An 83-year-old man was admitted to our hospital for evaluation of general malaise. He had a 10-year history of chronic atrial fibrillation and hypertension and had been treated with candesartan (8 mg/day) and warfarin (2 mg/day). Two weeks before presentation, the patient had visited a urologist because of transient urinary tract hemorrhage. Detailed examination had shown no abnormalities of the urinary tract. He had been advised to drink enough water to prevent urinary obstruction by blood clots for 1-2 weeks. In response, the patient started drinking about 4 L of water per day. One week later, he became aware of fatigability and gait disturbance but continued drinking extra water. His symptoms gradually worsened until he was admitted to the general medicine department of our hospital. The patient had no relevant medical or family history. He was a non-smoker and non-drinker.
On admission, the patient's weight was 58 kg and his blood pressure was 102/72 mmHg. He was alert and afebrile. The patient complained of gait disturbance, but physical and neurological examination showed no abnormalities. Electrocardiography showed atrial fibrillation. Plain computed tomography of the neck, chest, and abdomen showed no significant abnormalities. Notably, laboratory tests showed a markedly decreased serum sodium level (105 mEq/L, normal: 138-145 mEq/L). Plasma and urine osmolality were 225 and 140 mOsm, respectively. Urine sodium level was undetectable. Levels of plasma adrenocorticotropic hormone, cortisol, and antidiuretic hormone were normal, suggesting the possibility of water intoxication. The patient received 0.5 L of normal saline solution in the emergency department and was transferred to a general medicine bed 4 h after emergency department presentation. His serum sodium level increased by 4 mEq/L over 4 h. Administration of 5% glucose solution was started at a rate matching urine output to prevent a further increase in serum sodium level. On day 2, the patient's serum sodium level rose to 113 mEq/L. His serum sodium level on day 3 was 121 mEq/L. Thereafter his serum sodium level increased by 5 mEq/L per day.
On day 5, the patient's serum sodium level was 130 mEq/L. He was alert and was improving. However, he suddenly developed twitching of the left arm lasting for 30 s, consistent with FIAS, followed by FTBTCS lasting for about 40 min. Assisted ventilation was started; intravenous diazepam (10 mg) was administered twice but was ineffective. Therefore, intravenous fosphenytoin sodium (1300 mg) was subsequently administered. FTBTCS stopped after administration of the first dose of fosphenytoin. However, intermittent twitching of the left arm with impaired awareness resulting from FIAS continued several times per hour, with each episode lasting more than 5 min. Moreover, the patient had five episodes of recurrent FTBTCS lasting for about 30 min each in the first 24 h with prolonged impaired awareness, despite the addition of continuous intravenous fosphenytoin (400 mg/day). Ictal electroencephalogram (EEG) during FTBTCS showed bilateral polyspikes but was obscured by artifact; ictal EEG during FIAS showed rhythmic 5-9 Hz theta activity in the right frontotemporal region (data not shown). EEG recorded during an interseizure period revealed irregular right frontal sharp waves with theta and delta activities (Figure 1). Magnetic resonance imaging (MRI) of the brain showed no obvious signs suggesting osmotic demyelination syndrome (ODS); however, marked atrophy of the hippocampus and temporal lobe was seen (Figure 2). Further questioning of the patient's family revealed that he had been diagnosed with AD 2 years before admission. Although atrophy of the hippocampus and temporal lobe has been associated with seizures in patients with AD, no symptomatic epileptic seizures had been recognized before hospitalization. On day 6, the frequency of FTBTCS decreased, but intermittent FIAS and FTBTCS did not completely disappear. Correction of hyponatremia was suspended to lower serum sodium to 125 mEq/L. Fosphenytoin administration was discontinued and was replaced with intravenous levetiracetam (1000 mg/day); however, FTBTCS continued intermittently. The addition of perampanel (4 mg/day) and clonazepam (3 mg/day) to levetiracetam was ineffective at controlling seizures. Administration of lamotrigine (200 mg/day), carbamazepine (600 mg/day), and levetiracetam (1000 mg/day) on day 7 was also ineffective. Continuous intravenous infusion of midazolam (5 mg/h) was introduced to treat SE on day 8. Thereafter, both FIAS and FTBTCS subsided. Repeat MRI of the brain on days 7, 14, and 28 revealed no obvious lesions suggesting ODS on diffusion-weighted, T2-weighted, or fluid attenuation inversion recovery imaging. Reduction of the midazolam dose was not possible because of relapsing seizures. The patient's general status gradually deteriorated; he died of aspiration pneumonia on day 58.