Please disclose any financial or other conflicts of interest that might bias your contributions, or give rise to the perception of such bias. Relevant financial ties can include consultantships, memberships in speaker's bureaus, grants, research support, salaries, royalties, ownership, equity positions, stock options, or other financial arrangements wherein you stand to gain substantially from an increase of stock value or corporate revenues.

Disclosures and acknowledgements will be linked to the author name(s) and will display along with appointments and affiliations. Disclosures, acknowledgements, and affiliations can be entered and updated via the "Update My Profile" link in the Online Submission System. Alternatively, you may send such information along with your updated manuscript.

Thumbnail

So that MedLink Corporation can highlight your clinical summary and your authorship on the MedLink Neurology home page and in our weekly email to subscribers, we ask that you provide here a brief overview of your subject (about 50 to 100 words) aimed at enticing readers to view this clinical summary. For updates, please include a sentence that refers to something new you have added. Refer to yourself in the 3rd person (eg, Dr. Doe of Superior Institution explains the basics…). For more information and examples of thumbnails, please see the Instructions to Authors, which can be downloaded from your "My Writing Assignments" page in the Online Submission System (http://www.medlinkoss.com).

Historical note and nomenclature

The term "hemiconvulsion-hemiplegia syndrome" was first used by Gastaut (Gastaut et al 1957) to describe the following sequential combination: unilateral or predominantly unilateral clonic seizures (usually of long duration), occurring during the first 2 years of life and immediately followed by a flaccid hemiplegia (usually permanent), ipsilateral to the clonic seizure.

The term "hemiconvulsion-hemiplegia-epilepsy syndrome" was used to describe the complete form of the syndrome. It included the consequent development of a partial epilepsy, usually occurring after 1 year to several years following the initial hemiconvulsion-hemiplegia episode. Partial seizures were considered to be of temporal origin.

Further studies (Roger et al 1972; 1982; Chauvel et al 1991; Chauvel and Dravet 2002) have demonstrated that the initial episode may be observed in various situations and that the subsequent partial epilepsy can be temporal, extratemporal, or multifocal.

It can be argued that, taken separately, both the initial episode (hemiconvulsion-hemiplegia) and the subsequent development of epilepsy cannot be considered to be proper "syndromes." In fact, the hemiconvulsion-hemiplegia episode corresponds to a unique episode of partial status epilepticus responsible of a unilateral motor deficit, and the later development of epilepsy corresponds to a partial symptomatic epilepsy. However, the stereotyped sequence of events that characterizes hemiconvulsion-hemiplegia epilepsy allows us to consider it as a syndrome. Thus, hemiconvulsion-hemiplegia-epilepsy was reintroduced as a syndrome in the recently published report of the ILAE Task Force on Classification and Terminology (Engel 2001).

Clinical manifestations

The first sign of the syndrome is a sudden, prolonged hemiconvulsion in the form of status. It occurs in a child without antecedents, between 5 months and 4 years old, with a peak incidence during the first 2 years of life. A febrile episode is almost always associated, but in many cases, no cause is obvious (Aicardi and Chevrie 1983). The onset of convulsions may pass unnoticed, the child being discovered convulsing in bed.

If untreated, hemiconvulsions may last for several hours. They present as predominantly unilateral clonic jerks. The rhythm is variable, and the jerks can be asynchronous. Impairment of consciousness is not a permanent or even constant feature. In long-lasting convulsions, jerks may diffuse to the opposite side or change sides. Adversion of head and eyes may be observed, sometimes even before the occurrence of jerks. Autonomic symptoms (hypersalivation, cyanosis, etc.) may be associated.

Massive flaccid hemiplegia immediately follows the unilateral seizure. When jerks change sides, it is usually the side involved last that remains hemiplegic. Evolution of hemiplegia is variable. It can either remain as a permanent neurologic deficit with signs of spasticity or decrease progressively, leaving behind a slight hemiparesis. To differentiate hemiplegia from Todd paralysis, a minimum duration of 7 days is arbitrarily set. In more than 80% of the cases, the hemiplegia is permanent (Gastaut et al 1960). Rarely, it may disappear completely, although some degree of spasticity and pyramidal signs usually persist. In contrast with congenital hemiplegia, the face is constantly involved, and aphasia is present in left-sided cases.

In almost 80% of the cases, partial epilepsy will develop 1 year to 3 years later (hemiconvulsion-hemiplegia-epilepsy syndrome). Partial seizures with secondary generalization and episodes of status are not uncommon. In addition to partial epilepsy, most of the children having experienced a hemiconvulsion-hemiplegia-epilepsy syndrome present with some degree of mental impairment.

Clinical vignette

At the age of 23 months while on holiday in a Third World country, a 19-year-old girl had experienced a status epilepticus, comprising predominantly a left-sided seizure during an acute febrile attack. The seizures lasted 90 minutes. No cause was found. This episode of partial status was followed initially by a flaccid left hemiplegia, which gave way to a permanent and severe spastic hemiparesis not affecting the face. During the next 3 years, she received treatment with phenobarbital and physiotherapy. Her motor handicap concerned mainly the left hand. She initially went to normal school but always had some difficulties. EEGs showed clear-cut asymmetry, and CT scan evidenced hemispherical atrophy.

Ten years later, she started having partial seizures. They usually began with elementary visual hallucinations followed by automatisms mainly of the right arm. Secondary generalization was rare. She also described a feeling of contraction of the left arm. Frequency was rather variable, but she could experience up to 6 episodes in a day. A few years later, she was obliged to abandon normal school; her IQ was evaluated at 59. Several antiepileptic drugs, at optimal doses, failed to control her seizures. Last year, she took gabapentin and topiramate and experienced a considerable reduction in seizure frequency and intensity. Regular injection of botulin toxin allowed her to partially use her left hand.

Etiology

Prolonged clonic convulsions with a marked unilateral predominance usually occur in the course of a febrile disease. Causes of the initial convulsions are multiple. A number of acute cerebral disorders have been occasionally related to the occurrence of the syndrome (meningitis, subdural effusions, head trauma, etc.). In many cases, no cause is obvious (idiopathic hemiconvulsion-hemiplegia-episode syndrome), and such cases may represent only prolonged febrile convulsions that do not otherwise differ from common febrile convulsions. In such cases the seizure activity itself could be responsible for the appearance of new lesions occurring in a previously normal brain. Alternatively, the presence of a preexisting asymptomatic lesion of perinatal or prenatal origin may be responsible in a number of cases (symptomatic hemiconvulsion-hemiplegia-episode syndrome) for the initiation or localization of the seizure. The prolonged seizure would then produce or contribute to the development of irreversible brain damage with resultant partial epilepsy (Aicardi and Chevrie 1970; Lennox-Buchtal 1973; Roger et al 1974; Roger et al 1982; Aicardi 1998; Arzimanoglou et al 2003).

The role of long-lasting febrile convulsions, as part of a hemiconvulsion-hemiplegia-episode, in the genesis of hippocampal sclerosis and consequent mesial temporal lobe epilepsy remain disputed. A statistical association is well demonstrated (Rocca et al 1987), and there are strong arguments in favor of an etiological relationship (Holthausen 1994); however, the presence or absence of other contributing factors is not clearly established (Shinnar et al 2001; Scott et al 2002; Arzimanoglou et al 2003). Furthermore, partial epilepsy in hemiconvulsion-hemiplegia-episode syndrome can be temporal, extratemporal, or multifocal.

Pathogenesis and pathophysiology

The pathophysiological mechanisms involved are not elucidated. The existence of a predisposing genetic factor has been discussed (Ounsted et al 1996). A high incidence of family history of febrile convulsions is frequently present (Chevrie and Aicardi 1975; Aicardi 1994). Tanaka and colleagues reported ictal and postictal SPECT findings in a 5-month-old boy (Tanaka et al 1994). When the SPECT was realized during left-sided hemiconvulsions and during the third day after partial status, diffuse hyperperfusion was revealed in the right hemisphere. On the seventh and tenth day after status, diffuse hypoperfusion was exhibited in the right hemisphere. Striking neuroimaging findings suggestive of diffuse cytotoxic edema confined to 1 hemisphere, including extensive diffusion-weighted imaging abnormalities, were reported by Freeman an colleagues following early MRI screening (Freeman et al 2002). Chauvel and Dravet recently reviewed the hypotheses on the pathogenesis of the syndrome (Chauvel and Dravet 2002).

Epidemiology

The exact incidence and prevalence of the syndrome are unknown. Few additional studies have been published since the initial description of the syndrome. However, all authors agree that hemiconvulsion-hemiplegia syndrome has its peak incidence during the first 2 years of life, with only occasional patients presenting the first hemiconvulsions at 4 years of age or older.

In one of his first papers on the syndrome, Gastaut reported on 150 cases (Gastaut et al 1960). In 1972 Roger and colleagues reported 59 cases (Roger et al 1972). Four years later, Vivaldi in his PhD thesis analyzed 45 cases, 25 that occurred between 1955 and 1965 and only 10 thereafter (Vivaldi 1976). In the epidemiological study of Beaumanoir in the district of Geneva, the number of cases of hemiconvulsion-hemiplegia-episode syndrome reported between 1967 and 1978 decreased from 7.77 to 1.64 (of 10,000 children under 5 years of age) (Chauvel et al 1991). The incidence has declined considerably during the past 10 years in countries where emergency care is highly developed and prompt use of intravenous or rectal benzodiazepines for the treatment of febrile convulsions became common practice. The mean age at onset in the 6 patients they describe corresponds to the start of the rapid development in social welfare and health care in Saudi Arabia (Salih et al 1997). Hemiconvulsion-hemiplegia-episode syndrome is notably absent from studies of status epilepticus over the past 2 decades.

Prevention

Hemiconvulsions being the first symptom in previously asymptomatic patients, prophylactic treatment is not feasible. Postconvulsive hemiplegia may be prevented with appropriate vigorous and early management of acute episodes. Thus, the most important factor is the prompt recognition and treatment of the hemiclonic seizure.

Differential diagnosis

The hemiconvulsion-hemiplegia-epilepsy syndrome constitutes a unique sequence of events. Differential diagnosis aims to identify the causative factors of the initial episode of prolonged partial status. Workup primarily includes elimination of infections of the CNS (eg meningitis and encephalitis). Lumbar puncture is advised in children younger than 18 years old and especially younger than 6 months of age. Herpes encephalitis often manifests initially in infants with febrile partial seizures and may pose a real problem (Aicardi 1994).

A prolonged hemiconvulsion in the course of a febrile episode may be the first manifestation of severe myoclonic epilepsy of infants (Dravet syndrome). In contrast with hemiconvulsion-hemiplegia-epilepsy syndrome, Dravet syndrome is characterized, at this stage of the disease, by multiple recurrences of hemiconvulsions in the months following the initial episode. Changes in the side of hemiconvulsions is a frequent feature. Furthermore, in Dravet syndrome, postconvulsive hemiplegia, when present, is always of short duration and corresponds to Todd paralysis (Dravet et al 2002; Arzimanoglou et al 2003).

When the context of the hemiconvulsion-hemiplegia episode and the sequence of events are not well established, other causes of acquired hemiplegia, particularly of vascular origin such as arterial thrombosis or embolism, should be eliminated. Epilepsia partialis continua, especially when related to Rasmussen encephalitis, only superficially resembles hemiconvulsion-hemiplegia-episode syndrome.

Acquired postconvulsive hemiplegia may be difficult to distinguish from congenital hemiplegia when it occurs in infants, especially as seizures may reveal a previously unrecognized deficit. Flaccidity and facial involvement are strong arguments in favor of an acquired hemiplegia (Aicardi 1998).

Diagnostic workup

EEG. The EEG discharge associated with the initial hemiconvulsion is characterized by high-voltage, rhythmic (2 c to 3 c per second) slow waves, which may be unilateral but usually involve both hemispheres, more or less asymmetrically. Amplitude is higher on the hemisphere contralateral to the clinical seizure. High amplitude spikes or sharp waves and recruiting rhythms (10 c per second) mainly concerning the posterior regions intermingle with slow waves only on the side contralateral to the clinical jerks. Occasionally, especially toward the end of a seizure, the spikes and slow waves may alternate as in true spike-wave complexes. Onset of the ictal discharge is generally recorded over the central-posterior part of the hemisphere but diffusion is rapid. Polygraphic recordings do not demonstrate any consistent relationship between muscle jerks and EEG discharges.

Postictal patterns. Spontaneous termination of the seizure is generally brisk. Slow waves and spikes are followed by a brief extinction of all rhythms, then by delta slowing, with higher amplitude on the hemisphere ictally engaged, alternating with short periods of suppression of activity. Contralaterally, physiological rhythms intermingled with slow waves reappear (Gastaut et al 1957).

When the seizure stops following IV injection of a benzodiazepine, the ictal discharge progressively vanishes. Anomalies persist longer to the ictally engaged hemisphere. Postictal asymmetry is obvious, with abundant fast rhythms invading the opposite hemisphere.

Neuroradiological findings. In the acute stage, immediately after the initial convulsive episode, CT scan may show swelling and edema of the hemisphere involved in the epileptic discharge. Later, a rather characteristic, uniform hemiatrophy follows prolonged episodes (Gastaut et al 1957; Aicardi and Baraton 1971; Isler 1971; Chauvel et al 1991). Hippocampal sclerosis may be demonstrated by MRI in some children with hemiconvulsion-hemiplegia-episode syndrome.

Prognosis and complications

Prognosis clearly depends on prompt treatment of the initial prolonged episodes. Following the initial febrile episode, prophylactic treatment of febrile convulsions is indicated. This may prevent recurrence of febrile convulsions, but it doesn't seem to prevent the later development of partial epilepsy.

In an attempt to further characterize the types of epilepsy within the setting of hemiconvulsion-hemiplegia-epilepsy syndrome, Chauvel and Dravet analyzed a series of 37 adult patients at Sainte-Anne Hospital in Paris for surgical therapy (Chauvel and Dravet 2002). The age of HH syndrome ranged from 1 month to 9 years. Only 19% presented the initial episode after the age of 3 years. By definition, and on the basis of the inclusion criteria used, all patients presented with drug resistant epilepsy, and they all had an hemicorporeal motor deficit of variable degree. The majority of the patients had several seizure types, whereas only 9 patients (24%) had one type of seizures. The epileptogenic zone was considered unifocal in 29 patients and multifocal in 8 patients. In the unifocal group, a striking predominance of suprasylvian localizations was found, as compared to the pure temporal lobe epilepsies in 5 patients. In 14 patients of the 29 patients (nearly 50%), the epileptogenic zone included the frontocentral and parietocentral regions; prefrontal epilepsies were rare, and no pure occipital epilepsy was reported. In the multifocal group, a predominant involvement of the parietal lobe was noticed in 7 patients out of 8 patients.

Management

Most cases of fever and prolonged convulsions occur during the first 18 months of life. Early and vigorous treatment of prolonged infantile seizures of whatever origin, especially of febrile convulsions, seems to be the only way to reduce the incidence of postconvulsive hemiplegia and late onset partial epilepsy. Symptomatic therapy of the acute convulsive episode utilizes mainly benzodiazepines, particularly diazepam. It can be administered easily by either venous or rectal route. The usual dosage is 0.2 mg/kg to 0.5 mg/kg given as a single dose. The dose may be repeated after 10 minutes to 20 minutes. Clonazepam, midazolam, or lorazepam may also be used. Antithermic drugs are used in combination. According to the eventual causal agent, additional anti-infectious therapy is required. The incidence of hemiconvulsion-hemiplegia-epilepsy syndrome has declined considerably during the past years (Roger et al 1982) in countries where emergency care is highly developed. In the complete form of the syndrome, partial seizures of temporal or extratemporal origin should be treated as any other type of partial epilepsy using antiepileptic drugs such as carbamazepine, sodium valproate, gabapentin, vigabatrin, lamotrigine, phenytoin, or topiramate. Surgical treatment is an alternative. However, epilepsies due to extended brain damage may prove difficult to handle surgically. The possibility for a limited cortectomy will usually need an invasive presurgical evaluation to be performed by a group that specializes in epilepsy surgery. Of the 37 patients explored in Sainte-Anne (Chauvel and Dravet 2002), surgery was estimated to be possible in only 20 patients. Following surgery, 9 patients (45%) became seizure free or experienced less than 1 seizure per year; 3 patients (15%) showed a significant reduction (by 40%) in seizure frequency, and no change was obtained in 7 patients (35%). One patient deceased during a postoperative status.

Hemispherectomy (total, subtotal, or “functional”) may be another surgical alternative, particularly when limited cortectomie is not feasible. Delalande included 7 children with hemiconvulsion-hemiplegia-epilepsy syndrome in a series of 53 patients submitted to hemispherectomy (Delalande 2001). Indications and clinical outcomes of hemispherectomy for epilepsy of various etiologies have been recently reviewed (Devlin et al 2003).

Kwan and colleagues reported on 4 years follow-up in 3 children who underwent callosotomy (Kwan et al 200). All patients experienced a significant reduction of “generalized tonic seizures,” but partial seizures of the sensory type remained unchanged.

Pregnancy

Not applicable

Anesthesia

Not applicable

References cited

Aicardi J. Epilepsy in children, 2nd edition, New York: Raven Press, 1994:194-9.

Aicardi J. Febrile convulsions and other occasional seizures. In: J. Aicardi, Diseases of the nervous system in childhood, 2nd edition, Cambridge: University Press, 1998:605-7.

Aicardi J, Baraton J. A pneumoencephalographic demonstration of brain atrophy following status epilepticus. Dev Med Child Neurol 1971;13:660-7.

Aicardi J, Chevrie JJ. Consequences of status epilepticus in infants and children. In: AV Delgado-Escueta, CG Wasterlain, DM Treiman and RJ Porter, editors. Advances in neurology, vol. 34, Status Epilepticus, New York: Raven Press, 1983:115-25.

Aicardi J, Chevrie JJ. Convulsive status epilepticus in infants and children: a study of 239 cases. Epilepsia 1970;11:187-97.**

Arzimanoglou A, Guerrini R, Aicardi J. Aicardi’s epilepsy in children, 3rd edition, Philadelphia: LWW, 2003.

Chauvel P, Dravet C. The HHE syndrome. In: Roger J, Bureau M, Dravet CH, Genton P, Tassinari CA, Wolf P, editors. Epileptic Syndromes in Infancy, Childhood and Adolescence. 3rd edition. Paris: John Libbey and Company, 2002:247-63.

Chauvel P, Dravet C, Di Leo M, Roger J, Bancaud J, Talairach J. The HHE syndrome. In: Luders H, editor. Epilepsy surgery. New York: Raven Press, 1991:183-96.

Chevrie JJ, Aicardi J. Duration and lateralization of febrile convulsions. Etiological factors. Epilepsia 1975;16:781-9.

Delalande O, Fohlen M, Jalin C, Pinard JM. From hemispherectomy to hemispherotomy. In: Luders HO and Comair Y, editors. Epilepsy Surgery. Philadelphia: Lippincott-Raven, 2001:741-6.

Devlin AM, Cross JH, Harkness W, et al. Clinical outcomes of hemispherectomy for epilepsy in childhood and adolescence. Brain 2003;126(Pt 3):556-66.

Dravet C, Bureau M, Oguni H, Fukuyama Y, Cokar O. Severe myoclonic epilepsy in infancy (Dravet syndrome). In: Roger J, Bureau M, Dravet CH, Genton P, Tassinari CA, Wolf P, editors. Epileptic syndromes in infancy, childhood and adolescence. 3rd edition. Paris: John Libbey and Company, 2002:81-103.

Engel J Jr; International League Against Epilepsy (ILAE). A proposed diagnostic scheme for people with epileptic seizures and with epilepsy. Report of the ILAE Task Force on Classification and Terminology. Epilepsia 2001;42(6):796-803

Freeman JL, Coleman LT, Smith LJ, Shield LK. Hemiconvulsion-hemiplegia-epilepsy syndrome: characteristic early magnetic resonance imaging findings. J Child Neurol 2002;17(1):10-6.

Gastaut H, Poirier F, Payan H, Salomon G, Toga M, Vigoroux M. HHE syndrome: hemiconvulsions-hemiplegia-epilepsy. Epilepsia 1960;1:418-47.

Gastaut H, Vigoroux M, Trevisan C, Regis H. Le syndrome "hemiconvulsion-hemoplegie-epilepsie" (syndrome HHE). Rev Neurol 1957;97:37-52.

Holthausen H. Febrile convulsions, mesial temporal sclerosis and temporal lobe epilepsy. In: Wolf P, editors. Epileptic seizures and syndromes. London: John Libbey, 1994:449-67.

Isler W. Acute hemiplegias and hemisyndromes in childhood. In: Clinics in Developmental Medicine No 41/42; London: Heinemann, 1971:131-41.

Kwan SY, Wong TT, Chang KP, et al. Postcallosotomy seizure outcome in hemiconvulsion-hemiatrophy-epilepsy syndrome. Zhonghua Yi Xue Za Zhi (Taipei) 2000;63(6):503-11.

Lennox-Buchtal MA. Febrile convulsions. A reappraisal. Electroencephalogr Clin Neurophysiol 1973;32:1-132.

Ounsted C, Lindsay J, Norman R. Biological factors in temporal lobe epilepsy. Clinics in developmental medicine, No 2. London: Spastics Society and Heinemann Medical, 1996.

Rocca WA, Sharbrough FW, Hauser WA, Annegers JF, Schoenberg BS. Risk factors for complex partial seizures: a population-based case-control study. Ann Neurol 1987;21(1):22-31.

Roger J, Bureau M, Dravet C. et al. Cerebral hemiplegias in children. EEG data and epileptic manifestations related to childhood cerebral hemiplegia in children. Rev Electroencephalogr Neurophysiol Clin 1972;2(1):5-28.

Roger J, Dravet C, Bureau M. Unilateral seizures (hemiconvulsion-hemiplegia syndrome and hemiconvulsion-hemiplegia-epilepsy syndrome). Electroencephalogr Clin Neurophysiol Suppl 1982;(35):211-21.

Roger J, Lob H, Tassinari CA. Status Epilepticus. In: Vinken PJ, Bruyn GW, editors. Handbook of neurology, Vol. 15, The Epilepsies. Amsterdam: North Holland Publishing Company, 1974:145-88.

Salih MA, Kabiraj M, Al-Jarallah AS, Desouki M, Othman S. Palkar VA. Hemiconvulsion-hemiplegia-epilepsy syndrome. A clinical, electroencephalographic and neuroradiological study. Childs Nerv Sys 1997;13:257-63.

Scott RC, Gardian DG, King MD, et al. Magnetic Resonance imaging findings within 5 days of status epilepticus in childhood. Brain 2002;125:1951-9.

Shinnar S, Pellock JM, Berg AT, et al. Short-term outcomes of children with febrile status epilepticus. Epilepsia 2001;42(1):47-53.

Tanaka Y, Nakanishi Y, Hamano S, Nara T, Aihara T. Brain perfusion in acute infantile hemiplegia studied with single photon emission computed tomography. No To Hattatsu 1994;1:68-73.

Vivaldi J: Les crises hemicloniques de l'enfant; Modalites evolutives. These. Marseille. France, 1976.

ILAE
ILAE Copyright Notice

ICD code

342.9

Synonyms

HHE

HHES

Subtopics

Febrile status epilepticus

Partial epilepsy

Associated disorders

Febrile convulsions

Partial status

Major keyword descriptors

epilepsy

febrile episode

flaccid hemiplegia

hemiconvulsions

hemispherectomy

partial status epilepticus

postictal hemiplegia

prolonged febrile convulsions

Minor keyword descriptors

cerebral hemiatrophy

convulsions

jerks

seizures

Age of presentation

01-23 months

02-05 years

Age of typical presentation

01-23 months

02-05 years

Population group(s) preferentially affected

none selectively affected

Occupation group(s) preferentially affected

none selectively affected

Sex

male=female

Family history

none

Heredity

heredity may be a factor for prolonged febrile convulsions

Illustration captions

Fig 1: Ictal EEG showing unilateral paroxysms in a case of partial status, first manifestation of an hemiconvulsion-hemiplegia-epilepsy syndrome.

Fig 2: CT scan of a girl with hemiconvulsion-hemiplegia-epilepsy syndrome.

Legend: The right hemisphere is uniformly atrophic with ventricular dilatation and cortical atrophy.

Permuted topic, synonyms, variants

Hemiconvulsion-hemiplegia-epilepsy syndrome

hemiplegia-epilepsy syndrome, Hemiconvulsion-

epilepsy syndrome, Hemiconvulsion-hemiplegia-

epilepsy, Partial

status epilepticus, Febrile

epilepticus, Febrile status

Related topics

Epilepsy

Febrile seizures

Late onset childhood occipital epilepsy

Differential diagnosis

Dravet syndrome

Todd paralysis

Epilepsia Partialis Continua

Rasmussen encephalitis