Topiramate is effective for status epilepticus and seizure control in neuraminidase deficiency

Topiramato é efetivo no tratamento de estado de mal epiléptico e controle de crises na deficiência de neuraminidase

LETTERS

Topiramate is effective for status epilepticus and seizure control in neuraminidase deficiency

Topiramato é efetivo no tratamento de estado de mal epiléptico e controle de crises na deficiência de neuraminidase

José Augusto Bragatti^I; Carolina Machado Torres^I; Cristina Brinckmann Oliveira Netto^II; Leonardo Vedolin^III; Eliana Garzon^IV; Carlos Roberto de Mello Rieder^I; Ida Vanessa Doederlein Schwartz^II,IV; Marino Muxfeldt Bianchin^I

^IDivision of Neurology, Hospital de Clínicas de Porto Alegre, Porto Alegre RS, Brazil

^IIMedical Genetics, Hospital de Clínicas de Porto Alegre, Porto Alegre RS, Brazil

^IIIDivision of Radiology, Hospital Moinhos de Vento, Porto Alegre RS, Brazil

^IVUniversity of São Paulo School of Medicine, Neurology Department, São Paulo SP, Brazil

^VDepartment of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre RS, Brazil

^{Correspondence}

Sialidosis, a rare lysosomal storage disorder is caused by a deficiency of the enzyme α-N-acetyl neuraminidase, resulting from mutations in the NEU1 gene^1-5. Its main phenotypes are Sialidosis types I (milder form) and II (earlier onset)^{1 -5}. Sialidosis type II is characterized by developmental delay, macular cherry-red spot, viscero-megaly, coarse facies, dysostosis multiplex, and myoc-lonus^1-5 . We report a case of status epilepticus (SE) in a patient with Sialidosis type II which had good response to topiramate.

CASE

A 16 years -old girl was admitted to our emergency unit with SE. She was using valproate 30 mg/Kg/day, primidone 10 mg/Kg/day, and clobazam 0.20 mg/Kg/day (maximum tolerated doses). Sialidosis type II was diag-nosed nine years before, by detection of high levels of urinary sialil- oligossacharides, and deficient neuramin-idase activity in leukocytes. Myoclonic seizures started at the age of eleven, and further became refractory to pharmacological treatment. Before admission, she was presenting weekly myoclonic seizures. She had neuro-psychological delay, short stature, mild dysostosis mul-tiplex, and a cherry-red spot on retinal exam. Intra-venous midazolam was increased till 0.4 mg/kg/hour without any benefit. MRI revealed cerebellar and brain atrophy. Interictal EEG showed multifocal spikes, mainly involving bilateral parassagital regions. Seizures were easily provoked by tactile stimulus, and characterized by a extensor tonic spasm in four extremities, followed by tonic arms flexion and facial muscle contraction. These movements were followed by several massive general-ized myoclonic jerks (Figure). Ictal EEG showed a train of 15 Hz rhythmic spikes, predominantly in frontal re-gions, rapidly evolving to a polispike-slow wave complex with fast fading away, and replaced by a generalized de-pression of the background activity. Seizures occurred every 5 minutes, with total duration of 30 seconds. Val-proic acid was increased to 75 mg/Kg/day without ben-efit. Next day, we introduced topiramate 2.5 mg/Kg/day. There was improvement in seizure control, and 8 hours later patient was seizure-free. After discharge, she used this scheme for two years, with brief myoclonic jerks oc-curing in a monthly frequency.

DISCUSSION

Drugs used for treatment of SE are phenytoin, bezo-diazepines, phenobarbital, and propofol^1,2, but treatment of SE in myoclonic progressive epilepsies is still not es-tablished. Midazolam was not effective here. Other op-tions were propofol or barbiturates. Phenobarbital was already in use. Propofol is useful during acute phase but is not an option for long-term seizure control. Phenytoin could aggravate the myoclonic seizures of our patient.

For the same reason, benzodiazepines would not be an option, because tonic seizures, a not uncommon type of seizure in the epileptic encephalopathies, could be originated by it. Newer agents (valproate, levetiracetam, or topiramate) might be an interesting option¹ . These drugs are also useful as antiepileptic drugs after SE. Le-vetiracetam was not available to us. We tried topiramate and fortunately obtained a good response with a rela-tively low dosage. Then, we suggest topiramate for treat-ment of both, SE and seizures, in Sialidosis. Topiramate is possibly also a useful drug for other forms of progres-sive myoclonic epilepsies. Further studies are necessary to clarify these matters.

Received 24 January 2011

Received in final form 18 February 2011

Accepted 3 March 2011

Support: The authors receive financial support from FAPERGS, FIPE and CNPq. Dr. Bianchin and Dr Schwartz were further supported by CNPq (#305501/2007-0 and # 305147/2007-2, respectively).

• 1. Bleck TP. Intensive care unit management of patients with status epilep-ticus. Epilepsia 2007;48(Suppl 8):S59-S60.
• 2. Costello DJ, Cole AJ. Treatment of acute seizures and status epilepticus. J Intensive Care Med 2007;22:319-347.
• 3. Gopaul KP, Crook MA. The inborn errors of sialic acid metabolism and their laboratory investigation. Clin Lab 2006;52:155-169.
• 4. Lowden JA, O'Brien JS. Sialidosis: a review of human neuraminidase defi-ciency. Am J Hum Genet 1979;31:1-18.
• 5. Pshezhetsky AV, Richard C, Michaud L, et al. Cloning expression and chro-mosomal mapping of lysossomal sialidase and characterization of muta-tions in sialidosis. Nat Genet 1997;15:316-320.

Publication Dates

• Publication in this collection
  19 July 2012
• Date of issue
  June 2011