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  Diagnosis of NCC
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NI FEATURE - COMMENTARY: JOURNEY THROUGH THE EONS
Year : 2018  |  Volume : 66  |  Issue : 4  |  Page : 919-927

Evolution of concepts in the management of cysticercosis of the brain: Then (1970) and now (2018)


Department of Neurological Sciences, Christian Medical College Hospital, Vellore, Tamil Nadu, India

Date of Web Publication18-Jul-2018

Correspondence Address:
Dr. Vedantam Rajshekhar
Department of Neurological Sciences, Christian Medical College Hospital, Vellore - 632 004, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.236969

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How to cite this article:
Rajshekhar V. Evolution of concepts in the management of cysticercosis of the brain: Then (1970) and now (2018). Neurol India 2018;66:919-27

How to cite this URL:
Rajshekhar V. Evolution of concepts in the management of cysticercosis of the brain: Then (1970) and now (2018). Neurol India [serial online] 2018 [cited 2018 Nov 18];66:919-27. Available from: http://www.neurologyindia.com/text.asp?2018/66/4/919/236969




Prior to the 1990s, there were relatively few articles on neurocysticercosis (NCC) or cysticercosis of the brain from Indian centers. This contrasts with the voluminous and significant scientific contributions of Indian clinicians and pathologists in the field of central nervous system tuberculosis, during the same period. It is, therefore, appropriate to highlight and discuss one of the earliest articles on NCC that was published in our Journal in 1970,[1] 18 years after the publication of the first issue of the Journal. This also gives us the opportunity to analyze the differences in the understanding of the disease at that time and at present and study the reasons for these differences.

Dinakar et al.,[1] from Christian Medical College (CMC), Vellore, put together data from 25 cases of “proven” NCC in this article. Although the authors do not mention the time period over which the cases were managed, it is reasonable to presume that their series spans nearly 20 years, that is, since the establishment of the Department of Neurological Sciences at Christain Medical College (CMC), Vellore, in January 1949. That works out to an average of about one patient with NCC being diagnosed every year in CMC during that period. This would lead the readers to conclude that NCC was relatively rare in India in those days (as CMC, Vellore, attracted patients with neurological disorders from all over the country). We now know that this is not true.

The authors mention in the Introduction section of their article that there were sporadic reports of NCC from India since the early 1900s. Interestingly, there were at least two reports of NCC from CMC, Vellore, during this time. The first was a report in 1948 from the pathology department in a pathology journal and the second was a report of NCC in children from the Department of Neurological Sciences in 1958 authored by the last author of the article in discussion, namely, Prof. Jacob Chandy.[2],[3] Although Dinakar et al., cite the pathology report by Gault and Balasubramanyam,[2] they seem to have overlooked the second article by Jacob Chandy.


  Demographics of Patients with NCC Top


Dinakar et al., reported that NCC affects both genders almost equally and the age of the patients ranged from 5 to 56 years, that is, virtually encompassing the entire age spectrum, considering that the average life expectancy of Indians at that time was only between 45 and 50 years. This demographic spread of NCC has held true to the present day, although due to the availability of neuro-imaging [computed tomography (CT) and magnetic resonance (MR)], the diagnosis of NCC is made even in children less than a year old, and due to the increase in life expectancy, even in individuals over age 70 or 80 years. The majority of Indian patients with NCC are, however, in the second and third decades.[4]


  Pork Consumption and NCC Top


The authors have rightly highlighted the fact that a person does not have to consume pork to acquire NCC. There is a common misconception that exists to this day, not only among the lay public but also among many doctors including neurologists and neurosurgeons, that those who do not consume pork are not at risk for acquiring the infection. NCC is caused by the larval form of Taenia solium and humans get cysticercosis or NCC when they consume the eggs of the parasite in contaminated food or water. Food or water gets contaminated with taenia eggs which are shed in the feces of persons who have taeniasis. Taeniasis (infection with adult worm which resides in the small intestine), unlike NCC, is only seen in persons who consume pork infected by the larval form of the worm (measly pork or pork with cysticercosis). Interestingly, 5 of the 25 patients in this report had taeniasis. Persons with taeniasis can get NCC when they auto-infect themselves with the taenia eggs shed in their feces, due to poor hand hygiene, or like other non-taenia carriers, through consumption of food or water contaminated with taenia eggs.

The take away point from this information is that clinicians should strongly consider NCC in patients, presenting with seizures and other neurological symptoms, who reside in regions endemic for NCC such as India, even if they do not consume pork.


  Varied Symptoms and Signs Top


NCC is often a chronic illness, although the initial presentation is acute with most patients presenting with seizures. The average duration of symptoms reported by the authors was 1.9 years, ranging from as short as 3 weeks to as long as 11 years.

One of the significant messages in this article is that the presentation of NCC can be varied. Seizures or epilepsy is the commonest symptom and, in keeping with what has been reported in literature, was present in 80% of their patients. Features of raised intracranial pressure in the form of diminished vision due to papilledema and secondary optic atrophy were noted in as many as 18 of the 25 patients (72%). Focal motor and sensory symptoms and signs were seen in 60% of the patients. The authors also reported that nine of their patients had subcutaneous nodules, seven of which were proven to be due to cysticercosis through biopsy.

From the authors' documentation of the symptoms and signs, NCC appears to be a serious illness which causes debilitating symptoms in most patients. This is probably due to the late presentation of patients in that era. Even if they did seek medical help, it is likely that at that time most clinicians had a nihilistic approach to patients with neurological illnesses and persuaded them to let nature takes its course.

It is now established that NCC in most Indian patients (nearly two-thirds) presents in its most benign form, namely, as a single cerebral parenchymal granuloma [solitary cysticercus granuloma (SCG)] causing seizures. SCG was described by workers in CMC, Vellore, in the late 1980s.[5] In nearly 85% of patients with SCG, anti-epileptic drugs (AEDs) can be withdrawn safely after resolution of the granuloma, either spontaneously or with albendazole therapy.[6] Seizures recur in about 15% of these patients after the withdrawal of AEDs, and the risk factors for such recurrence are the presence of a calcific residue, the occurrence of more than two seizures, and the presence of breakthrough seizures.[6]

It is also interesting to note that most Indian patients with NCC do not have subcutaneous nodules.[7] The high incidence of subcutaneous nodules reported by the authors can have two possible explanations. First, there was a bias toward identifying such patients as a diagnosis could be confirmed easily in such patients in an era when CT or MR scans were unavailable. Second, subcutaneous nodules are more often noted in patients with disseminated NCC who are also likely to be more seriously affected by the disease. In other words, patients with more benign forms of the disease such as those with SCG are unlikely to be associated with subcutaneous nodules when compared with those with disseminated NCC. Only 1 of 459 patients with a SCG seen by us had subcutaneous nodules suggestive of cysticercosis.[7] Since presently, nearly two-thirds of Indian patients with NCC have a SCG, a very small proportion of Indian patients with NCC will have subcutaneous nodules. Thus, most Indian patients with NCC will not have subcutaneous nodules unlike what has been documented in this report.


  Diagnosis of NCC Top


The fact that routine blood and cerebrospinal fluid (CSF) analysis does not contribute to the diagnosis of NCC has been spelt out clearly by the authors with data from their study. Eosinophilia in blood or cerebrospinal fluid (CSF) is not diagnostic of NCC and is present in a small proportion of patients. Hence, routine testing of blood and CSF for esoinophilia is not recommended.

A definitive diagnosis of NCC cannot be achieved in most patients without contrast-enhanced CT or MR imaging. The authors did not have access to either CT or MR imaging, both of which were invented after the publication of this article. The authors did not also have access to immunological tests to detect antibodies to the larval antigen such as the older enzyme-linked immunosorbent assay (ELISA) or the present gold standard, the enzyme-linked immune transfer blot (EITB).[8] Hence, the authors relied on histopathological demonstration of the larva in brain samples obtained at surgery or autopsy (16 patients), from samples obtained from subcutaneous nodules (7 patients), or by the diagnosis of taeniasis demonstrable by the intraventricular filling defects on pneumoencephalograms (intraventricular cysticercal cysts).

The challenges in making a definitive diagnosis of NCC even with the availability of CT or MR imaging continue to exist today. In several patients, a definitive diagnosis is elusive and clinicians are forced to rely on diagnostic criteria that have been proposed by a group of experts.[9],[10] Unfortunately, these diagnostic criteria have not been validated and indeed are difficult to validate, given the fact that in several instances, a histological diagnosis (the “gold standard”) is neither feasible nor desirable, given the location of the parasite in eloquent and deep-seated regions of the brain. Therefore, the surrogate “gold standard” is the resolution of brain lesions either spontaneously or following cysticidal drug therapy.


  Categorization of NCC Top


The authors discuss two classification systems proposed by other authors and finally propose their own classification which is a modification of the previously proposed systems and is essentially based on clinical presentation. The first category is the meningoencephalitis group (seven patients), which is characterized by a short duration of symptoms and altered sensorium. The second group is composed of those patients who presented with a brain tumor syndrome (nine patients) with focal deficits or hydrocephalus with a fourth ventricular cyst. The third group had basal arachnoiditis (one patient). The last and fourth group presented with seizures (convulsive disorder; eight patients) with no features of raised intracranial pressure or focal deficits.

Presently, a syndromic classification of NCC is not recommended. In the present-day diagnosis of NCC, the location of the cysts in the brain is specified – parenchymal, subarachnoid (racemose), and intraventricular. In the case of parenchymal cysts, the stage of involution (vesicular, colloidal, granular-nodular, and calcific) can also be identified. For example, a patient might be diagnosed with “NCC – multiple parenchymal granulomas” or “NCC – fourth ventricular cyst.” Most patients have parenchymal disease, and seizures are the commonest presentation seen in nearly 80% of patients with NCC. Patients may have cysts in more than one location in the brain. The category of “cysticercotic encephalitis” is characterized by multiple (too numerous to count) granulomas (enhancing lesions) with severe brain edema.

The present-day diagnosis and categorization of NCC are, of course, only possible due to the availability of CT and MR imaging which precisely reveal the location of the cysts in the brain and also help in characterizing their stage of involution. Degenerating cysts are identified by the enhancement of their walls on contrast injection and also by the presence of edema around them. The immense advantage that we have in diagnosing cysticercosis of the brain is illustrated with the different imaging presentations of the disease [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5].
Figure 1: (a-c) Solitary cysticercus granuloma. (a) Gadolinium-enhanced T1weighted (w) axial image showing a typical SCG. (b) Contrast-enhanced CT scan showing a ring enhancing SCG in the right inferior frontal lobe with edema. (c) Contrast-enhanced CT scan showing a disc SCG

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Figure 2: Multiple parenchymal granulomas. Gadolinium-enhanced MR showing multiple enhancing cysticercal granulomas with surrounding edema

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Figure 3: Multiple parenchymal live cysticercal cysts. T2W MR image showing multiple live cysts with scolices seen as hypointense dots within the hyperintense cysts. Note the absence of edema around the live cysts. Also note the subcutaneous cysts in the scalp on both sides

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Figure 4: (a-c) Intraventricular cysticercal cysts. (a) T2W image showing a small cysticercal cyst in the right atrium. (b) Heavy T2W image showing a large anterior third ventricular cysticercal cyst. (c) T1W sagittal image showing a fourth ventricular cysticercal cyst

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Figure 5: Plain CT scan showing a solitary calcification in the right parietal lobe suggestive of healed cysticercal granuloma

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  Management of NCC Top


The authors could only use surgery and AEDs as their modes of management as cysticidal drugs (praziquantel and albendazole) had not yet been introduced at that time. They had to rely on surgery not only for diagnosis but also as a therapeutic procedure. They operated on 14 patients of whom 4 (28%) died. The mortality rate (75%) was the highest in their meningoencephalitis group. Patients in the brain tumor syndrome group had the best surgical and long-term outcome.

In contrast, the present-day management of patients with NCC rarely involves surgery.[11] Surgery is used predominantly in patients with intraventricular cysts, where endoscopic surgery has made the exercise very safe and quick [Figure 4]. The other indications for surgery in these patients are the presence of hydrocephalus (shunt surgery), large colloidal cysts causing a mass effect (craniotomy and excision), and some atypical SCG (craniotomy and excision for diagnosis) [Figure 6].[12] Occasionally, patients with a solitary lesion may present with intractable epilepsy which mandates excision of the lesion with or without surgery for a coexistent second lesion such as medial temporal sclerosis.[13]
Figure 6: Atypical SCG. Gadolinium-enhanced MR showing an “atypical” SCG which is associated with severe edema. Patient presented with raised intracranial pressure with one generalized seizure. Excision biopsy revealed a cysticercal granuloma

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Cysticidal drugs have been found to be useful in hastening the resolution of parenchymal cysts and granulomas although their beneficial effects on seizure outcome are still contested.[14],[15] Steroids are used in patients with “cysticercotic encephalitis” and as a adjunct during cysticidal therapy.


  Prognosis Top


The authors reported a good outcome in patients with brain tumor syndrome, and a poor outcome in those with meningoencephalitis syndrome and in the single patient with basal arachnoiditis. They did not comment on the follow-up outcome in patients in the convulsive disorder group.

It is well documented that the prognosis in patients with a SCG is very good with 85% of them being seizure-free following the withdrawal of AEDs after granuloma resolution.[6] Those with multiple parenchymal lesions need AEDs for several years, if not life-long.[16] Patients with a single ventricular cyst can hope to achieve a cure with surgical excision. Patients with racemose disease and those with cysticercotic encephalitis have the worst outcome with several succumbing to the disease.


  Why was NCC Under-Recognized in India? Top


NCC was generally considered more prevalent in Latin American countries, particularly Mexico, mostly due to the abundant literature on NCC which emerged, almost exclusively, from those countries till the 1980s. Although Dixon and Lipscomb published their landmark article on NCC in British soldiers returning from a tour of duty in India,[17] there was a paucity of literature on cysticercosis of the brain from India up to the 1990s. To my knowledge, this article by Dinakar et al., was the first large case series of NCC published in our Journal.

Given the present understanding of the prevalence of NCC in India, it is quite clear that most patients with NCC were not diagnosed during the period of the authors' study. A major reason for this was the lack of CT or MR imaging at that time. But one can argue that even Latin American countries (and indeed the rest of the world) did not have CT or MR imaging in the 1940s to 1970s and yet they published so much literature on NCC. The difference is that in Latin American countries, NCC in most patients had a florid presentation with a higher cyst load in the brain. This is unlike the scenario in India where SCG is seen in a smaller proportion of patients.

Therefore, till the early 1980s only those Indian patients with NCC who had altered sensorium, focal neurological deficits, or had seizures with subcutaneous nodules could hope to have a definite diagnosis of NCC. Since SCG requires a CT or MR scan to be recognized, this group of patients who contribute to nearly 60%–70% of the NCC disease burden in India would have been missed. This led to the belief that NCC was relatively uncommon in India when compared with brain tuberculosis. Brain tuberculomas are most often associated with progressive symptoms of raised intracranial pressure with or without focal neurological deficits, and hence, were likely to be rigorously investigated and diagnosed by clinicians (even in the pre-CT era) when compared to those with SCG, who present only with seizures without focal deficits or raised intracranial pressure.

Hence, when solitary enhancing lesions were seen initially in Indian patients with seizures in the early 1980s, it is not surprising that most radiologists and clinicians considered a diagnosis of an “immature” brain tuberculoma (to distinguish it from the typically larger brain tuberculoma) rather than NCC.[18] This empirical diagnosis was considered to have been confirmed when these solitary lesions “resolved” following the administration of anti-tuberculous therapy (ATT). The possibility that these solitary lesions (SCG) could resolve spontaneously (without ATT) was not even considered. The fortuitous and serendipitous discovery of the spontaneous resolution of these lesions (“disappearing lesions”) in 1985 was the first evidence of their non-tuberculous nature.[19] This spurred research into these lesions which ultimately led to our discovery of the entity of SCG based on pathological examination of the excised granuloma in 15 patients.[5]

The ready availability of CT and later MR scanning facilities in India from the 1980s has led to the publication of data from several centers in India which confirm the widespread prevalence of NCC in our country.[20],[21],[22],[23],[24],[25],[26],[27] A large community-based epidemiological study of more than 50,000 persons showed that nearly one-third of them with active epilepsy in our country are related to NCC and at least 1.3 million people in our country have active epilepsy due to NCC (which manifests most commonly as one or two small calcifications on the CT image).[28] Since several more persons have a single seizure or have had epilepsy due to NCC which is not active, NCC affects more patients in India than suggested by this number.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

[Additional file 1]

 
  References Top

1.
Dinakar I, Mathai KV, Chandy J. Cysticercosis of the brain. Neurol India 1970;18:165-70.  Back to cited text no. 1
    
2.
Gault EW, Balasubramanyam M. A case of cerebral cysticercosis. J Path Bact 1948;60:505.  Back to cited text no. 2
    
3.
Chandy J, Vaishnava S. Cysticercosis of the brain in children. Ind J Child Health 1958;7:441-7.  Back to cited text no. 3
    
4.
Rajshekhar V, Chandy MJ. Incidence of solitary cysticercus granulomas. In: Rajshekhar V, Chandy MJ, editors. Solitary Cysticercus Granuloma. Chennai: Orient Longman Ltd., 2000.  Back to cited text no. 4
    
5.
Chandy MJ, Rajshekhar V, Prakash S, Ghosh S, Joseph T, Abraham J, et al. Cysticercosis causing single small CT lesions in Indian patients with seizures. Lancet 1989;1:390-1.  Back to cited text no. 5
    
6.
Rajshekhar V, Jeyaseelan L. Seizure outcome in patients with a solitary cerebral cysticercus granuloma. Neurology2004;62:2236-40.  Back to cited text no. 6
    
7.
Rajshekhar V. Chandy MJ. Clinical manifestations of solitary cysticercus granuloma. In: Rajshekhar V, Chandy MJ, editors. Solitary Cysticercus Granuloma. Chennai: Orient Longman Ltd., 2000.  Back to cited text no. 7
    
8.
Tsang VCW, Brand JA, Boyer AE. An enzyme-linked immunotransfer blot assay and glycoprotein antigens for diagnosing human cysticercosis (Taenia solium). J Infect Dis1989;159:50-9.  Back to cited text no. 8
    
9.
Del Brutto OH, Rajshekhar V, White AC, Tsang VC, Nash TE, Takayanagui OM, et al. Proposed diagnostic criteria for neurocysticercosis. Neurology 2001;57:177-83.  Back to cited text no. 9
    
10.
Del Brutto OH, Nash TE, White AC, Rajshekhar V, Wilkins PP, Singh G, et al. Revised diagnostic criteria for neurocysticercosis. J Neurol Sci 2017;372:202-10.  Back to cited text no. 10
    
11.
Garcia HH, Evans CAW, Nash TE, Takayanagui OM, White AC Jr, Botero D,et al. Current consensus guidelines for the treatment of neurocysticercosis. Rev Med Microbiol 2002;15:747-56.  Back to cited text no. 11
    
12.
Rajshekhar V. Surgery for neurocysticercosis. A review. Int J Surg2010;8:100-4.  Back to cited text no. 12
    
13.
Rathore C, Thomas B, Kesavadas C, Abraham M, Radhakrishnan K. Calcified neurocysticercosis lesions and antiepileptic drug-resistant epilepsy: A surgically remediable syndrome? Epilepsia 2013;54:1815-22.  Back to cited text no. 13
    
14.
Garcia HH, Pretell EJ, Gilman RH, Martinez SM, Moulton LH, Del Brutto OH, et al. A trial of antiparasitic treatment to reduce the rate of seizures due to cerebral cysticercosis. N Engl J Med 2004;350:249-58.  Back to cited text no. 14
    
15.
Carpio A, Kelvin EA, Bagiella E, Leslie D, Leon P, Andrews H, et al. and the Ecuadorian Neurocysticercosis Group. The effects of albendazole treatment on neurocysticercosis: A randomized controlled trial. J Neurol Neurosurg Psychiatry 2008;79:1050-5.  Back to cited text no. 15
    
16.
Del Brutto OH. Prognostic factors for seizure recurrence after withdrawal of antiepileptic drugs in patients with neurocysticercosis. Neurology 1994;44:1706-9.  Back to cited text no. 16
    
17.
Dixon HBF, Lipscomb FM. Cysticercosis: An analysis and follow up of 450 cases. Medical Research Council Special Report. Series no. 299. London: Her Majesty's Stationery Office, 1961. p. 1-58.  Back to cited text no. 17
    
18.
Bhargava S, Tandon PN. Intracranial tuberculomas: A CT study. Br J Radiol 1980;53:935-45.  Back to cited text no. 18
    
19.
Sethi PK, Kumar BR, Madan VS, Mohan VS. Appearing and disappearing CT abnormalities and seizures. J Neurol Neurosurg Psychiatry 1985;48:866-9.  Back to cited text no. 19
    
20.
Jena A, Sanchetee PC, Gupta RK, Khushu S, Chandra R, Lakshmipathi N. Cysticercosis of the brain shown by magnetic resonance imaging. Clin Radiol 1988;39:542-6.  Back to cited text no. 20
    
21.
Dhamija RM, Venakataraman S, Sanchetee PC, Roy AK, Bhatia HC. Computerised tomography spectrum of neurocysticercosis. J Assoc Phys Ind 1990;38:566-8.  Back to cited text no. 21
    
22.
Puri V, Sharma DK, Kumar S, Choudhury V, Gupta RK, Khalil A. Neurocysticercosis in children. Indian Pediatr 1991;28:1309-17.  Back to cited text no. 22
    
23.
Sanchetee PC, Venkataraman S, Dhamija RM, Roy AK. Epilepsy as a manifestation of neurocysticercosis. J Assoc Phys Ind 1991;39:325-8.  Back to cited text no. 23
    
24.
Singhi P, Ray M, Singhi S, Khandelwal N. Clinical spectrum of 500 children with neurocysticercosis and response to albendazole therapy. J Child Neurol 2000;15:207-13.  Back to cited text no. 24
    
25.
Sardana V, Ojha P, Sharma D, Sharma SK, Saxena S, Rai NN. Disseminated cysticercosis. Neurol India 2016;64:1058-60.  Back to cited text no. 25
[PUBMED]  [Full text]  
26.
Garg RK, Uniyal R, Malhotra HS. Be careful while using albendazole/praziquantel in neurocysticercosis. Neurol India 2017;65:924-6.  Back to cited text no. 26
[PUBMED]  [Full text]  
27.
Vikrant S, Verma BS. Disseminated cysticercosis presenting as status epilepticus, rhabdomyolysis, and acute kidney injury: An unreported complication. Neurol India 2018;66:241-4.  Back to cited text no. 27
[PUBMED]  [Full text]  
28.
Rajshekhar V, Raghava MV, Prabhakaran V, Oommen A, Muliyil J. Active epilepsy as an index of burden of neurocysticercosis in Vellore district, India. Neurology 2006;67:2135-9.  Back to cited text no. 28
    


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