Epikpsiu, 32(5):7 12-7 15, 199I

Raven Press, Ltd.. New York 0 International League Against Epilepsy

Treatment of Porphyric Convulsions with Magnesium Sulfate

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M. Sadeh, I. Blatt, G. Martonovits, A. Karni, and Y. Goldhammer Department of Neurology, The Chaim Sheba Medical Center, Tel Hashomer, und Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

Summary: We report a 16-year-old girl with acute intermittent porphyria who had abdominal pain, generalized tonic-clonic and simple partial seizures, and inappropriate antidiuretic hormone secretion. Because most antiepileptic drugs are contraindicated in porphyria, she was treated with magnesium sulfate i. v. Soon after starting

treatment, seizures stopped, returned, and then again responded in several trials with discontinuation and reinstitution of i.v. magnesium sulfate. Our experience encourages the use of magnesium sulfate for treatment of seizures in patients with porphyria. Key Words: Acute intermittent porphyria-Magnesium sulfate-Epilepsy.

Epileptic seizures occur commonly in acute intermittent (AIP) and other porphyrias and their treatment poses a unique difficulty. Barbiturates (Wirtschafter et al., 1960), hydantoins (Gretter et al., 1963; Magnussen et al., 1975; Bonkowsky et al., 1980), ethosuximide (Birchfield and Cowger, 1966), primidone (Magnussen et al., 1975), carbamazepine (Larson et al., 1978), valproate (Garcia-Merino and Lopez-Lozano, 1980), clonazepam (Bonkowsky et al., 1980), diazepam (Rifkind, 1976; Moore, 1980) and paraldehyde (Rifkind, 1976; Moore, 1980) have been reported either to induce an acute exacerbation of porphyria o r t o worsen the porphyric metabolic state. All are porphyrinogenic in chick embryo hepatocyte cultures, providing an experimental model of acute porphyria (Granick, 1966; Bonkowsky et al., 1980; Reynolds and Miska, 1981; Shedlofsky and Bonkowsky, 1984), and considered unsafe in these patients. Bromides, although safe (Bonkowsky et al., 1980; Magnussen et al., 1975), are not suitable for status epilepticus. Taylor (1981) recommended magnesium sulfate in acute uncontrolled generalized seizures and mentioned its successful employment against status epilepticus in a patient with AIP, but no further details were provided in his letter. We report the effective treatment of porphyric convulsions with magnesium sulfate.

CASE REPORT

A 16-year-old girl was healthy until a week prior to admission to another hospital because of abdominal pain, vomiting, and lethargy. After being treated with metronidazole, metoclopramide, and antispasmodics for entamoeba histolytica and ascariaris infestation she had several generalized tonic-clonic seizures and lapsed into coma. Hyponatremia of 111 mmol/L was found with serum osmolarity of 248 mOsmol/kg and urinary sodium of 148 mmol/L. These results were suggestive of inappropriate antidiuretic hormone (ADH) secretion. After correction of hyponatremia she regained consciousness though with fluctuating levels and the onset of continuous simple partial seizures. A brain computed tomography scan was normal. When referred to this department she was conscious and cooperative but suffered from continuous simple partial seizures, at approximately one per second, of the left facial muscles and occasionally of the right trapezius. There was moderate proximal weakness of all limbs, hyperactive tendon reflexes, and bilateral extensor responses, all more pronounced on the left. Treatment with phenytoin (PHT) i.v. was started; however seizures persisted, involving the right face and arm, left face and arm, right sternomastoid and trapezius muscles, and both shoulders. She gradually became comatose. An EEG, recorded during a period of seizures of the left hand, showed diffuse theta and delta activity and movement artifacts, but no epileptic dis-

Received May 1990; revision accepted August 1990. Address correspondence and reprint requests to Dr. M. Sadeh at Department of Neurology, The Chaim Sheba Medical Center, Tel Hashomer 52621. Israel.

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MAGNESIUM SULFATE IN PORPHYRfC CONVULSIONS

charges. Serum sodium level was 130 mmol/L, plasma osmolarity 270 mOsmol/kg, urine sodium 196 mmol/L, and urine osmolality 570 mOsmol/kg, compatible with inappropriate ADH secretion. Three days after admission, increased urinary excretion of porphyrins was discovered and the diagnosis of AIP was made, confirmed subsequently by further blood, urine, and feces analysis (Table 1). Treatment with PHT was stopped and infusion of 20% glucose into a central vein started at a rate of 20 g/h. Hematin was not available. In addition, magnesium sulfate i.v. was instituted. After a loading dose of 3 g, drip infusion of I g/h was continued and within 3 h, seizures ceased. She remained in deep coma and the following day because of generalized flaccidity and areflexia of the lower limbs the magnesium infusion was discontinued. Multifocal seizures of face and upper and lower limbs then recurred and a magnesium drip was reinstituted at 0.75 g/h, again with cessation of seizures; a day later she regained consciousness, and indicated that she was suffering from severe abdominal pain. Treated with glucose, magnesium sulfate, and hypertonic saline, her condition was stable for the next 2 days. Serum magnesium level was 5.3 mEq/L and sodium, 128 mmol/L. Because of rapidly increasing weakness of upper limbs, magnesium was stopped but 3 h later simple partial seizures involving back, trunk, and shoulder muscles reappeared. Serum magnesium level prior to stopping treatment was 9.2 mEq/L. Treatment was renewed with cessation of seizures, which returned temporarily during the night because of technical interruption and responded quickly after resumption of the infusion. During the next 4 days of treatment with magne-

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sium sulfate, no seizures were observed. She was conscious and cooperative but unable to move her tongue, to swallow or to speak. Eye movements were normal; there was severe weakness of all limbs more pronounced proximally. Tendon reflexes were normal, plantar responses were extensor on the left and indifferent on the right. Conduction velocities of upper and lower limb motor and sensory nerves and facial nerve were normal, as were F wave latencies. The blink reflex could not be elicited by supraorbital nerve stimulation. An electromyograph showed no spontaneous activity, normal muscle action potentials, and poor recruitment consistent with the weakness. Serum magnesium levels were kept in a range of 4.0-7.2 mEq/L for a week and then treatment was discontinued without recurrence of seizures and with no change in neurological status. Unfortunately, the patient’s mother removed the gastric feeding tube and fed her through the mouth. Massive aspiration ensued with cardiac and respiratory arrest and despite resuscitation attempts she suffered from severe anoxic brain damage, remained comatose, and died several weeks later. DISCUSSION

Acute intermittent porphyria is an autosomal dominant disease in which porphobilinogen (PBG) deaminase activity is reduced to approximately half the normal, causing decreased synthesis of heme. Heme inhibits the activity of delta aminolevulinic acid (ALA) synthase, the first and rate-limiting enzyme in the heme biosynthesis pathway. Reduced feedback inhibition of ALA synthase by heme re-

TABLE 1. Results of biochemical studies Precursors and porphyrins in urine (pg/g creatinine) Thin layer chromatography

Patient Normal

ALA

PBG

Total porphyrins

Uroporphyrin 111

Heptacarboxyporphyrin

Coproporphynn I11

183

Treatment of porphyric convulsions with magnesium sulfate.

We report a 16-year-old girl with acute intermittent porphyria who had abdominal pain, generalized tonic-clonic and simple partial seizures, and inapp...
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