Hemiconvulsion Hemiplegia Epilepsy Research Articles

Idiopathic Hemiconvulsion Hemiplegia Epilepsy in an Eight-Year-Old Boy! Is It the Time to Revisit the HHE Definition?

AbstractIdiopathic hemiconvulsion hemiplegia epilepsy (IHHE) syndrome is characterized by the combination of unilateral convulsive status epilepticus, mainly clonic, followed by transient or permanent ipsilateral hemiplegia. It occurs in infants during the course of a nonspecific febrile illness, mainly in the first 2 years of life and in any case before the age of 4 years. Most studies have mentioned that disease occurs in children younger than 4 years. The exact cause of unilateral involvement is not clear. Occurrence of this condition beyond 4 years of age has rarely been described. We report here a previously healthy 8-year-old boy who presented with right hemiclonic seizures for almost 2 weeks occurring along with nonspecific viral illness. He had residual right hemiparesis and his magnetic resonance imaging (MRI) of the brain showed left hemispheric cortical edema with diffusion restriction. The workup for neuroinfections, mitochondriopathy, and MR angiography was negative. The child improved with injection methyl prednisolone pulse therapy along with multiple intravenous and oral antiseizure medications. This case report suggests that IHHE can also occur beyond 4 years of age, and there is a need to revise the diagnostic criteria of IHHE.

A nutritional Vitamin B12 deficiency (infantile tremor syndrome) presenting as hemiconvulsion hemiplegia epilepsy syndrome

Hemiplegia Hemiconvulsion Epilepsy syndrome (HHE syndrome) is a condition characterized by the acute onset of unilateral seizures, which progress to cortical atrophy, hemiplegia and later develop epilepsy over weeks to years. Various aetiologies include infectious causes, especially meningitis, encephalitis, trauma, vascular insults, and sometimes idiopathic. Here, we present a 13-month-old female child, first in birth order, born to a non-consanguineous marriage, who presented with mild global developmental delay with acute onset right focal seizures followed by right-sided weakness and drug-resistant epilepsy. The child was found to have clinical and biochemical features of vitamin B12 deficiency with right-sided weakness. MRI of the brain initially showed edema of the left cerebral hemisphere and later atrophy on the left side. The electroencephalogram showed low voltage activity over the left cerebral hemisphere. Post-treatment with cobalamin, improvement in development was noted, with partial improvement in weakness and persistent epilepsy. In the current report, we highlight Hemiplegia Hemiconvulsion Epilepsy (HHE) syndrome on the background of nutritional vitamin B12 deficiency.

Fever, Seizures and Encephalopathy: From Bush Fires to Firestorms.

Fever-associated seizures and febrile encephalopathy are common neurological problems in children. Infections of the nervous system are responsible for the majority of cases. However, there is a spectrum of infection-associated and inflammatory conditions associated with the triad of fever, seizures, and encephalopathy. Apart from complex febrile seizures and febrile status epilepticus, fever infection-related epilepsy syndrome of childhood (FIRES), infantile hemiconvulsion hemiplegia epilepsy syndrome (IHHE), acute encephalopathy with delayed diffusion restriction (AESD), acute necrotizing encephalopathy of childhood (ANE), and reversible splenial lesion syndrome (RESLES) are age-related clinical phenotypes of fever-related epilepsy and encephalopathy. Awareness of these entities is important for appropriate diagnosis and the prompt use of immunomodulatory/immunosuppressive therapies. In this review, we discuss the pathophysiology, clinical phenotypes, and management approaches of these fever-related seizure and encephalopathy states.

Calcium Channels Genes and Their Epilepsy Phenotypes

AbstractCalcium (Ca2+) channel gene mutations play an important role in the pathogenesis of neurological episodic disorders like epilepsy. CACNA1A and CACNA1H genes are involved in the synthesis of calcium channels. Mutations in the α1A subunit of the P/Q type voltage-gated calcium channel gene (CACNA1A) located in 19p13.13, which encodes for the transmembrane pore-forming subunit of CAV2.1 voltage-dependent calcium channel, have been correlated to a large clinical spectrum of epilepsy such as idiopathic genetic epilepsy, early infantile epilepsy, and febrile seizures. Moreover, CACNA1A mutations have been demonstrated to be involved in spinocerebellar ataxia type 6, familiar hemiplegic migraine, episodic ataxia type 2, early-onset encephalopathy, and hemiconvulsion–hemiplegia epilepsy syndrome. This wide phenotype heterogeneity associated with CACNA1A mutations is correlated to different clinical and electrophysiological manifestations. CACNA1H gene, located in 16p13.3, encodes the α1H subunit of T-type calcium channel, expressing the transmembrane pore-forming subunit Cav3.2. Despite data still remain controversial, it has been identified as an important gene whose mutations seem strictly related to the pathogenesis of childhood absence epilepsy and other generalized epilepsies. The studied variants are mainly gain-of-function, hence responsible for an increase in neuronal susceptibility to seizures. CACNA1H mutations have also been associated with autism spectrum disorder and other behavior disorders. More recently, also amyotrophic lateral sclerosis has been related to CACNA1H alterations. The aim of this review, other than describe the CACNA1A and CACNA1H gene functions, is to identify mutations reported in literature and to analyze their possible correlations with specific epileptic disorders, purposing to guide an appropriate medical treatment recommendation.

Hemiconvulsion-hemiplegia-epilepsy syndrome (HHE): Electro-clinical aspects in the acute phase and in the later course in 15 children

Objectives Hemiconvulsion-hemiplegia epilepsy (HHE) syndrome is a rare condition occurring in infancy and early childhood, characterized by prolonged clonic convulsions with unilateral predominance followed by ipsilateral hemiplegia during a febrile illness. After a free interval of variable duration, most patients develop epilepsy. HHE may occur either in patients with previous structural brain pathology or without any identified cause, so-called “idiopathic HHE”. We aimed to characterize the electro-clinical aspects observed in the acute phase and in the later course of the disease. Methods Between January 1997 and December 2016, 15 patients (8 girls, 7 boys), presenting with hemiconvulsion-hemiplegia were identified. Mean age was 10 years (range 3–21years) with a mean follow-up of 53 months (range 1–19 years). Electro-clinical features in the acute stage and evolution are described. Two patients died, one girl during the acute phase (on day 7). Results Median age at onset of convulsive status was 27.73 months (range 9–84 months). Status epilepticus lasted 30 minutes up to several days, and was characterized by unilateral clonic seizures in 10 patients and generalized seizures with unilateral predominance in 5 patients. In the acute phase interictal EEG disclosed inter-hemispheric asymmetry (14/15), background slowing (15/15), and spikes and slow sharp-waves (5/15). Seizures were recorded in 3 patients. Periodic lateralized epileptiform discharges were observed in one patient, who died during the acute phase on day 7. All patients presented ipsilateral hemiplegia (10/15 left, 5/15 right). The motor deficit (hemiplegia or hemiparesis) disappeared in 3 patients and persisted in 11, in two of them spastic hemiplegia developed. Eleven patients developed epilepsy after a free interval lasting up to 80 months, in 2 of them pharmaco-resistant. At the end of the observation period, all children with follow-up presented learning difficulties. Conclusion We describe electro-clinical features in the acute phase and in the later course in 15 patients presenting with HHE syndrome.

Hemispheric multiple fungal brain abscesses due to Scedosporium apiospermum following surgery

We report an interesting and rare case of hemispheric multiple brain abscesses due to Scedosporium apiospermum which developed following neurosurgery and mimicked hemiconvulsion hemiplegia epilepsy syndrome on initial scans. Interestingly all the abscesses were only on the right side of cerebral hemisphere which later on spread to the other side. All the lesions had hemorrhagic walls seen as hypointensities on susceptibility weighted imaging. The patient succumbed to this fatal fungal brain infection.

Hemiconvulsion–Hemiplegia–Epilepsy syndrome associated with inflammatory-degenerative hystopathological findings in child with congenital adrenal hyperplasia

Hemiconvulsion–Hemiplegia (HH) syndrome represents an uncommon consequence of prolonged unilateral clonic or hemiconvulsive status epilepticus in childhood, usually occurring during a febrile illness, followed by ipsilateral hemiplegia. The subsequent appearance of focal seizures configures the so called Hemiconvulsion–Hemiplegia–Epilepsy (HHE) syndrome. The pathogenesis of HH/HHE syndrome is still unclear. We describe the case of a 4 year-old girl with congenital adrenal hyperplasia (CAH) whom developed HH/HHE syndrome with drug resistant seizures at the age of 21 months and underwent left cerebral hemispherotomy at the age of 3 years and 6 months. Histopathological findings showed the presence of an underlying inflammatory-degenerative process. Disregulation of the inflammatory cascade has been proposed as one of the possible pathogenetic mechanisms underlying HH/HHE syndrome. To our knowledge however, this is the first report of an association with a histologically documented inflammatory process. The clinical and histopathological findings of our reported case lend support to the possible role of inflammation in the pathogenesis of HH/HHE syndrome.

Hemiconvulsion–hemiplegia–epilepsy syndrome with 1q44 microdeletion: Causal or chance association

Hemiconvulsion-hemiplegia-epilepsy (HHE) syndrome is a rare syndrome characterized by childhood onset partial motor convulsions, hemiplegia, and epilepsy in sequence. Exact pathogenesis is not clear. Here we are describing a 3-year-old girl with HHE syndrome with cytogenetic microarray (CMA) showing deletion of 1.8 Mb in 1q44 region. Along with HHE syndrome, the patient also had global developmental delay, subtle facial dysmorphism, and preaxial polydactyly. Clinical phenotype of 1q44 microdeletion syndrome is quite variable. Main clinical features are microcephaly, seizures, and abnormality of corpus callosum. We compared the patient's phenotype with other patients in 10 previously published papers of 1q44 microdeletion syndrome. HNRNPU and FAM36A are two important genes in the deleted region. HNRNPU gene mediate long range control of SHH gene which is likely explanation of preaxial polydactyly in the present patient. HHE may be a chance co-occurrence.

Low incidence of SCN1A genetic mutation in patients with hemiconvulsion–hemiplegia–epilepsy syndrome

Genetic mutations in SCN1A account for more than two-thirds of patients with classic Dravet syndrome. A role for SCN1A genetic mutations in the development of hemiconvulsion-hemiplegia-epilepsy (HHE) syndrome was recently suggested based on the observation that HHE syndrome and classic Dravet syndrome share many clinical features. We previously identified a 2 bp-deletion mutation in SCN1A in a Dravet patient, and we found out the patient also had HHE syndrome upon clinical re-evaluation. We subsequently screened 10 additional HHE patients for SCN1A. Among the 11 patients who were diagnosed with HHE syndrome, six patients had no other etiology with the exception of prolonged febrile illness, therefore classified as idiopathic HHE syndrome, whereas five patients were classified as symptomatic HHE syndrome. Direct sequencing of all coding exons and flanking intronic sequences of the SCN1A gene was performed, but we failed to identify additional mutations in 10 patients. The patient with SCN1A mutation had the earliest onset of febrile convulsion and hemiparesis. Our study suggests that SCN1A genetic mutation is only a rare predisposing cause of HHE syndrome.

Late-onset epilepsy in children with acute febrile encephalopathy with prolonged convulsions: A clinical and encephalographic study

The aim of this study is to analyze the characteristics of epilepsies as the sequelae of acute febrile encephalopathy with prolonged convulsions during childhood. Sixteen patients (M:F=9:7) aged 2–13years (mean 6.1years) with history of febrile acute encephalopathy were retrospectively reviewed. These patients experienced febrile encephalopathy at the age of 11months to 4years, with 11 individuals presenting with findings of a biphasic clinical course (n=5), frontal predominant (n=8) lesions, and/or reduced diffusivity in the cerebral white matter on magnetic resonance imaging (MRI; n=3). The remaining 5 patients had unilateral lesions that manifested the phenotype of hemiconvulsion–hemiplegia–epilepsy syndrome (HHES). Epilepsy emerged with a latent period of 2months to 2years after the acute phase of febrile encephalopathy. Head nodding or spasm with subsequent motion arrest and brief tonic seizures were the main seizure phenotypes. Ictal records of epileptic seizures were available in 9 patients. Epileptiform discharges with a focal or uneven distribution appeared at the seizure onset and lasted less than 1s in all patients; these were followed by either generalized attenuation or fast activity in 8 patients with head nodding, spasm, or brief tonic seizures, and by localized fast activity in 1 patient with versive tonic seizures. Notably, the seizure onset area was often located outside the severe lesions on MRI, i.e., in the parietal areas in patients with frontal predominant lesions, and in the spared hemisphere of HHES. Although phenobarbital, zonisamide, carbamazepine, clobazam, clonazepam, and clorazepate were partially effective in some patients, daily seizures persisted in 11 patients. Callosotomy was performed in 2 patients, and beneficial effects were observed in both. These characteristics suggested a broad distribution of augmented excitability in these patients, resulting in the rapid propagation of epileptic activity in the initial phase of ictal phenomena. Thus, this study investigates the most severe subgroup of epilepsy following febrile acute encephalopathy and provides the basis for further exploration of the pathogenesis and treatment of characteristic seizures in this population.

Focal encephalopathy with recurrent episodes of epileptic status and cluster mimicking hemiconvulsion–hemiplegia–epilepsy syndrome

Hemiconvulsion–hemiplegia–epilepsy syndrome is characterized by unilateral convulsions during fever, transient hemiplegia, and subsequent partial epilepsy with atrophy in the cerebrum. A 9-year-old boy with a history of West syndrome and hypoglycemic attacks had three episodes of epileptic status and clusters mimicking HHE syndrome over a 2-year period. Magnetic resonance imaging revealed the involvement of the right and left cerebrums. Because no abnormalities were detected in an endocrine examination, screening tests for metabolic errors, or magnetic resonance spectroscopy, a diagnosis of metabolic errors was not supported. Immunohistochemistry using the patient’s sera showed binding of the serum immunoglobulin with neurons in the temporal and occipital cerebral cortices, indicating the possible involvement of autoimmune mechanisms in this case. Focal encephalopathy should be considered in children showing convulsions, psychiatric disorders, and/or involuntary movements for several months in a row. In such cases, immunohistochemistry using the patient’s sera may be useful for the investigation of the pathogenesis of the illness.

Acute encephalopathy in two cases with severe congenital hydrocephalus

We report acute encephalopathy in two cases with severe congenital hydrocephalus. Case 1 was a 23-month-old girl, born at of 36 weeks gestation and delivered by cesarean section due to congenital hydrocephalus. Magnetic resonance imaging (MRI) showed prominent ventricular dilation associated with hydrocephalus, Dandy–Walker variant and cortical malformation. The blood test for toxoplasmosis, syphilis, varicella-zoster, rubella, cytomegalovirus, and herpes simplex virus (TORCH) complex and various metabolic tests of blood and urine specimens yielded unremarkable results. She was admitted to our hospital for respiratory failure with fever and her clinical course deteriorated, progressing to hemiconvulsion hemiplegia epilepsy syndrome. Case 2 was a 17-month-old boy, born by spontaneous vertex delivery at 39 weeks. Severe, asymmetrical ventricular dilation associated with hydrocephalus, cerebellar and brainstem hypoplasia, and punctuate calcifications of the thalamus, third and fourth ventricles, around the aqueduct, were observed on computed tomography (CT). The blood test for TORCH complex and various metabolic tests of blood and urine specimens yielded unremarkable results. He was admitted to our hospital for status epilepticus with fever and his clinical course progressed to hemorrhagic shock and encephalopathy syndrome. In patients with brain disorders, diagnosis and treatment are likely to be delayed and prognosis may thereby be worsened. When status epileptics or prolonged coma manifests even in patients with severe brain disorders, we must consider encephalopathy in the differential diagnosis.

The surgical treatment of hemiconvulsion hemiplegia epilepsy syndrome

Objective To summarize the clinical characteristics and prognosis of surgical treatment on hemiconvulsion hemiplegia epilepsy(HHE)syndrome. Method We included 7 patients who were diagnosed with HHE syndrome and underwent surgical treatment for intractable epilepsy at our hospital. The multidisciplinary presurgical evaluations included brain MRI, video - EEG monitoring and analysis of serum. Hemispherectomy, cortical resection for multilobe epileptogenic lesion were performed according to the results of presurgical evaluations. Results 5 cases were diagnosed as primary HHE,while 2 cases secondary HHE. 4 cases were operated with Adame's modified hemispherectomy(AH), 2 cases were operated with functional hemispherectomy(FH)and 1 case with cortical resection for multilobe epileptogenic lesion. During 5 to 32 months follow up,4 cases had seizure free(Engel Ⅰ),3 cases with alleviation of seizures(2 cases with Engel Ⅱ and 1 with Engel Ⅲ). Conclusions Surgical intervention may be helpful in patients with intractable epilepsy in HHE syndrome. Hemispherectomy is a viable alternative, which should be considered in the treatment of HHE based on the pre - evaluations. Key words: Hemiconvulsion hemiplegia epilepsy syndrome; Epilepsy; Surgical procedures,operative

Long-term cognitive outcome of hemiconvulsion–hemiplegia–epilepsy syndrome affecting the left cerebral hemisphere

Long-term cognitive outcome following hemiconvulsion-hemiplegia-epilepsy (HHE) syndrome has been poorly studied, with little attention to the implications of side of involvement in HHE. This retrospective study describes language lateralization and cognitive performance in five patients with HHE syndrome affecting the left cerebral hemisphere. All of the patients had to have intracarotid sodium amytal testing (IAT) to be included in this study. The mean age of the patients was 30.2 years (range: 13-50). All patients had their hemiconvulsive seizures before age 1(1/2) years (range: 6-13 months). All patients had right-sided hemiatrophy of the body, left mesial temporal sclerosis, and seizures originating from the left temporal lobe. The habitual seizures began at a mean age of 4.5 years (range: 1.5-12 years). Performance on tests of intelligence, verbal memory, and visual memory was examined. Language was represented in the right cerebral hemisphere in three patients, the left hemisphere in one patient, and both hemispheres with predominance on the right side in the fifth patient. Intellectual functioning was in the borderline to extremely low range among the patients with right hemispheric or bilateral representation for language. These patients were variably impaired on measures of verbal and visual memory. The patient with left hemispheric representation for language performed in the average range on tests of intellectual functioning and verbal memory, whereas scores on visual memory were variable. This study demonstrated that reorganization of language to the right cerebral hemisphere or its bilateral representation is common in patients with HHE syndrome affecting the left cerebral hemisphere, and is associated with poor cognitive outcome.

Decompressive hemicraniectomy in a space-occupying presentation of hemiconvulsion–hemiplegia–epilepsy syndrome

A case of an acute life-threatening presentation of hemiconvulsion–hemiplegia–epilepsy (HHE) syndrome requiring an urgent decompressive hemicraniectomy is described. A 9 month-old baby had a status epilepticus following a sustained fever, leading to a comatose state and a right pupillary dilatation associated with a left hemiplegia. The MRI showed a swelling right hemisphere with marked temporal herniation. The baby underwent a decompressive right hemicraniectomy with temporal cortical biopsies. The post-operative course was favourable. The histological findings were unspecific, showing a gliotic spongiosis with disseminated granular cells. The post-operative MRI depicted a right hemisphere atrophy. To our knowledge, a space-occupying presentation of HHE syndrome requiring surgical decompression has never been described before while only a few reports dealt with the neuropathological aspects of this syndrome.

Hemiconvulsion–hemiplegia–epilepsy syndrome: Early magnetic resonance imaging findings and neuroradiological follow-up

We describe a case of hemiconvulsion–hemiplegia–epilepsy (HHE) syndrome documented by longitudinal magnetic resonance imaging (MRI). A two-year and nine-month-old boy had a prolonged hemiconvulsion during fever followed by right hemiparesis. Seven days later the imaging abnormality on T2 and diffusion-weighted images (DWI) was limited to the white matter of the left hemisphere. One month later severe gliosis and unilateral brain atrophy were already evident. MRI is useful in the early stages of prolonged seizures and T2 and DWI abnormalities appear to be well correlated with parenchymal damage that results from sustained ictal activity. The neuroradiological findings in our case and in the few HHE patients reported in the literature seem to be very characteristic and, if confirmed in larger series, could permit an early diagnosis.