JAGS

JANUARY 2012–VOL. 60, NO. 1

ACKNOWLEDGMENTS
Conflict of Interest: The editor in chief has reviewed the
conflict of interest checklist provided by the authors and
has determind that the authors have no financial or any
other kind of personal conflicts with this paper.
Author Contributions: All authors participated in
study concept and acquisition of data. NM edited the
manuscript. MC wrote the letter.
Sponsor’s Role: None.

REFERENCES
1. Handke M, Harloff A, Bode C et al. Patent foramen ovale and cryptogenic
stroke: A matter of age? Semin Thromb Hemost 2009;35:505–514.
2. Hagen PT, Scholz DG, Edwards WD. Incidence and size of patent foramen
ovale during the first 10 decades of life: An autopsy study of 965 normal
hearts. Mayo Clin Proc 1984;59:17–20.
3. Overell JR, Bone I, Lees KR. Interatrial septal abnormalities and stroke:
A meta-analysis of case–control studies. Neurology 2000;55:1172–1179.
4. Cabanes L, Mas JL, Cohen A et al. Atrial septal aneurysm and patent foramen ovale as risk factors for cryptogenic stroke in patients less than
55 years of age. A study using transesophageal echocardiography. Stroke
1993;24:1865–1873.
5. Adams HP Jr., del Zoppo G, Alberts MJ et al. Guidelines for the early management of adults with ischemic stroke. A Guideline from the American
Heart Association/American Stroke Association Stroke Council, Clinical
Cardiology Council, Cardiovascular Radiology and Intervention Council,
and the Atherosclerotic Peripheral Vascular Disease and Quality of Care
Outcomes in Research Interdisciplinary Working Groups. Stroke
2007;38:1655–1711.
6. Wu LA, Malouf JF, Dearani JA et al. Patent foramen ovale in cryptogenic
stroke. Current understanding and management options. Arch Intern Med
2004;164:950–956.
7. Lethen H, Flachskampf FA, Schneider R et al. Frequency of deep vein
thrombosis in patients with patent foramen ovale and ischemic stroke or
transient ischemic attack. Am J Cardiol 1997;80:1066–1099.
8. Caputi L, Carriero MR, Falcone C et al. Transcranial Doppler and transesophageal echocardiography: Comparison of both techniques and prospective clinical relevance of transcranial Doppler in patent foramen ovale
detection. J Stroke Cerebrovasc Dis 2009;18:343–348.
9. Kefer J, Sluysmans T, Hermans C et al. Percutaneous transcatheter closure
of interatrial septal defect in adults: Procedural outcome and long term
results. Catheter Cardiovasc Interv 2011 Apr 26. doi: 10.1002/ccd.23119.
[Epub ahead of print].

A CASE OF PHYSICAL AND MENTAL ADVERSE
DRUG REACTIONS ASSOCIATED WITH
LEVETIRACETAM IN POST-STROKE EPILEPSY
To the Editor: A 72-year-old man was admitted with a seizure in March 2011. He had suffered a right total anterior
circulation stroke in September 2010 with left hemiparesis,
facial palsy, and dysphasia. Subsequent successful rehabilitation saw him discharged home, walking independently
with a cane. His GP had started him on low-dose citalopram for reactive depression secondary to his stroke, but he
was cognitively unimpaired.
Admission medications were amitriptyline 25 mg, citalopram 20 mg, indapamide 2.5 mg, digoxin 125 lg, simvastatin 40 mg, and codeine 30 mg. (Warfarin had been
commenced for atrial fibrillation but discontinued after a
fall and subdural hematoma.) Initially, he was postictal
but examination and baseline investigations were normal
other than mild left-sided weakness. A computed tomography (CT) scan showed the old infarction and chronic subdural hematoma. After discussion with neurology, he was

LETTERS TO THE EDITOR

159

started on levetiracetam 250 mg twice daily with the
intention of uptitrating to a treatment dose of 1,500 mg.
Baseline function was quickly regained, and his discharge
was planned.

THE CASE
Over 7 days, he deteriorated, becoming drowsy and incontinent and displaying reduced mobility. Neurological
examination showed increased weakness on the left side
and an Abbreviated Mental Test Score (AMTS) of 6 out of
10, which had been 10 out of 10 previously. Blood tests
were performed and were unremarkable, with no evidence
of sepsis. A repeat CT scan excluded further bleeding or
other pathology, but his AMTS dropped further to 4 out
of 10, and power on neurological examination was now
scored 0 out of 5 on the left side. He developed significant
signs of depression, including reduced eye contact and
interaction and a slow monotonous voice, followed by
frank psychotic symptoms (persecutory delusions and hallucinations). A psychiatry review was requested and concluded that he had depression and acute delirium. After
further neurological review, lamotrigine 25 mg was substituted for levetiracetam.
Four days after stopping levetiracetam, he had significantly improved and was orientated to time and place, his
paranoia had resolved, and he was walking with his cane
and following instructions. His AMTS had returned to 10
out of 10, and power was 3 out of 5 on the Medical
Research Council scale on the left side, and he was discharged home.

DISCUSSION
Levetiracetam can cause dizziness, fatigue, headache, somnolence, and rarely psychiatric disorders.1 It is believed
that these adverse reactions are not related to the speed of
introduction of the drug.2 Having reviewed the current
published literature, reactions in terms of depression and
psychosis such as in this case are well described in adults
and children. There are case reports of psychosis in adolescence3 and childhood.4 Both of these reports showed the
symptoms appearing and resolving over a period of time
similar to that in the current case. Small studies in 2003
reported psychiatric side effects with the use of levetiracetam;5 10.1% of 517 participants experienced psychiatric
side effects. This was again documented in 2007,6 with a
positive association with previous personal and psychiatric
history.
Fewer data were found on psychiatric side effects in
older adults. A few case reports that described delirium
and depression were found7,8 but no significant evidence
or study data. Also, in the current case, the physical deterioration preceded delirium, which appeared the following
week. This has not been previously reported as a side
effect of levetiracetam.
The deteriorations in physical and subsequently mental health all followed commencement of the drug. If this
is assessed as a reaction using the Naranjo criteria,9 the
score is 6 out of 10, indicating a probable adverse drug
reaction. There is no competing explanation for this individual’s deterioration and rapid recovery. The symptoms

LETTERS TO THE EDITOR

JANUARY 2012–VOL. 60, NO. 1

JAGS

started to develop just days after he started levetiracetam
and resolved within 5 days of cessation.
The reduction in mobility and the psychotic symptoms
were most likely due to levetiracetam. Given that there is
not sufficient literature on such side effects involving older
adults and the unique feature of reduced mobility, it was
felt that this warranted highlighting.
Anne Robins, MBchB
Martyn Patel, MBchB
Abul Azim, MBBS
West Suffolk Hospital,
Suffolk, UK

Figure 1. Abdominal computed tomography scan showing
acute cholecystitis.

ACKNOWLEDGMENTS
Conflict of Interest: The editor in chief has reviewed the
conflict of interest checklist provided by the authors and
has determined that the authors have no financial or any
other kind of personal conflicts with this paper.
Author Contributions: Robins: Preparation of manuscript. Patel: Literature search and data collection. Azim:
Lead consultant.
Sponsor’s Role: None.

REFERENCES
1. Wilmore LJ, Wheless JW, Pellock JM. Adverse effects of anti-epileptic drugs.
In: Pellock JM, Dodson WE, Bourgeois BF. Pediatric Epilepsy. New York:
Demos. 2001, pp 343–355.
2. Cereghino JJ, Biton V, Abon-khalil B et al. Levetiracetam for partial seizures. Neurology 2000;55:236–242.
3. Kossoff EH, Bergey GK, Freeman JM et al. Levetiracetam psychosis in children as epilepsy. Epilepsia 2001;42:1611–1613.
4. Youroukos S, Lazopoulou D, Michelakou D et al. Acute psychosis associated with levetiracetam. Epileptic Disord 2003;2:117–119.
5. Mula M, Trimble MR, Yuen A et al. Psychiatric adverse events during levetiracetam therapy. Neurology 2003;61:704–706.
6. Mula M, Trimble MR, Sander JW. Are Psychiatric adverse events of antiepileptic drugs unique entity? A study on topiramate and levetiracetam. Epilepsia 2007;48:2322–2326.
7. Foley KT, Bugg KS. Separate episodes of delirium associated with levetiracetam and amiodarone treatment in an elderly woman. Am J Geriatr Pharmacother 2010;8:170–174.
8. VandeGriend JP, Linnebur SA, Bainbridge JL. Probable Levetiracetam associated depression in the elderly: Two case reports. Am J Geriatr Pharmacother 2009;7:281–284.
9. Naranjo CA, Busto U, Sellers EM et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239–245.

AN UNUSUAL CASE OF CHOLECYSTITIS AND
LIVER ABSCESSES IN AN OLDER ADULT
To the Editor: A 76-year-old man was admitted to the
emergency department (ED) for anorexia, weight loss of
5 kg in 2 months, fatigue, and anhedonia after his sole sister’s death. He had no other complaints: no abdominal
pain, transit abnormalities, fever, or chills. He had a
history of type 2 diabetes mellitus, severe chronic kidney
failure, peripheral neuropathy, hypertension, stage 2 lower
extremity vascular disease, hypothyroidism, and atrial
fibrillation. His regular medication consisted of acetylsalicylic acid, venlafaxine, hydrochlorothiazide, torasemide,
levothyroxine, atenolol, and insulin.

Upon admission, he was awake and responsive but
weak and appeared depressed. Temperature, blood pressure, and heart rate were normal. Abdominal examination
showed active bowel sounds, no tenderness or rebound
tenderness, and no masses. Lower liver border was not
palpable, and Murphy maneuver was negative.
Initial laboratory values showed normocytic anemia
(hemoglobin 10.0 g/dL), leukocytosis with no left shift
(white blood cell count 14,000 cells/lL) and C-reactive protein (CRP) of 246 mg/dL. Electrolytes were normal despite
severe chronic renal failure (calculated creatinine clearance
of 21 mL/min according to the Cockroft formula). Liver
enzymes were normal except for a slightly high gammaglutamyltranspeptidase (76 IU/L, normal <40 IU/L) and
bilirubin (1.75 mg/dL, normal <1.46 mg/dL).
Because of suspected depression, he was referred to a
specialized geriatric ward where a combined follow-up by
geriatricians and psychiatrists is provided. During the following days, he developed no new symptoms but still
refused any food. Biological inflammatory markers
remained high. Liver enzymes remained unchanged except
for normalization of bilirubin values. Chest X-ray was normal. Urine and blood cultures were negative. The dose of
venlafaxine was doubled at admission to 75 mg/d and
thereafter remained unchanged.
Because of persistent inflammation, he underwent a
thoracoabdominal computed tomography scan without
contrast injection. The imaging revealed a dilated gallbladder (9.6 9 5.3 cm in the axial cross-section) with thickened walls, compatible with acute cholecystitis, and
multiple hypodense lesions of liver segments V and VIII,
suggestive of liver abscesses (Figure 1).
Cholecystectomy and surgical drainage were performed. Cultures grew Escherichia coli. He was prescribed
ceftriaxone for 3 weeks. He was discharged 2 months
later, after a normal abdominal ultrasound and major
mood improvement. Signs and symptoms consistent with
normal grieving remained.

DISCUSSION
We present the case of an older adult with acute cholecystitis and multiple liver abscesses, with no suggestive
symptoms except for anorexia and biological signs of
inflammation. Atypical presentation of acute cholecystitis
is frequent in older adults, with 5–25% presenting without

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