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 Thalamus Non-specific thalamic nuclei 1.Midline 2.Intralaminar 3.Reticular 4.Ventral anterior Peri-acqueductal gray matter Dorsal pons Cortex 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 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 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

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 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