Parasitic Diseases Within the Spinal Cord and Nerve Roots · Keywords Parasitic .Schistosomiasis...
Transcript of Parasitic Diseases Within the Spinal Cord and Nerve Roots · Keywords Parasitic .Schistosomiasis...
MEDICINE
Parasitic Diseases Within the Spinal Cord and Nerve Roots
Benjamin Rahmani1 & Shrey Patel1 & Omar Seyam1& Jason Gandhi1,2 & Gunjan Joshi3 &
Inefta Reid1& Noel L. Smith4
& Sardar Ali Khan1,5
Accepted: 20 September 2019# Springer Nature Switzerland AG 2019
AbstractParasitic diseases of the spinal cord and nerve roots are a potentially deadlymatter. They are mainly found in areas where there arepoor sanitary conditions such as Africa, theMiddle East, and theWest Indies. Themost common diseases include schistosomiasisand neurocysticercosis. Furthermore, it is clear that through an understanding of all the various diseases there are, it is imminentthat patients are treated as soon as possible to avoid the deadly outcomes that the diseases can have to the body. This disease canhave several impacts on individuals that include epilepsy, health problems, and implications on various organs.
Keywords Parasitic . Schistosomiasis . Neurocysticercosis . Imaging .Malariasis . Syphilis . Central nervous system . Parasites
Introduction
Parasitic diseases of the central nervous system (CNS),particularly those pertaining to the spinal cord region,are a potentially deadly matter. Parasitic spinal infec-tions are commonly found in areas where there are poorsanitary conditions such as countries that are developingor not as well-equipped in the medical field as countriessuch as the USA [1]. These diseases are generally treat-able, and it is urgent that they are detected and treatedas early as possible to avoid complications [2]. Theresults of leaving these diseases undetected can includeirreversible neurological deficits, as seen in spinal cys-ticercosis [3].
There are a large number of causes for spinal infections.Among the wide range of agents, bacteria, such asBacteroidales and Clostridiales, are the most commonagents, although other organisms also can cause bacterialspinal injuries [4–6]. The bacteria are either single-celledprotozoa or multicellular metazoa [7]. More examples ofbacterial spinal infections include spinal epidural bacterialabscess, Pott’s disease which is also known as tuberculousspondylitis, Lyme disease which is also known asneuroborreliosis, and syphilis which can be classified as ameningovascular disease which is classified by thickened,inflamed meninges, or a parenchymatous disease which isclassified through gummas in the cord [8–12]. Viral spinalinfections can also be found in practice and may have adifferent treatment and course of action compared to bacte-rial diseases [8]. Viral infections can include, but are notlimited to, flaviviruses such as West Nile, varicella zoster,and Epstein-Barr virus [13–15]. This review focuses on par-asitic diseases of the spinal cord and nerve roots, which arewidespread and have the potential to be extremely lethal andinfectious. Such diseases include schistosomiasis, which iscommon in endemic regions, and neurocysticercosis, whichis the most common parasitic disease of the spinal cord[16–18]. Radiologists are very important in this field, as theyare responsible for detecting the disease and working along-side the clinicians to facilitate the appropriate testing neededfor correct treatment and to diagnose it early. Furthermore,radiology has been found to be most effective in diagnosiswhen using detailed structural images, rather than modernmagnetic resonance (MR) techniques [1].
This article is part of the Topical Collection on Medicine
* Sardar Ali [email protected]
1 Department of Physiology and Biophysics, Renaissance School ofMedicine at Stony Brook University, Stony Brook, NY, USA
2 Medical Student Research Institute, St. George’s University Schoolof Medicine, West Indies, Grenada
3 Department of Internal Medicine, Stony Brook SouthamptonHospital, Southampton, NY, USA
4 Foley Plaza Medical, New York, NY, USA5 Department of Urology, Health Sciences Center T9-040, Stony
Brook University Renaissance School of Medicine, 101 NicollsRoad, Stony Brook, NY 11794-8093, USA
https://doi.org/10.1007/s42399-019-00156-4SN Comprehensive Clinical Medicine (2019) 1:869–881
/Published online: 28 October 2019
Parasitic diseases, such as those outlined in Table 1, arefound throughout the world. However, they are much morecommon in developing countries with poor sanitary condi-tions such as Africa, the Middle East, and the West Indies[1, 19–23]. Despite this, they are still common in NorthAmerica, as they often transfer when people travel to lessdeveloped territories and carry the disease back to areas thatdid not have it beforehand [1]. Most parasitic diseases humansare of CNS origin [24]. Parasitic conditions in the spinal cordinclude cysticercosis, schistosomiasis, trypanosomiases, andechinococcosis [2]. This review fully examines these commonand rare parasitic diseases of the spinal cord. Using detailedstructural images, histology is a common means for diagnosis[2].We also review the course of action that must be taken, theimplications it has on patients, and the epidemiology of dis-ease development.
Methods
A literature search using theMEDLINE® and Google Scholardatabases was conducted using terms relevant to parasitic spi-nal cord diseases. The search results were restricted to casereports and review articles. There were no language restric-tions. We selected papers that revealed artifacts for pathogen-esis, clinical manifestations, imaging, and treatment of eachparasitic spinal cord disease.
Spinal Cord Disease Manifestations
There are several clinical manifestations to spinal cord dis-eases. In the neurological disorder of the spinal cord calledmyelitis, there are several pertinent clinical manifestations.This includes parasitic or fungal infection symptoms presentas paresthesia from the feet with possible back pain, motordeficits impacting the flexors of legs and extensors of arms,bowel and bladder dysfunctions, temperature dysregulation,
and hypertension [25]. Over 2/3 of patients that have thisdisorder have lasting disabilities despite treatment [25].Another disorder is acute traumatic central cord syndrome.However, this is most commonly caused by cervical spinalcord injury. The clinical manifestations for this include motordeficits that are more severe in the upper extremities than inthe lower extremities. In addition, there is a bilateral loss ofpain and thermal dysfunction, and possible sphincter dysfunc-tion [26, 27]. Another example of a spinal cord disorder isanterior spinal cord syndrome, caused mainly by aortic surgi-cal interventions. The clinical manifestations include possiblequadriparesis and could onset with no previous symptoms[28]. In the following sections, subtypes of parasitic diseasesassociated with the spinal cord will be discussed, and theirspecific clinical manifestations will be mentioned.
Schistosomiasis
Schistosomiasis is one of the most common parasitic diseasesand impacts approximately 200 million people throughout theworld, and ultimately causing symptoms in about 60% of thesecases [8, 16]. This disease is caused by the trematodeSchistosoma [29]. It is often found in sub-Saharan Africa,South America, and Asia but it is also more recently moving toareas that it was not as common previously due to tourism [19,30]. It can occur at any time through parasitic infection [31].
Pathogenesis
The usual causes of this disease can be due to Schistosomamansoni, Schistosoma haematobium, and Schistosomajaponicum. The main way that this disease is transmitted isthrough a transmission of eggs in either the stool or the urinefor the genus Schistosoma [19, 20, 32]. Once this occurs, it canbe transmitted to humans through freshwater snails and penetrat-ing cercariae [20]. Eggs are then shed day-to-day following 6–8 weeks of initial contact, with variable amounts of sheddingthrough each day depending on how much contact with fresh-water therewas and the parasite burden on the affected individual[23, 33–36]. This type of diagnosis is referred to asBparasitological diagnosis^ as there is direct evidence that thereis a pathogen in the body of an individual [19]. There are alsoother types of diagnoses which are through patient serum that aremore sensitive to the extent that low-intensity schistosomiasiscan be detected as well [23, 37–39]. Through this serology, an-tibodies can be detected to note that the disease is in the patient.These antibodies can be directed against any of the four stages ofthe Schistosoma genus which includes penetrating cercariae,schistosomula which is the migration of juvenile worms, thepresence of adult worms, and eggs produced by worms throughmating [23, 32, 35]. For the serological assays that have beentaken, some have been found to be specific for endemic regions
Table 1 List ofimpactful parasiticdiseases of the spinalcord
Schistosomiasis
Neurocysticercosis
Echinococcosis (hydatid disease)
Toxoplasmosis
American trypanosomiasis (Chagas disease)
Malariasis
African trypanosomiasis (sleeping sickness)
Neurotoxocariasis
Baggio-Yoshinari syndrome (BrazilianLyme-like disease)
Paragonimiasis
Syphilis
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of various specificity levels while others are for diagnosis thatrelates to important or travel-related schistosomiasis [30, 38–56].
Clinical Manifestations
This parasitic disease is more commonly reported in childrenand adolescents than older patients [8]. As the disease evolvesand moves to the central nervous system through migration ofpairs of adult worms or embolization of eggs through retro-grade venous means into the Batson venous plexus, caudaequina syndrome has been found to develop [29, 57]. Thissyndrome is a complication that includes back pains due todisc herniation in the spinal cord or spinal tumors [58, 59].When diagnosing schistosomiasis with MRI, it is often diag-nosed as spinal cord neoplasm. This is due to the extremesensitivity associated with MR [60]. There are three forms ofspinal cord schistosomiasis, with a potential progression fromone of the cases that have lower severity to a higher one(Table 2) [59]. Symptoms of acute schistosomiasis includefever, headache, myalgia, diarrhea, and abdominal pain [29].
Imaging
MRI is important in developing a diagnosis for this disease. Inmany cases, this disease is in the medullary form due to ahyperintensity that is patchy in T2-weighted images (T2WIs), anoticeably enlarged spinal cord, and a lower cord and conusmedullaris heterogeneous contrast enhancement on T1WIs [1,24, 31, 59, 62, 63]. Furthermore, this appearance is similar to acord neoplasm [1, 2]. MRI also displays thickening of the spinalcord and allows the eggs and granulomas to be detected throughlinear radicular contrast enhancement [1, 33, 62, 64].
Treatment
For the treatment of schistosomiasis, praziquantel is the mostused immediately following diagnosis after starting corticoste-roid treatment [64, 65]. However, before a patient is officiallydiagnosed but doctors speculate that schistosomiasis is possi-ble, corticosteroids are used as the primary treatment [66].
Neurocysticercosis
Neurocysticercosis (NCC) is another extremely common par-asitic disease of the spinal cord and CNS [67, 68]. This diseaseis caused by pork tapeworm, known as Taenia solium inhumans. Humans are the intermediate host of the pork tape-worm and allow it to survive and induce harmful effects [1].Approximately 50 million people throughout the world havethis specific type of spinal cord disease, and it is much morecommon in endemic areas similar to schistosomiasis, such asAfrica, some regions in Asia, and Eastern Europe and Centraland South America. It affects approximately 3 to 6% of thepopulation in these areas [69]. In addition, due to travel tothese countries, many people become carriers and transferthe disease to non-endemic areas, such as North America[70]. NCC is significant because it has a major onset of epi-lepsy due to intraparenchymal brain cysts [8].
Pathogenesis
NCC occurs following the ingestion of T. solium-infestedeggs. Once these eggs hatch, embryos are ultimately releasedinto the small intestines and invade several different tissuesthroughout the body, including the eyes, skin, and muscles,but the majority of it is implicated in the CNS complications[67, 71]. After the embryos are released and dislodged into thesmall intestines, they then enter neural and subcutaneous tis-sues and then enter skeletal and ocular globes and continuetheir development [1]. When in the CNS, cysticerci can de-velop anytime between 3 weeks and 2 months following theinitial oncosphere formation [1, 17].
There are many types of larval forms for this disease.The most common of these is Cysticercus cellulosae[1]. This type contains a scolex and has implicationson the CNS by causing intraparenchymal lesions inthe brain [1]. Furthermore, Cysticercus racemosus is an-other type, but it is less common and does not have ascolex [1, 2]. Overall, the cysticerci are only 1 cm indiameter and are located in the cerebral cortex or thebasal ganglia [1, 69].
Table 2 Spinal schistosomiasis subtypes [29, 59, 61]
Clinical form Clinical manifestations Imaging
Medullary (most involved in thespinal cord only)
Commonly has high eosinophil CNS levels, symmetric distribution ofsensorimotor abnormalities, spinal cord atrophy in untreated patients.
Hyperintensity in the T2 region with enlargement of thespinal cord is seen. This is associated with mild andheterogeneous enhancement.
Conus-cauda equina syndrome Slower development of symptoms, atrophic leg muscles, asymmetricsensorimotor alterations, high eosinophil CNS levels.
The cauda equina is shown to be thickened; there is agadolinium enhancement of the conus medullaris.
Myeloradiculopathy (involvedwith the spinal cord and rootsof the nerves)
Intermediate form. Necrosis, vacuolization, and further atrophy of thespinal cord tissue occur. Radicular pain in the lower limbs, muscularweakness, sensory disturbances, high eosinophil CNS levels.
Spinal nerve root thickening and leptomeningealenhancement seen.
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Clinical Manifestations
There is a wide range and non-specific clinical manifestationfor cysticercosis that depends on location of the parasite,amount of parasites, and inflammation [1]. In most cases,there is a cyst degeneration in the basal ganglia and edemawhich leads to neurological implications that can often includechronic headaches, focal neurologic deficits, intracranial hy-pertension, and decline in cognition [72]. Most of the spinalcysts are in the lumbosacral regions [73]. Furthermore, inspinal cases of NCC with basal subarachnoid disease, it isimminent that an MRI is done [73].
When cysts occur, it can lead to several different complica-tions including nerve entrapments, hydrocephalus, gait disorders,chronic meningitis, vasculitis, spinal or cerebral stroke, or lym-phocytic meningitis if they rupture [74]. In terms of this diseaseand how it is associated with the spinal cord, it is quite rare and isassociated with other parts of the CNSmore, as it is implicated inthe spinal cord for just 1.2 to 5.8% of reports [1, 75].
Diagnosis
To diagnose patients with this type of disease, serological testingand fundoscopy can be performed to detect the parasite in pa-tients. However, histological review and imaging is the mostcommonmethod to diagnosis, as it allows amore comprehensiveunderstanding of the specific form of neurocysticercosis that thepatient has [76, 77].
Del Brutto et al. have proposed specific diagnostic criteriafor the diagnosis of NCC. This combines clinical history, neu-roimaging, immunological evidence, and epidemiologicalguidelines to ultimately establish defined guidelines that allowthe diagnosis of NCC [67, 78]. For the absolute criteria, theremust be an ability to see the parasite through a spinal cordlesion located in the body. For the neuroimaging of the abso-lute criteria, a scolex must be visible within the cystic lesion.Furthermore, in a fundoscopy, sub-retinal parasites will beseen. For the major criteria of the disease, the lesions willsuggest NCC, EITB assays will detect T. solium antibodies,and cysticidal drug therapy would display a resolution of thelesion following albendazole or praziquantel treatment. Theminor criteria will also show lesions that suggest NCCand there will be symptoms suggesting NCC, and a CSFELISAwould show T. solium antibodies or antigens and cys-ticercosis that is outside the CNS. Pursuing this further, theepidemiological criterion has an origin endemic for the patientcountry and the patient must be living in the endemic area andtravel to endemic areas where there is NCC often.Furthermore, the household that the patient lives in must havehad contact with T. solium in order for it to develop as well[66, 67, 77].
The various diagnoses for NCC can be defined as definitiveor probable. A definitive diagnosis will have 1 absolute
criterion or 2 major criteria and 1 minor and 1 epidemiologicalcriterion. For a probable diagnosis, one must have 1 majorcriterion and 2 minor criteria or could have 1 major and 1minor and 1 epidemiological criterion applicable or 3 minorand 1 epidemiological criterion applicable [66, 67, 77].
Imaging
For this specific type of disease, there are four stages of devel-opment and regression that have been found throughCTandMRimaging. The first stage involves vesicular implications and seescysts and scolex through imaging. The second stage has colloidalinvolvement and has ring enhancement and edema. The thirdstage had nodular-granular involvement and has decreased en-hancement and edema and initiation of calcification. The fourthstage is more calcification and this is seen through a CT or MRI[77]. It is important to note that multiple anatomical sites areinvolved for patients that have this parasitic disease [1, 70, 79,80]. Furthermore, neuroimaging has been shown to be the pre-ferred method for diagnosis in NCC through CT and MRI [66].This is because it allows visualization of the infections and as-sesses the number and location of it [66]. Calcifications, whichoccur in about half of all NCC patients, are seen through the highsensitivity of CT scans of NCC which has a starry sky appear-ance due to several cysts implicated with it [67, 71, 81]. Thereason that MRIs are also effective is that they allow distinctionof the degenerative cysticerci stage and detect parasites in theposterior fossa, basal cisterns, and ventricles that CT scans arenot able to detect [67, 80].
Treatment
Effective methods of treatment for NCC have been developed[8]. In order to control the inflammation that is caused fromthis disease, albendazole with glucocorticoids is administered[82]. Alternatively, praziquantel with corticosteroids or a com-bination of albendazole and praziquantel, if there are morethan 2 active parenchymal cysts, is a recommended drug treat-ment option [65].
A controversial topic for treatment of NCC is cysticidaldrugs. This is because it is believed that it may cause moreharm than benefit to patients as this treatment could increasethe risk for ICP and potentially result in death [67, 83].Therefore, patients should only be treated with regard to theirsymptoms without cysticidal therapy [67, 84].
Due to the fact that neurological issues are a clinical man-ifestation of NCC, anti-epileptic therapies have also been rec-ommended [67, 80]. In these cases, phenobarbitone and car-bamazepine should be used to control seizures, but this is alsonot without controversy, as relapse is quite common followingimprovement while no improvement has also been shown insome cases [17, 67, 68, 84].
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If calcification is present, anti-parasitic treatments shouldnot be administered. The reason for this is because there canbe a potentiation on the excessive inflammatory responses thatare occurring in the brain. For such cases, treatment optionsinclude the aforementioned corticosteroids, osmotic diuretics,and decompressive craniotomy. This will allow control ofbrain edema [85].
Echinococcosis (Hydatid Disease)
Echinococcosis, also known as hydatid disease, is caused bythe larval stage of Echinococcus [1]. The most common hostsof these parasites include carnivores and canines. Unlike theprevious parasites, these are found near the countryside or inhomes that are located in forest areas [1]. When humans havewater or ingest food that are contaminated with eggs of thisparasite, they will then develop the disease as well [1].Furthermore, the most common form of this disease is cysticechinococcosis, which is caused byEchinococcus granulosus,and alveolar echinococcosis, which is due to Echinococcusmultilocularis [1, 86].
Pathogenesis
Asmentioned, it is extremely rare for this disease to be associatedwith the spine, but there are still some cases that have beenreported. In these cases, the segment of the spine that is mostassociated is the thoracic segment as it is 50% of all cases, thenext most frequent is lumbar and sacral which is 20% for each,and the least is cervical segments, which represent only 10% ofall spinal cases [1, 87]. Furthermore, the disease is located inepidural regions in most of the cases [88, 89].
Clinical Manifestations
This disease, when associated with the spinal cord, is mani-fested as isointense cystic lesions without any peripheral ede-ma that is associated with significance [1, 90]. The fibrouscapsules in the body are hypointense on T2WIs and displayperipheral enhancement through inflammations [1, 91].Furthermore, the more common cysts are intradural-extramedullary cysts and present at a young age [87].
Diagnosis
In order to diagnose this disease, serological and imag-ing tests are used. Furthermore, while it is still possibleto have CNS and spinal involvement of this disease, itis only in about 1 to 2% of all cases, as most cases areinvolved with the liver and lungs [1, 77, 86–88, 92].The diagnosis can also be confirmed through surgery byobserving a laminated cyst membrane [88].
For the diagnosis of this disease, the intradural-extramedullaryor intramedullary cysticerci is a copy of echinococcosis [1, 93].Furthermore, a mimic of alveolar echinococcosis and spinalsparganosis can be cestode infections, but this is in more rarecases [1]. This disease can also be classified as spinal arachnoidor spinal aneurysmal bone cysts, confirmed through higher eo-sinophil CNS levels [87].
Treatment
The primary treatment of choice for this specific parasiticdisease is removal through surgical means. However, it isimportant that if the surgery were to occur, there should notbe a perforation of the cyst wall. This can potentially lead todissemination and anaphylactic reactions [88, 94].Furthermore, to avoid this disease from recurring, anti-helminthic therapy and follow-up visits for MRIs after theoperation are imminent [88, 95]. Recurrence and mortalityare quite high for this disease, as they are approximately40% each, showing that diagnosing and treating affected in-dividuals is critical [88, 89, 96]. Albendazole or mebendazoleshould also be taken, regardless of whether there will be sur-gery or not [65].
Toxoplasmosis
Toxoplasmosis can be localized in multiple parts of the spinalcord. It arises from the protozoan Toxoplasma gondii whichcan be found in regions anywhere in the world [1, 97]. It isfrequent in pregnant women and this ultimately results in birthdefects and could lead to a return of weak immunity if indi-viduals had an immune disease previously, leading to enceph-alitis [1, 97, 98]. The pathology of the spinal cord is because ofdeficits in CD4 T cells that are linked to AIDS or T cell leu-kemia or lymphoma [1, 99, 100]. A previous study has shownthat there are only 18 reported cases of spinal cord toxoplas-mosis in AIDS patients [101, 102].
Clinical Manifestations
Several permutations of manifestations occur with thisdisease including pain in the spinal region, a defect inthe motor and sensory system, and complications in theurinary sphincter [1, 98].
Diagnosis
To assist in diagnosing patients with this disease, it is commonthat patients will have a fever, a sensory loss below a specificspinal cord level, urinary retention, and extreme weaknessalso known as paraparesis [103]. In order to definitely diag-nose an individual with spinal toxoplasmosis, a biopsy must
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be done to definitely detect that there is an organism for thisparasitic disease in the body of an individual, but this has beenhighly morbid [103]. Therefore, as an alternative, individualscan be diagnosed if their CD4 lymphocyte cell count is lessthan 100 cells/mm3 [101].
Imaging
In these patients, there are mass effects and edema.Furthermore, cerebral toxoplasma lesions that are also foundin patients assist in diagnosis for spinal toxoplasmosis [1, 2].MRI is also utilized in order to ensure that patients have spinaltoxoplasmosis, rather than bony lesions, epidural abscess, her-pes myelitis, or an HIV vacuolated myelopathy [101, 103].
Treatment
There are multiple methods of treatment for toxoplasmic en-cephalitis. Specifically, in patients with AIDS, pyrimethamine(200 mg dose, 50 mg/day), sulfadiazine (5–6 g/day), andfolinic acid (10–25 mg/day) should be combined and admin-istered daily [101]. Alternative treatments, specific to thespine, include trimethoprim-sulfamethoxazole, which hasbeen found to be most effective, pyrimethamine withatovaquone, pyrimethamine with azithromycin, or sulfadia-zine with atovaquone [101, 104, 105].
American Trypanosomiasis
American trypanosomiasis, or Chagas disease, occurs mainlyin Latin America and some Western countries [1, 77, 106].The parasite responsible for it is Trypanosoma cruzi. Thecause of the disease onto humans is through Triatominae(i.e., conenose or kissing bug), which suck the blood out ofhumans and then can transfer the disease onto them [1, 77].
Clinical Manifestations
The clinical manifestations of this disease can be distin-guished into an acute phase which lasts 6–8 weeks and chron-ic phases [107]. In these acute cases, patients are often foundto have fever, malaise, headache, and hepatosplenomegaly[1]. In chronic cases, some patients develop other complica-tions that include cardiac, gastrointestinal, or both [107–109].The association that this disease has with the spinal cord isthrough acute meningitis or nodular encephalitis, but this is inrarer cases [1, 110]. The direct symptoms that have been foundwhen it is linked to the spinal cord are abnormalities anddeficits in the sensory and motor parts of the body, dementia,and confusions [1, 111]. Furthermore, Chagas disease is oftenconfused as a presentation of AIDS at first, but the other
clinical manifestations allow a final diagnosis of Chagas dis-ease to be confirmed when it is the case [1, 24, 111].
Diagnosis
In order to diagnose Chagas disease, histology, serologic, andCSF tests are often used. Through these methods, abnormal-ities in the CSF are quite common and can confirm the diag-nosis of Chagas disease [1, 24].
Imaging
The way that this disease is seen through MRI and CT imag-ing is expanding hyperintense lesions on T2WIs. When it isfound in the spinal cord, it demonstrated extensive edema andmass effect [1, 24, 110, 112].
Treatment
Due to difficulties with obtaining the drugs that are needed totreat people that have this disease, most cases are left withouttreatment [107, 108, 113, 114].
Malariasis
Malariasis is caused by the agent Plasmodium sp. and is anextremely rare case of a parasitic spinal cord disease. It isimportant to note that it is quite common in endemic areasthat are located in tropical countries [1]. Symptoms are similarto those observed in acute disseminated encephalomyelitis. Inorder to diagnose this disease, imaging is used to detect aspinal cord lesion and potential nerve root enhancement [1].
African Trypanosomiasis
African trypanosomiasis, or sleeping sickness, is also a raredisease of the spinal cord and is caused by the agentTrypanosoma brucei, T. congolense, T. vivax, T. evansi, andT. equiperdum [1, 115]. It is most commonly found in Centraland Western Africa and impacts approximately 70 millionpeople in this region [115, 116]. The manifestation that ithas associated with the spinal cord is meningoencephalitis.Through imaging, meningeal enhancement, lesions of the bas-al ganglia, and white matter diffusions are shown which ulti-mately leads to thickening in the spinal region [1, 117].Because of a lack of vaccines due to variations in hosts, it isdifficult to treat this parasitic disease [115].
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Neurotoxocariasis
Neurotoxocariasis is a rare parasitic disease that arises fromToxocara sp. It can be found in any part of the world. Theclinical manifestations associated with this disease includeassociations with eosinophilic meningitis and optic neuritis.In order to diagnose this disease through imaging, longitudinalextensive myelopathy can be seen in addition to hyperintenseT2WI lesions [1, 118, 119].
Baggio-Yoshinari Syndrome
Baggio-Yoshinari syndrome, previously known as BrazilianLyme-like disease, originates from Brazil [1]. It is transmittedthrough Amblyomma and Rhipicephalus as they release theirticks that will have latent behaviors. The disorders that areassociated with this disease include immune weakness and arecurrence of complications that patients may have had previ-ously [1].
Clinical Manifestations
The symptoms associated with this disease are similar to that ofinfluenza and Lyme disease [1, 120]. Following invasion, there isan infection in the neurological region evident bylymphomonocytary meningitis, cranial neuritis, peripheralradiculopathy, and encephalomyelitis [1, 121, 122]. It is impor-tant to note that similar to the previously discussed disease, thereis a high relapse rate that is associated with it. Furthermore, it iscritical that patients that have this disease are found in the earlyand acute stages; otherwise, there is a much higher chance thatrelapse will occur for these patients [1, 121, 122].
Imaging
Through imaging that has been done in this disease, it is com-monly found that there are multifocal hyperintense lesions onT2WIs, demyelinating lesions, and cranial enhancements onpost-contract T1WIs. When this is seen through MRI exami-nation, it facilitates the diagnosis of this disease [1, 123–126].
Treatment
It is critical that patients are treated for this disease quite in theearly stages to avoid the latent stage, when it becomes irre-versible [127]. Antibiotics has been a common therapy for thedisease, such as ceftriaxone, as well as doxycycline, amoxi-cillin, or penicillin [127].
Syphilis
Syphilis is caused by Treponema pallidum [1]. It is a sexuallytransmitted disease and when it is found in the spine, it in-volves syphilitic gummas, stemmed from leptomeningeal in-flammation and low signal intensity found on T2WIs [8–12].Syphilis peaked during WWII, with a decline due to thefounding of penicillin, yet it is still prevalent as a sexuallytransmitted disease [128, 129].
Although it is extremely rare, this disease could also becaused by tabes dorsalis which is the tertiary form. In thisspecific type, the posterior location of the spinal cord isharmed, evident through imaging that has shown atrophyand hyperintensity on T2WIs [1, 77, 130, 131].
For syphilis in the spinal region, patients are treated withbenzathine penicillin [128, 132]. In addition, it is critical thatpatients are treated rapidly, as complications can arise.
South American Blastomycosis(Paracoccidioidomycosis)
South Amer ican b las tomycos i s , a l so known asparacoccidioidomycosis, is a systemic disease that is causedby Paracoccidioides brasiliensis [1]. It is most commonlyfound in South American regions, hence its name [1, 133].Furthermore, the prevalence of this disease is between 5.6 and17.5% [1, 133, 134].
Pathogenesis
When the fungus of the disease is inhaled, it will thenaffect the CNS as well as other parts of the body in-cluding the kidney, spleen, adrenal gland, and bonesthroughout the body [1].
Diagnosis
Through biopsies, one is able to diagnose an individualwith South American blastomycosis. The correct lesionsfor this biopsy are found in the lungs through CT im-aging [1, 113, 114].
Imaging
For only 4.0% of CNS cases of this disease will there belocalization in the spinal cord [133–135]. The lesions associ-ated with this disease can also be linked to the meningeal formthrough diffuse leptomeningeal enhancement [1, 136].
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Table3
Casestudiesof
parasitic
spinalcord
diseases
Reference
Sym
ptom
sIm
aging
Diagnosis
Treatment
Outcome
Mikulichet
al.[65]
28-year-oldSu
danese
man
with
lower
back
pain,flaccid
paraplegia,sensory
level(T8),
andurinaryretention.
MRIshow
edincreasedsignal/m
asseffectin
spinalcord
from
T6to
conusmedullaris.A
mild
patchy
enhancem
entw
asalso
present
followingIV
contrast.
Differentiald
iagnosisincluded
astrocytom
a,ependymom
a,hemangioblastom
a,schistosom
iasis,andmetastasis.
MRIfindings
suggestspinal
cord
schistosom
iasis.
Dexam
ethasone
at4mg4tim
esperday.3
dosesof
praziquantel25
mg/kg,and
prednisolone
1mg/kg.
Exhibiteddram
aticclinical
improvem
ent.Decreasein
abnorm
alsignalandsw
ellingin
spinalcord.
Zhang
etal.[150]
59-year-oldwom
anwith
paininbilaterallow
erlim
bsandleftlower
limb.Increasing
urinaryfrequency.Hypoesthesiaalong
S2–S
5derm
atom
eson
bilaterallow
erlim
bsanddecreasedperianalsensationon
theleft
side.
Intraduralextram
edullary
lesionsfrom
L1/2to
S1thatwas
hyperintense
atT2and
hypointenseatT1.Thin-walledcystwas
identifiedwith
clearfluidfrom
L2–S1
that
was
8cm
.
Lum
barspinalintradural
neurocysticercosis
Cystic
masswas
removed,fixed
in10%
form
alin
for8hatroom
temperature.
Patient
was
then
treatedwith
albendazoleat15
mg/kg/day
fora
period
of4weeks.
Noadditio
nalcom
plications
andthe
patient
ultim
atelyrecovered.
Abarrategui
etal.[151]
29-year-oldBolivianwom
anwith
headache
for
3days,fever,and
nausea.C
SFglucose
levelsdroppedto
less
than
20%
ofglycem
ia.Inthirdweek,patient
reported
acuteradicularpain
inrightS
1region.L
Pshow
edclearCSF
containing
265WBCs,
73mg/dL
proteins,and
glucoseat
45mg/dL
.
CTscan
displayedscattered
cortical-subcorticalcalcifications
upto
2.5mm.M
RIof
S1territo
ryshow
eda
roundedlesion
atS1
–S2,16
mm
indiam
e-terthatwas
intradural,extramedullary,and
hyperintense
inT2.
Virallymphocyticmeningitis
was
theinitialetiology.
Neurocysticercosiswas
thefinal
diagnosis.
Patient
was
treatedwith
analgesics
toreduce
pain.
Improved
gradually
andfinalL
Pshow
edglycorrhachiaat50%
ofbloodglucoselevels.
Xuet
al.[152]
30-year-oldKazakhstanmalepresentin
gback
andlefthippain,headache,andweaknessin
lower
leftlim
bs.M
inor
epilepsywas
present,musculartension
wasabovenorm
alrange.
MRIandCTresults
displayedlesionsin
head,
lungs,spleen,kidneys,right
scapula,left
second
costalarch,the
leftacetabulum
,the
thirdleftrib,andT5–T8thoracicvertebrae.
Initially
diagnosedas
thoracic
alveolarechinococcus
(AE)due
toback
pain
andthoraciccanal
decompression.T
hepatientwas
ultim
atelydiagnosedas
multiple-organ
AE.
Thoraciclesionsweretreatedwith
canal
posteriordecompression
andfixedwith
hooksandrods.P
atient
was
given
2-yearalbendazoletreatm
ent.
Patient
returned
dueto
progressionof
intracerebralA
Eandwas
given
anotheroperationto
treatit.
Perez-Lazoet
al.[153]
33-year-oldwom
anwith
ahistoryof
10years
ofHIV
andpulm
onarytuberculosis
admitted
dueto
paraparesisin
lower
limbs,
urinaryretention,andsensitive
involvem
ent
atT8level.CSF
studiesdisplayed20
lymphom
ononuclearcells,
hyperproteinorrachia,glucorrachia,and
adenosinedeam
inaseatnorm
allevels.
MRIof
thespinalandspinalcord
show
edintram
edullary
contrastgaugingwith
perilesionaledem
aatT8.
Toxoplasmosis.
Sulfam
ethoxazole/trim
ethoprim
IVwas
givenat5mg/kg
twiceadayfor
4weeks
with
dexamethasone
IV8mg
for7days.T
reatmentthencontinued
with
2weeks
ofsulfam
ethoxazole/trim
ethoprim
taken
orally.P
atient
continued
anti-tuberculosistherapywith
sulfam
ethoxazole/trim
ethoprim
160/800mgsplit
forevery12
h.
Imagingshow
edim
provem
ento
fintram
edullary
lesionswith
adecrease
inthesize
andthelower
contrastenhancem
ent.Muscle
strength
also
improved.
Streitetal.[154]
60-year-oldwom
anwith
fevers,chills,
myalgias,headache,and
2erythematous,
pruriticareas3–4cm
indiam
eter
onher
back
returned
from
Botsw
anaand
Zim
babw
eon
atripwhereshewascanoeing
andcamping.L
abtestsshow
edmild
leu-
kopeniaandmoderatethrombocytopenia.
N/A
African
trypanosom
iasis
Pentam
idineIV
and5dosesof
suramin
through3weeks.
Fatiguedforseveralm
onthsfollowing
treatm
ent.
Uraletal.[155]
44-year-oldmalepatient
with
back
pain
re-adm
itted
with
initialtransverse
myelitis
(TM)diagnosis.W
eaknessandnumbnessin
lower
extrem
ity.C
SFexam
inationshow
edWBCsat20/m
m,protein
at45
mg/dL
,glucoseandchloride
werenorm
allevels.
MRIdiagnosedTM
inlower
segm
ent.
Neurotoxocariasis.
Mebendazolewith
corticosteroid
for
6weeks.
Significant
improvem
entinmyelitis
findings.
Kim
etal.[156]
44-year-oldfemalewith
severeneurogenic
claudicationatL4–L5.Right
side
homonym
oushemianopsiaand
monoparesisin
rightarm
.Paragonimus-specificantibodyinCSF
was
norm
al.
MRIo
flum
berspine
show
edintraduralmasses
hypointenseon
T2andT1show
edmasses
hypointense.There
was
aslight
peripheral
rim
enhancem
ento
nT1.CTshow
edcalcifiednodulesinlumbarintraduralspace.
BrainMRIshowed
nodularorcystic
masses
inleftoccipitaland
parietallobes.
Spinalandcerebralparagonimiasis.
Lum
barfusion
forcoincident
spondylolisthesis,hem
ilaminectomyof
L3,andexcision
ofcysticmasses.
N/A
SN Compr. Clin. Med. (2019) 1:869–881876
Treatment
Antifungal drugs have been shown to be effective in treatingthis disease. This includes azole derivatives such as ketocona-zole, fluconazole, itraconazole, voriconazole, posaconazole,and isavuconazole, sulfonamide derivative, amphotericin B,and terbinafine B [137–145]. In mild cases, itraconazole at200 mg per day is recommended and the duration can rangeanywhere between 9 and 18 months [137].
Prevention and Control of Parasitic SpinalDiseases
In 2011, theWorld Health Organization (WHO) outlined threeessential criteria that are important to preventing and control-ling the parasitic diseases of the CNS [65, 146]. This includeda focus and understanding of the population and the interven-tion that is necessary in general rather than for each specificdisease, innovative tools to detect parasites of the CNS andcontrol them, and a multi-disease, intersectoral, andinterprogrammatic approach [65, 146]. In order for these strat-egies to work, it is important that they are ethical, economi-cally, agriculturally, and environmentally friendly, and havechemoprevention, community sensitization, case and symp-tomatic management, vector control, veterinary public health,and proper sanitary and hygienic conditions [65, 146].
These interventions have been successful since the WHOgave these criteria for prevention and control. For example, ma-laria interventions have reduced malaria by 30% throughout theworld and 34% in Africa [65]. This interventionmethod used theideas that the previous paragraph outlined, and it has been quitesuccessful most notably in Africa, despite a recent increase in theAfrican population that live in areas where malaria transmissionrates are high [65, 147]. There has also been work in other coun-tries in preventing schistosomiasis through means of providingsanitation, constructing dams, and delivering potable water [65,146]. With this said, the outreach throughout the world for theimportance of prevention and control, not just through the workof doctors and medical staff, has been increasing.
Overall, the concept of Bone health^ has risen to increasecollaboration between human health care practitioners, veterinar-ians, and public health and environmental health professional toreduce gaps between prevention and control [65, 148]. Thismethod has also been cost-effective and has been significantlybeneficial in areas that may have not had any collaboration in thepast, such as neglected populations [65, 149]. Through means ofprevention and control, over one billion people in low-incomeendemic areas will have better health and well-being, leading toan abundance of opportunities [65]. Proper control can be threat-ened by difficult or a complex diagnosis, so is important forphysicians to be aware of the case studies (Table 3) as to not befooled by an atypical presentation of a parasitic spinal disease.T
able3
(contin
ued)
Reference
Sym
ptom
sIm
aging
Diagnosis
Treatment
Outcome
Baiet
al.[157]
44-year-oldman
with
lower
back
pain
and
radiatingpain
atthelower
extrem
ities.
Num
bnesswas
presentbelow
thekneesand
theankles
wereweakening.S
pinal
movem
entinthelumbarregionwaslim
ited.
X-ray
oflumbarspineshow
edanarrow
ingof
theintervertebralspacebetweenL4andL5.
Fortheankle,therewas
destructions
atthe
Charcot
joint.Fu
rtherm
ore,aCTscan
displayedan
osteolyticlesionsandnew
bone
form
ationatL4–L5.MRIshow
edbone
destructionandskeletalsofttissue
form
ationatL4.
Neurosyphilis.
Posteriordebridem
ent,andan
allograft
bone
fusion
from
L3toS1
.Treated
with
penicillinGbenzathine
at2.4mUone
timeaweekfor3weeks.
Residualb
ackpain
andleftlower
numbness.After
12months,the
bone
graftswerecompletely
absorbed
andL4moved
forw
ard
progressively.The
patient
ultim
atelydied
ofacutehemorrhage
dueto
aduodenalulcer18
months
followinghisoperation.
SN Compr. Clin. Med. (2019) 1:869–881 877
Conclusion
Though there are several different types of parasitic diseasesof the spinal cord, there is usually a common theme betweenall of them—their immediate need for attention and treatment.Specific criteria have been established for these diseases andhow to properly treat them in order to avoid the significantimplications they can have on individuals. The parasitic dis-eases are most commonly found in endemic areas, althoughthis is not the case for all of them. In addition, traveling tothese endemic areas and returning to locations where the par-asitic diseases are not present may lead to an introduction ofthe disease to a new site if individuals become host to theparasite when in the endemic area. Imaging is often used todetect that the parasitic diseases are present in individuals, dueto several noted discrepancies from the imaging of normalindividuals, as noted throughout the paper. Prevention andcontrol of this disease are extremely important and should beutilizing methods of collaboration and specific guidelinesestablished by the WHO [65, 146].
Acknowledgments The authors are thankful to Drs. Kelly Warren, ToddMiller, and Peter Brink for departmental support, as well as Mrs. WendyIsser and Ms. Grace Garey for literature retrieval.
Compliance with Ethical Standards
Conflict of Interest The authors declare that they have no conflict ofinterest.
Ethical Approval All research conducted including literature reviewthrough PubMed met all ethical standards through the Stony BrookUniversity Renaissance School of Medicine Department of Physiologyand Biophysics.
Informed Consent The study did not contain any human subjects forresearch purposes, and informed consent was thus not applicable.
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