General description
Of the 1,136 incident patients registered in the clinic over the two-year period, 835 were attended to and had records available for review. The majority of missing records were for patients who were registered in the clinic, had an appointment booked but did not attend. Thirty patients out of the 835 reported exposure to cerebral malaria of whom, 23 fulfilled the inclusion criteria. Original hospitalisation notes were obtained for 11 of these patients. Seven patients did not have sufficient information to exclude other central nervous system infections. The median age on exposure was 30 (5-72) months and 13 were males.
Types of severe sequelae
The majority of patients had been discharged with multiple deficits. Severe neurological sequelae included loss of speech (14), hearing impairment (9), motor deficits (14), behaviour problems (11), epilepsy (12), blindness (12) and cognitive impairment (9). Figure 1 is a summary of the distribution of sequelae in individual patients.
a) Pattern of neurological sequelae
Based on the time of onset, severe neurological sequelae could be categorized into two;
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i.
Immediate onset sequelae - evident on discharge from hospital. The majority of these patients had prolonged coma and status epilepticus during the acute illness (Additional file 1). Again, two forms were recognisable:
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a.
Focal sequelae such as hemiplegia and focal seizures.
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b.
Multifocal or generalized sequelae with spastic quadriparesis, movement disorders, cognitive impairment, blindness, loss of social skills, speech or hearing impairment.
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ii.
Late onset sequelae - developed within months (behaviour problems) or months to years (epilepsy) after the insult.
b) Specific types of sequelae
Blindness
Cortical blindness has been described in earlier studies and because it is reversible, its pathogenesis has been attributed to transient ischaemia. In this series, blindness was observed in 12/23 subjects and often, was one of many deficits on discharge. The shortest time to resolution was one month. Visual acuity in ten of the remaining patients improved over a 2-6 months period and in all cases, almost normal vision was restored by 7 months.
Hearing impairment
Hearing impairment has rarely been reported in previous series. In this series, severe hearing impairment was reported in 9/23 children. Two other children had milder degrees of hearing impairment. Five of the nine children with severe impairment had formal audiometric testing: 3 had profound impairment and 2 had severe impairment with a hearing threshold of 80 decibels. The parents of only one child could afford hearing aids.
Loss of speech
Aphasia was reported in 14 children. Three other children had dysarthria. All three had oro-motor problems. Although speech therapy was offered at weekly or fortnightly intervals, over the follow up period, no full recovery was reported suggesting that loss of speech after childhood cerebral malaria has a poorer prognosis.
Gross motor deficits
Gross motor deficits following cerebral malaria include hemiplegia, diplegia, quadriparesis or quadriplegia[17]. In this study, severe motor deficits of GMFCS grades III-V were reported in 14/23 children. Six of the fourteen children also had movement and gait disorders (ataxia, choreoathetosis, dystonia and poor neck control). Motor deficits were aggravated by concurrent movement and gait problems and associated with regression in milestones and feeding difficulties (some previously ambulant children were discharged unable to sit unsupported or walk). Function however improved with physiotherapy and resolving ataxia.
Behaviour problems
Behaviour problems observed in 11 children were some of the most striking difficulties. Using items in the DSM IV-TR criteria, 3 types of behaviour problems could be recognized:
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a)
Hyperactivity, impulsiveness and inattentiveness as in ADHD;
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b)
Conduct disorders (aggressive, destructive and obsessive behaviour);
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c)
Autistic spectrum and pervasive developmental disorder-like behaviours with or without other neuro-psychiatric problems (eating rubbish, running away from home and self injurious behaviour).
The earliest behavioural symptoms developed within two weeks of discharge. The most common were ADHD-like symptoms. These often were associated with poor night-time sleep. Symptoms improved over 1-3 weeks with haloperidol and/or small doses of methylphenidate. Worsening hyperactivity developed in a child with self injurious behaviour following the initiation of phenobarbitone to treat epilepsy. Behaviour problems in the 12th child were presumed to be an adverse reaction to phenobarbitone and the symptoms improved when this drug was withdrawn.
Aggressive behaviour included beating up peers, throwing stones at people and cars with no or minimal provocation and in two cases, uncontrollable anger. One child with gelastic seizures and a history of febrile seizures in multiple family relations would in addition to anger and aggressive behaviour get prolonged bouts of laughter.
Parents of two other children with labile moods reported bouts of excessive crying following minimal scolding. In the first of the two children, these crying episodes started two weeks after discharge from hospital; the child would cry continuously for over two hours. The electroencephalogram was normal.
Three other children were said to wander off and would sometimes get lost unless closely watched. Parents of one would tie him up in the house. The strain on the family was so immense that one parent described life at home almost like, "hell" and grandparents were called in to help care for two of the other children. These symptoms appeared to improve with haloperidol: in 2/3 cases (including the child who was being tied up), the wandering stopped within a month.
Other than socialization, the effect of the behaviour problems on school attendance in previously school-going children was detrimental; teachers could not cope, school performance declined significantly and all dropped out of school. A brain CT scan was performed in two children - one, a child with intractable epilepsy and aggressive behaviour who was initially discharged with blindness, loss of hearing and speech. The scans showed no focal lesions in the brain parenchyma but bilateral atrophy of the temporal lobes. The second CT scan was in a child discharged with hemiplegia, blindness, feeding difficulties, loss of speech and who later developed ADHD-like symptoms. The acute CT showed brain swelling and meningeal enhancement over the temporo-parietal area and the convalescent CT, cortical atrophy in the same area.
Epilepsy
EEG was performed in 8 of the 12 patients with epilepsy. In patients with generalized seizures, diffuse epileptiform discharges were observed on the electroencephalogram. Localized discharges over the temporal region were seen in two patients. Two children had multiple seizure types with more than 10 seizures a day. Seizures in these two were unresponsive to therapy with phenobarbitone (later withdrawn) and carbamazepine. Although seizures in one eventually improved on sodium valproate, in the second child who in addition had severe behavioural problems, sodium valproate did not reduce the seizure frequency. Instead, the frequency reduced and the behaviour problems improved upon the initiation of clonazepam.
Other problems
Several patients with multiple sequelae had severe cognitive impairment. Child neglect and malnutrition were evident especially among those who presented >6 months after exposure. Malnutrition was compounded by feeding difficulties in the spastic children.