Vithyalakshmi Selvaraj

Levetiracetam associated acute hepatic failure requiring liver transplantation: case report

Levetiracetam (LEV) is a widely used antiepileptic medication. With regards to side effect profile, it is considered as one of the safest antiepileptic medication with less than 1 % of patient showing evidence of transient elevation of liver enzymes. To our knowledge, there is only one other case report of acute fulminant liver failure that was attributed to LEV [1]. We hereby report a case of acute hepatic failure that required transplantation associated with LEV and Olanzapine combination treatment. The patient is a 50 year old male with past medical history of seizure disorder secondary to Hashimoto’s encephalopathy, hypertension, chronic obstructive pulmonary disease, tobacco abuse and methamphetamine abuse in remission. The patient reports consuming alcohol occasionally. He was commenced on LEV and methylprednisolone sodium succinate for management of his seizure disorder. The only other medication that was coadministered is olanzapine. Eight weeks after initiation of LEV his liver enzymes were elevated into the hundreds. Twelve weeks after initiating LEV and olanzapine, his alanine transaminase (ALT) was 1456 IU/L, aspartate transaminase (AST) was IU/L and total bilirubin was normal. Consequent to his elevated liver enzymes, olanzapine was discontinued. However, LEV was continued and a liver biopsy was planned. Before the liver biopsy, the patient was admitted to the emergency room with jaundice, nausea, vomiting, and diarrhea. The laboratory work showed ALT of 4800 IU/L, AST in the 7000 IU/L, total bilirubin was 20.4, and his INR was found to be 11. He was admitted to ICU and he displayed the features of encephalopathy such as confusion, poor attention span and memory impairment. Extensive evaluations were carried out to ascertain the cause for the acute hepatic failure. All tests were inconclusive. An abdominal ultrasound ruled out masses, cirrhosis, and Budd-Chiari. Blood tests were negative for Hepatitis B and Hepatitis C. Immuno staining for Cytomegalovirus and adenovirus were negative. There were no viral inclusions present. His liver biopsy demonstrated moderate hepatocellular disarray and patchy confluent areas of hepatocellular necrosis—etiology undetermined. The patient was not on any other medication which could have contributed to his presentation. Liver transplantation was performed immediately as he developed features of hepatic encephalopathy. The hepatologists concluded that LEV might have led to this acute hepatic failure as no other etiology could be found which was discontinued before transplantation. Our patient clearly demonstrates signs of drug induced liver failure. Though methamphetamine and alcohol abuse can cause acute liver failure, his liver enzymes were in the normal range during his routine lab investigation before initiating LEV and olanzapine therapy. The question of which of the two drugs LEV or olanzapine caused the adverse drug reaction is more difficult to resolve because & Vithyalakshmi Selvaraj vidyaselvaraj@creighton.edu

Escitalopram-Induced Amenorrhea and False Positive Urine Pregnancy Test

Escitalopram is a selective serotonin reuptake inhibitor antidepressant approved by the Food and Drug Administration for the treatment of major depressive disorder and generalized anxiety disorder. A 34-year-old female patient with major depressive disorder developed amenorrhea and had a false-positive urine pregnancy test after initiation of escitalopram treatment. To our knowledge, no published case report of amenorrhea and false-positive urine pregnancy tests in women taking escitalopram exists. This case report suggests that women of child-bearing age should be carefully monitored for amenorrhea while they are on an antidepressant treatment regimen.

Urinary Incontinence due to Overactive Detrusor Muscle: A Rare Side Effect of Venlafaxine

We report a case of reemergence of urinary incontinence (UI) in a patient with benign prostatic hyperplasia (BPH) after starting treatment with venlafaxine who was stabilized on tamsulosin and finasteride for about 6 years. A 66-year-old Caucasian male with prior history of major depressive disorder developed UI within a week of starting venlafaxine 75 mg per day. He described symptoms in the form of involuntary leakage of urine both during the day and at night. His symptoms of UI resolved after stopping the venlafaxine. To the best of our knowledge, there are only four case reports of venlafaxine induced urinary incontinence which have been published.

A case of cocaine-induced myopathy

To the Editor: Cocaine use is one of the most common causes of drug-induced medical problems in the United States.1 Cocaine can cause muscle injury ranging from asymptomatic creatine phosphokinase (CK) elevation to massive rhabdomyolysis with acute renal failure.1 In the following case report, we describe a unique clinical scenario of a patient presenting with myalgia, muscle weakness, and elevated CK levels, which is suggestive of an acute-on-chronic pathology affecting the skeletal muscles. Case report. Ms A, a 35-year-old African American woman, presented to the emergency department due to complaints of “hurting all over” and “weakness.” On the day of admission, the patient had a urine drug screen positive for cannabinoids and cocaine. She has a significant past medical history that included bipolar disorder, posttraumatic stress disorder, and cocaine dependence. She reported having stopped trazodone, lithium, and fluoxetine for the previous 3 weeks because she ran out of them. She had also been smoking marijuana on the day prior to the admission, reporting that she usually abused cannabis when she ran out of her psychiatric medications. During assessment, Ms A was mildly confused and could not provide a detailed history. She reported normal mood and no neurovegetative symptoms. The patient denied suicidal ideation or homicidal ideation. She endorsed auditory hallucinations for the past 2 days, but no visual hallucinations. She was oriented to place and person but not to time. She denied manic or hypomanic symptoms. On neurologic examination, Ms A had strength of 4+/5 in both upper and lower extremities and significant tenderness to muscle palpation. She had decreased sensation to both temperature and touch in the upper and lower extremities bilaterally. She also had decreased vibratory sensation bilaterally in the lower extremities. The ankle reflex was 2/4, and the knee reflex was 1+/4; upper extremity reflexes were 2+/4 bilaterally and appeared to be symmetrical. The rest of the neurologic and systemic examination revealed no abnormalities. There were no other signs or symptoms of acute cocaine intoxication. The biochemical profile was as follows: serum CK level was 605 U/L at admission and decreased to 116 on the fifth day of admission. The lithium level was less than 0.1 mmol/L. The patient’s urine drug screen was positive for marijuana and cocaine. Findings of the metabolic panel and hemogram were within normal limits. The computed tomography scan of the brain revealed no abnormality. Findings of the electromyography/nerve conduction velocity study, which was performed on the third day after admission, were normal. On the fifth day after admission, there was a significant improvement in her condition, with no weakness or muscle tenderness. The CK values returned to normal. More than 14 million people worldwide abuse cocaine.2–4 Cocaine acts by blocking the presynaptic reuptake pump as well as enhancing neurotransmission of monoamines such as dopamine, norepinephrine, and serotonin in the central and peripheral nervous systems.4 Cocaine is unique among stimulant drugs in having a second action of blocking voltage-gated membrane sodium ion channels. This action accounts for its local anesthetic effect and may contribute to cardiac arrhythmias.4 About 24% of cocaine users have been reported to develop muscle injury and/or damage. Many of these instances are not predictable from history or physical examination, making laboratory evaluation essential.1 The significance of the biochemical profile in patients with possible drug use should be highlighted.1 We reviewed the literature on cocaine-induced muscle injury.4–10 In one report, at least 5% of cocaine users presenting to one emergency department had evidence of muscle injury based on CK elevation.7 Muscle injury in cocaine use can be caused by multiple pathophysiologic mechanisms.4–10 It may result from the markedly increased sympathomimetic activity.4 Severe arterial vasoconstriction that can cause skeletal muscle ischemia and infarction in the same manner as cocaine-induced vasospasm causes myocardial, cerebral, skin, or digital infarction.4 The underlying cellular process of rhabdomyolysis in cocaine addiction is due to the ischemic insult caused by impairment of muscle adenosine triphosphate (ATP) production.6–8,10 Depletion of ATP results in loss of membrane transporter function with sarcolemmal injury. Finally, myocyte membrane rupture results in the release of intracellular components, including the isoenzyme CK, myoglobin, aldolase, lactate dehydrogenase, potassium, phosphates, urea, purines, and carbon anhydrase,6–8,10 producing the classic laboratory profile of rhabdomyolysis. An alternative mechanism is cocaine-induced inhibition of the reuptake of catecholamines at α-adrenergic receptors, which in turn leads to high intracellular calcium levels in muscle cells and subsequent cell damage and muscle damage.5–8 Cocaine users with muscle injury usually present to emergency departments with other problems, including delirium, fever, seizure, cardiovascular collapse, or chest pain, and are found incidentally to have muscle involvement.4–8 In some cases, however, myalgia is an important presenting symptom. Muscle injury can occur after oral or intranasal cocaine use, but may be more common after intravenous use or after smoking the alkaloid freebase (crack cocaine) because of the more rapid effect and higher blood levels of the drug achieved via those routes. Muscle injury can occur after a one-time use of the drug or after repeated use.4–10 The onset of muscle involvement is usually within hours after drug administration. Affected patients usually present with proximal muscle weakness, which is more prominent in the lower than in the upper extremities.1,4–10 The patients with the highest CK levels are at greatest risk for acute myoglobinuric renal failure. These individuals usually have additional risk factors for rhabdomyolysis resulting from cocaine use, including marked fever, agitation, hypotension, seizures, coma, or concomitant use of heroin, amphetamines, or phencyclidine, which are the other drugs associated with muscle damage.1,4–10 The biochemical test in hospital has a great importance in the early diagnosis and treatment of cocaine-induced myopathy. Creatine phosphokinase elevation ranges from a few times normal to marked elevations of greater than 50,000 U/L.1,4–10 The normal CK range is 10–150 U/L. In one report, for example, the mean maximum elevation of CK in 39 patients with cocaine-associated myopathy was 12,187 U/L.1,4–10 Electromyography and nerve conduction studies will show myopathic changes along with axonal polyneuropathy that could be asymptomatic with a clinical presentation consisting of mild sensory symptoms and decreased deep tendon reflexes.1,4–10 Muscle biopsy shows vacuolar changes in muscle cells that are seen best on frozen sections, since the vacuoles are often damaged by paraffin fixation. The vacuoles are usually shown to be of lysosomal origin by special stains and electron microscopy.1,4–10 Our report of a patient who presented with elevated CK levels with weakness, myalgia, and sensory symptoms represents a seldom-reported clinical scenario. Our case is suggestive of the acute-on-chronic nature of the muscle pathology. The patient’s progress and the return of CK values to within normal limits by the fifth day after admission support the rapid recovery made by the patient. Cocaine intoxication frequently causes a clinical syndrome that is suggestive of increased central nervous system and sympathomimetic activity,1,4–10 but in this case report the clinical findings were limited to myopathy with laboratory evidence of mild rhabdomyolysis. Our findings suggest that patients with chronic cocaine abuse have a decreased threshold for muscle injury and rhabdomyolysis. Hence, it could be construed that any other accompanying precipitant of muscle injury in a chronic cocaine abuser can facilitate myopathic damage. It is important that cocaine abuse be included as one of the differential diagnoses in patients presenting exclusively with acute myopathy.

Transient ischemic attack associated with trazodone therapy: a case report.

To the Editor: Trazodone is a tetracyclic antidepressant commonly prescribed for insomnia. We report the emergence of neurologic symptoms suggestive of transient ischemic attack (TIA) in a patient following the initiation of trazodone. To the best of our knowledge, no reports of such an occurrence have been published. Case report. Mr A, a 40-year-old man with a history of mood disorder not otherwise specified (DSM-IV criteria), was admitted to a psychiatric inpatient unit in 2010 for suicidal ideation and depressed mood. He developed depressive symptoms about a year prior to this presentation when he got laid off from his job of over 4 years. Mr A had attempted suicide twice in the preceding year (the first time, he attempted to asphyxiate himself, and the second time, he overdosed on hydrocodone tablets) and was hospitalized at a psychiatric inpatient unit on both occasions. During his most recent admission (2 months prior to this presentation), he was started on fluoxetine treatment, which he discontinued after discharge. The stressors precipitating his current admission included homelessness, unemployment, financial constraints, and impending divorce. He endorsed depressed mood, decreased interest, poor energy, sleep difficulties, poor appetite, and suicidal ideation with a plan to stab himself. He denied auditory or visual hallucinations, psychotic symptoms, and drug or alcohol abuse. He had experimented with cocaine and marijuana during high school. There was no evidence of homicidal ideation or delusions. His medical history was significant for irritable bowel syndrome and tinnitus. Findings of his physical examination were unremarkable, and he was not taking any medications at the time of presentation. He did not tolerate valproic acid and citalopram initiated during this admission. He tolerated lithium carbonate 300 mg 3 times daily but complained of insomnia. He reported a past history of nonresponse to zolpidem. Five days after the admission, he was started on trazodone 50–100 mg at bedtime as needed for insomnia. Twelve hours later, he developed slurred speech, neck pain, facial tingling sensations, vertigo, dizziness, lack of coordination, muscle weakness, blurred vision, and diplopia. His serum lithium level was 0.5 mEq/L. An immediate computed tomography scan of the head was performed, which was negative for hemorrhage or ischemia. He was unable to walk and required wheelchair support. We discontinued trazodone, which led to rapid resolution of all his neurologic symptoms, except for his dizziness, within 24 hours. Neurologic examination on day 2 revealed no abnormalities, but the neurologist recommended magnetic resonance imaging of the brain and angiography of the neck to rule out stroke; findings of both tests were within normal limits. He received a single 325-mg dose of aspirin and was started on meclizine 25 mg/d. His dizziness improved on day 2 after cessation of trazodone therapy. We decided to continue lithium since the serum lithium level was low and all his symptoms resolved. A temporal relationship between drug initiation and emergence of neurologic symptoms and, most importantly, complete remission on discontinuation suggests TIA possibly as an adverse event following trazodone use. The literature shows that serotonergic drugs cause cerebral vasoconstriction. Paroxetine, a selective serotonin reuptake inhibitor (SSRI), has caused TIA and stroke.1–3 It was postulated that paroxetine and other SSRIs may result in changes of the vasculature and subsequent ischemic events in predisposed patients.1 Normally, serotonin secreted by platelets stimulates 5-HT2A receptors, which mediate vasoconstriction. This is counterbalanced by the release of the vasodilator nitric oxide upon serotonin stimulation of endothelial 5-HT1 receptors. In addition to their serotonergic activity, SSRIs such as paroxetine weakly inhibit norepinephrine reuptake and nitric oxide production, which increases the risk of cerebrovascular events.1 The combination of lithium, trazodone, and paroxetine as well as the combination of lithium, trazodone, and bupropion has been implicated in stroke.2 It is possible that the combination of lithium and trazodone in our patient has a role in the evolution of vasoconstriction, given their serotonergic effects. Similarly, ergot derivatives, amphetamine, and cocaine cause stroke due to their sympathomimetic and serotonergic effects.4 Trazodone possibly increases the serotonin release from platelets by its antagonistic and reuptake inhibitor effect at serotonin receptor, which may cause vasoconstriction. Trazodone has an effect on vascular and coagulation system like that of SSRIs, which may implicate that trazodone is associated with cerebrovascular accidents. Our case emphasizes that when vasoconstriction is suspected, serotonergic drugs should be discontinued.