Transcript WARNING: Side effects may include…

WARNING: Side effects may include…
A Pictorial Review of Iatrogenic Drug Related
Complications in Neuroimaging
Rebecca Dumont Walter, MD
Daniel Chow, MD
Christopher Filippi, MD
David Wilson, MD
Disclosures
The authors have no disclosures
Background
Epidemiology
Adverse drug reactions are unfortunately common,
occurring in up to 15% of patients.
Expected to become more frequent in the face of
increasing polypharmacy.
Background
Side effects may include…
Many of these complications may adversely affect the
central nervous system (CNS) and may be seen with
both emergent inpatient and routine outpatient
settings.
These reactions represent a diagnostic challenge
for referring clinicians given the variability in
presentation and timing.
Purpose
It is important for the neuroradiologist to recognize
potential iatrogenic complications.
The purpose of this educational exhibit is to present a
pictorial review of imaging findings of CNS drugrelated complications.
Acetaminophen (Tylenol)
Posterior Reversible Encephalopathy Syndrome
Acetaminophen (Tylenol) has an excellent safety profile
when administered at the proper dose.
With misuse, hepatic toxicity may ensue.
• 50,000 cases of toxicity due to acetaminophen
• Second most common cause of liver failure requiring
transplantation.
Posterior reversible encephalopathy syndrome may result
from acetaminophen induced hepatorenal failure due to
loss of normal cerebrovascular autoregulation
Acetaminophen (Tylenol)
Posterior Reversible Encephalopathy Syndrome
58 year old female presenting with seizure after attempted suicide with
acetaminophen.
Axial images through the brain show confluent FLAIR hyperintensity
throughout the posterior parietal and occipital subcortical and deep
white matter, in a distribution typical for PRES.
Vaccinations
Acute Disseminated Encephalomyelitis (ADEM)
Vaccine related ADEM is rare, accounting for < 5% of
ADEM cases.
• Estimated between 1 to 2 per 1,000,000 vaccinations
More frequently associated with primary vaccination
(rather than revaccination)
Associated with multiple vaccines, including flu, dPT,
MMR, and hepatitis B.
Reported to occur within 1 day to 3 weeks of vaccination.
Vaccinations
Acute Disseminated Encephalomyelitis (ADEM)
5 year old presenting with
myelopathy 3 weeks after
influenza vaccination
Sagittal T2 (left) and T1
post contrast (right) images
through the spine
demonstrate expansile T2
hyperintensity with intense
contrast enhancement
drom the mid thoracic cord
through the level of the
conus.
Vaccinations
Acute Disseminated Encephalomyelitis (ADEM)
Axial FLAIR (left, middle) and T1 post contrast images through the brain
demonstrate multifocal areas of white matter FLAIR hyperintensity, some of
which demonstrate patch enhancement.
Tacrolimus (Prograf)
Leukoencephalopathy
Tacrolimus (FK-506) is an immunosuppressant used
following solid organ transplantation.
Adverse reactions:
• Minor : Headache & Tremor
• Major: Leukoencephalopathy (1 – 6%)
Leukoencephalopathy is reported to occur within 3 months
of transplantation.
Good prognosis, most reporting recovering after dose
reduction or cessation.
Tacrolimus (Prograf)
Leukoencephalopathy
Young child on Tacrolimus
therapy following liver
transplant with altered
mental status.
Labs notable for high levels
of tacrolimus.
Patient made full recovery
following cessation of
medication.
Axial diffusion weighted image
of the brain shows multifocal
abnormal cortical restricted
diffusion.
Total Parenteral Nutrition (TPN)
Manganese Deposition
TPN is administered intravenously to patients with GI tract
dysfunction, such as short bowel syndrome.
Intrinsic T1 hyperintensity in the bilateral lentiform nuclei
has been reported in patients receiving long term TPN,
which is thought to be due to deposition of the
paramagnetic trace metal manganese from dysregulation
of autoregulatory mechanisms in the GI tract and liver.
Similar findings are seen in patients with cirrhosis, portal
vein occlusion, or occupational exposure (i.e. welders).
Imaging findings typically resolve following cessation of
TPN, or cessation of manganese exposure.
Total Parenteral Nutrition (TPN)
Manganese Deposition
61 year old female on TPN for 3 years due to complications related to vagotomy,
MRI was obtained for persistent headaches.
T1 (left) and T2
(right) weighted
images through
the basal ganglia
demonstrate
intrinsic T1
hyperintensity of
the lentiform
nuclei bilaterally.
Natalizumab (Tysabri)
Progressive Multifocal Leukoencephalopathy (PML)
Natalizumab is a monoclonal antibody used to treat
patients with relapsing-remitting multiple sclerosis, which
has been associated with PML.
PML is a rare but devastating complication of a variety of
immunosuppressed states, in which the JC virus infects
oligodendrocytes and causes widespread demyelination.
Prognosis is generally poor with progressive neurologic
decline, leading to coma and death. Treatment with
HAART may prolong survival.
Natalizumab (Tysabri)
Progressive Multifocal Leukoencephalopathy (PML)
61 year old female on TPN for 3 years due to complications related to vagotomy,
MRI was obtained for persistent headaches.
FLAIR (left) image
demonstrates confluent
FLAIR hyperintensity
throughout the frontal
and parietal white
matter with
involvement of the
subcortical U fibers
with patchy reduced
diffusion on DWI
(right).
Levamasole (Ergamisol)
Fulminant Demyelination
Originally used as an anthelmintic to treat worm
infestations.
Withdrawn in 1999 within the US due to multiple
complications, including:
• Agranulocytosis and an immune-mediated vasculitis
• Multifocal inflammatory leukoencephalopathy
However, > 90% of cocaine is currently adulterated with
Levamasole. Therefore, recognizing neurotoxicity related
to Levamasole remains relevant.
Levamasole (Ergamisol)
Fulminant Demyelination
Axial FLAIR demonstrates innumerable hyperintense lesions in the subcortical
white matter, which are ovoid shaped and in a perivenular distribution. Many of
these lesions demonstrate reduced diffusion and characteristic incomplete ring
enhancement
Ifosfamide (Ifex)
Wernicke Encephalopathy
Ifosfamide is an alkylating chemotherapy agent, used to
treat germ cell tumors, lymphgoma, and other solid organ
cancers.
Wernicke-like encephalopathy is a known complication,
presenting in 10-30% of patient.
Mechanism thought related to its metabolite,
chloracetaldehyde, which impairs thiamine function.
Presents within 2-48 hours.
Generally reversible.
Ifosfamide (Ifex)
Wernicke Encephalopathy
Axial FLAIR MR image demonstrates increased signal intensity involving
the thalami bilaterally (left) as well as increased signal intensity in the
mammillary bodies, bilaterally (right).
Metronidazole (Flagyl)
Neurotoxicity
Metronidazole is used to treat a variety of bacterial and
protozoal infections.
Can rarely lead to CNS toxicity, including:
• Cerebellar dysfunction
• Altered mental status
• Seizures
Nearly all cases show FLAIR hyperintense lesions in the
cerebellum on imaging, particularly the dentate nucleus,
in addition to the corpus callosum and brain stem.
Good prognosis following cessation of therapy, with 3%
reported to experience permanent cognitive impairment.
Metronidazole (Flagyl)
Neurotoxicity
20 year old female profoundly altered after receiving Flagyl for diarrhea
Axial FLAIR images demonstrate abnormal hyperintensity in the vestibular nuclei,
periaqueductal gray matter, and splenium of the corpus callosum.
Phenytoin (Dilantin)
Diffuse Cerebellar Volume Loss
Phenytoin is a well-known and often-prescribed
anticonvulsant.
Cerebellar atrophy due to loss of Purkinje cells can be
seen with both acute and chronic phenytoin use, as well
as long-standing uncontrolled seizure disorders.
Patients may report cerebellar symptoms (nystagmus,
diplopia, dysarthria, ataxia) or be asymptomatic.
Conclusion
No medication or therapy is free from side
effects, and iatrogenic effects of medications
remains a cause of morbidity and mortality in
both inpatient and outpatient settings.
Knowledge of these effects is important for
recognition and diagnosis of potentially severe
CNS complications.
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
Mettananda S. Posterior reversible encephalopathy syndrome in a survivor of valproate-induced
acute liver failure: a case report. J Med Case Rep. 2013; 7: 144
Machicado JD. Acute disseminated encephalomyelitis following seasonal influenza vaccination in
an elderly patient. Clin Vaccine Immunol. 2013 Sep;20(9):1485-6.
Lee KC, Ladizinski B, Federman DG. Complications associated with use of levamisolecontaminated cocaine: An emerging public health challenge. Mayo Clin Proc. 2012;87(6):581-586.
doi:10.1016/j.mayocp.2012.03.010.
Mirowitz SA, Westrich TG. Basal ganglia signal intensity alterations: reversal after
discontinuation of parenteral manganese administration.Radiology 1992;185:535–36
Hook CC, Kimmel DW, Kvols LK, et al. Multifocal inflammatory leukoencephalopathy with 5fluorouracil and levamisole. Ann Neurol. 1992;31(3):262-267. doi:10.1002/ana.410310306.
Wu V-C, Huang J-W, Lien H-C, et al. Levamisole-Induced Multifocal Inflammatory
Leukoencephalopathy. Medicine (Baltimore). 2006;85(4):203-213.
doi:10.1097/01.md.0000230250.95281.60.
Chow KM, Szeto CC. Cerebral atrophy and skull thickening due to chronic phenytoin
therapy. CMAJ 2007;176(3):321–323.
Crooks R, Mitchell T, Thom M. Patterns of cerebellar atrophy in patients with chronic epilepsy: a
quantitative neuropathological study. Epilepsy Res 2000;41(1):63–73.
De Marcos FA, Ghizoni E, Kobayashi E, Li LM, Cendes F. Cerebellar volume and long-term use of
phenytoin. Seizure2003;12(5):312–315.