We describe an otherwise healthy 68-year-old woman who was receiving prophylactic antimalarial doses of chloroquine (100 mg daily) while traveling in India. She had no history of epilepsy or alcohol abuse and was receiving no other medication. Twelve days after starting chloroquine, she suddenly had difficulties in finding her words and began to stammer. She exhibited erratic behavior, continuously opening, rummaging in, and closing her handbag for no obvious reason. These symptoms fluctuated, lasting from minutes to hours.

One day after the onset of the symptoms, the patient was admitted to our hospital. At admission, the patient had no fever, and she was well oriented and vigilant, although she could not recall some details of the last days of her journey. Results of the neurologic examination showed intermittent motor dysphasia and verbal and semantic paraphasia. No lateralizing deficits were noted. Laboratory results were all within the normal range. Chloroquine plasma concentrations were also within the normal range for malaria prophylaxis (472 nmol/L) [1]. Results of serologic tests for herpes simplex virus types 1 and 2; poliomyelitis types 1, 2, and 3; human immunodeficiency virus; syphilis; mumps; picornaviridae; toxoplasmosis; and borreliosis were all negative. Her cerebrospinal fluid was normal, and results of serologic tests of cerebrospinal fluid for herpes simplex virus types 1 and 2, syphilis, and borreliosis were negative. Electrocardiography, continuous 24-hour electrocardiographic monitoring, cerebral computed tomography and magnetic resonance imaging, and carotid color Doppler ultrasound all showed normal results. On the third day after admission, the electroencephalogram [EEG], recorded in a state of wakefulness, showed a slightly irregular background activity of about 10 Hz alternating with rhythmic sharp and slow waves, respectively; irregular spikes; and slow waves discharging at about 1 Hz, predominantly in the frontal regions with a tendency to generalize. This examination was considered to be compatible with nonconvulsive status epilepticus Figure 1, top), and a bolus of 2 mg of clonazepam was injected intravenously while the recording continued. Thirty seconds after the end of the injection, the EEG had returned to normal and showed only a generalized ß activity Figure 1, bottom). The patient's motor dysphasia disappeared, and her speech became fluent. Chloroquine was stopped, and she was further treated with 600 mg of carbamazepine daily. She remained free of symptoms. An EEG recorded 2 months later, 10 days after antiepileptic treatment was discontinued, and another EEG recorded 6 months after cessation of antiepileptic treatment were normal.

View larger version (40K): [in this window] [in a new window]   Figure 1. Top. Nonconvulsive status epilepticus. The electroencephalogram (EEG) shows irregular sharp and slow wave complexes, 0.5 to 1.0 per second, predominant in the frontal regions with a tendency to generalize. Clinically, the patient had motor dysphasia. Bottom. Electroencephalogram from the same patient 1 minute after intravenous injection of 2 mg of clonazepam. The EEG shows a ß activity of 16/s. The patient's symptoms had resolved.

The clinical presentation and the EEG recording Figure 1, top), as well as the response to clonazepam, meet the diagnostic criteria of complex partial status epilepticus [2]. With no other cause apparent [3], we believe that complex partial status epilepticus is the consequence of prophylactic antimalarial treatment with chloroquine. To our knowledge, nonconvulsive status epilepticus has not previously been reported as an adverse effect of chloroquine treatment, whereas generalized convulsive epilepsy is a rare but well-known side effect of this drug, especially in epileptic patients [4, 5]. Mental changes, including psychotic episodes, anxiety, and personality changes, have been reported as adverse effects of chloroquine [4, 5]. Some of these symptoms could be related to complex partial status epilepticus, and an EEG should be done in such patients to rule out nonconvulsive status epilepticus.