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Hemiconvulsion-hemiplegia-epilepsy syndrome in Niger: A retrospective case series
Journal of Clinical Neuroscience 65 (2019) 121–124
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Clinical study
Hemiconvulsion-hemiplegia-epilepsy syndrome in Niger: A retrospective case series Hamid Assadeck a,b,⇑, Moussa Toudou Daouda a,⇑, Zakaria Mamadou a, Mahadi Moussa Konate c, Fatimata Hassane Djibo a, Dijbo Douma Maiga b a b c
Department of Neurology, National Hospital of Niamey, Niamey, Niger Department of Medicine and Medical Specialties, Faculty of Medicine and Pharmacy, Abdou Moumouni University, Niamey, Niger Department of Neurology, General Reference Hospital of Niamey, Niamey, Niger
a r t i c l e
i n f o
Article history: Received 13 January 2019 Accepted 8 March 2019
Keywords: HHE syndrome Epidemiology Niger Sub-Saharan Africa
a b s t r a c t Objective: To report the demographic, clinical and paraclinical characteristics as well as the outcomes during follow-up visits of HHE syndrome in Niger. Patients and methods: It was a retrospective study conducted at the Neurology Outpatient Clinic of the National Hospital of Niamey (Niger) between May 2003 and May 2018. Results: During the period of study, 882 patients with epilepsy aged 20 years or less were seen in consultation among whom we collected 22 cases of HHE syndrome with a hospital prevalence of 2.5%. They were 14 men and 8 women (sex ratio = 1.75) with a mean age of 3.76 years (range: 1 and 20 years). At the time of diagnosis, 81.8% of patients were aged under 6 years. The antecedent of febrile convulsions in childhood was found in only 31.8% of cases. The mean age of onset of hemiplegia was 1.9 years (range: 9 months and 5 years). The mean age of onset of epileptic seizures was 2.94 years (range: 1 and 8 years). The mean interval between the onset of hemiplegia and onset of epileptic seizures was 9 months (range: 1 month and 4 years). 31.8% of patients had a delay of acquisitions at the time of diagnosis. 95.5% of patients had drug-resistant epilepsy. Conclusion: HHE syndrome is still seen in the countries of Sub-Saharan Africa. The high morbidity and mortality in children with HHE syndrome highlight the need to improve emergency care for febrile clonic seizures in childhood and the early and adequate management of infectious diseases in the child. Ó 2019 Elsevier Ltd. All rights reserved.
1. Introduction Described for the first time in 1957 by Gastaut et al. [1], hemiconvulsion-hemiplegia-epilepsy (HHE) syndrome is a rare consequence of prolonged febrile seizures in childhood. It is characterized sequentially by the occurrence of prolonged clonic seizures with unilateral predominance that occurred in the course of a febrile illness in a child usually younger than 4 years, followed by the development of ipsilateral hemiplegia of variable duration occurs and subsequentially the development of late focal epilepsy. Epilepsy develops after a free interval of variable duration after initial convulsions [2 –4]. At the time of the first clonic seizures, cerebral magnetic resonance imaging (MRI) showed edematous swelling of the concerned cerebral hemisphere followed after a
few weeks to a few months by cerebral hemiatrophy [5]. The interictal electroencephalogram (EEG) showed unilateral or bilateral slow waves with higher amplitude on the affected cerebral hemisphere, focal spikes or slow spike-waves, or paroxysmal diffuse activity [6,7]. HHE syndrome has become rare in developed countries today due to the early and adequate management of fever and febrile convulsions in children. In sub-Saharan Africa, the HHE syndrome is still seen due to the high frequency of infectious diseases responsible for prolonged febrile seizures in children. Few studies had been published on HHE syndrome in sub-Saharan Africa. In this study, we describe through a series of 22 patients the demographic, clinical and paraclinical characteristics as well as the outcomes during follow-up visits of HHE syndrome in Niger. 2. Patients and methods
⇑ Corresponding authors at: Department of Neurology, National Hospital of Niamey, PO Box 238, Niamey, Niger. E-mail addresses: [email protected] (H. Assadeck), moussatoudou@ gmail.com (M. Toudou Daouda). https://doi.org/10.1016/j.jocn.2019.03.008 0967-5868/Ó 2019 Elsevier Ltd. All rights reserved.
We retrospectively report all cases of HHE syndrome diagnosed at the Neurology Outpatient Clinic of the National Hospital of Niamey (Niger) between May 2013 and May 2018 (5 years). The study
122
H. Assadeck et al. / Journal of Clinical Neuroscience 65 (2019) 121–124
was approved by the Institutional Review Board of the Faculty of Medicine of Abdou Moumouni University of Niamey (Niger) in accordance with the Declaration of Helsinki. Written informed consent of patients was not required because the data were extracted anonymously and the management of these patients was not affected. All authors had participated in the writing and critical revision of the manuscript for important intellectual content. All authors read and approved the final version of the manuscript as written. Authors alone are responsible for the content and writing of the paper and assume total responsibility for the integrity of the data. We included in this study patients who met the following criteria: 1) antecedent of febrile convulsions or not in childhood, 2) occurrence of hemiplegia at the time of febrile convulsions or after a free interval, 3) absence of motor deficit at birth or secondary causes at the time of onset of hemiplegia such as cerebrovascular disease, meningitis or meningoencephalitis, intracranial expansive process or head trauma, 4) development of usual epileptic seizures. For each patient, we collected the following information: age at diagnosis, sex, past medical history, father’s profession, the age of onset of hemiplegia, the age of onset of usual epileptic seizures, type of seizures, the EEG and brain CT scan findings, antiepileptic drugs, and outcomes during follow-up visits. All patients were followed and evaluated during the period of study by neurologists. The response to antiepileptic treatment was evaluated during the follow-up visits. Epilepsy was considered as drug-resistant in this study in case of failure to achieve sustained seizure freedom despite adequate trials of two well-tolerated and appropriately chosen antiepileptic drugs prescribed as monotherapies or in combination according to the definition of drug resistance proposed by ILAE [8].
3. Results Between May 2013 and May 2018, 882 patients with epilepsy aged 20 years or less were seen in consultation among which we collected 22 cases of HHE syndrome with a hospital prevalence of 2.5%. They were 14 men and 8 women (sex ratio = 1.75) with a mean age of 3.76 years (range: 1 and 20 years). Tables 1 and 2
detail the characteristics of the 22 patients. At the time of diagnosis, 81.8% of patients (n = 18) were aged under 6 years. The majority of patients’ parents had a low socioeconomic level (77.3%, n = 17) which are farmers, tailors, masons, and maneuvers. The antecedent of febrile convulsions in childhood was found in only 31.8% of cases (n = 7). Other past medical history found were birth asphyxia (31.8%) and malaria (36.4%, n = 8). The mean age of onset of hemiplegia was 1.9 years (range: 9 months and 5 years). The mean age of onset of epileptic seizures was 2.94 years (range: 1 and 8 years). The mean interval between the onset of hemiplegia and onset of epileptic seizures was 9 months (range: 1 month and 4 years). We noted a predominance of partial secondarily generalized seizures (81.8%). Seven patients (31.8%) had a delay of acquisitions (oral language, cognition) at the time of diagnosis. Two patients (9.1%) had a loss of acquisitions at the time of diagnosis. Hemiplegia/hemiparesis was found in all patients at the time of diagnosis. The brain CT scan allowed to rule out other causes that could explain hemiplegia and seizures in all patients. It was normal in 4 patients (18.2%). Cerebral hemiatrophy was found in the other patients. The interictal EEG showed unilateral slow waves in 9 cases (40.9%) and unilateral slow spike-waves in 13 cases (59.1%). All patients had received in first intention carbamazepine as the antiepileptic drug. In patients with recurrent epileptic seizures, carbamazepine was associated with sodium valproate and/or phenobarbital. Almost all patients (95.5%) had drug-resistant epilepsy.
4. Discussion In this retrospective study of 5 years, we determine the demographic, clinical and paraclinical characteristics as well as the outcomes during follow-up visits of HHE syndrome in Niger. The hospital prevalence of HHE syndrome in patients aged 20 years or less was 2.5% in Niger with a predominance of male sex (sex ratio at 1.75) and a mean age of patients at the time of diagnosis of 3.76 years. The HHE syndrome occurs in a child usually younger than 4 years [6,7]. In our study, 72.7% of patients were aged 4 years or less at the time of diagnosis. The antecedent of febrile convulsions
Table 1 Demographic and clinical characteristics of the patients. Patients
Age at diagnosis
Sex
Past medical history
Fathers profession
Age of onset of hemiplegia
Age of onset of seizures
Type of seizures
Associated clinical signs
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22
1 year 5 years 2 years 5 years 18 months 1 year 3 years 2 years 21 months 20 years 6 years 3 years 1 year 2 years 18 months 8 years 2 years 2 years 2 years 7 years 4 years 2 years
M F M F F M M M M M F M F M M F F M M M F M
FCC FCC FCC FCC FCC BA Malaria Malaria Malaria FCC FCC Malaria Malaria Malaria Malaria BA BA BA BA BA BA Malaria
Farmer Farmer Farmer Farmer Tailor Farmer Trader Mason Trader Farmer Farmer Farmer Farmer Schoolteacher Schoolteacher Farmer Maneuver Farmer Farmer Trader Farmer Farmer
1 year 4 years 18 months 3 years 18 months 1 year 2 years 1 year 21 months Unknown 5 years 2 years 1 year 1 year 18 months Unknown 18 months 1 years 9 months 3 years 3 years 18 months
1 year 5 years 2 years 4 years 18 months 1 year 3 years 2 year 21 months Unknown 6 years 3 years 1 year 2 years 18 months 8 years 2 years 2 years 2 years 7 years 4 years 2 years
GTCS SGPS SGPS SGPS GTCS GTCS SGPS SGPS SGPS SGPS SGPS SGPS GTCS SGPS SGPS SGPS SGPS SGPS SGPS SGPS SGPS SGPS
– LA – DA – – DA – – DA DA LA – – – DA – – – DA DA –
M: Male; F: Female; FCC: Febrile convulsions in childhood; BA: Birth asphyxia; GTCS: Generalized tonic-clonic seizures; SGPS: Secondarily generalized partial seizures; LA: Loss of acquisitions; DA: Delay of acquisitions.
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H. Assadeck et al. / Journal of Clinical Neuroscience 65 (2019) 121–124 Table 2 Paraclinical and therapeutic characteristics and outcomes during follow-up visits of the patients. Patients
Cerebral CT Scan
EEG abnormalities
Antiepileptic drugs therapy
Outcomes
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22
Normal Left cerebral hemiatrophy Left cerebral hemiatrophy Left cerebral hemiatrophy Normal Normal Right cerebral hemiatrophy Right cerebral hemiatrophy Left cerebral hemiatrophy Left cerebral hemiatrophy Left cerebral hemiatrophy Right cerebral hemiatrophy Normal Left cerebral hemiatrophy Right cerebral hemiatrophy Left cerebral hemiatrophy Right cerebral hemiatrophy Right cerebral hemiatrophy Left cerebral hemiatrophy Left cerebral hemiatrophy Left cerebral hemiatrophy Right cerebral hemiatrophy
Left unilateral slow waves Left fronto-temporal spike-waves Left unilateral slow waves Left fronto-temporal spike-waves Right unilateral slow waves Right unilateral slow waves Right fronto-temporal spike-waves Right fronto-temporal spike-waves Left unilateral slow waves Left unilateral slow waves Left unilateral slow waves Right fronto-temporal spike-waves Left fronto-temporal spike-waves Left fronto-temporal slow spike-waves Right fronto-temporal slow spike-waves Left fronto-temporal slow spike-waves Right fronto-temporal slow spike-waves Right unilateral slow waves Left fronto-temporal slow spike-waves Left unilateral slow waves Left fronto-temporal slow spike-waves Left fronto-temporal slow spike-waves
CBZ, CBZ, CBZ, CBZ, CBZ, CBZ, CBZ, CBZ, CBZ, CBZ, CBZ, CBZ, CBZ, CBZ, CBZ, CBZ, CBZ, CBZ, CBZ, CBZ, CBZ, CBZ,
Drug-resistance Drug-resistance Drug-resistance Drug-resistance Drug-resistance Drug-resistance Drug-resistance Drug-resistance Drug-resistance Drug-resistance Drug-resistance Drug-resistance Drug-resistance Drug-resistance Drug-resistance Drug-resistance Drug-resistance Drug-resistance Drug-resistance Drug-resistance Drug-resistance Seizure control
VPA VPA VPA VPA PB PB PB PB PB PB PB PB PB, VPA PB, VPA PB, VPA PB, VPA PB, VPA PB, VPA VPA VPA VPA PB
CT Scan: Computed tomography scan ; EEG: electroencephalogram; CBZ: Carbamazepine; VPA: Valproate; PB: Phenobarbital.
in childhood was found in only 31.8% of our patients. In a South African study of 8 patients with HHE syndrome, the antecedent of febrile convulsions in childhood was found in only one patient [3]. However, two Moroccan studies reported the antecedent of febrile convulsions in childhood in all patients [2,4]. Teixeira et al. [9] report as far as they are concerned the antecedent of febrile convulsions in 12.1% of their patients. After the episode of hemiconvulsion-hemiplegia, epilepsy appears after a free interval of variable duration occurs. In the present study, this free interval was less than one year in 50% of patients. Van Toorn et al. [3] report a free interval less than 1 year in 57% of their patients. The types of epilepsy observed during the HHE syndrome are variable and include simple or complex partial seizures, generalized tonicclonic seizures, psychiatric manifestations, etc. [6]. Bourrous et al. [4] report a predominance of generalized tonic-clonic seizures in their patients (72.7%). In our study, we noted a predominance of partial secondarily generalized seizures (81.8%). Similar findings had been reported in a recent Moroccan study [2]. Outside of late epilepsy, they are also encountered cognitive disorders in the course of HHE syndrome such as language or memory disorders, intellectual disorders, etc. [2–4,10]. These disorders are considered as a complication of HHE syndrome and appear most often late. In the present study, we found 31.8% of cases of delay of acquisitions at the time of diagnosis. Cerebral MRI may also show afar the onset of HHE syndrome hippocampal sclerosis outside of cerebral hemiatrophy [2,5,10]. This association with hippocampal sclerosis favors the installation of drug-resistant epilepsy. In our study, no patient received cerebral MRI. Carbamazepine was the antiepileptic drug of the first choice in this study prescribed as monotherapy or in combination with valproate or phenobarbital. Drug-resistance was observed in 95.5% of patients. Similar findings had been reported in the literature [2,10]. In patients with severe drug-resistant epilepsy, the use of surgical treatment is considered. The surgery consists of anterior temporal lobectomy, cortical resection, functional hemispherectomy or callosotomy [11]. On the other hand, in the acute phase of HHE syndrome with intracranial hypertension related to hemispheric cerebral edema, decompressive hemicraniectomy is proposed [12,13]. In our study, many patients should have been proposed to the surgical treatment for epilepsy, but unfortunately, this sur-
gery is not available in Niger. In addition, these patients do not have financial funding to be referred abroad to a specialized center for surgery epilepsy.
5. Conclusion HHE syndrome is still seen in developing countries particularly in sub-Saharan African countries. The high morbidity and mortality in children with HHE syndrome highlight the need to improve emergency care for febrile clonic seizures in childhood and the early and adequate management of infectious diseases in the child.
Declaration of interest The authors declare that they have no conflicts of interest related to this article. References [1] Gastaut H, Vigouroux M, Trevisan C, Regis H. Le syndrome ‘‘hémiconvulsionhémiplégie-épilepsie” (syndrome H.H.E.). Rev Neurol 1957;97:37–52. [2] Albakaye M, Belaïdi H, Lahjouji F, Errguig L, Kuate C, Maiga Y, et al. Clinical aspects, neuroimaging, and electroencephalography of 35 cases of hemiconvulsion-hemiplegia syndrome. Epilepsy Behav 2018;80:184–90. https://doi.org/10.1016/j.yebeh.2017.12.018. [3] van Toorn R, Janse van Rensburg P, Solomons R, Ndondo AP, Schoeman JF. Hemiconvulsion-hemiplegia-epilepsy syndrome in South African children: insights from a retrospective case series. Eur J Paediatr Neurol 2012;16 (2):142–8. https://doi.org/10.1016/j.ejpn.2011.06.009. [4] Bourrous M, Lagmiri K, Amine M, Abidi M, Bouskraoui M. Le syndrome hémiconvulsion-hémiplégie-épilepsie de l’enfant. J Pediatr Pueric 2010;23 (6):322–7. https://doi.org/10.1016/j.jpp.2010.07.004. [5] Toldo I, Calderone M, Boniver C, Dravet Ch, Guerrini R, Laverda AM. Hemiconvulsion-hemiplegia-epilepsy syndrome: early magnetic resonance imaging findings and neuroradiological follow-up. Brain Dev 2007;29 (2):109–11. https://doi.org/10.1016/j.braindev.2006.06.005. [6] Gastaut H, Poirier F, Payan H, Salamon G, Toga M, Vigouroux MHHE. syndrome; hemiconvulsions, hemiplegia, epilepsy. Epilepsia 1960;1:418–47. https://doi. org/10.1111/j.1528-1157.1959.tb04278.x. [7] Chauvel P, Dravet C. Le syndrome hémiconvulsion-hémiplégie-épilepsie. Les syndromes épileptiques de l’enfant et l’adolescent. 4ème édition. Montrouge: John Libbey 2005:277–94. [8] Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Allen Hauser W, Mathern G, et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia 2010;51 (6):1069–77. https://doi.org/10.1111/j.1528-1167.2009.02397.x.
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[9] Teixeira RA, Zanardi VA, Li LM, Santos SL, Cendes F. Epilepsy and destructive brain insults in early life: a topographical classification on the basis of MRI findings. Seizure 2004;13(6):383–91. https://doi.org/10.1016/ j.seizure.2003.10.001. [10] Mirsattari SM, Wilde NJ, Pigott SE. Long-term cognitive outcome of hemiconvulsion-hemiplegia-epilepsy syndrome affecting the left cerebral hemisphere. Epilepsy Behav 2008;13(4):678–80. https://doi.org/10.1016/j. yebeh.2008.07.008. [11] Kim DW, Kim KK, Chu K, Chung CK, Lee SK. Surgical treatment of delayed epilepsy in hemiconvulsion-hemiplegia-epilepsy syndrome. Neurology
2008;70(22 Pt 2):2116–22. https://doi.org/10.1212/01. wnl.0000289192.50924.93. [12] Berhouma M, Chekili R, Brini I, Kchir N, Jemel H, Bousnina S, et al. Decompressive hemicraniectomy in a space-occupying presentation of hemiconvulsion-hemiplegia-epilepsy syndrome. Clin Neurol Neurosurg 2007;109(10):914–7. https://doi.org/10.1016/j.clineuro.2007.07.027. [13] Beier AD, Jannotta GE, Sandler ED, Abram HS, Sheth RD, Aldana PR. Survival following decompressive hemicraniectomy for hemiconvulsion-hemiplegiaepilepsy syndrome: case report. J Neurosurg Pediatr 2016;18(3):344–9. https://doi.org/10.3171/2016.3.PEDS15677.
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Clinical study
Hemiconvulsion-hemiplegia-epilepsy syndrome in Niger: A retrospective case series Hamid Assadeck a,b,⇑, Moussa Toudou Daouda a,⇑, Zakaria Mamadou a, Mahadi Moussa Konate c, Fatimata Hassane Djibo a, Dijbo Douma Maiga b a b c
Department of Neurology, National Hospital of Niamey, Niamey, Niger Department of Medicine and Medical Specialties, Faculty of Medicine and Pharmacy, Abdou Moumouni University, Niamey, Niger Department of Neurology, General Reference Hospital of Niamey, Niamey, Niger
a r t i c l e
i n f o
Article history: Received 13 January 2019 Accepted 8 March 2019
Keywords: HHE syndrome Epidemiology Niger Sub-Saharan Africa
a b s t r a c t Objective: To report the demographic, clinical and paraclinical characteristics as well as the outcomes during follow-up visits of HHE syndrome in Niger. Patients and methods: It was a retrospective study conducted at the Neurology Outpatient Clinic of the National Hospital of Niamey (Niger) between May 2003 and May 2018. Results: During the period of study, 882 patients with epilepsy aged 20 years or less were seen in consultation among whom we collected 22 cases of HHE syndrome with a hospital prevalence of 2.5%. They were 14 men and 8 women (sex ratio = 1.75) with a mean age of 3.76 years (range: 1 and 20 years). At the time of diagnosis, 81.8% of patients were aged under 6 years. The antecedent of febrile convulsions in childhood was found in only 31.8% of cases. The mean age of onset of hemiplegia was 1.9 years (range: 9 months and 5 years). The mean age of onset of epileptic seizures was 2.94 years (range: 1 and 8 years). The mean interval between the onset of hemiplegia and onset of epileptic seizures was 9 months (range: 1 month and 4 years). 31.8% of patients had a delay of acquisitions at the time of diagnosis. 95.5% of patients had drug-resistant epilepsy. Conclusion: HHE syndrome is still seen in the countries of Sub-Saharan Africa. The high morbidity and mortality in children with HHE syndrome highlight the need to improve emergency care for febrile clonic seizures in childhood and the early and adequate management of infectious diseases in the child. Ó 2019 Elsevier Ltd. All rights reserved.
1. Introduction Described for the first time in 1957 by Gastaut et al. [1], hemiconvulsion-hemiplegia-epilepsy (HHE) syndrome is a rare consequence of prolonged febrile seizures in childhood. It is characterized sequentially by the occurrence of prolonged clonic seizures with unilateral predominance that occurred in the course of a febrile illness in a child usually younger than 4 years, followed by the development of ipsilateral hemiplegia of variable duration occurs and subsequentially the development of late focal epilepsy. Epilepsy develops after a free interval of variable duration after initial convulsions [2 –4]. At the time of the first clonic seizures, cerebral magnetic resonance imaging (MRI) showed edematous swelling of the concerned cerebral hemisphere followed after a
few weeks to a few months by cerebral hemiatrophy [5]. The interictal electroencephalogram (EEG) showed unilateral or bilateral slow waves with higher amplitude on the affected cerebral hemisphere, focal spikes or slow spike-waves, or paroxysmal diffuse activity [6,7]. HHE syndrome has become rare in developed countries today due to the early and adequate management of fever and febrile convulsions in children. In sub-Saharan Africa, the HHE syndrome is still seen due to the high frequency of infectious diseases responsible for prolonged febrile seizures in children. Few studies had been published on HHE syndrome in sub-Saharan Africa. In this study, we describe through a series of 22 patients the demographic, clinical and paraclinical characteristics as well as the outcomes during follow-up visits of HHE syndrome in Niger. 2. Patients and methods
⇑ Corresponding authors at: Department of Neurology, National Hospital of Niamey, PO Box 238, Niamey, Niger. E-mail addresses: [email protected] (H. Assadeck), moussatoudou@ gmail.com (M. Toudou Daouda). https://doi.org/10.1016/j.jocn.2019.03.008 0967-5868/Ó 2019 Elsevier Ltd. All rights reserved.
We retrospectively report all cases of HHE syndrome diagnosed at the Neurology Outpatient Clinic of the National Hospital of Niamey (Niger) between May 2013 and May 2018 (5 years). The study
122
H. Assadeck et al. / Journal of Clinical Neuroscience 65 (2019) 121–124
was approved by the Institutional Review Board of the Faculty of Medicine of Abdou Moumouni University of Niamey (Niger) in accordance with the Declaration of Helsinki. Written informed consent of patients was not required because the data were extracted anonymously and the management of these patients was not affected. All authors had participated in the writing and critical revision of the manuscript for important intellectual content. All authors read and approved the final version of the manuscript as written. Authors alone are responsible for the content and writing of the paper and assume total responsibility for the integrity of the data. We included in this study patients who met the following criteria: 1) antecedent of febrile convulsions or not in childhood, 2) occurrence of hemiplegia at the time of febrile convulsions or after a free interval, 3) absence of motor deficit at birth or secondary causes at the time of onset of hemiplegia such as cerebrovascular disease, meningitis or meningoencephalitis, intracranial expansive process or head trauma, 4) development of usual epileptic seizures. For each patient, we collected the following information: age at diagnosis, sex, past medical history, father’s profession, the age of onset of hemiplegia, the age of onset of usual epileptic seizures, type of seizures, the EEG and brain CT scan findings, antiepileptic drugs, and outcomes during follow-up visits. All patients were followed and evaluated during the period of study by neurologists. The response to antiepileptic treatment was evaluated during the follow-up visits. Epilepsy was considered as drug-resistant in this study in case of failure to achieve sustained seizure freedom despite adequate trials of two well-tolerated and appropriately chosen antiepileptic drugs prescribed as monotherapies or in combination according to the definition of drug resistance proposed by ILAE [8].
3. Results Between May 2013 and May 2018, 882 patients with epilepsy aged 20 years or less were seen in consultation among which we collected 22 cases of HHE syndrome with a hospital prevalence of 2.5%. They were 14 men and 8 women (sex ratio = 1.75) with a mean age of 3.76 years (range: 1 and 20 years). Tables 1 and 2
detail the characteristics of the 22 patients. At the time of diagnosis, 81.8% of patients (n = 18) were aged under 6 years. The majority of patients’ parents had a low socioeconomic level (77.3%, n = 17) which are farmers, tailors, masons, and maneuvers. The antecedent of febrile convulsions in childhood was found in only 31.8% of cases (n = 7). Other past medical history found were birth asphyxia (31.8%) and malaria (36.4%, n = 8). The mean age of onset of hemiplegia was 1.9 years (range: 9 months and 5 years). The mean age of onset of epileptic seizures was 2.94 years (range: 1 and 8 years). The mean interval between the onset of hemiplegia and onset of epileptic seizures was 9 months (range: 1 month and 4 years). We noted a predominance of partial secondarily generalized seizures (81.8%). Seven patients (31.8%) had a delay of acquisitions (oral language, cognition) at the time of diagnosis. Two patients (9.1%) had a loss of acquisitions at the time of diagnosis. Hemiplegia/hemiparesis was found in all patients at the time of diagnosis. The brain CT scan allowed to rule out other causes that could explain hemiplegia and seizures in all patients. It was normal in 4 patients (18.2%). Cerebral hemiatrophy was found in the other patients. The interictal EEG showed unilateral slow waves in 9 cases (40.9%) and unilateral slow spike-waves in 13 cases (59.1%). All patients had received in first intention carbamazepine as the antiepileptic drug. In patients with recurrent epileptic seizures, carbamazepine was associated with sodium valproate and/or phenobarbital. Almost all patients (95.5%) had drug-resistant epilepsy.
4. Discussion In this retrospective study of 5 years, we determine the demographic, clinical and paraclinical characteristics as well as the outcomes during follow-up visits of HHE syndrome in Niger. The hospital prevalence of HHE syndrome in patients aged 20 years or less was 2.5% in Niger with a predominance of male sex (sex ratio at 1.75) and a mean age of patients at the time of diagnosis of 3.76 years. The HHE syndrome occurs in a child usually younger than 4 years [6,7]. In our study, 72.7% of patients were aged 4 years or less at the time of diagnosis. The antecedent of febrile convulsions
Table 1 Demographic and clinical characteristics of the patients. Patients
Age at diagnosis
Sex
Past medical history
Fathers profession
Age of onset of hemiplegia
Age of onset of seizures
Type of seizures
Associated clinical signs
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22
1 year 5 years 2 years 5 years 18 months 1 year 3 years 2 years 21 months 20 years 6 years 3 years 1 year 2 years 18 months 8 years 2 years 2 years 2 years 7 years 4 years 2 years
M F M F F M M M M M F M F M M F F M M M F M
FCC FCC FCC FCC FCC BA Malaria Malaria Malaria FCC FCC Malaria Malaria Malaria Malaria BA BA BA BA BA BA Malaria
Farmer Farmer Farmer Farmer Tailor Farmer Trader Mason Trader Farmer Farmer Farmer Farmer Schoolteacher Schoolteacher Farmer Maneuver Farmer Farmer Trader Farmer Farmer
1 year 4 years 18 months 3 years 18 months 1 year 2 years 1 year 21 months Unknown 5 years 2 years 1 year 1 year 18 months Unknown 18 months 1 years 9 months 3 years 3 years 18 months
1 year 5 years 2 years 4 years 18 months 1 year 3 years 2 year 21 months Unknown 6 years 3 years 1 year 2 years 18 months 8 years 2 years 2 years 2 years 7 years 4 years 2 years
GTCS SGPS SGPS SGPS GTCS GTCS SGPS SGPS SGPS SGPS SGPS SGPS GTCS SGPS SGPS SGPS SGPS SGPS SGPS SGPS SGPS SGPS
– LA – DA – – DA – – DA DA LA – – – DA – – – DA DA –
M: Male; F: Female; FCC: Febrile convulsions in childhood; BA: Birth asphyxia; GTCS: Generalized tonic-clonic seizures; SGPS: Secondarily generalized partial seizures; LA: Loss of acquisitions; DA: Delay of acquisitions.
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H. Assadeck et al. / Journal of Clinical Neuroscience 65 (2019) 121–124 Table 2 Paraclinical and therapeutic characteristics and outcomes during follow-up visits of the patients. Patients
Cerebral CT Scan
EEG abnormalities
Antiepileptic drugs therapy
Outcomes
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22
Normal Left cerebral hemiatrophy Left cerebral hemiatrophy Left cerebral hemiatrophy Normal Normal Right cerebral hemiatrophy Right cerebral hemiatrophy Left cerebral hemiatrophy Left cerebral hemiatrophy Left cerebral hemiatrophy Right cerebral hemiatrophy Normal Left cerebral hemiatrophy Right cerebral hemiatrophy Left cerebral hemiatrophy Right cerebral hemiatrophy Right cerebral hemiatrophy Left cerebral hemiatrophy Left cerebral hemiatrophy Left cerebral hemiatrophy Right cerebral hemiatrophy
Left unilateral slow waves Left fronto-temporal spike-waves Left unilateral slow waves Left fronto-temporal spike-waves Right unilateral slow waves Right unilateral slow waves Right fronto-temporal spike-waves Right fronto-temporal spike-waves Left unilateral slow waves Left unilateral slow waves Left unilateral slow waves Right fronto-temporal spike-waves Left fronto-temporal spike-waves Left fronto-temporal slow spike-waves Right fronto-temporal slow spike-waves Left fronto-temporal slow spike-waves Right fronto-temporal slow spike-waves Right unilateral slow waves Left fronto-temporal slow spike-waves Left unilateral slow waves Left fronto-temporal slow spike-waves Left fronto-temporal slow spike-waves
CBZ, CBZ, CBZ, CBZ, CBZ, CBZ, CBZ, CBZ, CBZ, CBZ, CBZ, CBZ, CBZ, CBZ, CBZ, CBZ, CBZ, CBZ, CBZ, CBZ, CBZ, CBZ,
Drug-resistance Drug-resistance Drug-resistance Drug-resistance Drug-resistance Drug-resistance Drug-resistance Drug-resistance Drug-resistance Drug-resistance Drug-resistance Drug-resistance Drug-resistance Drug-resistance Drug-resistance Drug-resistance Drug-resistance Drug-resistance Drug-resistance Drug-resistance Drug-resistance Seizure control
VPA VPA VPA VPA PB PB PB PB PB PB PB PB PB, VPA PB, VPA PB, VPA PB, VPA PB, VPA PB, VPA VPA VPA VPA PB
CT Scan: Computed tomography scan ; EEG: electroencephalogram; CBZ: Carbamazepine; VPA: Valproate; PB: Phenobarbital.
in childhood was found in only 31.8% of our patients. In a South African study of 8 patients with HHE syndrome, the antecedent of febrile convulsions in childhood was found in only one patient [3]. However, two Moroccan studies reported the antecedent of febrile convulsions in childhood in all patients [2,4]. Teixeira et al. [9] report as far as they are concerned the antecedent of febrile convulsions in 12.1% of their patients. After the episode of hemiconvulsion-hemiplegia, epilepsy appears after a free interval of variable duration occurs. In the present study, this free interval was less than one year in 50% of patients. Van Toorn et al. [3] report a free interval less than 1 year in 57% of their patients. The types of epilepsy observed during the HHE syndrome are variable and include simple or complex partial seizures, generalized tonicclonic seizures, psychiatric manifestations, etc. [6]. Bourrous et al. [4] report a predominance of generalized tonic-clonic seizures in their patients (72.7%). In our study, we noted a predominance of partial secondarily generalized seizures (81.8%). Similar findings had been reported in a recent Moroccan study [2]. Outside of late epilepsy, they are also encountered cognitive disorders in the course of HHE syndrome such as language or memory disorders, intellectual disorders, etc. [2–4,10]. These disorders are considered as a complication of HHE syndrome and appear most often late. In the present study, we found 31.8% of cases of delay of acquisitions at the time of diagnosis. Cerebral MRI may also show afar the onset of HHE syndrome hippocampal sclerosis outside of cerebral hemiatrophy [2,5,10]. This association with hippocampal sclerosis favors the installation of drug-resistant epilepsy. In our study, no patient received cerebral MRI. Carbamazepine was the antiepileptic drug of the first choice in this study prescribed as monotherapy or in combination with valproate or phenobarbital. Drug-resistance was observed in 95.5% of patients. Similar findings had been reported in the literature [2,10]. In patients with severe drug-resistant epilepsy, the use of surgical treatment is considered. The surgery consists of anterior temporal lobectomy, cortical resection, functional hemispherectomy or callosotomy [11]. On the other hand, in the acute phase of HHE syndrome with intracranial hypertension related to hemispheric cerebral edema, decompressive hemicraniectomy is proposed [12,13]. In our study, many patients should have been proposed to the surgical treatment for epilepsy, but unfortunately, this sur-
gery is not available in Niger. In addition, these patients do not have financial funding to be referred abroad to a specialized center for surgery epilepsy.
5. Conclusion HHE syndrome is still seen in developing countries particularly in sub-Saharan African countries. The high morbidity and mortality in children with HHE syndrome highlight the need to improve emergency care for febrile clonic seizures in childhood and the early and adequate management of infectious diseases in the child.
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