CPC

1
CPC7February 28, 2006

• Victor C. Urrutia, MD
• Assistant Professor of Neurology
• Cerebrovascular Division
• Johns Hopkins University

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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

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Case summary

• History of retinal vein thrombosis, hypertension,
  oral thrush and Lupus related serositis.
• Blood pressure120/55, temperature 37.5C.
• 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.

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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

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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
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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

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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

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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

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Focal/Space Occupying Lesion

• Tumor
• Abscess
• Infarct
• Hemorrhage
• Hydrocephalus
• Edema

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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.

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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

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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

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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

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Differential diagnosis3

• 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

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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

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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
• 0.431,000,000 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

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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
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Final Diagnosis

• Primary CNS Lymphoma

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Recommendation

• Biopsy of the lesion