Neuroparasitology and Tropical Neurology, a new volume in The Handbook of Clinical Neurology, provides a comprehensive and contemporary reference on parasitic infections of the human nervous system. Parasitic infections are varied and some are resolved by the host's immune system, other infections may become established even though unnoticed, and some cause severe disease and death. In our modern world, neuroparasitoses are no longer geographically isolated and these infections now appear worldwide. Outside of a very few well understood pathologies, most parasitic infections have been neglected in the neurological literature and most neurologists have never diagnosed such an infection. This volume details how, with the advent of modern neuroimaging techniques, improved diagnostic applications of molecular biology, more accurate immunodiagnosis, and minimally invasive neurosurgery, human nervous system parasitoses are now diagnosed and treated, with increasing frequency. The book is divided into six sections, and begins with an introduction to the mechanisms of infection, diagnosis, and pathology of parasitic diseases. Subsequent chapters detail protozoan diseases and a section covering each of the major classes of human-infecting helminths: nematodes (roundworms), trematodes (flukes), and cestodes (tapeworms). The final section contains chapters on other important areas of tropical clinical medicine including the neurological complications of venomous bites and tropical nutritional deficiencies. Neuroparasitology and Tropical Neurology will be of interest to neurologists, neurosurgeons and other health professionals encountering patients with parasitic infections. - A comprehensive reference resource on the diagnosis and treatment of parasitic infections of the human nervous system - Focuses on the impact of modern neuroimaging techniques, improved diagnostic applications of molecular biology, more accurate immunodiagnosis, and minimally invasive neurosurgery to diagnose parasitoses - International list of contributors including the leading workers in the field

Cysticercosis, an infection caused by the cystic larvae of the pork tapeworm Taenia solium, is one of the most frequent parasitic infections of the human nervous system (neurocysticercosis). It is endemic in most of Latin America, the sub-Saharan Africa, and vast parts of Asia, including the Indian subcontinent. It has also been increasingly diagnosed in developed countries because of migration of people from endemic zones and exposure in travelers. The life cycle involves the development of the adult tapeworm in the human small intestine (after ingesting infected pork with cysts) and larval infection in pig tissues (after ingesting human stools containing the eggs of the tapeworm). Humans get infected by the fecal-oral route, most often from a direct contact with an asymptomatic Taenia carrier. Most common clinical presentations are seizures (particularly late-onset seizures), chronic headaches, and intracranial hypertension. However, cysticerci can locate anywhere in the human nervous system, thus potentially causing almost any neurological syndrome and making clinical diagnosis a difficult task. Neuroimaging is the main diagnostic tool, and specific serology confirms the diagnosis and helps to define the diagnosis when images are unclear. Factors such as location (extraparenchymal versus intraparenchymal), number, size and evolutive stage of the parasites determine the clinical manifestations, therapeutic approach, and prognosis. Management includes symptomatic drugs (analgesics, antiepileptic drugs, anti-inflammatory agents) and in many cases cysticidal drugs, either albendazole or praziquantel. In recent years, efforts have focused on transmission control and potential elimination in endemic regions.

Published reviews vary on the question of whether geohelminth infections affect cognitive development: some claim that the scarcity of evidence means that it is unlikely that they do; others present modest evidence for an effect; and others raise the possibility that the damage is considerable but largely unresearched. This chapter reviews the characteristics of the geohelminths themselves and the pathways by which they could affect the development of children in endemic areas. It describes the progress made in the last decade in conceptualizing children's brains as complex adaptive systems, with the suggestion that infections at different stages in brain development might have different neurobehavioral consequences. An examination of research reports and review articles highlights the difficulties inherent in assessing the effects of geohelminth infections: other serious obstacles to healthy development in the same population may mask the effects of the geohelminths, and consequently the intensity and pathogenicity of the infection is probably an important issue. Selecting cognitive measures suitable for assessing development in very young children is no simple matter, and careful statistical analysis is required to tease out the primary and secondary factors at work. The insights gained from a broad range of relevant research reports have placed us in a better position to conduct more telling research into the effects of these widespread, but neglected, tropical diseases.

Snake and spider bites, as well as scorpion sting envenoming, are neglected diseases affecting millions of people all over the world. Neurological complications vary according to the offending animal, and are often directly related to toxic effects of the venom, affecting the central nervous system, the neuromuscular transmission, the cardiovascular system, or the coagulation cascade. Snake bite envenoming may result in stroke or muscle paralysis. Metalloproteinases and other substances (common in vipers and colubrids) have anticoagulant or procoagulant activity, and may induce ischemic or hemorrhagic strokes. The venom of elapids is rich in neurotoxins affecting the neuromuscular transmission at either presynaptic or postsynaptic levels. The clinical picture of scorpion sting envenoming is dominated by muscle weakness associated with arterial hypertension, cardiac arrythmias, myocarditis, or pulmonary edema. These manifestations occur as the result of release of catecholamines into the bloodstream or due to direct cardiac toxicity of the venom. Cerebrovascular complications have been reported after the sting of the Indian red scorpion. Intracranial hemorrhages occur in the setting of acute increases in arterial blood pressure related to sympathetic overstimulation, and cerebral infarctions are related to either cerebral hypoperfusion, consumption coagulopathy, vasculitis, or cardiogenic brain embolism. Three main syndromes result from spider bite envenoming: latrodectism, loxoscelism, and funnel-web spider envenoming. Latrodectism is related to neurotoxins present in the venom of widow spiders. Most cases present with headache, lethargy, irritability, myalgia, tremor, fasciculation, or ataxia. Loxoscelism is caused by envenoming by spiders of the family Sicariidae. It may present with a stroke due to a severe coagulopathy. The venom of funnel-web spiders also has neurotoxins that stimulate neurotransmitter release, resulting in sensory disturbances and muscle paralysis. Proper management of the envenomed patient, including prompt transport to the hospital, correction of the hemostatic disorder, ventilatory support, and administration of antivenom, significantly reduce the risk of neurological complications which, in turn, reduce the mortality and improve the functional outcome of survivors.

Schistosomiasis is a parasitic disease caused by blood flukes of the genus Schistosoma. Currently 200 million people worldwide are infected. Neurological manifestations are a result of the inflammatory response of the host to egg deposition in the brain and spinal cord and is usually seen in patients with recent infection with no evidence of systemic illness. Cerebral and cerebellar disease can result in headache, seizure, and increased intracranial pressure. Cerebral schistosomiasis is more common in Schistosoma japonicum, but increasing cases due to Schistosoma mansoni are being reported in the literature. Other complications of cerebral schistosomiasis include delirium, loss of consciousness, visual field impairment, focal motor deficits, and ataxia. Myelopathy is the most common neurological manifestation of Schistosoma mansoni and the conus medullaris and cauda equine are the most common sites of involvement. Severe disease can result in flaccid paraplegia with areflexia, sphincter dysfunction, and sensory disturbance. Early recognition and prompt treatment are essential when physicians are faced with schistosomiasis involving the central nervous system. Schistosomicidal drugs, such as praziquantel, steroids and surgery, are the mainstay of therapy for this severe form of schistosomiasis.

Leishmaniasis is a spectral disease, caused by obligate intracellular protozoa of the species Leishmania. There are multiple reported instances where neurological manifestations, whether central or peripheral, are described. In this review we describe neurological manifestations seen during infection with Leishmania spp. Taken together, the material discussed here suggests that in patients from Leishmania-endemic areas, when observing neurological symptoms, causation secondary to infection with Leishmania spp. may be considered.

Filarial infections cause a huge public health burden wherever they are endemic. These filaria may locate anywhere in the human body. Their manifestations and pathogenic mechanisms, except the most common ones, are rarely investigated systematically. Their neurological manifestations, however, are being increasingly recognized particularly with onchocerciasis or Loa loa infections, Wuchereria bancrofti, or Mansonella perstans. The risk of developing these manifestations may also increase in cases that harbor multiple filariasis or coinfections, for instance as with Plasmodium. The microfilaria of Onchocerca and Loa loa are seen in cerebrospinal fluid. The pathogenesis of neurological manifestations of these infections is complex; however, pathogenic reactions may be caused by mechanical disruption, e.g., degeneration often followed by granulomas, causing fibrosis or mass effects on other tissues, vascular lesions, e.g., vascular block of cerebral vessels, or disordered inflammatory responses resulting in meningitis, encephalitis or localized inflammatory responses. The chances of having neurological manifestations may also depend upon the frequency and“heaviness”of infection over a lifetime. Hence, this type of infection should no longer be considered a disease of the commonly affected areas but one that may produce systemic effects or other manifestations, and these should be considered in populations where they are endemic.

Many cestodes are capable of invading the central nervous system (CNS), and several are highly prevalent in the developing world. Neurocysticercosis due to Taenia solium and echinococcosis due to Echinoccocus granulosus are two of the most common parasitic infections affecting humans, but other less well-known parasites can also infect the nervous system. Coenurosis, caused by Taenia spp. such as T. multiceps, T. serialis, or T. brauni; sparganosis, caused by Spirometra spp., and neurocysticercosis caused by T. crassiceps are three less frequent zoonotic conditions that should be considered in the differential diagnosis of patients presenting with CNS infection – especially if they have lived in or traveled through areas where these infections are endemic. Diagnosis of these infections is typically made through a combination of serological testing, histopathology, and neuroimaging.

Neglected tropical diseases are a group of mostly infectious diseases that thrive among poor populations in tropical countries. A significant proportion of the conditions affecting the neurological system in such countries can be attributed to neglected tropical diseases of helminth, protozoan, bacterial, or viral origin. The neurological burden of neglected tropical diseases has not been thoroughly investigated yet, but is expected to be significant; its full appreciation, estimation, and recognition present significant challenges, as shown by the case of the “silent epidemic” of epilepsy. While tropical infections involving the nervous system are today largely preventable or treatable, as vaccines or chemotherapeutic agents are available to kill or neutralize the responsible agents, associated morbidity – when established – cannot be cured. In resource-poor settings it is likely that many infections will not be treated and will therefore progress into their advanced and severe stages, thus being increasingly associated with irreversible morbidity; this is also the case for neurological morbidity, which often entails permanent disability. Public health should aim at reducing the burden of tropical neurological diseases through interventions addressing the infection, the associated morbidity, and the disability deriving from it.

Babesiosis is a worldwide emerging infectious disease caused by intraerythrocytic protozoa that are transmitted by Ixodid ticks, or less commonly through blood transfusion or transplacentally. Although headache and lethargy are common symptoms, babesiosis is uncommonly associated with specific neurological dysfunction in humans. Decreased level of consciousness or coma are rare complications that are associated with severe and often fatal disease but the pathogenesis is unclear.