Clinical , aetiological and evolutive aspects of West syndrome in Yaoundé ( Cameroon ) *

Background: West syndrome (WS) is an epileptic syndrome of the infant occurring between the 3 and 12 months of life and characterized by the triad: infantile spasms in flexion, extension or mixed; global developmental delay; and hypsarrythmia on the electroencephalogram (EEG). Its incidence varies between 2.9 and 4.5 per 10,000 live births. West syndrome is caused by a brain dysfunction whose origins can be prenatal, neonatal and postnatal. Sometimes the aetiology is genetic or unknown. Purpose: To determine the main clinical, aetiological and major evolutive aspects of West syndrome in child neurology unit in a university-affiliated hospital in Yaoundé. Materials and Methods: It was a retrospective descriptive study conducted from September 2011 to January 2012 in the child neurology unit of the Yaoundé gynaeco-obstetric and paediatric hospital. The medical records of 68 children followed for West syndrome (WS) in the service during the period from February 2008 to January 2012 (48 months) were used. All infants of 1to 16-month-old with the diagnosis of WS were included. The diagnosis of WS was based on clinical evidence of spasm in flexion and/or in extension with global development delay, and EEG evidence of hypsarythmia or focal/multifocal epileptic abnormalities when hypsarythmia is absent. For each included infant, relevant medical history and complete physical examination were performed. The following data were collected and reported on a standardized questionnaire: prenatal, perinatal and postnatal past histories, age at onset of spasms, age at diagnosis, semiology of spasms, psychomotor development, the EEG and CT aspects and the evolutive modes of WS under treatment. Psychomotor development was assessed using the Denver developmental screening test (DDST) which assesses the mental age compared to chronological age. Results: The age of onset of spasms varied between 1 and 16 months with a mean of 4.69 (±1.98) months. Males were highly represented with a sex ratio of 1.72. Flexion spasms were the most common clinical presentation (79.41%). 82.83% of the patients had a global developmental delay on the onset of spasms. Structural causes or symptomatic West syndrome was the most frequent presentation (77.94%). Perinatal aetiologies were highly represented (73.58%) with the main cause being neonatal asphyxia (55.88%). A hypsarrythmic tracing was found on the electroencephalogram (EEG) in 73.53% of cases. The most frequent CT abnormality was cortico-subcortical atrophy (38.24%). At the end of our study, global developmental delay persisted in 89.72%. Conclusion: The main aetiologies of West syndrome in our context are the sequelae of neonatal asphyxia and viral embryofoetopathies. There is a high incidence of associated global developmental delay. More prevention methods on risk factors for foetal distress and proper monitoring of deliveries to minimize severe neonatal asphyxia are indispensable.

diagnosis, semiology of spasms, psychomotor development, the EEG and CT aspects and the evolutive modes of WS under treatment.Psychomotor development was assessed using the Denver developmental screening test (DDST) which assesses the mental age compared to chronological age.Results: The age of onset of spasms varied between 1 and 16 months with a mean of 4.69 (±1.98) months.Males were highly represented with a sex ratio of 1.72.Flexion spasms were the most common clinical presentation (79.41%).82.83% of the patients had a global developmental delay on the onset of spasms.Structural causes or symptomatic West syndrome was the most frequent presentation (77.94%).Perinatal aetiologies were highly represented (73.58%) with the main cause being neonatal asphyxia (55.88%).A hypsarrythmic tracing was found on the electroencephalogram (EEG) in 73.53% of cases.The most frequent CT abnormality was cortico-subcortical atrophy (38.24%).At the end of our study, global developmental delay persisted in 89.72%.Conclusion: The main aetiologies of West syndrome in our context are the sequelae of neonatal asphyxia and viral embryofoetopathies.There is a high incidence of associated global developmental delay.More prevention methods on risk factors for foetal distress and proper monitoring of deliveries to minimize severe neonatal asphyxia are indispensable.
West syndrome is caused by a brain dysfunction whose origins can be prenatal, neonatal and postnatal.Sometimes the aetiology is genetic or unknown.It is an epileptic encephalopathy in which the deterioration of brain functions (cognitive, sensory and motor) is due to seizure.Stopping these seizures sometimes leads to a normal psychomotor development [10].Certain brain lesions which are responsible for West syndrome can be prevented.
To date in Cameroon, few studies have been carried out on the subject.The objective of this study was to determine the main aetiologies and describe the major evolutive aspects of West syndrome in our milieu.

METHODOLOGY
It was a retrospective descriptive study conducted from September 2011 to January 2012 in the child neurology unit of the Yaounde Gynaeco-Obstetric and paediatric hospital.
The medical records of 68 children followed for West syndrome (WS) in the service during the period from February 2008 to January 2012 (48 months) were used.All infants of 2-to 16-month-old with the diagnosis of WS were included.The diagnosis of WS was based on clinical evidence of spasm in flexion and/or in extension with global development delay, and EEG evidence of hypsarythmia or focal/multifocal epileptic abnormalities when hypsarythmia are absent.
For each included infant, relevant medical history and complete physical examination were performed.The following data were collected and reported on a standardized questionnaire: prenatal, perinatal and postnatal past histories, age at onset of spasms, age at diagnosis, semiology of spasms, psychomotor development, the EEG and CT aspects and the evolutive modes of WS under treatment.
All patients underwent an EEG recording and a head CT-scan.The EEG was performed by an acquisition unit of 32 channels of Micromed-France.The setup used was in accordance with the international 10/20 with 10 electrodes.CT protocol comprised of unenhanced and contrast enhanced CT scans using a single detector CT scanner.Image acquisition was spiral from skull base to vertex, using 3 -5 mm-thick slices.The images were reviewed by one radiologist.
Psychomotor development (developmental milestone) was assessed using the Denver II test which assesses the mental age compared to chronological age.Data collected using the questionnaires were analysed using the software Statistic Package for Social Sciences (SPSS) 17.0.The chi-square test of Pearson was used to study the relationship between two qualitative variables.Differences were considered statistically significant for p values < 0.05.
Informed consent was obtained from parents and an ethical clearance was obtained from the National Ethics Committee.

RESULTS
Sixty eight infants aged between 2 and 16 months (mean: 7.10 ± 2.24 months) were included in this study.The sex ratio was 1.72% with 63.24% males.Age to sex distribution of patients is shown in Table 1.
The mean age of onset of West syndrome was 4.69 (±1.98) months (Figure 1).
Table 2 shows that symmetric flexion spasms were the most common clinical manifestation in our patients.
Neonatal asphyxia was the main etiological factor (55.88%) as shown in Table 4.   Head CT-scans unveiled several types of cerebral lesions with the main one being hypoxo-ischemic lesions (Table 5 and Figure 2).
Fifty of the 68 patients (73.53%) had a hypsarythmic EEG tracing on the EEG (Figure 3).
There is an association between the aetiology and prognosis (chi-square = 10.991Pearson, P = 0.004).Developmental delay was greater in west syndromes with structural aetiologies (Table 7).

DISCUSSION
The age of onset of symptoms in this series ranged from 1 to 16 months with a mean of 4.69 ± 1.98 months.Sixty-three out of 68 patients (92.64%) were 3 to 6 months old.This is quite similar to the findings of most authors who reported a peak incidence between 3 and 7 months in 50% of cases [7][8][9]11].Mbonda et al. [8] found in their study that seizures began in the neonatal period.Spasms in the neonatal period are not necessarily related to West syndrome because they can be observed in early infantile encephalopathy or early myoclonic encephalopathy.These two nosological entities have spasms in their clinical expression.Male predominance with a sex ratio of 1.72 corroborated data from many other studies [2,3,[7][8][9].Spasms in flexion represented 79.41% (54/68) of the clinical forms.Several authors describe the flexion spasms as the most frequent clinical presentation of West syndrome [4].Symmetrical high frequency of spasms in our series reflects the widespread nature of this form of epilepsy in WS.
An etiological factor probably playing a role in the onset of the disease was found in 77.94% patients (53/68).From other authors [4,[6][7][8]11] an etiological factor is determined in 64% to 90% of cases.The main etiological factor in our series was the effects of hypoxo-ischemic neonatal brain lesions (55.88%).In one study, Hwang [4] founded that neonatal asphyxia was the main etiological factor (50.8%) followed by cerebral malformations (21.4%) and neuro-cutaneous syndromes (8.6%).For Mohamed et al. [7], the first etiological factor is brain injury secondary to prematurity, followed by cortical malformations, Bourneville tuberous sclerosis and hypoxic-ischemic injury.Brain malformations encountered in 8.82% of our cases (malformations and cortical tubers).Magnetic resonance imaging [13,14] which is the goal standard imaging examination for epilepsy was not performed in our patients due to its cost and availability.Its implementation could probably increase the frequency of cerebral lesions in our patients.In spite of its low sensitivity, CT-scan remains our means of cranio-encephalic imaging.Trans-cranial ultrasounds could be an imaging alternative but was limited by the size or the closure of fontanelles, or by incomplete brain exploration.Antenatal ultrasound could have detected some abnormalities related to cerebral malformations or embryofoetopathies.The sequelae of congenital cytomegalovirus (CMV) infection were the second group of aetiology in our study.Indeed because of its high cost, CMV serology is not systematically requested in the assessment of antenatal serology in our milieu.
At the end of this study, we observed complete regression of spasms in 66 patients (97.06%), persistent of spasms in 2.94%, a change to another type of seizures in 51.47%.The prevalence of global developmental delay in this group at the end of this study was 89.71%.According to other authors, complete regression of spasms is observed in 50% to 90% of cases [15][16][17], evolution to other types of seizures in 50% to 70% of cases [15,17], and persistency of cognitive delay in 70% to 90% of cases [4,9,15,16].In Hwang's study [4], evolution to a global developmental delay was found in 75.4% of cases and a shift to other types of seizures in 11.2%.Riikonen et al. [18] found a persistent spasm in 2.7% of patients.Mbonda et al. [8] in Cameroon concluded to complete regression of spams in 70.30% of patients and their persistency in 13.51% at the end of follow-up.The high incidence of developmental delay in our study could be explained by the fact that most symptomatic (or structural) West syndrome are strongly associated with a poor prognosis [5,16].Factors associated with a poor prognosis in our study were: the structural character (or symptomatic) of the west syndrome, global developmental delay, early onset of spasms and delay in starting treatment.These factors are also described in literature [5,16,19].

CONCLUSION
The two main aetiologies of West syndrome in our con-text are the sequelae of neonatal asphyxia and viral embryofoetopathies.There is a high incidence of associated global developmental delay.Antenatal assessments including search for CMV seroconversion and identification of cerebral anomalies on antenatal ultrasounds should be emphases.More prevention methods on risk factors for foetal distress and proper monitoring of deliveries to minimize severe neonatal asphyxia are indispensable.

Figure 1 .
Figure 1.Distribution of patients by age at onset of symptoms and gender.

Figure 2 .
Figure 2. CT lesions of west syndrome.Hypoxo-ischemic lesion associating diffused subcortico-cortical hypodensities and proencephalic cavities (a), (b), in an infant of 5 months with a past history of severe neonatal asphyxia.Infant of 6 months with proved CMV embryofoetopathy (c): parenchymal destruction, calcification and enlargement of lateral ventricles.Lissencephaly/pachygyry (d) on the CT scan of a 5 months infant with west syndrome.

Table 1 .
Distribution of patients according to age and sex.
*Age at diagnosis (in months).

Table 2 .
Clinical presentation of patients.

Table 3 .
Distribution of patients according to the cause of West syndrome.

Table 5 .
Main brain CT damage found in symptomatic patients (N = 53).

Table 6 .
Clinical course of our patients at the end of the study.

Table 7 .
Association between aetiology and prognosis.