Article Text
Summary
Alterations in electrolyte homeostasis associated with major surgery and critical illness are common but usually non-specific. We report an unusual case of hypomagnesaemia induced seizures in a 73-year-old woman who was recovering from ileal resection and limited right hemicolectomy for small bowel volvulus. Hypomagnesaemia as a de novo cause of seizures is rarely reported.
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Background
Magnesium has shown anti-seizure effects in animal studies1,2 and is frequently used for seizure prophylaxis in pre-eclamptic patients.3 Hypomagnesaemia is associated with seizures in the neonatal period, but a literature search revealed only two similar cases in adults.4,5
Nutritional deficiencies are common after bowel resection and in inflammatory bowel disease. This case highlights a common presentation of an uncommon underlying (but preventable and treatable) cause.
Case presentation
A 73-year-old woman was admitted with a 2-day history of intermittent colicky abdominal pain. Her past medical history included bilateral osteoarthritis of the knee joints.
Her clinical condition deteriorated rapidly with the development of shock, requiring inotropic support. CT scan of abdomen and pelvis showed a small intestinal obstruction but no evidence of perforation.
The patient underwent limited resection of the ileum and right colectomy. The patient progressed well post-operatively. Electrolyte abnormalities, notably hypokalaemia and hypomagnesaemia, were duly corrected.
She was transferred for in-patient rehabilitation. During this period she developed deep vein thrombosis of the left lower limb for which she was anti-coagulated with warfarin, and superficial wound dehiscence, which was treated conservatively.
Her abdominal wound was healing well, her INR was within therapeutic range and she was walking well with a walking frame. However, 2 months post-operatively she developed two generalised tonic–clonic seizures within the span of an hour. On both occasions seizure activity spontaneously ceased after approximately 1 min.
Investigations
An urgent CT brain scan showed old bilateral occipital infarcts and a right internal capsule infarct but no acute intracranial pathology (figure 1). Investigations carried out immediately after the seizures showed hypokalaemia (3.3 mmol/l), hypomagnesaemia (0.25 mmol/l) and hypocalcaemia (corrected calcium 2.03 mmol/l). Further investigations including renal functions, 24 h urinary electrolytes, liver functions and full blood count were within normal limits. The parathyroid hormone level was normal at 5.45 pmol/l (normal: 1.3–7.6). ECG changes during the hypomagnesaemic phase showed sinus rhythm, inverted T wave (V2–4) and prolonged QT (QTC: 517).
Differential diagnosis
At the time of seizure occurrence in our patient the only significant findings were hypocalcaemia and hypomagnesaemia. The hypocalcaemia was too mild to have caused the seizures (corrected calcium 2.03 mmol/l). The main electrolyte abnormality was severe hypomagnesaemia (0.25 mmol/l) which required intravenous replacement over several days.
CT brain scan revealed old occipital infarcts which could have served as an epileptiogenic focus. However, the patient was asymptomatic before she became ill and had no history of seizures.
Treatment
The patient received one intravenous phenytoin infusion after the second seizure (as per hospital protocol) and hypomagnesaemia was corrected with intravenous replacement. After achieving normal levels, long term oral magnesium sulphate supplementation was started. No further seizures were noted. However, phenytoin was switched to lamotrigine (to avoid the interaction of phenytoin and warfarin) which was tapered off after 6 months without further seizures.
Outcome and follow-up
The patient has been seizure free for 8 months without any anti-epileptic medication.
Discussion
Magnesium is the second most abundant intracellular cation and the fourth most abundant cation in the body. It is essential for synthesis of nucleic acids and proteins, for intermediary metabolism and for specific actions in the neuromuscular and cardiovascular systems. Over 300 enzymes are dependent on magnesium.6
A healthy adult contains approximately 1000 mmol of magnesium (22–26 g). About 60% of magnesium is present in bone, 20% is in skeletal muscle, 19% in other soft tissues and less than 1% in extracellular fluid. In healthy adults, total serum magnesium ranges between 0.70 and 1.10 mmol/l.6 The recommended daily allowance for magnesium in adults is 4.5 mg/kg/day and in general the intake of magnesium is directly related to energy intake.6
Most magnesium absorption occurs in the ileum and colon via the paracellular and transcellular pathways. Recently, TRPM6 and TRPM7 proteins have been shown to play a role in transcellular absorption. Mutations in the TRPM6 gene have also been shown to be the cause of familial hypomagnesaemia, which presents in infancy with hypocalcaemic-hypomagnesaemic seizures.7,8 Factors controlling magnesium absorption are not well understood. Studies suggest a role for parathyroid hormone in regulating magnesium absorption, but the role of vitamin D and 1,25 dihydroxyvitamin D is more controversial.
The kidney plays a major role in magnesium homeostasis. Under normal circumstances, 80% of the total plasma magnesium is ultrafiltrable (84 mmol) and 95% of this is reabsorbed leaving about 3–5 mmol to appear in urine.6
Magnesium is thought to regulate potassium levels by acting a cofactor in the sodium–potassium pump. It also affects calcium levels through its effects on parathyroid hormone release and its peripheral action. Hence magnesium deficiency is often associated with both hypocalcaemia and hypokalaemia that is resistant to correction until the magnesium deficit has been corrected.
Magnesium has a depressant effect on the central nervous system9 and has been shown to have anti-epileptic activity in animal studies.1,2 Although the exact mechanism by which it exerts its effects is uncertain, magnesium has also been used effectively to prevent eclamptic seizures since 1929.3,10 Low serum magnesium levels have also been correlated with increased seizure frequency in patients with idiopathic epilepsy.9
Hypomagnesaemia usually has non-specific presentations, ranging from weakness and muscle cramps to tachycardia. More severe hypomagnesaemia can cause neuromuscular irritability with hyperactive tendon reflexes, cramps and Trousseau and Chvostek signs similar to calcium deficiency. It also causes central nervous system hyperexcitability, disorientation and psychosis.
Seizures and cardiac arrhythmias, in particular Torsades de pointes, can occur as a result of magnesium deficiency.
Cases of hypocalcaemic-hypomagnesaemic convulsions have been reported as an initial presentation in neonates with primary hypomagnesaemia; however, hypomagnesaemia as a de novo cause of seizures is rarely reported.4,5
Learning points
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Screening for nutritional deficiencies should be routinely performed for patients in intensive care and following major surgery (ie, intestinal resection) in order to avoid life threatening complications.
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Underlying treatable pathologies should be investigated when the clinical presentation is unusual or unexpected.
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Hypomagnesaemia can present with hypokalaemia and hypocalcaemia which are resistant to standard replacement therapy unless magnesium is corrected.
Footnotes
Competing interests: None.
Patient consent: Patient/guardian consent was obtained for publication.