Neurocisticercosis in critical stageFoyaca-Sibat, H, Ibañez-Valdés L, Awotedu, A. Fernandez-Mena C. Department of neurology, Department of Family mMdicine and Department of Internal Medicine, Faculty of Health Sciences, Umtata South Africa.
Article AbstractNeurocyticercosis (NCC) is the most common parasitic infection of the nervous system and can cause epileptic attacks in most of the patients and also status epilepticus (SE) can be one of the form of presentation. We select 32 patients randomly for a three years designed therapeutic trial with Praziqualtel/prednisone or placebo plus the classic management of SE. We found that patients under antiparasitic approaches revealed a faster response to anticonvulsant drug and the mortality rate was also less therefore based on our findings, to associate antiepileptic treatment and antihelmintic medication in the management of SE in patient with NCC could be advisable.
Introduction.Neurocisticercosis(NCC) is an 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. Figure 1 shows its reproductive circle The occurrence of 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 NCC may remain asymptomatic for months to years and is commonly a diagnosis made incidentally when neuroimaging is performed. However, the many symptomatic forms predominate. Symptoms are related both to the parasite and to the inflammatory response that its presence generates. Diagnostic criteria for NCC have been well-established recently1 and those criteria were used as selection method for this study. Based on these studies, categories of Absolute criteria is acceptable when the histological demonstration of the parasite from biopsy of the brain or spinal cord lesion is made, or cystic lesion showing the scolex on CT or MRI, or when subretinal parasites can be visualized by fundoscopy examination, other options such as Major, Minor or Epidemiologic criteria can be reviewed in the Del Bruto's report (1). According to the International League Against Epilepsy, cysticercosis is probably the single most common cause of acquired epilepsy in the developing world, where prevalence rates of active epilepsy are twice those of developed countries (2) . One type of presentation of epileptic seizures secondary to NCC is status epilepticus (SE), which is a medical emergency that may result, is significant morbidity and mortality if not addressed in a timely and effective manner (3). Bleck (4) defined SE as a state in which seizures last, or are frequently repeated without clinical recovery, for a period exceeding 20 minutes. Other criteria such as paroxysmal event, characterized by seizure lasting more than 30 minutes, or repeated seizures between which the patient does not regain consciousness were also accepted. Emergency evaluation of the patient with SE is well documented in the literature (i.e. Smith (3) ) and will not be further addresses here. Patients and MethodThirty-two patients fulfilling the diagnostic criteria of NCC (Absolute criteria) in SE were identified prospectively for the study among patients referred to Department of neurology in Umtata General Hospital during a three-years period. This is a terminal hospital of the former Transkei (South Africa) providing neurology service for 25 peripheral hospital and a population of 6,2 million of people approximately. Eligible patients had active and/or chronic forms of NCC with or without signs of raised intracranial pressure. An experienced neurologist evaluated all patients, none patients had no previous history of any other neurological disease apart from epilepsy and those with concomitant disease such HIV/AIDS, tuberculosis, metabolic disorders or an associated infections were excluded. No patients receiving treatment for any other disease requiring inmunomodulatory agents within the past six months were admitted to the study. Other exclusion criteria included alternative cause for intracranial calcifications or suspicion of tuberculomas, pyogenic brain abscesses, mycotic granulomas, and primary or metastatic brain tumors. Apart from antiepileptic drugs, steroids medications and antiparasite treatment, other concomitant treatment was prohibited for patient while participating in the study. Because EEG was not available upon arrival in the emergency room, attempts to diagnose subtle generalized convulsive SE, complex-partial SE, or absence SE were not possible however all selected patients qualified clinically for generalized tonic-clonic SE and a CT Scan of the brain for all of them were done.
Study designThe study was designed as a double-blind, placebo-controlled, randomized trial over a predesigned 3-years period. The patients were assigned to receive 40 mg of prednisone orally for 5 days and 50 mg/Kg/day of Praziquantel per os over the course of 2 or 3 consecutive weeks from the beginning of SE or placebo in the similar way and during the same period of time by block-randomization procedure. To preserve the blind, all medication were prepared by the same people and delivered to staff nurse enclosed in non-transparent numbered plastic bags. The principal investigator, physicians and staff nurses were unaware of which type of tables was administered. All patients received the same antiepileptic treatment during the management of the SE.
Outcome measuresResponse to antiepileptic medication and an associated anti-parasite treatment were assessed with the Neurology UGH scale in which 0 is the lowest: no response, 1 equivalent to decreased frequency of seizures but the patient remains unconscious, 2: diminished frequency and duration of seizures but patient still unconscious, 3: reduced frequency, and duration of epileptic attacks and the level of consciousness is stupor, 4 free of seizures with affected higher cortical functions including level of consciousness (drowsiness) and 5 points, the highest: free of fits, fully conscious, and no cognitive dysfunction. Each patient received the same supporting treatment and was evaluated throughout the study by the same personnel.
StatisticsTwo-side t.test were used to analyses the primary outcome measure between baseline and the end of the treatment. ResultsAbsolute criteria for NCC based on neuroimaging findings were present in all selected patients considering the cystic lesion with scolex, patognomonic. Figure 2: Cystic lesions showing the scolex on CT brain scan. The scolex is visualized as a bright nodule within the cyst, producing the so-called "hole-with-dot" imaging in some vesicular cysts located in the brain parenchyma, the subarachnoid space, or the ventricular system Efficacy analysis included 16 patients (9 women and 7 men, mean age 47,17 years, range 13 to 69) treated with Praziquantel/prednisone and 16 (8 women and 8 men, mean age 45.28 years, range 15 to 72) with placebo. At baseline no difference in UGH scale was found between group treated with Praziquantel and group treated with placebo (Praziquantel 0.08 ±1.02 versus placebo 0.03 ±1.06, p=0.56). At the end of the treatment, improvement was seen when comparing UGH scale results between two different groups (mean SE, 0,84 ± 0.16 versus -0.2 ± 0.2, 0.73 ± 0.25, mean difference ± SE; p=0.006) during the first hour of treatment. In the Praziquantel group 79 % improved in frequency and duration of fits plus early normalization of the level of consciousness. Patients receiving Praziquantel showed improvement that increase with time (2nd hour: Praziquantel 0.40 ± 0.12 versus placebo 0.09 ± 0.6, mean ± SE, mean difference ± SE 0.37 ± 0.16; p=0.054; and 3rd hour Praziquantel 0.48 ±- 0.14 versus placebo 0.03 ± 0.13 + - SE, 0.44 ± SE; mean difference ± SE, 0.43 ± 0.25; p= 0.043 One patient died in Praziquantel/prednisone group while four patients died in placebo group; in all of them the post-mortem examination did not reveal other pathological findings. Figure 3 shows some cysticercus on brain cortex.
DiscussionThe total UGH scores at baseline in both groups were similar securing adequacy of randomization. Our report provides documentation that Praziquantel/prednisone are effective in patients with NCC in SE. Using a UGH score as the primary outcome variable, we found a highly significant difference between Praziquantel/prednisone and placebo. The difference were seen during the first and second hours of management of SE and because the same therapeutic program was used on similar groups of patient we have hypothesized about the advantages to combine the antiepileptic drug and antiparasite medication even for patients in SE where the diagnose of active form on the CT or MRI is not certain, or in patient qualifying for Major or Minor criteria of NCC. In a Praziquantel/prednisone group we had one death, that patient came to neurology OPD from a very far place and was fitting before arriving there for more than three hours without specific treatment, however four patients died in placebo group under better managing program regarding frequency and duration of epileptic seizures; we have considering that we lost those patient due to sudden unexpected death in epilepsy (SUDEP) which is a common cause of death among epileptic patients (5) .Death has been directly related to generalized convulsive seizures in an animal model of SUDEP (6) , other risk factor for SUDEP such as mental retardation and the number of anticonvulsant drug used, have been recently identified by Walczak et al (7) they also found in their study that increased number of seizure frequency is associated with SUDEP and that risk appeared to be associated with tonic-clonic seizures rather than with seizures of any type7 Unfortunately SUDEP can not be prevented because the current information does not allow firm recommendations for preventing it but every effort should be made to prevent recurrent tonic-clonic seizures with fewest anticonvulsants possible and to reduce simultaneously the collateral effect of NCC at the same time. Signs of raised intracranial pressure usually associated to epilepsy in NCC were practically absent in our series of patients. Trials using Praziquantel/prednisone, as part of treatment in patients with NCC and SE has not been reported as yet but our results justify the use of this combination for this kind of patients. However a recommendation that it be used as "first choice" for SE in patient with Major or Minor criteria for NCC must be examined in comparison with other available therapeutic approaches.
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