Case Presentation: 46-year-old lady with past medical history of polysubstance abuse, seizures, HIV on treatment, mood disorder on quetiapine/valproic acid was brought to hospital by a family member for drowsiness. They reported that she has been drowsy since one week and had history of recent heroin use. Patient intermittently awake could give history of her right wrist being painful with redness of skin for one week. She denied any fever, chills, recent overdose as per her, alcohol use. She had prior history of admissions in inpatient detox unit for opiates and benzodiazepines. On the physical exam she was lethargic, confused, intermittently agitated, impaired memory/attention, concentration, dysarthric speech. Pupils were dilated, and skin examination showed right-hand dorsal surface erythema, edema, and warmth with the area extending up to the wrist. There were no cranial nerve/motor deficits. Complete blood count, liver function test, kidney function test and serum electrolytes were normal except for hypokalemia of 3 mMol/L (3.5 -4.5 mMol/L). Urine drug screen positive for cocaine and marijuana. Ethanol, toxic alcohol levels, acetaminophen and salicylate were negative. Valproate levels were normal 70 ug/mL (50-100 ug/mL). Computerized Tomography of the head did not show any acute intracranial pathology. HIV RNA titers were undetectable, CD4 count 984 /cu mm. She was started on broad spectrum antibiotics, and consults to Neurology and Psychiatry were placed. Electromyography was done which showed generalized theta continuous slowing with occasional intermittent delta slowing seen suggestive of diffuse encephalopathy. Levetiracetam was started given her history of provoked seizures in the past and broad-spectrum antibiotics for cellulitis of right hand. Clinical Opiate Withdrawal Scale (COWS) protocol initiated along with Clinical Institute Withdrawal Assessment for Alcohol (CIWA) score for possibility of GABA withdrawal. Valproic acid and quetiapine were held and as there was poor clinical improvement in one-day ammonia levels was sent and found to be elevated at 122 uMol//L (9-33 uMol/L). L-carnitine supplementation was started, and ammonia levels returned to normal five days later. Valproate was restarted on the seventh day when somnolence abated at 500 mg twice daily dosing along with the continuation of L-carnitine. Magnetic resonance imaging of the hand was done and showed tenosynovitis along with cellulitis. The patient got clinically better and was discharged to nursing home with three weeks of antibiotics.
Discussion: The mechanism of valproate induced hyperammonemia is poorly understood, most recent theory suggesting that propionic acid, a metabolite of VPA disrupts the urea cycle (2). VPA raises the ammonia levels by causing depletion of carnitine essential in fatty acid oxidation pathway (2). There is no relationship between dosing and severity of the VHE. Currently there is no consensus for the treatment of hyperammonemia in such cases and supplementation of L-carnitine is reasonable in patients with coma, severe hepatotoxicity and VHE. (3, 4)
Conclusions: Although it is common for patients to develop high ammonia levels, it will require high index of suspicion to prevent disastrous consequences in patients who do not have liver dysfunction and have confounding factors to bias clinicians’ evaluation of encephalopathy like this patient with mood disorders, drug use and infection.