Table of Content - Volume 7 Issue 2 - August 2017

Seizures in adult cases of cerebral malaria in rural based teaching hospital – A Review of literature

Umesh Babu¹, Nishant T², Venkateshwarlu Nandyala^3*, Sripada Muvvagopal⁴

Professor, Department of Medicine, SVS Medical College, Mahabubnagar, Telangana, INDIA.

Email: umeshdoc@rediffmail.com, nishanttrao@yahoo.com, venkatatreya@gmail.com, muvvagopal@gmail.com

Abstract Background: In adults the incidence of seizure in cerebral malaria varies grossly from around one or two per cent cases of cerebral malaria 80 % in the literature. The study was planned and executed at semi-urban hospital. Materials and Methods: A total of confirmed 1219 cases of malaria admitted in the Department of Internal Medicine, 954patients satisfied the World Health Organization (WHO) criteria of severe malaria guidelines 2010¹¹ with cerebral malaria and admitted in Medical Intensive Care Unit of SVS Medical College Hospital. Detailed history of symptoms and signs and necessary investigations including CT scan or MRI scan and EEG Observations and Results: Out of 1219 cases of malaria admitted in the Department of Internal Medicine, 954patients satisfied the World Health Organization (WHO) criteria of severe malaria guidelines 2010¹ with cerebral malaria. Our study observed convulsion in cerebral malaria in 64 [8.25%] cases had convulsions. Extensive search was done in the literature to know the incidence and outcome of convulsions in severe malaria. Discussion: Malaria is common disease in India. Severe malaria and cerebral malaria are also common in these parts of the country. Though not common feature, convulsions are ominous symptoms of this disease in adults

Key Words: Cerebral malaria, CT/ MRI Brain, EEG, Seizure activity.

INTRODUCTION

Seizure is one of the important problem of emergency admission. One to 5% of epilepsies were presumed to be due to central nervous system infections in countries like the United States, Norway and Israel ¹. This incidence may be higher in developing countries. Malaria affects 5% of the world population at any one time and causes more than a million deaths worldwide annually. In adults the incidence of seizure in cerebral malaria varies. In the 1980’s 50% of cerebral malaria patients in Thailand and Vietnam was reported to have generalized tonic-clonic seizures². Seizure activity had been noted in around 80 % of South African children and around 20–40 % of South Asian adult cases of Cerebral Malaria [Idro et al]. In the 1990’s the same countries reported an incidence of 20% or less³. In 1989, Kochar et al reported a 23% incidence of seizures in Rajasthan, India⁴. Most of the seizures in adults were generalized. In children about 30% of all malarial patients had seizures^5,6 while 60% to 85% of cerebral malarial patients had seizures^6-9. More than 75% of seizure occurred in uncomplicated malaria and more than 70% of cerebral malarial patients had more than one seizure. In endemic and hyperendemic areas in Africa the commonest seizure is partial, which accounts for 52-84% of all seizures; 34% is generalizes and another 14% partial with secondary generalized^5,7. In Papua New Guinea, on the other hand, generalized seizure accounts for 85% of seizures, and 53% of cerebral malarial patients have status epilepticus⁶. 217 million were affected with malaria annually in 2015, 21 % reduction in incidence and a reduction of 29 % reduction in mortality¹⁰.

MATERIALS AND METHODS

The present study was conducted in SVS Hospital, Mahabubnagar, a tertiary care teaching hospital. This was a hospital based clinico-epidemiological study. Cerebral malaria (CM) was defined as a clinical syndrome of coma (inability to localize a painful stimulus) at least an hour after termination of a seizure or correction of hypoglycemia, detection of asexual forms of malarial parasite on peripheral blood smear and exclusion of other causes of encephalopathy¹¹.Cases of confirmed malaria patients admitted between January 2007 to December 2016 were collected in a preformed proforma. Out of 1219 cases of malaria admitted in the Department of Internal Medicine, 954patients satisfied the World Health Organization (WHO) criteria of severe malaria guidelines 2010¹¹ with cerebral malaria and admitted in Medical Intensive Care Unit. We further studied the clinical profile, treatment and outcome of these patients. Data was collected in a preformed proforma and analysed by SPSS 20.0 software. Values are expressed in number and percentage (%).

OBSERVATIONS AND RESULTS

Table 1 shows the details of cases admitted to SVS Medical College Hospital from 1-1-2007 till 31-12-2016.

Table 1: Total cases of Malaria with respect to species encountered in SVS Hospital during study period of 10 years (1-1-2007 to 31-12-2016)

Description	Number	Percentage %
Total number of positive Malaria cases	1219	100
Total number of severe Malaria cases	954	78.26
Total number of Cerebral Malaria	660	54.14
Total cases presented with seizure activity	164	13.45 [of total Malarial case] 24.85 [of cerebral Malarial cases]
Known cases of Epilepsy	11	-
Lost to follow up	13	-
Total number of cases included in this study	150	12.30 [of total malaria cases] 22.73 [of cerebral malarial cases]

CT [Computed Tomography] scan or MRI [Magnetic Resonance Imaging] scan done in 240 cases of cerebral malaria cases and EEG [ Electro-encephalography] done in 120 cases. The findings are tabulated in following tables.

Table 2: Showing CT Brain abnormalities in 308

CT finding	Number	Percentage
Normal	198	64.29
Cerebral edema	92	29.87
Periventricular infarct	10	3.24
Cerebellar infarct	8	2.59

Table 3: Showing MRI Brain abnormalities in 265 cases

MRI finding	Number	Percentage
Normal	92	34.71
Cerebral edema	140	52.83
Cerebral infarct	12	4.53
Periventricular hemorrhagic infarct	11	4.15
Myelin changes	10	3.77

Table 4: Various abnormalities in this study

Report of EEG	Number of cases	Percentage
Normal	34	28.33
Diffuse spike waves	38	31.67
Focal seizure activity	36	30
Slow waves in occipital region	12	10
Total	120	100

Of 86 abnormal EEG cases only 42 patients had repeat EEG done at 6 weeks only 3 had showed residual abnormality. These three patients were treated like epilepsy. Patients were followed for at least a period of 2 years. Last case of malaria with convulsions included in this study was admitted on 20^th October 2015. In 10 years of the present study 660 cases of cerebral malaria admitted to SVS Medical College Hospital, Mahabubnagar, Telangana State. 164 patients had seizure activity. Fortunately, we had only 16 cases of cerebral malaria expired. Of these 14 patients presented with status epilepticus.

DISCUSSION

Cerebral malaria is a medical emergency demanding urgent clinical assessment and treatment. The diagnosis requires presence of neurologic symptoms and asexual forms of the parasite on peripheral blood smears. Every effort was taken, and necessary investigations were done to exclude other causes of coma. Seizure activity was noticed more in children up to 80% while 20% of adults had convulsions. [Idro et al 2007] An extensive search was done from the literature. The table V shows the detailed summary of incidence of seizures in various earlier studies. The table explains mainly study population and incidence of seizure activity. Image studies EEG and other investigations mainly were more of nonspecific and mainly to exclude other causes.

Table 5: Summary of the earlier studies with the present study

Serial Number	Study	Comments
1	Schutzhard E and Gerstenbrand F 1984¹³	Study of Tanzanian children; two-thirds had convulsions
2	White NJ et al 1988⁵	Study of Thai adults; one third cases had convulsions
3	Kochar et al 1989⁴	Reporting from Bikaner, Rajasthan India, Kochar et al reported 23% incidence of seizures.6
4	Brewster DR, Kwiatkowski D, White NJ. 1990¹⁴	Study of 65 children; Sixty-two percent of patients had seizures following admission, of whom half had an episode of status epilepticus. Fifty-two percent of seizures were partial motor, 34% generalized tonicclonic, and 14% partial with secondary generalization
5	Bondi 1992¹⁵	Of 78 children with cerebral malaria from Ibadan, Nigeria, between March 1987 and October 1988, 16 (20.5%) died and 62 (79.5%) survived. 11[17.7%] had neurological problems like severe recurrent convulsions.
6	Akpede G, Sykes R, Abiodun F 1993¹⁶	Study of 487 children; 42% patients presented with tonic clonic, 16% had focal convulsions becoming generalized while 21% presented both generalized and focal fits.Twenty-six percent of the active epilepsy group initially had EEG abnormalities. [9.2%].
7	Asindi et al 1993¹⁷	134 children febrile convulsions 55% are cerebral malaria
8	Molyneux ME et al 1995⁸	131 Malawian children admitted with cerebral malaria; 12 patients [9%] had neurological sequelae like convulsions
9	Lallo et al 1996¹⁸	17% children presented with convulsions at the start of presentation to hospital.
10	Waruiru CM, Newton CR, Forster D, et al. 1996⁷	1324 children admitted in the pediatric ward of the Kilifi District hospital in Kenya, over a year period and found seizures in 15.8% of children as part of their illness, with malaria accounting for 69% of the causes of seizures. Most seizures occurred between the ages of 6 months and 5 years and 64.3% of malaria-associated seizures occurred greater than two years old.
11	Crawley J, Smith S, and Kirkham F et al 1996⁹	65 patients (38 female) admitted to Kilifi Hospital in 1994.Fifty-two percent of seizures were partial motor, 34% generalized tonic clonic, and 14% partial with secondary generalization.
12	Bajia, Kochar et al 1997¹⁹	40 (21.62%) patients had convulsions at the time of presentation. 17 (42.5%) of them died, 185 patients
13	Crawley J, Smith S, Muthinji P, Marsh K and Kirkham F et al 2001²⁰	Fifty-two percent of cerebral malaria in children had partial motor seizures, 34% generalized tonicclonic, and 14% partial with secondary generalization.
14	Kochar et al 2002²¹	In an Indian study from Bikaner, Rajasthan on 441 patients of strictly defined cerebral malaria, 21.31% had convulsion
15	Carter JA, Neville BGR, White S, et al. 2004²²	487 children (aged 6-9 years). 9.2 % of cerebral malaria had seizures. The most commonly reported seizure types were tonic-clonic (42%), focal becoming secondarily generalized (16%), and both (21%). Twenty-six percent of the active epilepsy group initially had EEG abnormalities.
16	Idro et al 2007¹²	Of 19,560malaria children, 9,313 were cerebral malaria; 6,563 had seizures.
17	Genton et al 2008²³	Out of 9,537 (55%) had a confirmed Plasmodium parasitaemia, 2.5% of Pf had convulsions and 1.1% cases of Pv had repeated convulsions.
18	Sarkar and Bhattacharya 2008²⁴	3 adult male cases cerebral malaria with convulsions
19	Jain et al 2008²⁵	A clinico-epidemiological study in central India consisting of 404 cases of Plasmodium falciparum and 18 cases of P vivax, 119 were cerebral malaria; seizures were noted in 40% cases.
20	Tanwar et al 2011²⁶	11 children out 13 cases of cerebral malaria had convulsions
21	Mohapatra MK et al 2012²⁷	Convulsion noted in 110(14.3%)of P falciparum cases.
22	Jagjit Singh et al 2013²⁸	110 patients – 3 had cerebral malaria convulsions
23	S Nandwani et al²⁹	Out of 160 patients, 110 (68.75 %) had P. vivax, 30 (18.75 %) had P. falciparum and 20 (12.5 %) had co-infection due to P. vivax and P. falciparum 2 cases of p f had GTCS.
24	Kumar et al 2014³⁰	Observational study of cerebral malaria. 2/27 p v [7.40%], 1/26 pf [3.84%], 2/4 [50%] mixed infection had convulsions
25	Islam et al 2016³¹	Of 187 cases from Bangladesh, 29 patients (15.5%) had convulsion before or after admission.
26	Veer Bahadur Singh et al 2016³²	This was a prospective observational study in 170 patients with a clinical diagnosis of malaria admitted in of PBM Hospital, Bikaner during epidemic of malaria. 5 [4.55%] had convulsions.
27	Jelia et al 2016³³	Four out of 32 cases [12.5%] of falciparum malaria had convulsions
28	Present study 2018	660 cases of cerebral malaria admitted to SVS Medical College Hospital, Mahabubnagar, Telangana State. 164 [8.25%] patients had seizure activity.

Of the 16 patients fourteen presented with status epilepticus. This fact conforms with earlier studies.

CONCLUSION

This is a prospective study spread over 10 years executed at a semi-urban tertiary Hospital attached to SVS Medical College. A total 1219 positive malaria cases were recorded in various wards of SVS Hospital;660 adult cases were of cerebral malaria. 164 patients had seizure activity. Of 16 deaths 14 cases presented with status epilepticus. An adult patient presenting with convulsions and fever a diagnosis of cerebral malaria should strongly be considered in tropical countries like ours and intense search for the diagnosis of malaria even if smear for malaria parasite is negative once, a repeated search in the presence of temperature and chills or PCR or antigen detection in RDT. Status Epilepsy in cerebral malaria may be an ominous sign for prognosis though statistically not significant. Further studies are needed for the confirmation.

Limitations: This was a prospective observational study without comparing control group, which was the main limitation of this study.

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