gondii, C. parvum,* and *Pneumocystis carinii (*Hong, 1991; Chai et al., 1996; Choi et al., 1997). The first one affects the nervous system more than others. Before AIDS, reactivation of neurotoxoplasmosis occurred most often in patients with hematologic malignancies. Because many of these patients receive immunosuppressive therapy, the relative contribution of immune dysfunction from malignancy versus immune suppression from drugs is difficult to define. (Dukes, 1997). neurotoxoplasmosis can also occur in patients receiving immunosuppressive chemotherapy after organ transplantation or for collagen vascular disorders. *Toxoplasma gondii* is a causal agent. *T.gondii* is an intracellular protozoan parasite. Most human infections with *T. gondii* are asymptomatic, but it can potentially cause four syndromes as can be seen in Table 3:


Table 3. Clinical presentation of neurotoxoplasmosis

The only definitive host for T. gondii is domestic cats. Transmission of T. gondii to humans occurs commonly, usually by eating undercooked meat or by inadvertent ingestion of oocysts from cat feces. Systemic parasitemia occurs after the invasion of the gut lining by toxoplasma and it is certainly associated with seizures and it is one of the most common opportunistic infections in advanced stage of HIV infections, so cases of neurotoxoplasmosis have increased dramatically since 1981. Neurotoxoplasmosis is responsible for over one-

Epilepsy Secondary to Parasitic Zoonoses of the Brain 313

Hymenolepis nana is also known as the Dwarf Tapeworm and it is the cestode that most commonly infects humans, especially school-aged children when they ingest infective eggs from accidental ingestion of insects (immature fleas, flour beetles, meal worms, cockroaches) that carry the parasite in their body cavities, most commonly by direct fecal-oral exposure. Infective eggs are ingested by insects and hatch in their guts. After hatching, they invade into the body cavity and become cysticercoid larvae, which are infectious for humans. After the insects are consumed and digested, the larvae are released in the small intestine and mature within 25 days into 50-cm adults. When the adult tapeworm begins to pass eggs,

Most infections produce no symptoms (Craip, 2007). Hymenolepis nana infestations are prevalent in highly populated areas where hygiene and sanitary conditions are poor. The symptom frequency seems to correlate with increasing worm burden and in order of decreasing frequency includes restlessness, irritability, diarrhea, abdominal pain, restless sleep, anal pruritus, and nasal pruritus. Rare symptoms include anorexia, increased appetite, vomiting, nausea, bloody diarrhea, hives, extremity pain, headache, dizziness,

Baylisascariasis is a rare parasitic infection caused by intestinal nematodes *Baylisascaris* procyonis, the raccoon roundworm (family Ascarididae) in the genus Baylisascaris. The three most pathogenic species are *Baylisascaris procyonis*, a parasite of raccoons (*Procyon lotor*), *B. melis*, which occurs in European badgers (*Meles meles*), and *B. columnaris*, which is found in skunks and was, at one time, thought to be the same species as *B. procyonis*. While fewer than 30 cases have been reported in the literature; the disease is likely under recognized. Raccoons have a high prevalence of infection and each worm is estimated to lay up to 179,000 eggs per day, and raccoons carry an average of 43-52 worms. Human infection occurs upon ingestion of viable eggs The larvae of these three species can cause extensive damage in their intermediate/paratenic hosts: they migrate extensively, continue to grow considerably within these hosts, and sometimes invade the brain (most often fatal) or the

Neural larva migrans occurs when the parasites migrate through the brain. The initial signs may be mild, with subtle behavioral changes, lethargy, somnolence or irritability, weakness, speech defects and/or mild changes in vision, but they can rapidly become severe. A variety of symptoms including ataxia, seizures, paresis or paralysis, developmental regression, tremors, torticollis, nystagmus and coma have been reported. Epileptic seizures are quite common and partial, secondarily generalized or generalized from the beginning can be seen. The antiepileptic medication of choice is oral carbamazepine from 200mg three times a day. The diagnosis of baylisascariasis is difficult in live patients; there is no available, noninvasive definitive test. Unless a brain biopsy is done and a larva is found, antemortem diagnosis usually depends on serology, with supporting evidence from other tests. In neural larva migrans, antibodies to *Baylisascaris* can be found in serum and cerebrospinal fluid (CSF); a rising titer is usually seen. An enzyme linked immunosorbent assay (ELISA), indirect immunofluorescence and immunoblotting (Western blotting) have been developed to detect anti-*Baylisascaris* antibodies.( Institute for International Cooperation in Animal Biologics, 2009). We have not experience in diagnosis based on CT/MRI images. Although

behavioural disturbances, and seizures. (Tolan, 2011; Chero et al., 2007).

eye including permanent blindness when the worms migrate into the retina.

**2.1.4 Neurohymenolepiasis** 

insect hosts can become infected again.

**2.1.5 Neurobaylisascariasis** 

third of neurologic symptoms in AIDS patients. (Dukes, 1997). (In contrast, both primary CNS and metastatic lymphoma account for approximately 5% each.) More than 95% of toxoplasmic encephalitis in patients with AIDS is due to reactivation of chronic latent infection. For most HIV-infected patients, toxoplasmic encephalitis develop after the CD4 count falls below 100. (Dukes, 1997). In the United States, 10–40% of AIDS patients are

latently infected, and 30–50% of these will develop toxoplasmic encephalitis. (Dukes, 1997) Clinical manifestations are variable, ranging from an insidious process to an acute confusional state. Reported seizure rates range from 18% to 29% and may include partial, complex partial, and generalized seizures (Porte & Sande, 1992; Ragnaud et al., 1993). Detection of antibodies to Toxoplasma in sera from patients suffering from recurrent unprovoked seizures were performed using "in-house" indirect hemagglutination assay and by commercially available anti-Toxoplasma immunoglobulin G and immunoglobulin M enzyme-linked immunosorbent assays. Serum antibody to toxoplasmosis were detected in 12.3% and 15.3% by indirect hemagglutination assay and enzyme-linked immunosorbent assays and respectively. Controls showed seropositivity of 5.7% for antibodies to Toxoplasma using the same methods. Seropositivity was higher in children compared to adults. Individuals with rural background (living in relatively unhygienic conditions) were more commonly affected compared to people living in urban areas. (Mirdha, 2003)

The presence of positive antibody titters to *Toxoplasma* and *Toxocara* in an adult epileptic population has been examined in relation to other observations of aetiological importance. With *Toxoplasma*, and more particularly with *Toxocara*, a higher incidence of positive antibody titters were recorded than in non-epileptic populations. Comparison with previous studies in childhood epilepsy indicate that the incidence of positive titres increased with age throughout adult life. Reported seizure rates range from 18% to 29% and may include partial, complex partial, and generalized seizures. (http://professionals.epilepsy.com/page/infectious\_toxoplas.html)

Despite attention to the age of onset of epilepsy, presumed etiological factors, and electroencephalographic and clinical observations, no causal relationship between parasitic infection and the etiology of epilepsy was established (Critchley et al., 1982). However, Stommel et al. (2001) found a statistically significant correlation between chronic *T. gondii* infection and cryptogenic epilepsy in a group of patients with cryptogenic epilepsy and they proposed that the dormant *T. gondii* cysts containing bradyzoites are responsible for some cases of cryptogenic epilepsy, although other explanations for this finding exist: (a) The cryptogenic subpopulation could be more susceptible to the parasitic infection for reasons unrelated to epilepsy; or (b) The cryptogenic epilepsy patients could be more susceptible to *T. gondii* infection and have intrinsic immunologic differences that predispose them to epilepsy, implying an immune basis to the epilepsy. Because there are certainly multiple etiologies for cryptogenic epilepsy, any statistical analysis may only partially reflect an etiology. In any case, antiparasitic and antiepileptic treatment is mandatory. For more detailed information about antiepileptic and antiseizures medicine please consult our book: "Treatment approach of epilepsy" ISBN 978-953-307-678-2

Therapy for toxoplasmic encephalitis is the combination of pyrimethamine and sulfadiazine. Clindamycin can be used as an alternative to sulfadiazine. Serial neuroimaging provides the best follow-up to assess treatment progress. Maintenance anticonvulsant therapy is usually required. Newborns of women contracting toxoplasmosis during pregnancy should be treated with clindamycin to reduce the likelihood of developing late neurologic sequelae, including seizures.(Georgiev, 1994)

#### **2.1.4 Neurohymenolepiasis**

312 Novel Aspects on Epilepsy

third of neurologic symptoms in AIDS patients. (Dukes, 1997). (In contrast, both primary CNS and metastatic lymphoma account for approximately 5% each.) More than 95% of toxoplasmic encephalitis in patients with AIDS is due to reactivation of chronic latent infection. For most HIV-infected patients, toxoplasmic encephalitis develop after the CD4 count falls below 100. (Dukes, 1997). In the United States, 10–40% of AIDS patients are latently infected, and 30–50% of these will develop toxoplasmic encephalitis. (Dukes, 1997) Clinical manifestations are variable, ranging from an insidious process to an acute confusional state. Reported seizure rates range from 18% to 29% and may include partial, complex partial, and generalized seizures (Porte & Sande, 1992; Ragnaud et al., 1993). Detection of antibodies to Toxoplasma in sera from patients suffering from recurrent unprovoked seizures were performed using "in-house" indirect hemagglutination assay and by commercially available anti-Toxoplasma immunoglobulin G and immunoglobulin M enzyme-linked immunosorbent assays. Serum antibody to toxoplasmosis were detected in 12.3% and 15.3% by indirect hemagglutination assay and enzyme-linked immunosorbent assays and respectively. Controls showed seropositivity of 5.7% for antibodies to Toxoplasma using the same methods. Seropositivity was higher in children compared to adults. Individuals with rural background (living in relatively unhygienic conditions) were

more commonly affected compared to people living in urban areas. (Mirdha, 2003)

(http://professionals.epilepsy.com/page/infectious\_toxoplas.html)

"Treatment approach of epilepsy" ISBN 978-953-307-678-2

including seizures.(Georgiev, 1994)

The presence of positive antibody titters to *Toxoplasma* and *Toxocara* in an adult epileptic population has been examined in relation to other observations of aetiological importance. With *Toxoplasma*, and more particularly with *Toxocara*, a higher incidence of positive antibody titters were recorded than in non-epileptic populations. Comparison with previous studies in childhood epilepsy indicate that the incidence of positive titres increased with age throughout adult life. Reported seizure rates range from 18% to 29% and may include partial, complex partial, and generalized seizures.

Despite attention to the age of onset of epilepsy, presumed etiological factors, and electroencephalographic and clinical observations, no causal relationship between parasitic infection and the etiology of epilepsy was established (Critchley et al., 1982). However, Stommel et al. (2001) found a statistically significant correlation between chronic *T. gondii* infection and cryptogenic epilepsy in a group of patients with cryptogenic epilepsy and they proposed that the dormant *T. gondii* cysts containing bradyzoites are responsible for some cases of cryptogenic epilepsy, although other explanations for this finding exist: (a) The cryptogenic subpopulation could be more susceptible to the parasitic infection for reasons unrelated to epilepsy; or (b) The cryptogenic epilepsy patients could be more susceptible to *T. gondii* infection and have intrinsic immunologic differences that predispose them to epilepsy, implying an immune basis to the epilepsy. Because there are certainly multiple etiologies for cryptogenic epilepsy, any statistical analysis may only partially reflect an etiology. In any case, antiparasitic and antiepileptic treatment is mandatory. For more detailed information about antiepileptic and antiseizures medicine please consult our book:

Therapy for toxoplasmic encephalitis is the combination of pyrimethamine and sulfadiazine. Clindamycin can be used as an alternative to sulfadiazine. Serial neuroimaging provides the best follow-up to assess treatment progress. Maintenance anticonvulsant therapy is usually required. Newborns of women contracting toxoplasmosis during pregnancy should be treated with clindamycin to reduce the likelihood of developing late neurologic sequelae, Hymenolepis nana is also known as the Dwarf Tapeworm and it is the cestode that most commonly infects humans, especially school-aged children when they ingest infective eggs from accidental ingestion of insects (immature fleas, flour beetles, meal worms, cockroaches) that carry the parasite in their body cavities, most commonly by direct fecal-oral exposure. Infective eggs are ingested by insects and hatch in their guts. After hatching, they invade into the body cavity and become cysticercoid larvae, which are infectious for humans. After the insects are consumed and digested, the larvae are released in the small intestine and mature within 25 days into 50-cm adults. When the adult tapeworm begins to pass eggs, insect hosts can become infected again.

Most infections produce no symptoms (Craip, 2007). Hymenolepis nana infestations are prevalent in highly populated areas where hygiene and sanitary conditions are poor. The symptom frequency seems to correlate with increasing worm burden and in order of decreasing frequency includes restlessness, irritability, diarrhea, abdominal pain, restless sleep, anal pruritus, and nasal pruritus. Rare symptoms include anorexia, increased appetite, vomiting, nausea, bloody diarrhea, hives, extremity pain, headache, dizziness, behavioural disturbances, and seizures. (Tolan, 2011; Chero et al., 2007).

#### **2.1.5 Neurobaylisascariasis**

Baylisascariasis is a rare parasitic infection caused by intestinal nematodes *Baylisascaris* procyonis, the raccoon roundworm (family Ascarididae) in the genus Baylisascaris. The three most pathogenic species are *Baylisascaris procyonis*, a parasite of raccoons (*Procyon lotor*), *B. melis*, which occurs in European badgers (*Meles meles*), and *B. columnaris*, which is found in skunks and was, at one time, thought to be the same species as *B. procyonis*. While fewer than 30 cases have been reported in the literature; the disease is likely under recognized. Raccoons have a high prevalence of infection and each worm is estimated to lay up to 179,000 eggs per day, and raccoons carry an average of 43-52 worms. Human infection occurs upon ingestion of viable eggs The larvae of these three species can cause extensive damage in their intermediate/paratenic hosts: they migrate extensively, continue to grow considerably within these hosts, and sometimes invade the brain (most often fatal) or the eye including permanent blindness when the worms migrate into the retina.

Neural larva migrans occurs when the parasites migrate through the brain. The initial signs may be mild, with subtle behavioral changes, lethargy, somnolence or irritability, weakness, speech defects and/or mild changes in vision, but they can rapidly become severe. A variety of symptoms including ataxia, seizures, paresis or paralysis, developmental regression, tremors, torticollis, nystagmus and coma have been reported. Epileptic seizures are quite common and partial, secondarily generalized or generalized from the beginning can be seen. The antiepileptic medication of choice is oral carbamazepine from 200mg three times a day.

The diagnosis of baylisascariasis is difficult in live patients; there is no available, noninvasive definitive test. Unless a brain biopsy is done and a larva is found, antemortem diagnosis usually depends on serology, with supporting evidence from other tests. In neural larva migrans, antibodies to *Baylisascaris* can be found in serum and cerebrospinal fluid (CSF); a rising titer is usually seen. An enzyme linked immunosorbent assay (ELISA), indirect immunofluorescence and immunoblotting (Western blotting) have been developed to detect anti-*Baylisascaris* antibodies.( Institute for International Cooperation in Animal Biologics, 2009). We have not experience in diagnosis based on CT/MRI images. Although

Epilepsy Secondary to Parasitic Zoonoses of the Brain 315

Cerebral malaria is caused by the protozoan parasite Plasmodium, transmitted to humans via the Anopheles mosquito. The disease is endemic to large parts of Africa, South America, and Southeast Asia. Cerebral malaria is an encephalopathy occurring in approximately 2% of outpatients and 10% of inpatients infected with Plasmodium. The World Health Organization definition of cerebral malaria requires some feature that can be seen in Table 5.

> Unarousable coma Evidence of acute infection with P. falciparum No other identifiable cause of coma

Clinical manifestations of cerebral malaria are diverse. Fever is nearly universal, as is comorbidity with clinical features of P. falciparum systemic infection. Clinicians working in tropical and subtropical regions regard any new CNS-attributable sign developing within the context of P. falciparum parasitemia as evidence of possible cerebral malaria. The cardinal feature is a disturbed level of consciousness, usually ranging from lethargy to stupor to coma, although an agitated delirium can also occur. To conform to the strict diagnosis of cerebral malaria, the patient must remain comatose for more than 6 hours after the seizure to distinguish the coma from postictal consciousness suppression. Generalized tonic-clonic seizures occur in more than 40% of adult patients. Partial seizures are uncommon. Seizures are associated with prolonged coma and increased risk of neurologic sequelae and death (Labar & Harden, 1997). Apart from brain edema other possible seizure

Antimalarial medicine include: chloroquine and mefloquine. Other metabolic disturbances secondary to malarial systemic effects should be considered as a cause of seizures(Labar & Harden, 1997). Neurologic sequelae of cerebral malaria, including epilepsy, affect approximately 10% of survivors; for unclear reasons, children tend to be more frequently affected than adults (Marsden, 1975). Cerebral malaria is a medical emergency and

Specific antimalarial therapy (quinine, quinidine, etc.)

Generalized seizures can be followed by rapid neurologic deterioration, so prompt treatment is required. Subclinical or nonconvulsive seizures should be suspected in patients

Table 5. Some clinical features of cerebral malaria

Cerebral hypoxia

Hypoglycemia Lactic acidosis

Drugs (including antimalarials) Table 6. Other possible causes of epileptic seizures due to malaria

> Management of coexistent seizures Treatment of associated superinfections.

causes are included in Table 6.

treatment is tripartite:

with persistent coma.

Fever

the potential for long-term sequelae is unknown, short-term recovery has been reported in anecdotic cases. (Pai et al., 2007).

List of parasitic zoonoses infecting the brain is increasing gradually by emergent and reemergent infection as can be seen in Table 4


\*Spargana can live up to 20 years in the human host

Table 4. Some parasitic zoonoses reported as affecting the brain

the potential for long-term sequelae is unknown, short-term recovery has been reported in

List of parasitic zoonoses infecting the brain is increasing gradually by emergent and re-

HOST(S)

INTERMEDIATE

NEUROLOGICAL PROBLEMS

Epilepsy and other symptoms and signs

neurocysticercosis

Epilepsy and other clinical manifestations of neurocoenurosis

Epilepsy, and other manifestations of neurognathostomiasis.

included seizures

Epilepsy and other

Epilepsy and other clinical manifestations of neurosparganosis

neuroparagonimiasis.

meningoenchephalitis, cranial nerve disorders

to neuroparagonimiasis

meningoencephalitis

signs of

Epilepsy,

Epilepsy and eosinophillic

Epilepsy and manifestation due to neurotoxocariasis

and seizures.

due to

anecdotic cases. (Pai et al., 2007).

AGENT DEFINITE

*Toxocara canis* 

*Taenia (multiceps)* 

*serialis* 

*Schistosoma* 

*Gnathostoma* 

*Echinococcus granulosus* 

*spp.* 

*Cryptosporidium* 

*Paragonimus spp.* 

*Spirometra* spp

*Baylisascaris* 

*Angiostrongylus* 

emergent infection as can be seen in Table 4

*Taenia solium* Human Pig

*(cati?)* Dogs, cats NA

*spinigerum* Dogs, mammals

HOST(S)

Dogs, foxes and

Dogs, other

Cattle, dogs,

Mammals, including humans

(Sparganum)\* Dogs and cats Fish, reptiles,

*procyonis* Raccoons, dogs Small mammals and

*cantonensis* Rats, Dogs African giant land

Table 4. Some parasitic zoonoses reported as affecting the brain

\*Spargana can live up to 20 years in the human host

cats, humans NA

jackals Sheep, goats

*japonicum* Mammals Snails Neuroschistosomiasis

frogs

Crustacean copepod, freshwater fish,

canidae Domestic ungulates Neuroechinoccosis

Snails (1ary), crabs & crayfish (2ndary)

amphibians,

birds

*Paragonimus* Snail and crayfish Epilepsy, blindness due

snails

Cerebral malaria is caused by the protozoan parasite Plasmodium, transmitted to humans via the Anopheles mosquito. The disease is endemic to large parts of Africa, South America, and Southeast Asia. Cerebral malaria is an encephalopathy occurring in approximately 2% of outpatients and 10% of inpatients infected with Plasmodium. The World Health Organization definition of cerebral malaria requires some feature that can be seen in Table 5.


Table 5. Some clinical features of cerebral malaria

Clinical manifestations of cerebral malaria are diverse. Fever is nearly universal, as is comorbidity with clinical features of P. falciparum systemic infection. Clinicians working in tropical and subtropical regions regard any new CNS-attributable sign developing within the context of P. falciparum parasitemia as evidence of possible cerebral malaria. The cardinal feature is a disturbed level of consciousness, usually ranging from lethargy to stupor to coma, although an agitated delirium can also occur. To conform to the strict diagnosis of cerebral malaria, the patient must remain comatose for more than 6 hours after the seizure to distinguish the coma from postictal consciousness suppression. Generalized tonic-clonic seizures occur in more than 40% of adult patients. Partial seizures are uncommon. Seizures are associated with prolonged coma and increased risk of neurologic sequelae and death (Labar & Harden, 1997). Apart from brain edema other possible seizure causes are included in Table 6.


Table 6. Other possible causes of epileptic seizures due to malaria

Antimalarial medicine include: chloroquine and mefloquine. Other metabolic disturbances secondary to malarial systemic effects should be considered as a cause of seizures(Labar & Harden, 1997). Neurologic sequelae of cerebral malaria, including epilepsy, affect approximately 10% of survivors; for unclear reasons, children tend to be more frequently affected than adults (Marsden, 1975). Cerebral malaria is a medical emergency and treatment is tripartite:


Generalized seizures can be followed by rapid neurologic deterioration, so prompt treatment is required. Subclinical or nonconvulsive seizures should be suspected in patients with persistent coma.

Epilepsy Secondary to Parasitic Zoonoses of the Brain 317

adult worm laid eggs that are excreted with stool or urine. Different mechanisms of invasion of the brain have been discussed: the eggs may reach the brain through the valveless venous plexus of Batson, which joins the deep iliac veins and inferior vena cava with veins of the spinal cord and brain, or eggs may migrate to the brain via pulmonary arteriovenous shunts, or portalpulmonary arteriovenous shunts. Finally, the worms themselves may enter the cerebral veins and place their eggs directly at the ectopic site, which could be the cerebrum, cerebellum, leptomeninges, brainstem, or choroid plexus (Wan et al., 2009) Neuroschistosomiasis usually follows the egg migration into the brain or spinal cord vasculature, leading to microinfarction or granuloma formation. Neurologic manifestations are rare, occurring in only 1– 2% of cases, but they can include a wide range of focal and nonfocal CNS symptoms, including seizures. . Neurologic disease during Katayama fever responds to steroids with or without antischistosomal therapy. Cerebral schistosomiasis may require surgical resection of the granuloma like masses. Praziquantel is the primary

antischistosomal agent. Antiepileptic drugs are used as needed (Schachter, 2004).

Same way in Iraq, Lebanon, Morocco, and Tunisia. (Karki, 2011).

associated with the hepatic stage of fascioliasis.

spp., *T. solium* and *Taenia asiatica*.

**2.3 Some major zoonotic cestodes (tapeworms)** 

Fascioliasis is a well-known parasite of herbivorous animals; it has a worldwide distribution on the animal reservoir host. A large variety of animals such as sheep, goat, cattle, buffalo, horses and rabbits show infection an rate that varies from 70% to 90% in some areas. Infection of the human host was very sporadic until the last two decades. However, it has now become an important trematode-borne infection of emerging concern until today. The estimated number of people infected is being estimated 2.4 million in 61 countries. An estimated number of populations at risk are considered more than 180 million throughout the world. Until today, largest number of infected people have been reported from Bolivia, China, Ecuador. Egypt, France Iran, Peru and Portugal. In Nepal's context, sporadic cases had been reported from human hospital since last decade,-while screening of human population has yet not been done.

Ectopic spinal localization of *Fasciola* may occur during the transmigration path of the parasite through the peritoneum or from the liver through the portal venous system and affect spinal cord causing paraplegia (Devendra et al., 2006). Park & Sohn (2010) reported the first case presenting cerebral lesions secondary to hepatic fascioliasis. Therefore seizures disorders does not represent a problem for this parasitism. CNS involvement can be

There are 2 kinds of cetodes, such as *Eucestoda* and *Cotyloda*. Cestodes are hermaphroditic and endoparasitic worms with an elongated flat body without a body cavity or alimentary canal. Their bodies are comprised of 3 parts, such as, scolex, neck, and strobila. *Eucestoda*  have 1 intermediate host, but *Cotyloda* have 2 or more intermediate hosts. In Cheju (South Korea) many years ago, the pigsty was located below the toilet, so that pigs were raised to eat the stool and infected with the eggs of *Taenia* spp. Humans were habituated to eat raw pork products, especially the liver, so they became infected with the metacestodes of *Taenia* 

Min (1990) reported a review paper on cestode infections such as: the Pseudophyllidea, i.e., *D. latum*, *Diphyllobothrium yonagoense*, sparganum of *Spirometra erinacei,* and the

**2.2.3 Neurofascioliasis** 

#### **2.2 Some major zoonotic trematodes (flukes)**

There are 3 kinds of trematodes, such as monogenean, aspidogastrean, and digenean trematodes, with digenean being the only zoonotic trematodes. The characteristics of digenean trematodes are dorsoventrally flattened, unsegmented, and leaf-like worms and have 1 or 2 suckers (oral and ventral suckers), rarely armed with hooks or clamps. All digenean trematodes have 1or 2 intermediate hosts and first intermediate hosts are molluscs. Almost all zoonotic trematodes have the 2nd intermediate hosts, such as cyprinoid freshwater fish or crustacean (Young, 2009)

### **2.2.1 Neuroparagonimiasis**

Paragonimiasis is a parasitic disease caused by *Paragonimus* trematodes, commonly known as lung flukes. Humans become infected by eating raw or undercooked crayfish (also known as crawfish and crawdads) or freshwater crabs that harbor the parasites. Paragonimiasis most frequently involves the lungs, but can affect other organs, including the brain and skin. In North America, *Paragonimus kellicotti* causes infections among dogs, cats, and wild carnivores, but rarely infects humans. After humans eat raw or undercooked crayfish that harbor *P. kellicotti*, the parasite penetrates through the intestinal wall into the peritoneal cavity, then through the diaphragm into the pleural space and lungs, and can migrate to other organs, including the brain (Chronic headache, epilepsy, etc.) and skin. Eggs laid in the lungs are excreted in the sputum, or swallowed and passed with stool. *Paragonimus* species are endemic in Africa, the Americas, and Asia, but the distribution of *P. kellicotti* is still being determined (Procop, 2009) Migration of the parasite to the brain can cause severe complications, including permanent blindness.

Liver and intestinal infections caused by fish-borne zoonotic trematodes (FZTs) are increasingly being recognized as serious public health problems and are especially widespread in Southeast Asia, including Vietnam, Lao People's Democratic Republic, Thailand, Cambodia, People's Republic of China, and North and South Korea . Liver flukes are associated with high incidence of bile duct cancer (WHO, 1995, 2002), and cause serious pathologic changes in the heart, brain, and spinal cord (Chai, 2005). The epidemiology of FZTs is complex because humans and reservoir hosts, such as dogs, cats, pigs, and fisheating birds, harbor egg-shedding adult stages. (Thien et al., 2007;Chi et al., 2008; Phan et al., 2010)

#### **2.2.2 Neuroschistosomiasis**

Schistosomiasis is an important parasitic disease, occurring in more than 200 million people worldwide. Neuroschistosomiasis causes focal and generalized seizures; headache; and myeloradiculopathy with lower limb and back pain, bladder dysfunction, paresthesia, and weakness. Dizziness, nausea, and increased intracranial pressure can also occur in cerebellar schistosomiasis.(Wan et al., 2009). Visual scintillation from occipital mass has been described. (Fowler et al., 1999)

Schistosomiasis is endemic throughout much of the tropics. Three different schistosomal species (*S haematobium, S japonicum, and S mansoni*) can cause infection that involves the brain and spinal cord. Brain involvement is found in about 4% of all patients infected by *S mansoni*. The life cycle starts with cercariae, which penetrate the human skin and transform into schistosomulae. From there they migrate to the lungs and the liver. The organisms then mature into mating pairs of male and female worms, which settle in the mesenteric veins the adult worm laid eggs that are excreted with stool or urine. Different mechanisms of invasion of the brain have been discussed: the eggs may reach the brain through the valveless venous plexus of Batson, which joins the deep iliac veins and inferior vena cava with veins of the spinal cord and brain, or eggs may migrate to the brain via pulmonary arteriovenous shunts, or portalpulmonary arteriovenous shunts. Finally, the worms themselves may enter the cerebral veins and place their eggs directly at the ectopic site, which could be the cerebrum, cerebellum, leptomeninges, brainstem, or choroid plexus (Wan et al., 2009) Neuroschistosomiasis usually follows the egg migration into the brain or spinal cord vasculature, leading to microinfarction or granuloma formation. Neurologic manifestations are rare, occurring in only 1– 2% of cases, but they can include a wide range of focal and nonfocal CNS symptoms, including seizures. . Neurologic disease during Katayama fever responds to steroids with or without antischistosomal therapy. Cerebral schistosomiasis may require surgical resection of the granuloma like masses. Praziquantel is the primary antischistosomal agent. Antiepileptic drugs are used as needed (Schachter, 2004).

#### **2.2.3 Neurofascioliasis**

316 Novel Aspects on Epilepsy

There are 3 kinds of trematodes, such as monogenean, aspidogastrean, and digenean trematodes, with digenean being the only zoonotic trematodes. The characteristics of digenean trematodes are dorsoventrally flattened, unsegmented, and leaf-like worms and have 1 or 2 suckers (oral and ventral suckers), rarely armed with hooks or clamps. All digenean trematodes have 1or 2 intermediate hosts and first intermediate hosts are molluscs. Almost all zoonotic trematodes have the 2nd intermediate hosts, such as cyprinoid

Paragonimiasis is a parasitic disease caused by *Paragonimus* trematodes, commonly known as lung flukes. Humans become infected by eating raw or undercooked crayfish (also known as crawfish and crawdads) or freshwater crabs that harbor the parasites. Paragonimiasis most frequently involves the lungs, but can affect other organs, including the brain and skin. In North America, *Paragonimus kellicotti* causes infections among dogs, cats, and wild carnivores, but rarely infects humans. After humans eat raw or undercooked crayfish that harbor *P. kellicotti*, the parasite penetrates through the intestinal wall into the peritoneal cavity, then through the diaphragm into the pleural space and lungs, and can migrate to other organs, including the brain (Chronic headache, epilepsy, etc.) and skin. Eggs laid in the lungs are excreted in the sputum, or swallowed and passed with stool. *Paragonimus* species are endemic in Africa, the Americas, and Asia, but the distribution of *P. kellicotti* is still being determined (Procop, 2009) Migration of the parasite to the brain can

Liver and intestinal infections caused by fish-borne zoonotic trematodes (FZTs) are increasingly being recognized as serious public health problems and are especially widespread in Southeast Asia, including Vietnam, Lao People's Democratic Republic, Thailand, Cambodia, People's Republic of China, and North and South Korea . Liver flukes are associated with high incidence of bile duct cancer (WHO, 1995, 2002), and cause serious pathologic changes in the heart, brain, and spinal cord (Chai, 2005). The epidemiology of FZTs is complex because humans and reservoir hosts, such as dogs, cats, pigs, and fisheating birds, harbor egg-shedding adult stages. (Thien et al., 2007;Chi et al., 2008; Phan et al.,

Schistosomiasis is an important parasitic disease, occurring in more than 200 million people worldwide. Neuroschistosomiasis causes focal and generalized seizures; headache; and myeloradiculopathy with lower limb and back pain, bladder dysfunction, paresthesia, and weakness. Dizziness, nausea, and increased intracranial pressure can also occur in cerebellar schistosomiasis.(Wan et al., 2009). Visual scintillation from occipital mass has been

Schistosomiasis is endemic throughout much of the tropics. Three different schistosomal species (*S haematobium, S japonicum, and S mansoni*) can cause infection that involves the brain and spinal cord. Brain involvement is found in about 4% of all patients infected by *S mansoni*. The life cycle starts with cercariae, which penetrate the human skin and transform into schistosomulae. From there they migrate to the lungs and the liver. The organisms then mature into mating pairs of male and female worms, which settle in the mesenteric veins the

**2.2 Some major zoonotic trematodes (flukes)** 

freshwater fish or crustacean (Young, 2009)

cause severe complications, including permanent blindness.

**2.2.1 Neuroparagonimiasis** 

2010)

**2.2.2 Neuroschistosomiasis** 

described. (Fowler et al., 1999)

Fascioliasis is a well-known parasite of herbivorous animals; it has a worldwide distribution on the animal reservoir host. A large variety of animals such as sheep, goat, cattle, buffalo, horses and rabbits show infection an rate that varies from 70% to 90% in some areas. Infection of the human host was very sporadic until the last two decades. However, it has now become an important trematode-borne infection of emerging concern until today. The estimated number of people infected is being estimated 2.4 million in 61 countries. An estimated number of populations at risk are considered more than 180 million throughout the world. Until today, largest number of infected people have been reported from Bolivia, China, Ecuador. Egypt, France Iran, Peru and Portugal. In Nepal's context, sporadic cases had been reported from human hospital since last decade,-while screening of human population has yet not been done. Same way in Iraq, Lebanon, Morocco, and Tunisia. (Karki, 2011).

Ectopic spinal localization of *Fasciola* may occur during the transmigration path of the parasite through the peritoneum or from the liver through the portal venous system and affect spinal cord causing paraplegia (Devendra et al., 2006). Park & Sohn (2010) reported the first case presenting cerebral lesions secondary to hepatic fascioliasis. Therefore seizures disorders does not represent a problem for this parasitism. CNS involvement can be associated with the hepatic stage of fascioliasis.

#### **2.3 Some major zoonotic cestodes (tapeworms)**

There are 2 kinds of cetodes, such as *Eucestoda* and *Cotyloda*. Cestodes are hermaphroditic and endoparasitic worms with an elongated flat body without a body cavity or alimentary canal. Their bodies are comprised of 3 parts, such as, scolex, neck, and strobila. *Eucestoda*  have 1 intermediate host, but *Cotyloda* have 2 or more intermediate hosts. In Cheju (South Korea) many years ago, the pigsty was located below the toilet, so that pigs were raised to eat the stool and infected with the eggs of *Taenia* spp. Humans were habituated to eat raw pork products, especially the liver, so they became infected with the metacestodes of *Taenia*  spp., *T. solium* and *Taenia asiatica*.

Min (1990) reported a review paper on cestode infections such as: the Pseudophyllidea, i.e., *D. latum*, *Diphyllobothrium yonagoense*, sparganum of *Spirometra erinacei,* and the

Epilepsy Secondary to Parasitic Zoonoses of the Brain 319

*trichiura* (whipworm), *Trichostrongylus orientalis,* and *Strongyloides stercoralis.* As imported zoonotic nematode infections, loiasis cases due to the Loa loa*.* As indigenous infections, there have been several human *Thelazia callipaeda* infections. *Dirofilaria immitis* infections are very popular among dogs but very scanty medical information about this parasite in human

Angiostrongyliasis is caused by the rat lungworm. *Angiostrongylus cantonensis* is endemic through Southeast Asia and the Pacific Islands. The infection in humans, an accidental host, is associated with eosinophilic meningitis. The dog tapeworm, Echinococcus granulosus, can infect humans with up to 2% of clinical cases presenting with brain cysts. The infection has a cosmopolitan distribution. Humans get infected with dog feces and CNS infection is usually associated with signs of increased intracranial pressure ( Hughes & Biggs, 2002, 2002a) and epileptic seizures. There is no established antiparasitic treatment. Comorbid seizures are managed under the similar protocol for other parasitic zoonoses infecting the

Gnathostomiasis is a parasitic infection caused by the third-stage larvae of the helminths *Gnathostoma spp*., which are seen mostly in tropical and subtropical regions. The genus *Gnathostoma* belongs to the order *Spirurida*, one of the largest groups of nematodes. The genus has 12 species These groups are characterized biologically by requiring one or more intermediate hosts in their life cycles It is a food-borne zoonosis endemic in areas where people are accidental hosts in which the parasite fails to reach sexual maturity after eating raw freshwater fish or shellfish, especially Thailand and other parts of Southeast Asia, Japan, and increasingly Latin America, particularly Mexico. (Daengsvang, 1981; Nawa, 1991) Visceral disease is more serious than the cutaneous manifestations and, in the case of central nervous system disease, may be fatal. (Herman & Chiodina, 2009). The main features of CNS involvement can cause radiculomyelitis, radiculomyeloencephalitis, eosinophilic meningitis, and subarachnoid hemorrhage. The hallmark symptoms are an acute onset of excruciating radicular pain and/or headache (subarachnoid hemorrhage or eosinophilic meningitis), with subsequent paralysis of the extremities and/or cranial nerve palsies. The typical clinical picture can be explained by the migratory pathway of the parasite, which gains entry to the spinal cord along nerve roots (cranial, cervical, thoracic, or lumbar), causing intense radicular pain (or headache in the case of cranial nerve or cervical root involvement) which usually lasts from 1 to 5 days. Cranial nerve palsies tend to occur after the onset of paralysis, and if multiple they signify a poor prognosis. Cerebral involvement is usually indicated by a depressed consciousness level or coma, but interestingly, mental

The main differential diagnosis of neurognathostomiasis is with *Angiostrongylus cantonensis*, another highly prevalent parasite in Southeast Asia. This may produce a similar eosinophilic menigoencephalitis, but the acute nerve root pain, signs of spinal cord compression, and hemorrhagic or xanthochromic spinal fluid seen in gnathostomiasis are absent with *Angiostrongylus*infection (Herman & Chiodini, 2009). The *Gnathostoma* larva is more invasive than that of *Angiostrongylus* and therefore produces more frequent focal neurological signs.

confusion does not tend to occur (Herman & Chiodini, 2009).

beings is found.

**2.4.1 Neuroangiostrongyliasis** 

brain (Schachter, 2004).

**2.4.2 Neurognathostomiasis** 

Cyclophyllidea, i.e., *H. diminuta, H. nana, Mesocestoides lineatus,T. saginata, T. solium,* and *E. granulosus.* He reported that the plerocercoid larva of *Spirometra* spp.(sparganum) infects humans through 16 kinds of animal hosts, such as, snakes, frogs, and so on.

Sparganosis first reported in swine in 1911 in Indochina. It is a disease found in snakes, reptiles, and mammals, including swine and man. It is caused by migration of the second larval stage (spargana) of the cestode *Spirometra*. (Mueller, 1974). Human sparganosis occurs worldwide. The majority of cases has been reported from China, Korea, Japan, and Southeast Asia. Approximately 70 cases of human sparganosis have been reported from the United States, most from the Southeast region of the country. Transmission to humans has occurred through intact mucous membranes, by the ingestion /handling of frogs and snakes, poultry, and pork, and by ingestion of contaminated water. Disease in man can produce subcutaneous, cerebral, ocular, visceral, and metastatic forms depending upon the migration of the parasite. (Pullar &McLenan 1949; Gordon, 1954; Gray et a., 1999).

#### **2.3.1 Neuroechinoccosis**

Echinococcosis is caused by tapeworms of the genus Echinococcus, common parasites of dogs and cats, who are the definitive hosts; humans can be intermediate hosts. The disease is endemic in countries around the Mediterranean: Greece, Turkey, and Lebanon have the highest prevalences. The small adult worms live in the definitive host's gut and discharge eggs into feces. If inadvertently ingested by a human, the eggs hatch in the human's gut, enabling the organism to penetrate the human's gut wall and spread hematogenously. Once located in a final tissue site, the organism forms a slowly enlarging cyst, a hydatid.When in the CNS, cysts usually locate in brain parenchyma. Clinical manifestations are secondary to this mass lesion, raised intracranial pressure, or both. Although praziquantel has activity against these organisms, the primary treatment of CNS hydatids is surgical. Antiepileptic management is a crucial adjunctive treatment. ( Schachter, 2004)

#### **2.3.2 Neurocoenurosis**

Another parasitic zoonosis which shows similar symptoms to NC is coenuriasis, due to invasion of the brain by the larval stage knowing by *Coenuruses cerebralis* (CC) of the tapeworm *Multiceps multiceps*. Watson and Lurie (1956) from Edendale Hospital in PieterMarisberg, South Africa reported five cases from 1951 to 1956 and described their anatomic-pathological finding on post-mortem examinations. One year later also in South Africa, Plumber et al (1957) reported some cases and reviewed the medical literature. At the time that they reviewed the available English-language medical literature a total 14 case from South Africa were found. From his anatomopathological report we could not find gross different from racemose NCC and other descriptions about CC. At the veterinary side, two rare clinical manifestations of coenuriasis in sheep we reported in two lambs of 6–7 weeks old. In humans, symptoms include headaches, seizures, vomiting, paraplegia, hemiplegia, dysphasias, and epilepsy.

#### **2.4 Some major zoonotic nematodes (roundworms)**

Nematodes are characterized as free-living or parasitic, unsegmented, cylindrical, and elongated round worms with a body cavity and alimentary canal. Almost all nematodes are sex-separated and their life cycles are direct or indirect. The major intestinal nematodes are *Ascaris lumbricoides* (roundworm), *Enterobius vermicularis* (pinworm), hookworms, *Trichuris*  *trichiura* (whipworm), *Trichostrongylus orientalis,* and *Strongyloides stercoralis.* As imported zoonotic nematode infections, loiasis cases due to the Loa loa*.* As indigenous infections, there have been several human *Thelazia callipaeda* infections. *Dirofilaria immitis* infections are very popular among dogs but very scanty medical information about this parasite in human beings is found.

#### **2.4.1 Neuroangiostrongyliasis**

318 Novel Aspects on Epilepsy

Cyclophyllidea, i.e., *H. diminuta, H. nana, Mesocestoides lineatus,T. saginata, T. solium,* and *E. granulosus.* He reported that the plerocercoid larva of *Spirometra* spp.(sparganum) infects

Sparganosis first reported in swine in 1911 in Indochina. It is a disease found in snakes, reptiles, and mammals, including swine and man. It is caused by migration of the second larval stage (spargana) of the cestode *Spirometra*. (Mueller, 1974). Human sparganosis occurs worldwide. The majority of cases has been reported from China, Korea, Japan, and Southeast Asia. Approximately 70 cases of human sparganosis have been reported from the United States, most from the Southeast region of the country. Transmission to humans has occurred through intact mucous membranes, by the ingestion /handling of frogs and snakes, poultry, and pork, and by ingestion of contaminated water. Disease in man can produce subcutaneous, cerebral, ocular, visceral, and metastatic forms depending upon the

Echinococcosis is caused by tapeworms of the genus Echinococcus, common parasites of dogs and cats, who are the definitive hosts; humans can be intermediate hosts. The disease is endemic in countries around the Mediterranean: Greece, Turkey, and Lebanon have the highest prevalences. The small adult worms live in the definitive host's gut and discharge eggs into feces. If inadvertently ingested by a human, the eggs hatch in the human's gut, enabling the organism to penetrate the human's gut wall and spread hematogenously. Once located in a final tissue site, the organism forms a slowly enlarging cyst, a hydatid.When in the CNS, cysts usually locate in brain parenchyma. Clinical manifestations are secondary to this mass lesion, raised intracranial pressure, or both. Although praziquantel has activity against these organisms, the primary treatment of CNS hydatids is surgical. Antiepileptic

Another parasitic zoonosis which shows similar symptoms to NC is coenuriasis, due to invasion of the brain by the larval stage knowing by *Coenuruses cerebralis* (CC) of the tapeworm *Multiceps multiceps*. Watson and Lurie (1956) from Edendale Hospital in PieterMarisberg, South Africa reported five cases from 1951 to 1956 and described their anatomic-pathological finding on post-mortem examinations. One year later also in South Africa, Plumber et al (1957) reported some cases and reviewed the medical literature. At the time that they reviewed the available English-language medical literature a total 14 case from South Africa were found. From his anatomopathological report we could not find gross different from racemose NCC and other descriptions about CC. At the veterinary side, two rare clinical manifestations of coenuriasis in sheep we reported in two lambs of 6–7 weeks old. In humans, symptoms include headaches, seizures, vomiting, paraplegia,

Nematodes are characterized as free-living or parasitic, unsegmented, cylindrical, and elongated round worms with a body cavity and alimentary canal. Almost all nematodes are sex-separated and their life cycles are direct or indirect. The major intestinal nematodes are *Ascaris lumbricoides* (roundworm), *Enterobius vermicularis* (pinworm), hookworms, *Trichuris* 

humans through 16 kinds of animal hosts, such as, snakes, frogs, and so on.

migration of the parasite. (Pullar &McLenan 1949; Gordon, 1954; Gray et a., 1999).

management is a crucial adjunctive treatment. ( Schachter, 2004)

**2.3.1 Neuroechinoccosis** 

**2.3.2 Neurocoenurosis** 

hemiplegia, dysphasias, and epilepsy.

**2.4 Some major zoonotic nematodes (roundworms)** 

Angiostrongyliasis is caused by the rat lungworm. *Angiostrongylus cantonensis* is endemic through Southeast Asia and the Pacific Islands. The infection in humans, an accidental host, is associated with eosinophilic meningitis. The dog tapeworm, Echinococcus granulosus, can infect humans with up to 2% of clinical cases presenting with brain cysts. The infection has a cosmopolitan distribution. Humans get infected with dog feces and CNS infection is usually associated with signs of increased intracranial pressure ( Hughes & Biggs, 2002, 2002a) and epileptic seizures. There is no established antiparasitic treatment. Comorbid seizures are managed under the similar protocol for other parasitic zoonoses infecting the brain (Schachter, 2004).

#### **2.4.2 Neurognathostomiasis**

Gnathostomiasis is a parasitic infection caused by the third-stage larvae of the helminths *Gnathostoma spp*., which are seen mostly in tropical and subtropical regions. The genus *Gnathostoma* belongs to the order *Spirurida*, one of the largest groups of nematodes. The genus has 12 species These groups are characterized biologically by requiring one or more intermediate hosts in their life cycles It is a food-borne zoonosis endemic in areas where people are accidental hosts in which the parasite fails to reach sexual maturity after eating raw freshwater fish or shellfish, especially Thailand and other parts of Southeast Asia, Japan, and increasingly Latin America, particularly Mexico. (Daengsvang, 1981; Nawa, 1991)

Visceral disease is more serious than the cutaneous manifestations and, in the case of central nervous system disease, may be fatal. (Herman & Chiodina, 2009). The main features of CNS involvement can cause radiculomyelitis, radiculomyeloencephalitis, eosinophilic meningitis, and subarachnoid hemorrhage. The hallmark symptoms are an acute onset of excruciating radicular pain and/or headache (subarachnoid hemorrhage or eosinophilic meningitis), with subsequent paralysis of the extremities and/or cranial nerve palsies. The typical clinical picture can be explained by the migratory pathway of the parasite, which gains entry to the spinal cord along nerve roots (cranial, cervical, thoracic, or lumbar), causing intense radicular pain (or headache in the case of cranial nerve or cervical root involvement) which usually lasts from 1 to 5 days. Cranial nerve palsies tend to occur after the onset of paralysis, and if multiple they signify a poor prognosis. Cerebral involvement is usually indicated by a depressed consciousness level or coma, but interestingly, mental confusion does not tend to occur (Herman & Chiodini, 2009).

The main differential diagnosis of neurognathostomiasis is with *Angiostrongylus cantonensis*, another highly prevalent parasite in Southeast Asia. This may produce a similar eosinophilic menigoencephalitis, but the acute nerve root pain, signs of spinal cord compression, and hemorrhagic or xanthochromic spinal fluid seen in gnathostomiasis are absent with *Angiostrongylus*infection (Herman & Chiodini, 2009). The *Gnathostoma* larva is more invasive than that of *Angiostrongylus* and therefore produces more frequent focal neurological signs.

Epilepsy Secondary to Parasitic Zoonoses of the Brain 321

because I also had a very good veterinarian friend. Without any doubt dogs are the most common pet animals worldwide and they perform a range of cultural, social, and economic functions at home and in our society. Dogs were domesticated from wolves as recently as 15000 years ago (Morey, 2006), or perhaps as early as 100000 years ago based on recent genetic fossil and DNA evidence (Savolainen *et al*., 2002, Lindbald-Toh, 2005). Evidence suggests that dogs were first domesticated in East Asia, possibly China, and the first people

Dogs are kept as pets and companions, for hunting, as guards, draught animals, for food, or for commercial purposes (Swai E et al., 2010). Some studies also suggest that keeping pets be associated with a higher level of self-esteem in children (Paul and Serpell, 1996; Knobel *et al*., 2008). It is fairly common for a dog to become infected with an internal or external parasite at some point in their lifetime. Parasites can infect your pet any time of year and there is a

External parasites, such as fleas and ticks may be less prevalent outside during certain times of the year however they often survive in the house during the winter months, creating an uninterrupted life cycle. Other internal parasites such as worms may affect your pet all year long. Nevertheless, dogs have been living with humans since early civilization, studies of dog's parasitic zoonoses affecting the human brain in sub- Saharan Africa are scanty and very limited information is available in the medical literature. Dogs can carry over a dozen forms of zoonotic diseases mainly to their owners if they do not practice appropriate hygiene and disease-control measures. And to some peoples are at a higher risk of contracting zoonotic diseases such as: peoples with malignancies, young children, immunocompromised patients, and over expose persons. Some zoonotic diseases are fairly

Apart from the tapeworm, other parasites can spread from dogs to humans (See figure 1). Hookworm and roundworm are both zoonotic infections that can be spread through the improper handling of contaminated dog feces. Several species of these parasites can thrive in the colons of both humans and dogs. Hookworm and roundworm can both be spread through the accidental ingestion of dog feces that is contaminated with parasite eggs or larvae. This can occur through improper handling of waste, and people may become infected by walking barefoot on soil that has been contaminated with infected dog feces. Nowadays, veterinary practices have the important responsibility of educating pet owners about the potential risk of zoonotic parasites and the different measures that can be taken

Another parasitic zoonosis associated with dogs and epilepsy is toxocariasis. The definitive hosts of *T. canis* and *T. cati* are dogs and cats, respectively. Infection in dogs is usually acquired in the uterus or through nursing. In the United States, it has been reported that up to 80% of puppies less than 6 weeks old are infected with *T. canis*. Hence, puppies are the most important sources of contamination of the environment. Cats of any age can contaminate the environment with *T. cati*. However, human infection with *T. cati* has been less often reported (Little, 2003)*..* Humans acquire the infection through ingestion of the eggs of the parasite that have been present in the environment for at least two weeks but that may have survived for several years. This make young children at a particularly high risk of infection due to their normal geophagy behavior. In the developing world, the environment is likely to be heavily contaminated with eggs that are infectious to humans.

to enter North America took dogs with them (Savolainen *et al*., 2002).

long list of them. (See figure 1)

common in dogs, while others are exceedingly rare.

for their control and prevention (CDC, 2004).

In contrast, the *Angiostrongylus* larva, which is considerably smaller (120 µm wide and 12 mm long) and usually multiple, more commonly causes a menigoencephalitis, and although neurotropic, it is rarely fatal (Herman & Chiodini, 2009).

The triad of eosinophilia, migratory lesions, and obvious exposure risk are highly suggestive of the diagnosis of gnathostomiasis. Eosinophilia of the cerebrospinal fluid (CSF) is also highly supportive of neurognathostomiasis, with reported levels of 5 to 94% and a total CSF white cell count of up to 500/mm3 (range, 20 to 1420/mm3), but may also be found with several other parasites, e.g., *Angiostrongylus cantonensis*, *Toxocara canis*, *Strongyloides stercoralis*, *Ascaris lumbricoides*, *Paragonimus westermani*, *Fasciola hepatica*, and *Trichinella spiralis* and with schistosomiasis, cystercercosis, and other infections such as coccidiodomycosis and aspergillus infection Because no single area of the nervous system is inaccessible to the highly invasive gnathostome lava and multiplicity and/or rapid progression of lesions beyond the degree of cerebral edema explained by further migration of the parasite. Therefore epileptic seizures and epilepsy can be expected and treated accordingly. Multiple cranial nerve palsies are signs of poor prognosis. (Boongird et al., 1977)

### **2.4.3 Neurotrichinellosis**

Trichinellosis also called trichinosis, trichinellosis or trichiniasis (Trich from Greek *thrix* meaning hair) is an infection due to nematodes of the genus *Trichinella*, most commonly *T spiralis*. Infection is initiated by ingestion of viable larvae in raw or undercooked meat. Digestive action liberates the larvae. The liberated larvae develop into adults in the duodenum and jejunum, where they mate and bear offspring. The adult worms are expelled in the stool. Eosinophilia develops in response to the presence of the worm. Patients who develop neurologic and cardiac dysfunctions have marked eosinophilia associated with arteriolar microthrombi, often simply from the numbers of larvae, leading to areas of cerebral and myocardial infarction.

Neurological involvement may occur in 0.2%–52% of cases with trichinellosis spirallis, generally in the most severely affected patients. However, another author refers that involvement of the central nervous system occurs in 10-20% and mortality rates may then approach 50% (Clausen, 1996). Apart from *Trichinella spiralis* other parasitic infections that may cause abnormal mental status and eosinophilia include toxocariasis (Despommier, 2003), angiostrongyloidiasis, and baylisascariasis (Gavin et al., 2005). Clinical signs and symptoms are meningitis, encephalitis, cranial nerve deficits, paresis, aphasia, convulsions and coma (Fourestie et al., 1993; Gay et al., 1982) Small hypodense areas in the white matter and in the cortex have been reported long time ago (Ellrodt et al., 1987). Absence of pets at home or contact with raccoons, the lack of eosinophils in the CSF, and the lack of ocular larva migrans on examination argue against trichinellosis. (Madariaga, 2007) Treatment of choice is thiabendazole and steroids. Epileptic seizures and epilepsy are managed following same protocol used routinely. For more details please consult the book : "Treatment approach for epilepsy" ISBN 978-953-307-678-2.

#### **May dogs cause epilepsy?**

Of course no, I always remember my parents when they said: "El perro es el mejor amigo del hombre" (The dog is the best man's friend) and they were right, I had a very good one

In contrast, the *Angiostrongylus* larva, which is considerably smaller (120 µm wide and 12 mm long) and usually multiple, more commonly causes a menigoencephalitis, and although

The triad of eosinophilia, migratory lesions, and obvious exposure risk are highly suggestive of the diagnosis of gnathostomiasis. Eosinophilia of the cerebrospinal fluid (CSF) is also highly supportive of neurognathostomiasis, with reported levels of 5 to 94% and a total CSF white cell count of up to 500/mm3 (range, 20 to 1420/mm3), but may also be found with several other parasites, e.g., *Angiostrongylus cantonensis*, *Toxocara canis*, *Strongyloides stercoralis*, *Ascaris lumbricoides*, *Paragonimus westermani*, *Fasciola hepatica*, and *Trichinella spiralis* and with schistosomiasis, cystercercosis, and other infections such as coccidiodomycosis and aspergillus infection Because no single area of the nervous system is inaccessible to the highly invasive gnathostome lava and multiplicity and/or rapid progression of lesions beyond the degree of cerebral edema explained by further migration of the parasite. Therefore epileptic seizures and epilepsy can be expected and treated accordingly. Multiple cranial nerve palsies are signs of poor prognosis. (Boongird et al.,

Trichinellosis also called trichinosis, trichinellosis or trichiniasis (Trich from Greek *thrix* meaning hair) is an infection due to nematodes of the genus *Trichinella*, most commonly *T spiralis*. Infection is initiated by ingestion of viable larvae in raw or undercooked meat. Digestive action liberates the larvae. The liberated larvae develop into adults in the duodenum and jejunum, where they mate and bear offspring. The adult worms are expelled in the stool. Eosinophilia develops in response to the presence of the worm. Patients who develop neurologic and cardiac dysfunctions have marked eosinophilia associated with arteriolar microthrombi, often simply from the numbers of larvae, leading to areas of

Neurological involvement may occur in 0.2%–52% of cases with trichinellosis spirallis, generally in the most severely affected patients. However, another author refers that involvement of the central nervous system occurs in 10-20% and mortality rates may then approach 50% (Clausen, 1996). Apart from *Trichinella spiralis* other parasitic infections that may cause abnormal mental status and eosinophilia include toxocariasis (Despommier, 2003), angiostrongyloidiasis, and baylisascariasis (Gavin et al., 2005). Clinical signs and symptoms are meningitis, encephalitis, cranial nerve deficits, paresis, aphasia, convulsions and coma (Fourestie et al., 1993; Gay et al., 1982) Small hypodense areas in the white matter and in the cortex have been reported long time ago (Ellrodt et al., 1987). Absence of pets at home or contact with raccoons, the lack of eosinophils in the CSF, and the lack of ocular larva migrans on examination argue against trichinellosis. (Madariaga, 2007) Treatment of choice is thiabendazole and steroids. Epileptic seizures and epilepsy are managed following same protocol used routinely. For more details please consult the book : "Treatment

Of course no, I always remember my parents when they said: "El perro es el mejor amigo del hombre" (The dog is the best man's friend) and they were right, I had a very good one

neurotropic, it is rarely fatal (Herman & Chiodini, 2009).

1977)

**2.4.3 Neurotrichinellosis** 

cerebral and myocardial infarction.

approach for epilepsy" ISBN 978-953-307-678-2.

**May dogs cause epilepsy?** 

because I also had a very good veterinarian friend. Without any doubt dogs are the most common pet animals worldwide and they perform a range of cultural, social, and economic functions at home and in our society. Dogs were domesticated from wolves as recently as 15000 years ago (Morey, 2006), or perhaps as early as 100000 years ago based on recent genetic fossil and DNA evidence (Savolainen *et al*., 2002, Lindbald-Toh, 2005). Evidence suggests that dogs were first domesticated in East Asia, possibly China, and the first people to enter North America took dogs with them (Savolainen *et al*., 2002).

Dogs are kept as pets and companions, for hunting, as guards, draught animals, for food, or for commercial purposes (Swai E et al., 2010). Some studies also suggest that keeping pets be associated with a higher level of self-esteem in children (Paul and Serpell, 1996; Knobel *et al*., 2008). It is fairly common for a dog to become infected with an internal or external parasite at some point in their lifetime. Parasites can infect your pet any time of year and there is a long list of them. (See figure 1)

External parasites, such as fleas and ticks may be less prevalent outside during certain times of the year however they often survive in the house during the winter months, creating an uninterrupted life cycle. Other internal parasites such as worms may affect your pet all year long. Nevertheless, dogs have been living with humans since early civilization, studies of dog's parasitic zoonoses affecting the human brain in sub- Saharan Africa are scanty and very limited information is available in the medical literature. Dogs can carry over a dozen forms of zoonotic diseases mainly to their owners if they do not practice appropriate hygiene and disease-control measures. And to some peoples are at a higher risk of contracting zoonotic diseases such as: peoples with malignancies, young children, immunocompromised patients, and over expose persons. Some zoonotic diseases are fairly common in dogs, while others are exceedingly rare.

Apart from the tapeworm, other parasites can spread from dogs to humans (See figure 1). Hookworm and roundworm are both zoonotic infections that can be spread through the improper handling of contaminated dog feces. Several species of these parasites can thrive in the colons of both humans and dogs. Hookworm and roundworm can both be spread through the accidental ingestion of dog feces that is contaminated with parasite eggs or larvae. This can occur through improper handling of waste, and people may become infected by walking barefoot on soil that has been contaminated with infected dog feces. Nowadays, veterinary practices have the important responsibility of educating pet owners about the potential risk of zoonotic parasites and the different measures that can be taken for their control and prevention (CDC, 2004).

Another parasitic zoonosis associated with dogs and epilepsy is toxocariasis. The definitive hosts of *T. canis* and *T. cati* are dogs and cats, respectively. Infection in dogs is usually acquired in the uterus or through nursing. In the United States, it has been reported that up to 80% of puppies less than 6 weeks old are infected with *T. canis*. Hence, puppies are the most important sources of contamination of the environment. Cats of any age can contaminate the environment with *T. cati*. However, human infection with *T. cati* has been less often reported (Little, 2003)*..* Humans acquire the infection through ingestion of the eggs of the parasite that have been present in the environment for at least two weeks but that may have survived for several years. This make young children at a particularly high risk of infection due to their normal geophagy behavior. In the developing world, the environment is likely to be heavily contaminated with eggs that are infectious to humans.

Epilepsy Secondary to Parasitic Zoonoses of the Brain 323

epileptic seizures. Lyme disease should be suspected in any patient with chronic lymphocytic meningitis or mild menigoencephalitis with associated cranial neuritis or radiculitis. Lab tests include serologic assays like immunofluorescent assay and enzymelinked immunoassay tests for anti–B. burgdorferi antibodies. Specific anti–B. burgdorferi antibody also appears in CSF, where it can be detected even when serum antibody tests are negative. (To establish whether these antibodies are synthesized intrathecally, serum and CSF antibody levels should be measured simultaneously. Treatment for epilepsy did not differ from other parasitic zoonoses although epilepsy seems to be a minor problem in this condition even in HIV-positive patients (van Burgel et al., 2010; Henningsson et al., 2010).

*Coccidiosis* is an intestinal disease that affects several different animal species including canines and humans. Coccidia is one of the most prevalent protozoal infections in North American animals, second only to giardia. Eimeria and Isospora are the two genera that are often referred to as "coccidia." These two genera contain a large number of species that infect a variety of animals throughout the world. The diseases caused by these microscopic protozoal parasites are referred to collectively as coccidiosis, and they vary tremendously in virulence. Some species cause diseases that result in mild symptoms that might go unnoticed (i.e., Mild diarrhea) and eventually disappear, while other species cause highly virulent infections that are rapidly fatal. The causative agent is a protozoan that has the ability to multiply rapidly. The major damage is due to the rapid multiplication of the parasite in the intestinal wall, and the subsequent rupture of the cells of the intestinal lining. Several stages of multiplication occur before the final stage, the oocyst, is passed in the feces. Oocysts are extremely resistant to environmental stress and are difficult to completely remove from the environment. Oocysts are frequent contaminants of feed and water and when the sporulated oocysts are ingested by other animals they start the life cycle over in the new host. Neurococcidiosis is characterized by epileptic seizures among other signs but

African trypanosomiasis, or sleeping sickness, is caused by Trypanosoma brucei. The tsetse fly is the arthropod vector. CNS involvement is the principal clinical consequence. An inflammatory nodule, a chancre, appears within several days at the site of parasite inoculations by the biting tsetse fly. Parasite replication and local tissue invasion are followed by lymphatic and bloodstream entry, causing a diffuse lymphadenopathy and

Recurrent cycles of hemo-lymphatic parasitemia follow, with corresponding bouts of fever alternating with periods of well-being. (African trypanosomiasis and malaria are two of the few causes of true intermittent fever. Trypanosomes eventually enter the CNS to cause meningoencephalitis, with a full range of neuropsychiatric signs and symptoms, including sleep-wake cycle abnormalities (e.g., Daytime drowsiness and nocturnal insomnia), from which the disease derived its name. Frequent episodes of awakening during sleep, blurring

Generalized convulsions become common as the disease progresses to later stages. If untreated, mortality approaches 100%. Of the three drugs usually used for treatment

of sleep stages, and irregular bursts of rapid EEG activity during stage 4 sleep occur.

it has been reported in calves and cows (Oliveira et al., 2009)

**2.6 Neuroccocidiosis** 

**2.7 African trypanosomiasis** 

parasitemia with high fever.

The fact that most communities are largely agricultural, that most pet animals freely roam everywhere and that there is a lack of sanitation could lead to a high risk of infection in persons of all ages. Dogs without veterinarian care are not our best friend. The choice is yours advise is mine.

Fig. 1. Rural community at the former Transkei in South Africa.

### **2.5 Neuroborreliosis**

Within days to weeks, *Borrelia burgdorferi* the causative agent of Lyme disease, spreads hematogenously and it probably enters the CNS at this time. One to two months postinfection, B. burgdorferi localizes and becomes sequestered in certain tissues. The nervous system is involved in up to 20% of untreated North American patients. Meningitis (typically lymphocytic) is the most common neuropathology abnormality in early disseminated of Lyme disease.

Neurologic deficits, including seizure, can be the initial clinical manifestation. Neurologic abnormalities that have been reported to be associated with early CNS Lyme disease include: acute aseptic meningitis, acute purulent meningitis chronic lymphocytic meningitis, recurrent meningitis, acute meningoenchephalitis, acute focal encephalitis, encephalomyelitis, leukoencephalitis, acute cerebellar ataxia, acute parkinsonian syndrome, acute transverse myelitis, subacute myelitis, cognitive deficits affective disturbance, and epileptic seizures. Lyme disease should be suspected in any patient with chronic lymphocytic meningitis or mild menigoencephalitis with associated cranial neuritis or radiculitis. Lab tests include serologic assays like immunofluorescent assay and enzymelinked immunoassay tests for anti–B. burgdorferi antibodies. Specific anti–B. burgdorferi antibody also appears in CSF, where it can be detected even when serum antibody tests are negative. (To establish whether these antibodies are synthesized intrathecally, serum and CSF antibody levels should be measured simultaneously. Treatment for epilepsy did not differ from other parasitic zoonoses although epilepsy seems to be a minor problem in this condition even in HIV-positive patients (van Burgel et al., 2010; Henningsson et al., 2010).

#### **2.6 Neuroccocidiosis**

322 Novel Aspects on Epilepsy

The fact that most communities are largely agricultural, that most pet animals freely roam everywhere and that there is a lack of sanitation could lead to a high risk of infection in persons of all ages. Dogs without veterinarian care are not our best friend. The choice is

Fig. 1. Rural community at the former Transkei in South Africa.

Within days to weeks, *Borrelia burgdorferi* the causative agent of Lyme disease, spreads hematogenously and it probably enters the CNS at this time. One to two months postinfection, B. burgdorferi localizes and becomes sequestered in certain tissues. The nervous system is involved in up to 20% of untreated North American patients. Meningitis (typically lymphocytic) is the most common neuropathology abnormality in early

Neurologic deficits, including seizure, can be the initial clinical manifestation. Neurologic abnormalities that have been reported to be associated with early CNS Lyme disease include: acute aseptic meningitis, acute purulent meningitis chronic lymphocytic meningitis, recurrent meningitis, acute meningoenchephalitis, acute focal encephalitis, encephalomyelitis, leukoencephalitis, acute cerebellar ataxia, acute parkinsonian syndrome, acute transverse myelitis, subacute myelitis, cognitive deficits affective disturbance, and

yours advise is mine.

**2.5 Neuroborreliosis** 

disseminated of Lyme disease.

*Coccidiosis* is an intestinal disease that affects several different animal species including canines and humans. Coccidia is one of the most prevalent protozoal infections in North American animals, second only to giardia. Eimeria and Isospora are the two genera that are often referred to as "coccidia." These two genera contain a large number of species that infect a variety of animals throughout the world. The diseases caused by these microscopic protozoal parasites are referred to collectively as coccidiosis, and they vary tremendously in virulence. Some species cause diseases that result in mild symptoms that might go unnoticed (i.e., Mild diarrhea) and eventually disappear, while other species cause highly virulent infections that are rapidly fatal. The causative agent is a protozoan that has the ability to multiply rapidly. The major damage is due to the rapid multiplication of the parasite in the intestinal wall, and the subsequent rupture of the cells of the intestinal lining. Several stages of multiplication occur before the final stage, the oocyst, is passed in the feces. Oocysts are extremely resistant to environmental stress and are difficult to completely remove from the environment. Oocysts are frequent contaminants of feed and water and when the sporulated oocysts are ingested by other animals they start the life cycle over in the new host. Neurococcidiosis is characterized by epileptic seizures among other signs but it has been reported in calves and cows (Oliveira et al., 2009)

#### **2.7 African trypanosomiasis**

African trypanosomiasis, or sleeping sickness, is caused by Trypanosoma brucei. The tsetse fly is the arthropod vector. CNS involvement is the principal clinical consequence. An inflammatory nodule, a chancre, appears within several days at the site of parasite inoculations by the biting tsetse fly. Parasite replication and local tissue invasion are followed by lymphatic and bloodstream entry, causing a diffuse lymphadenopathy and parasitemia with high fever.

Recurrent cycles of hemo-lymphatic parasitemia follow, with corresponding bouts of fever alternating with periods of well-being. (African trypanosomiasis and malaria are two of the few causes of true intermittent fever. Trypanosomes eventually enter the CNS to cause meningoencephalitis, with a full range of neuropsychiatric signs and symptoms, including sleep-wake cycle abnormalities (e.g., Daytime drowsiness and nocturnal insomnia), from which the disease derived its name. Frequent episodes of awakening during sleep, blurring of sleep stages, and irregular bursts of rapid EEG activity during stage 4 sleep occur.

Generalized convulsions become common as the disease progresses to later stages. If untreated, mortality approaches 100%. Of the three drugs usually used for treatment

Epilepsy Secondary to Parasitic Zoonoses of the Brain 325

meat, or using frog or snake meat as a poultice) might be a clue and offers supporting evidence for a presumptive diagnosis in cases of abnormal brain MR imaging results ( Song et al., 2007; Chiu et al., 2010; Wiwanitkit, 2010). 4 cases had a history of eating raw frogs or snakes. 5 showed eosinophilia in peripheral blood, all with positive anti-Sparganum mansoni antibody in serum and cerebrospinal fluid. Cerebral MRI showed placeholder in all patients. Diagnosis was confirmed by pathological examination of operations and species identification. All patients were cured by operation removal and praziquantel treatment.

Filariasis and onchocerciasis are parasitic helminth diseases that constitute a serious public health issue in tropical regions. The filarial nematodes that cause these diseases are transmitted by blood-feeding insects and produce chronic and long-term infection through suppression of host immunity. Disease pathogenesis is linked to host inflammation invoked by the death of the parasite, causing hydrocoele, lymphoedema, and elephantiasis in lymphatic filariasis, and skin disease and blindness in onchocerciasis. (Taylor et al., 2011) As far we know, epilepsy secondary to filariasis has not been

This capability, coupled with an integrated, multidisciplinary and ecological approach, makes possible the identification of parasitic infections and diseases likely to be particularly susceptible to climate change and, with adjustments for regional variations, the exploration of some of the possible consequences of accelerating climate change of the occurrence ofthese diseases and for animal and human health. This is a very urgent need, and without such an attempt to anticipate the possible, society is likely to be a more or less impotent

Neurocisticercosis (NC) is a parasitic infection of central nervous system (CNS) caused by the larval stage (Cysticercus cellulosae) of the pig tapeworm Taenia solium. This is the most common helminth to produce CNS infection in human being. The occurrence of acquired epilepsy or the syndrome of raised intracranial pressure in a person living in or visiting a region where taeniasis is endemic or even in one living in close contact with people who have taeniasis should suggest a diagnosis of cysticercosis; the NC may remain asymptomatic for months to years and sometimes its diagnosis is made incidentally when neuroimaging is performed. Symptoms and signs are related both to the parasite which can show a different biological behavior from one place to another, and to the inflammatoryinmunological response of the host. NC is the most common cause of acquired epilepsy worldwide and most of the patients taking phenytoin or carbamazepine for a proper control of their seizures, respond very well NC is also an important cause of ischemic stroke secondary to infectious vasculitis (Foyaca-Sibat & Ibañez-Valdés, 2003). The most common cause of epilepsy due to NC is calcified lesion with or without evidence of perilesional edema. The prognosis of this situation is worse when there is an associated intraventricular cyst (Figure 2) that usually does not respond well to praziquantel and albendazole should be prescribe (Foyaca-Sibat & Ibañez-Valdés, 2003). More information about NC can be found

spectator to the certainty of continual ecological calamities. (Polley, 2010).

(Chen & Shi, 2010).

**3.2 Neurofilariasis** 

**3.3 Neurocysticercosis** 

in this book.

reported.

(suramin, pentamidine, and melarsoprol), only melarsoprol penetrates the blood-brain barrier to be effective in CNS disease. Its use is complicated by an up to 18% incidence of severe, reactive arsenic encephalopathy, which can result in permanent neurologic damage or death. Consequently, melarsoprol should be used only in patients with CNS involvement. In a study of melarsoprol effects on patients with T. gambiense in the meningoencephalitic stage, EEG tracings before treatment showed marked abnormalities in the form of periodic delta outbursts. (Hamon & Camara, 1991)

#### **2.8 American trypanosomiasis**

American trypanosomiasis, also known as Chagas' disease, is an acute or chronic infection caused by *Trypanosoma cruzi* and occurs only in the western hemisphere. Chagas disease is the third most common parasitic infection worldwide after malaria and schistosomiasis. (WHO 2005). Seizures sometimes occur at stroke onset, and epilepsy is quite a frequent complication after chagasic stroke. Chronic vascular epilepsy, characterized by secondary generalised seizures, have been reported in around 20% of patients surviving chagasic stroke, whereas around 10% of stroke patients without the Chagas disease have seizures (Carod-Artal et al., 2005).The effect of uncontrolled seizures on cognition and disability in Chagas disease is unknown. No prospective epidemiological studies have addressed the risk of acute seizures and their recurrence in acute chagasic stroke (Carod-Artal & Gascon, 2010)
