Journal of Parenteral and Enteral Nutrition http://pen.sagepub.com/
Vitamin B6 Deficiency : A Potential Cause of Refractory Seizures in Adults
Anthony T. Gerlach, Sheela Thomas, Stanislaw P. Stawicki, Melissa L. Whitmill, Steven M. Steinberg and Charles H. Cook JPEN J Parenter Enteral Nutr 2011 35: 272 DOI: 10.1177/0148607110384118 The online version of this article can be found at: http://pen.sagepub.com/content/35/2/272
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Case Report
Vitamin B6 Deficiency: A Potential Cause of Refractory Seizures in Adults
Journal of Parenteral and Enteral Nutrition Volume 35 Number 2 March 2011 272-275 © 2011 American Society for Parenteral and Enteral Nutrition 10.1177/0148607110384118 http://jpen.sagepub.com hosted at http://online.sagepub.com
Anthony T. Gerlach, PharmD, FCCM, BCPS; Sheela Thomas, MS, RD, LD; Stanislaw P. Stawicki, MD; Melissa L. Whitmill, MD; Steven M. Steinberg, MD; and Charles H. Cook, MD FCCM
intraventricular bleed and developed new onset of refractory seizures. Interventions: Intravenous pyridoxine followed by oral pyridoxine. Measurement and Main Results: In all 3 cases, seizures persisted despite escalation of conventional antiepileptic medications but resolved within 2 days of pyridoxine supplementation. In each case, low serum pyridoxal 5′-phosphate concentrations normalized with pyroxidine administration. Conclusions: Although refractory seizures caused by vitamin B6 deficiency are rare in adults, it should be considered in critically ill adult patients with refractory seizures. (JPEN J Parenter Enteral Nutr. 2011;35:272-275)
Objective: In children, vitamin B6 (pyridoxine) deficiency has been described as a cause of seizures that are refractory to conventional antiepileptic medications. We describe the clinical presentation of 3 adults with refractory seizures (later diagnosed with vitamin B6 deficiency) that resolved after pyridoxine treatment. Design: Case series. Setting: Tertiary care surgical intensive care unit. Patients: In the first case, a 54-year-old male with history of alcoholic cirrhosis developed new-onset seizures refractory to phenytoin and levetiracetam 8 days after liver transplantation. In the second case, a 59-year-old male with hepatitis C infection developed intracranial hemorrhage and new-onset seizures refractory to phenytoin, levetiracetam, and pentobarbital. The third patient is a 78-year-old male with a history of alcohol dependence who was admitted for an
Keywords: vitamin B6; pyridoxine; seizures
S
The etiology of seizures in ICU patients is multifactorial. Although seizure events in the ICU often involve other primary neurological illnesses, seizures can also be secondary to critical illness itself or may be related to intensive care therapies.7 Among the common causes of seizures in the ICU are: (a) traumatic brain injury; (b) ischemic brain injury; (c) space-occupying lesions (ie, hemorrhage or tumor); (d) various infectious processes; (e) systemic metabolic abnormalities (ie, hepatic or uremic encephalopathy, hypoglycemia, hypocalcemia, hyponatremia); and (f) medications.2,7 Medicationinduced seizures can be a result of adverse effects (eg, imipenem or meperidine), drug overdose, drug withdrawal or intoxication (eg, alcohol, cocaine, or amphetamines), or noncompliance with antiepileptic drugs.1,2 Wijdicks et al reported that the most common causes of new-onset seizures in an ICU were sedative/opioid withdrawal (33%), severe metabolic abnormalities (33%), and drug intoxication (15%).4 For status epilepticus, Lowenstein et al reported the 2 main etiologies were antiepileptic withdrawal/noncompliance or alcohol.8 Treatment of seizures begins with basic life support, airway management, and close clinical monitoring. Regardless of seizure duration, occurrence should prompt aggressive evaluation for an underlying, correctable
eizures and status epilepticus are common neurologic conditions in various critical care settings.1,2 In general, critically ill patients with seizures/status epilepticus can be divided into 2 broad groups: (a) those who are admitted to the intensive care unit (ICU) for aggressive treatment of continuous or repetitive seizures and (b) those who develop seizures during their critical illness.1 Status epilepticus affects approximately 150,000 Americans every year, and the incidence of new-onset seizures is between 0.8%-3.5% in critically ill patients.3-5 Although status epilepticus is defined by most as >30 minutes of continuous seizure activity or recurrent seizures without return to consciousness, others define status epilepticus as seizures persisting >5 minutes despite aggressive treatment.1,6
From The Ohio State University Medical Center, Columbus, Ohio. Received for publication March 15, 2010; Accepted for publication July 27, 2010. Address correspondence to: Anthony T. Gerlach, PharmD, BCPS, Room 368 Doan Hall, 410 West 10th Ave, The Ohio State University Medical Center, Columbus, OH 43210; e-mail:
[email protected].
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Vitamin B6 Deficiency / Gerlach et al 273
anatomic cause, and while this anatomic evaluation is ongoing, pharmacologic intervention is often required. If the seizure episode resolves quickly and the cause can be determined and corrected, antiepileptic medications may not be required.1 In contrast, seizures lasting >5 minutes or recurring without an intervening period of full neurologic recovery should be treated aggressively.7 Benzodiazepines, such as lorazepam or diazepam, followed by phenytoin or fosphenytoin are first- and secondline therapies.1 Propofol, barbiturates, or midazolam are considered third-line agents.1 Approximately 5% of patients with status epilepticus are refractory to benzodiazepines, phenytoin, and/or barbiturates.9 Other antiepileptic agents such as valproate, levetiracetam, torpiramate, carbamazepine may be considered.1,3,8,9 Patients with refractory status epilepticus may require more aggressive therapy, including intubation, mechanical ventilation, and occasionally pharmacologic paralysis. We report 3 cases of seizures in critically ill patients that were refractory to traditional antiepileptic therapy but responded to pyridoxine therapy. All 3 cases were associated with low serum levels of the active form of vitamin B6, pyridoxal 5′-phosphate (PLP).
Case Presentations Case One A 54-year-old male with no known history of seizures was admitted for hepatic transplantation owing to advanced alcoholic cirrhosis and worsening encephalopathy. His home medications included furosemide, spironolactone, and lactulose. On hospital day 2, the patient underwent orthotopic liver transplantation. The patient’s postoperative course was complicated by intra-abdominal bleeding that required an exploratory laparotomy with evacuation of hematoma on postoperative day 1. On postoperative day 4, the patient received enteral nutrition, which was stopped the following day because of intolerance. The patient developed a new-onset seizure on postoperative day 8, for which he received a loading dose of 1000 mg of intravenous phenytoin, followed by 100 mg of phenytoin intravenously every 8 hours. Because of the patient’s intolerance of enteral feeding, parental nutrition was started, concurrently providing the patient with 6 mg of pyridoxine daily on postoperative day 8. The patient continued to have intermittent seizures, as confirmed by electroencephalography. On postoperative day 12, the serum free phenytoin concentration was 1 mg/L (therapeutic range 0.8-2.2 mg/L), and enteral feeding was restarted. Parenteral nutrition was discontinued on postoperative day 14, and enteral nutrition was advanced to goal rate, providing the patient with 4 mg of pyridoxine daily. Because of continued seizure episodes, the patient’s
phenytoin dose was increased to 350 mg intravenously every 24 hours (free phenytoin concentration
