Effects of acetazolamide on epileptic apnea in migrating partial seizures in infancy

doi:10.1016/j.eplepsyres.2011.05.007

Epilepsy Research

Volume 96, Issues 1–2, September 2011, Pages 185-189

https://doi.org/10.1016/j.eplepsyres.2011.05.007 Get rights and content

Summary

We report two cases of migrating partial seizures in infancy complicated with intractable epileptic apnea with severe desaturation. Ictal electroencephalography revealed migrating foci of epileptiform discharges, which spread to bilateral temporal areas resulting in the onset of apnea. Magnetoencephalography detected dipole sources at bilateral perisylvian areas. Single photon emission tomography revealed a significant ictal change in perfusion at bilateral anterior temporal lobes in one patient. Addition of acetazolamide to the regimen resulted in complete disappearance of epileptic seizures.

Introduction

Migrating partial seizures in infancy (MPSI) is a rare epileptic syndrome characterized by onset before six months of age, continuous migrating polymorphous focal seizures, ictal epileptic discharges arising independently and sequentially from both hemispheres, marked intractability to antiepileptic drugs, and developmental arrest after the onset of disease (Coppola et al., 1995, Caraballo et al., 2008). Autonomic manifestations including apnea, flushing, and cyanosis often accompany or predominate the ictal phenomena (Coppola et al., 1995, Caraballo et al., 2008). Apnea as a manifestation of epileptic seizures is also observed in patients with localization-related epilepsy (Watanabe et al., 1982, Akaike et al., 2008). This type of seizure can appear during sleep or wakefulness, can necessitate resuscitation and can also be lethal (Ramelli et al., 1998), and has been assumed to be partly responsible for sudden unexpected death in epilepsy. Within these seizures, ictal activity usually consists of rhythmic focal alpha to theta activity originating in the temporal lobes (Watanabe et al., 1982). Limbic structures are densely connected to the respiratory center in the brainstem, primarily through ipsilateral descending pathways (Hopkins and Holstege, 1978). Therefore, bilateral temporal lobe involvement is significantly linked to ictal desaturation during complex partial seizures in temporal lobe epilepsy (Seyal and Bateman, 2009).

Here we report two cases of infants with MPSI who suffered from intractable epileptic apnea accompanying ictal discharges of bilateral temporal areas. Acetazolamide (AZA) administration produced significant effects on these seizures, which is the first demonstration of its usefulness in the treatment of MPSI.

Section snippets

Patient 1

The one-year-old girl was born uneventfully and at term. Growth and development were normal until six months of age, when she experienced recurrent episodes of motion arrest and subsequent cyanosis with or without clonic movements of the upper limbs beginning on the right side. Although no abnormality was noted on interictal electroencephalogram (EEG), valproate (VPA) treatment was initiated. Blood and urine analyses found no evidence of metabolic disorders, and computed tomography (CT) of the

Discussion

Epileptic apnea without convulsive symptoms can be regarded as a type of complex partial seizure (Watanabe et al., 1982). Apart from patients with neonatal seizures, this type of seizure has been mainly observed in infancy. Because decreased consciousness is often difficult to assess precisely at this age, accompanying motion arrest and minor signs such as grimacing, drooling, or flushing provide clues to the diagnosis of epilepsy. EEG reveals that these seizures most frequently originate in

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Experimental evidence indicates the presence of dense interconnections between the limbic system and respiratory center in the brainstem [3]. Moreover, ictal electroencephalography (EEG) has suggested that epileptic apnea can be caused by epileptic discharges originating in the temporal lobes [4]. Here, we presented a case of with inherited GPI anchor deficiency and compound PIGT mutations, presenting with refractory epileptic apnea.
We report an 11-month-old boy with acetazolamide-responsive epileptic apnea and inherited glycosylphosphatidylinositol (GPI)-anchor deficiency who presented with decreased serum alkaline phosphatase associated with compound PIGT mutations. The patient exhibited congenital anomalies, severe intellectual disability, and seizures, including epileptic apnea with epileptiform discharges from bilateral temporal areas. Brain magnetic resonance imaging revealed delayed myelination and progressive atrophy of the brainstem, cerebellum, and cerebrum. Whole-exome sequencing revealed compound heterozygous mutations in PIGT (c.250 G > T, p.Glu84X and c.1096 G > T, p.Gly366Trp), which encodes a subunit of the GPI transamidase complex. Flow cytometry revealed decreased expression of CD16 (a GPI anchor protein) on granulocytes, supporting the putative pathogenicity of the mutations. Phenobarbital, clonazepam, and potassium bromide decreased the frequency of tonic seizure and acetazolamide decreased epileptic apnea. To our knowledge, this is the first reported case of intractable seizures accompanied by epileptic apnea associated with GPI anchor deficiency and a compound PIGT mutation.
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However, similar to our case, some patients suffer from severe adverse effects such as bromoderma and over-sedation [2,6]. Favorable responses to stiripentol [1,7], acetazolamide [8], and rufinamide [9] have also been reported. In the present case, however, we selected a ketogenic diet preferentially, because the patient already suffered from severe adverse effects of KBr, and we were concerned about further adverse effects of antiepileptic drugs.
Migrating partial seizures in infancy (MPSI) are an age-specific epilepsy syndrome characterized by migrating focal seizures, which are intractable to various antiepileptic drugs and cause severe developmental delay. We report a case of MPSI with heterozygous missense mutation in KCNT1, which was successfully managed by ketogenic diet. At age 2 months, the patient developed epilepsy initially manifesting focal seizures with eye deviation and apnea, then evolving to secondarily generalized clonic convulsion. Various antiepileptic drugs including phenytoin, valproic acid, zonisamide, clobazam, levetiracetam, vitamin B6, and carbamazepine were not effective, but high-dose phenobarbital allowed discontinuation of midazolam infusion. Ictal scalp electroencephalogram showed migrating focal seizures. MPSI was suspected and she was transferred to our hospital for further treatment. Potassium bromide (KBr) was partially effective, but the effect was transient. High-dose KBr caused severe adverse effects such as over-sedation and hypercapnia, with no further effects on the seizures. At age 9 months, we started a ketogenic diet, which improved seizure frequency and severity without obvious adverse effects, allowing her to be discharged from hospital. Ketogenic diet should be tried in patients with MPSI unresponsive to antiepileptic drugs. In MPSI, the difference in treatment response in patients with and those without KCNT1 mutation remains unknown. Accumulation of case reports would contribute to establish effective treatment options for MPSI.
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In two other children, a combination of sodium bromide, stiripentol, and levetiracetam led to a significant therapeutic response (Djuric et al., 2011). Further, rufinamide (Vendrame et al., 2011) and acetazolamide (Irahara et al., 2011) showed a potential efficacy in a few patients. Vigabatrin and carbamazepine may worsen seizure recurrence (Dulac, 2005).
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Short communicationEffects of acetazolamide on epileptic apnea in migrating partial seizures in infancy

Summary

Introduction

Section snippets

Patient 1

Discussion

Pediatr. Neurol.

Eur. J. Paediatr. Neurol.

Three infantile cases of temporal lobe epilepsy presenting as apnea

No To Hattatsu

Migrating focal seizures in infancy: analysis of the electroclinical patterns in 17 patients

J. Child Neurol.

Migrating partial seizures in infancy: a malignant disorder with developmental arrest

Epilepsia

Amygdaloid projections to the mesencephalon, pons and medulla oblongata in the cat

Exp. Brain Res.

Short communication
Effects of acetazolamide on epileptic apnea in migrating partial seizures in infancy