Margarita M. Miller MD

Department of Pediatrics University of Texas Southwestern Medical Center

Dallas, TX 75390-8579, USA

Children’s Medical Center at Dallas

Dallas, TX 75235, USA

doi:10.1016/j.ajem.2006.02.001

References

1. Wong CP, Chiu PKC, Chu LW. Zopiclone withdrawal: an unusual cause of delirium in the elderly. Age Ageing 2005;34:526 – 7.
2. Sepracor Inc. Lunesta (eszopiclone) tablets [drug insert] 2005. http:// www.lunesta.com.
3. Hajak G, Muller WE, Wittchen HU, Pittrow D, Kirch W. Abuse and dependence potential for the non-benzodiazepine hypnotics zolpidem and zopiclone: a review of case reports and epidemiological data. Addiction 2003;98:1371 – 8.
4. www.sepracor.com: Label for eszopiclone (Lunesta). Sepracor, Marl- borough, MA.
5. Stebbing J, Bower M. What can oncologists learn from HIV? Lancet Oncol 2003;4:438 – 45.

False-negative cerebral infarction on diffusion magnetic resonance imaging

A 31-year-old male patient presented to our center with vertigo, diplopia, and right facial sensory disturbance 12 hours after onset. He had experienced these symptoms immediately after ingestion of scallops and oysters with some amount of alcohol. He had no history of illness except atopic dermatitis. There were no conventional risk factors for stroke such as hypertension, diabetes mellitus, or heart disease except current cigarette smoking.

Before magnetic resonance imaging (MRI) was per- formed, the patient underwent an emergency clinical evaluation by a stroke neurosurgeon. neurologic findings revealed anisocoric pupils (right b left), right facial sensory disturbance, and pain sensory disturbance in the left upper and lower extremities.

Initial magnetic resonance examinations were performed 12 hours after onset on a 1.5-T magnetic resonance unit. Initial diffusion-weighted imaging (DWI) was considered negative for the diagnosis of recent arterial stroke because remarkable hyperintensity areas with reduced apparent diffusion coefficient (ADC) values were not observed; however, a questionable relatively high-intensity area was observed retrospectively in clinically relevant brain regions (Fig. 1A and B). A second MRI was performed 3 hours after the first MRI that showed a marked high-intensity area on both DWI and T2-weighted images (Fig. 1C and D). On the second day after admission, 3-dimensional computed tomography angiography was performed; right vertebral artery dissection immediately distal to the posterior inferior cerebellar artery was observed (Fig. 1E and F). Intravenous

saline and Antiplatelet therapy had been administered simultaneously since admission.

This patient was almost incorrectly diagnosed with shellfish poisoning because initial DWI and fluid-attenuated inversion recovery images showed no remarkable high- intensity area in the brain 12 hours after onset. The patient exhibited symptoms of Wallenberg syndrome; however, the signs and symptoms of the syndrome may vary from patient to patient. Therefore, we initially believed that these neuro- logic findings were caused by the shellfish toxin because the onset of the symptoms was observed immediately after ingestion of scallops.

Although it has been documented that DWI is highly sensitive for the diagnosis of acute ischemic stroke, there is increasing evidence that it may fail to detect acute stroke lesions. Three large-scale studies reported false-negative DWI findings in the acute phase of ischemic stroke lesions [1-3]. The rate of negative DWI studies in patients with acute ischemic stroke is highly variable, ranging from 0%

[4] to 21% [1,5]. The sensitivity of DWI for detecting acute ischemic stroke may not be as high as was initially believed. The lesion could be too small for the resolution of the DWI echoplanar sequence. On the other hand, the symptoms may not have been caused by infarction, but by ischemia of the brain at that time.

Yukinori Akiyama

Department of Traumatology and Critical Care Medicine

Sapporo Medical University Sapporo 003-0804, Japan Department of neurosurgery Sapporo Medical University Sapporo 003-0804, Japan

E-mail address: [email protected]

Yasufumi Asai

Department of Traumatology and Critical Care Medicine

Sapporo Medical University Sapporo 003-0804, Japan

Kiyohiro Houkin Department of Neurosurgery Sapporo Medical University Sapporo 003-0804, Japan

doi:10.1016/j.ajem.2006.02.010

References

1. Ay H, Furie KL, Yamada K, et al. diffusion-weighted MRI character- izes the ischemic lesion in Transient global amnesia. Neurology 1998; 51:901 – 3.
2. Lovblad KO, Laubach HJ, Baird AE, et al. Clinical experience with diffusion-weighted MR in patients with acute stroke. AJNR Am J Neuroradiol 1998;19:1061 – 6.

Fig. 1 Initial MRI shows no remarkable high-intensity area in the brain stem on both DWI and fluid-attenuated inversion recovery images. A and B, Second MRI findings demonstrate a marked high-intensity lesion on both DWI and T2-weighted images 3 hours after the first MRI (C, D). Three-dimensional computed tomography angiography shows enlarged left vertebral artery, which suggested dissection. It also shows that the left posterior inferior cerebellar artery is patent (E, F).

1. Oppenheim C, Stanescu R, Dormont D, et al. False-negative diffusion- weighted MR findings in acute ischemic stroke. AJNR Am J Neuro- radiol 2000;21:1434 – 40.
2. Gonzalez RG, Schaefer PW, Buonanno FS, et al. Diffusion-weighted MR imaging: diagnostic accuracy in patients imaged within 6 hours of stroke symptom onset. Radiology 1999:210;155-62.
3. Tong DC, Yenari MA, Albers GW, et al. Correlation of perfusion- and diffusion-weighted MRI with NIHSS score in acute (b6.5 hour) ischemic stroke. Neurology 1998;50:864 – 70.

Hemodialysis and hemoperfusion in a patient with an isolated phenytoin overdose^B

Phenytoin is a commonly used anticonvulsant medica- tion frequently associated with overdose and suprathera- peutic levels resulting in ataxia and nystagmus. Reports of serious morbidity or mortality are rare, and treatment usually consists of observation and Safety precautions. At therapeutic serum concentrations, hepatic metabolism is first order, with drug metabolism increasing as the drug concentration increases [1]. At supratherapeutic levels such as in the case of intentional drug overdose, hydroxylation of the parent drug in the liver is saturated and phenytoin metabolism occurs as a zero-order process (the amount of drug metabolized per a given period is constant), thereby undergoing a significantly prolonged elimination half-life increasing from 25 hours at therapeutic concentrations of 15 mg/L to more than 60 hours when levels exceed 40 mg/L [2]. Various methods to improve drug elimination in the rare case of severe overdose have been entertained. Because phenytoin has a small volume of distribution (V_d = 0.7 L/kg), is well adsorbed to activated charcoal, and may exceed total protein-binding capabilities of albumin in overdose, hemodialysis (HD) and charcoal hemoperfusion (HP), or even the use of the molecular adsorbent recirculating system, a blood-purification system based on albumin dialysis that includes a charcoal filter, offer some theoretical utility [3]. However, because of the size and high protein binding of phenytoin, it has been argued that these methods are unlikely to be helpful. We report on a case of Phenytoin toxicity with extremely high levels treated with HD and HP without evidence of improved clinical outcome.

A 32-year-old man arrived in the ED 1 hour after ingesting approximately 175 tablets of 100-mg phenytoin tablets. He was given 50 g of oral activated charcoal en route. He arrived at the ED with ataxia and nystagmus. His vital signs were as follows: blood pressure, 130/72; heart rate, 92; respiratory rate, 18; temperature, 37.48C. He was awake and alert and oriented with an initial 2-hour level of

41.2 mg/L. He was treated with an additional 25 g of activated charcoal and was admitted to the medicine ward. The repeat phenytoin level 6 hours later was 96 mg/L. Owing to his mental status, obtundation, and emesis leading

to possible aspiration, the patient was intubated and transferred to the intensive care unit. During the following days, the patient remained intubated and obtunded with a phenytoin level of 91 mg/L on hospital day 4. On hospital day 8, HP was planned as the patient was still intubated and obtunded with a level of 76 mg/L. Hemodialysis was performed owing to nonavailability of HP cartridges. Four hours after a 4-hour HD session, the phenytoin level was

51.7 mg/L. On day 10, the patient underwent HP as a result of persistent mental status alterations, ileus, and Aspiration pneumonia. Before a 4-hour HP session, his phenytoin level was 53 mg/L, and it fell to 38 mg/L 4 hours after the session (see Table 1). The level rebounded to 52 mg/L the next day. During the subsequent 2 weeks, the patient’s level fell and the patient was extubated. The patient has had 1 year of subsequent cognitive and functional impairment that has slowly improved with rehabilitation.

Hemodialysis is likely to be useful in small compounds that are water soluble, not protein bound, or that have weak binding constants to plasma proteins. Multiple-dose acti- vated charcoal and charcoal HP may be useful if a drug has low endogenous clearance, is weakly or incompletely protein bound, has a relatively small V_d, and is well bound to activated charcoal. Theoretically severe overdoses with protein-bound substances may saturate protein-binding sites and allow a better free drug-to-V_d ratio, making the drug more amenable to either HD or HP. Hemodialysis is more readily available and was used first in this case for that reason. Although it appears that HD did lower the Serum phenytoin concentration in this patient, there was no clinical change in the patient’s status. The use of HP did also appear to acutely lower the phenytoin concentration, although the level rebounded quickly and was unchanged the next day. It appears from this isolated case that HD may represent a method to remove phenytoin or substances with similar toxicokinetic properties when a patient is severely affected by such an overdose. However, use of HD, HP, or both must be tempered by comparing the known risks of these interventions, the complications of prolonged intuba-

Table 1 Hospital course

Time Phenytoin

(h) level (mg/L)

2 41.2

96

Relation of level

to intervention

1 h after 50 g of activated charcoal PO 6 h after 25 g of activated charcoal PO

Clinical status

Ataxia,

nystagmus

10

Progressive

obtundation

100 91 Intubated, obtunded