Transcript CPC#7 February 28, 2006

CPC#7
February 28, 2006
Victor C. Urrutia, MD
Assistant Professor of Neurology
Cerebrovascular Division
Johns Hopkins University
Case summary
• 59 y/o Korean woman
• “Chief complaint”: Change of mental status
• 4 week history of severe headaches and
increasing “confusion”
• Confusion described as: Somnolence and
difficulty speaking
• Diagnosed with proliferative and membranous
glomerulonephritis a year earlier and treated
with Prednisone and Mycophenolate Mofetil
Case summary
• History of retinal vein thrombosis,
hypertension, oral thrush and Lupus
related serositis.
• Blood pressure:120/55, temperature:
37.5°C.
• She was lethargic, not oriented to time,
had a right Hemiparesis and bilateral up
going toes. A MMSE was done 18/30. No
nuchal rigidity.
Localization
• An altered mental state localizes the
problem to a lesion affecting a structure of
the reticular activating system or its
projections to the cortex bilaterally
• The RAS is localized in the brainstem
Reticular Activating System
Cortex
Thalamus
Non-specific
thalamic
nuclei
1.Midline
2.Intralaminar
3.Reticular
4.Ventral
anterior
Peri-acqueductal
gray matter
Dorsal pons
Lateral medulla
Four basic mechanisms
• Meningeal irritation
– Meningitis, subarachnoid hemorrhage
• Focal/Space occupying lesion
– Tumor, abscess, infarction, hematoma,
hydrocephalus
• Metabolic/Toxic
– Drugs, renal, liver, fever, hypoxia, acid/base
• Seizures
Our case
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Right hemiparesis
No major metabolic abnormalities
No nuchal rigidity
No clinical history of seizures
• By examination her change in mental
status falls into the “Focal/Space
Occupying Lesion” category
History of Present Illness
• The history of present illness should give
us the “process”
• Her symptoms started 4 weeks ago with
headache and worsening mental status
with difficulty expressing herself
• There is a subacute history of
progression and onset of symptoms
Focal/Space Occupying Lesion
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Tumor
Abscess
Infarct
Hemorrhage
Hydrocephalus
Edema
CNS Involvement in Lupus
• Involvement of the CNS is a major source of
morbidity and mortality in Lupus
• 70% of patients with SLE have neurological
problems at some point of their course
• Neuropsychiatric disorders are the most
common
• Focal involvement is often thrombotic in the form
of stroke, dural sinus thrombosis, cerebral
vasculitis. A prothrombotic state due to
antiphospholipid antibodies is a major cause.
Differential diagnosis
• Lupus Cerebritis
– Seizures, psychosis
• Dural Sinus Thrombosis
– Headache, focal findings, seizures, alteration of
consciousness, history of retinal vein thrombosis
• Infection (Encephalitis, Meningitis or Abscess)
– Our patient does not have fever, nuchal rigidity
• Tumor
MRI
• Bilateral ring enhancing
lesions in the basal
ganglia
• Vasogenic edema
• DWI/ADC does not
suggest acute infarction
• Torcula opacifies normally
in the T1 images with
gadolinium
FLAIR
T1+C
DWI
ADC
Differential diagnosis #2
• Lupus Cerebritis
– Seizures, psychosis
• Dural Sinus Thrombosis
– Headache, focal findings, seizures, alteration of
consciousness
• Infection (Encephalitis, Meningitis or Abscess)
– Our patient does not have fever, nuchal rigidity
– Opportunistic infections: Toxoplasmosis
• Tumor
– Primary CNS Lymphoma
Differential diagnosis#3
• Toxoplasmosis
• Abscess
– Typical: Staphylococcus or Streptococcus
– Atypical: Cryptococcus, Nocardia, Listeria,Mycobacterium)
– No fever or elevated white count
• Primary Brain Tumor
– CNS Lymphoma
• Metastatic brain tumor
– Not likely. Metastasis are usually localized in the gray/white
junction. There is nothing in the history suggesting a primary
CNS Toxoplasmosis
• This is a common disease world wide
• Asymptomatic in an immunocompetent
host
• In immunocompromized hosts:
– Diffuse encephalopathy
– Meningoencephalitis
– Mass lesion
• Usually localized in the basal ganglia
Primary CNS Lymphoma
• Reported in Transplant recipients, and two
reports in patients treated for autoimmune
conditions are in the literature
• 1-6% of malignant tumors of the CNS
• 0.43:1,000,000 per year
• Location is most commonly in the hemispheres,
followed by the Corpus Callosum and last in the
basal ganglia
• Usually bilateral
• Ring enhancing lesion with prominent vasogenic
edema
Mycophenolate Mofetil
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•
Cellcept
Immune suppressant. A selective, noncompetitive, and reversible inhibitor
of inosine monophosphate dehydrogenase (IMPDH). Mycophenolic acid
(MPA) is the active metabolite. It acts by inhibiting the de novo synthesis
pathway of guanosine nucleotides
T and B lymphocytes are critically dependent for their proliferation on de
novo synthesis of purines, while other cell types can utilize salvage
pathways, MPA has potent cytostatic effects on lymphocytes.
MPA prevents the glycosylation of lymphocyte and monocyte glycoproteins
that are involved in intercellular adhesion of these cells to endothelial cells,
and may inhibit recruitment of leukocytes into sites of inflammation and graft
rejection
Suppression of cell-mediated immunity in organ transplant patients is
associated with an increased risk of benign and malignant
lymphoproliferative disorders, lymphomas, and skin cancers. Lymphomas
have developed in humans treated with mycophenolate, although a
definite causal relationship has not been established. Other neoplasms
have been reported infrequently.
Extracted from: USP DI® Drug Information for the Health Care
Professional
Final Diagnosis
• Primary CNS Lymphoma
Recommendation
• Biopsy of the lesion