Transcript Morning Report

Morning Report
Jieli Li
05/17/05
Chief Complaint
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AMS, HA, n/v, left-sided weakness
HPI
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59 y/o male with h/o DM, etoh abuse, htn, and
recently diagnosed with poorly differentiated gastric
Ca was brought in by wife with AMS, left sided
weakness, n/v, and HA.
Per wife, everything began within the last 24 hrs.
She noticed waxing & waning confusion, left
arm/leg weakness, speech difficulty. Also with HA,
neck pain & light sensitivity. + n/v 3-4x (food, no
blood). No constipation/diarrhea. Last drink was
about 5 days ago.
No f/c/CP/SOB/fall/trauma
HPI cont.
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During interview, pt had an episode of sudden head
and arm jerking movement for a few seconds, after
which pt appeared more confused/agitated, unable to
answer any questions.
PMH
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DM with neuropathy and retinopathy
Htn
Etoh abuse
Gastric Ca (recently diagnosed)
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EGD - diffuse thickened gastric folds throughout the
stomach with biopsy findings consistent with poorly
differentiated gastric adenocarcinoma
Abd CT - marked thickening and heterogeneity of the
gastric wall and regional LAD
GERD
History cont.
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All:
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NKDA
Meds:
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Benazepril 5 qd
Insulin NPH 20u qAM 20u qHS
Loratadine 10 qd
Metformin 500 bid
History cont.
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SH:
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Former welder, on disability b/c of DM, back pain, lives
with wife
Etoh – 12-24 beers/day until 1 month ago, then started
drinking 1 bottle of wine per day, last drink 5 days PTA
Tobacco – quit 10 yrs ago
Drugs – none per wife
FH:
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Unable to obtain
Physical Exam
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VS – T: 97.6, P: 91, BP: 129/64, RR: 20
Gen – thin hispanic male lying in bed, agitated following
jerking movements. Fluctuating cooperation with exam.
HEENT – NC/AT, anicteric, no oral lesions
Neck – + nuchal rigidity, unable to touch chin to chest, c/o
significant pain with this maneuver
Heart – rrr, s1s2, no m/r/g
Lungs – cta bilaterally
Abd – Soft, NT/ND, no mass appreciated, +BS
Ext – no e/c/c
PE cont.
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Neuro
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Confused and agitated, oriented to name only. Unable to
follow commands consistently. Mild left facial droop.
Babinsky down-going bilaterally. Withdraws all 4
extremities with noxious stimuli. Mild weakness of LLE
and decreased movement and dexterity of LUE.
Labs
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LP results:
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CSF opening pressure – 15
CSF chemistry – glucose 15 (low), protein 122
CSF cell count – 10 WBC, 90% lymphs, 1 RBC, 45%
atypical cells, sent for cytology
CSF cytology - “possible malignant cells vs. reactive
pleocytosis”.
Labs cont.
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14
6.7
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237
41.2
MCV 99.2, 80% neutrophils
129
89
13
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204
3.0
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26.5 0.9
Ca 9.8, Mg 1.6, P 2.6
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Alk phos 191
ALT 22
Total bili 1.8
U. tox – neg
Etoh - < 5
Troponin < 0.1
INR 1.1, PTT 25
UA - neg
Head CT
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Mild microvascular deep white matter ischemic
disease
No cortical infarct, mass, bleed, or midline shift
6 mm calcification in right parietal white matter.
May represent old cysticercosis vs. vascular
malformation such as cavernous hemangioma. No
surrounding edema or mass effect.
MRI/MRA of Brain
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Mild microvascular deep white matter ischemic
disease
Small focus of hypodensity in the right parietal
white matter, consistent with the focus of
calcification seen on CT
No acute infarct, early subacute ischemia, mass, or
bleed.
Unremarkable MRA
Hospital Course
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Neurology evaluated pt in ER. Pt was admitted to
HICU, loaded on dilantin and started on banana bag
and seizure precautions. He was initally started on
ceftriaxone, vanco, ampicillin, acyclovir and
dexamethasone but all cx’s and serologies came back
negative. Per ID recs all abx and antivirals were
stopped.
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Repeat MRI 1 week later showed “abnormal diffuse
dural and leptomeningeal enhancement of the
cerebrum and cerebellum consistent with
leptomeningitis”
Hospital Course cont.
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Cytology from repeat LP showed malignant cells
consistent with metastatic poorly-differentiated
gastric adenocarcinoma
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Pt’s symptoms improved within days without any
treatment. His n/v/HA resolved and so did his leftsided weakness. No further seizure episodes while
in house. Heme/onc was consulted and gave 1 dose
of intrathecal methotrexate for carcinomatous
meningitis. Pt was discussed in Tumor Board. On
discharge, pt was AAO x 3, but confused about
details.
Hospital Course cont.
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Pt was readmitted 1 month later from home hospice
for AMS, but again mental status improved without
intervention.
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Pt received another dose of intrathecal methotrexate
on GMED and was then discharged back to home
hospice.
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Pt died 2 months later
Carcinomatous and
Lymphomatous Meningitis
Introduction
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Definition:
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Neoplastic involvement of leptomeninges when malignant
cells gain entry into CSF.
Prevalence:
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4-7% of all cancer pts
Asymptomatic involvement is more common
20% in autopsy series
Most common solid tumors include breast Ca, lung Ca,
melanoma
Anatomy
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Meninges – dura mater, arachnoid and pia mater
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Leptomeninges – arachnoid and pia mater
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CSF runs in the subarachnoid space
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Normal adult has about 140cc of CSF, replaced more
than 5x daily
CSF Flow
Pathophysiology
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Tumor cells can gain access to the CSF by:
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Hematogenously through penetration of arachnoid vessels
Direct invasion through choroid plexus
Direct extension from either subdural, epidural, or
intraparenchymal mets
Tracking along peripheral nerves
Tumor directly arise within meninges
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Primary CSF lymphoma
Primary meningeal melanoma
Primary meningeal sarcomas
Clinical Presentation
Diagnosis
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CSF cytology
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CSF biological markers
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diagnostic gold standard
Excellent specificity, not very good sensitivity
20% of cases remain cytology neg despite proper handling
of specimen and repeating LP at least once
CSF assays for tumor antigens (CSF > serum)
CSF flow cytometry
PCR
Radiographic studies
Radiographic Studies
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Gadolinium-enhanced MRI
PET
Most common sites of radiographic and pathologic
leptomeningeal tumor involvement:
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Base of the brain
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basilar cisterns
posterior fossa
Base of the spine
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cauda equina
Treatment
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Treatment Goals
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improvement or stabilaization of neurologic status
Prolonging survival
Selection of Regimen
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Poor risk patients
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Good risk patients
Karnofsky Performance Scale
Poor Risk Patients
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Karnofsky score < 60
Multiple, serious, fixed neurologic deficits
Extensive systemic Ca with few therapeutic
options
Treatment geared towards palliation
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Focused XRT for symptomatic relief
Analgesics/Corticosteroids for pain
Anticonvulsants (for pts with seizures)
SSRI or stimulants for depression or fatigue
Good Risk Patients
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Karnofsky performance score > 60
Absence of or modest fixed neurologic deficits
Minimal disease burden or
Systemic cancer for which there are reasonable
treatment options
Treatment
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XRT to bulky or symptomatic areas of leptomeningeal
disease
Intrathecal therapy
Optimal systemic tx for the extraneural disease
component
Pretreatment Evaluation
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Prior to IT treatment, a CSF flow study via a radionuclide
cisternogram is imperative
Abnormal flow is seen in up to 2/3 of pts, frequently in the
absence of hydrocephalus or other abnormalities on
neuroimaging
Disturbed CSF flow interfere with the distribution of
intrathecally administered agents, can alter both efficacy and
toxicity
XRT to the sites of abnormal CSF flow can reverse the flow
abnormality and allow safe administration of IT chemo
Intrathecal Chemotherapy
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Goal is to forestall progression of disease & the
appearance of new neurologic symptoms
Injection of chemo agents directly into CSF through:
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A subcutaneous reservoir and ventricular catheter
Into the lumbar thecal sac via LP
Efficacious for small leptomeningeal deposits &
individual tumor cells floating in the CSF
Not good for bulky disease 2/2 limited diffusion of
drug
Technique of IT Administration
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Important!
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Intra-CSF fluid volume should NOT be greater following
chemotherapy than at the start of IT administration
Otherwise pt may suddenly develop HA, n/v,
obtundation, herniation
Therefore small amount of CSF should be removed
prior to chemo instillation to account for the volume
fo administered chemo
IT Agents
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Methotrexate
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Most frequently used for solid tumors
Toxicity
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Myelosuppression
leukoencephalopathy
Relative contraindications: renal insufficiency, large
pleural effusions, ascites, or abnormal CSF flow
Thiotepa
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More myelosuppressive
Neurotoxicity slightly less
Considered in pts who have failed prior MTX or have
MTX-induced leukoencephalopathy
IT Agents cont.
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Cytarabine
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Most frequently used for lymphomatous meningitis
Oral dexamethasone is often added for its lympholytic
effect
Sustained-release Cytarabine (DepoCyt)
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Major advantage is long half-life within CSF
Also has shown modest activity in some pts with solid
tumor
Oral dexamethasone should always be used in combo
because of high incidence of chemical meningitis when
oral steroids is not given
Systemic Chemotherapy
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Advantages
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Risk of surgery for placement of a ventricular reservoir
and reservoir-associated complications are avoided
Pts with an obstruction to normal CSF flow can be treated
without correction of the flow abnormality
May provide a more uniform distribution of drug
Bulky disease may also respond
Agents
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High-dose methotrexate
cytarabine
Radiation Therapy
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Provides more rapid relief of symptoms than does
chemo
XRT can be used for:
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Sites of symptomatic or bulky disease
Sites of CSF flow block as demonstrated by radionuclide
flow study
Major Adverse Effects
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Myelosuppresion
Mucositis/esophagitis
Leukoencephalopathy – esp common when used in combo
with IT or systemic chemo, particularly methotrexate
Emerging Therapies
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Intrathecal Interferon
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Particularly for lymphomatous meningitis
Toxicity:
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Severe fatigue
Chemical meningitis
Encephalopathy
Monoclonal antibody therapy (IV rituximab)
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In CNS lymphomas
Mild reversible side effects
Prognosis
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Median survival is 3-4 months
Reasons for poor outcome:
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Delayed diagnosis of leptomeningeal involvement
Irreversible neurologic deficits at the time of diagnosis
Progressive extraneural disease
Best median survival is 6-7 months for women with
breast Ca who are treated aggressively