Transcript Neurological Emergencies in Cancer Patients

Neurological Emergencies in
Cancer Patients
Pete Kang
Neurologic Emergencies in Cancer
Patients
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Neurologic sx’s present in 38% of
oncology-related ED visits
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Most common neurologic dx’s among cancer patients
@ Memorial Sloan-Kettering Cancer Center:
Brain mets 16%
Metabolic encephalopathy 10%
Bone mets 10%
Epidural tumor 8%
Neurologic Emergencies in Cancer
Patients
Brain tumors
 Epidural spinal cord compression
(ESCC)
 Leptomeningeal metastasis (LMM)
 Stroke
 Acute neurologic complications of
cancer treatment
 Paraneoplastic syndromes
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Brain Tumors: epidemiology
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Each year:
17,500 dx’d with primary brain tumors
66,000 dx’d with symptomatic brain metastases
lung, breast, skin, GU, GI account for majority
Incidence is increasing:
- improved diagnostic methodology
- better access to health care among the elderly
- improved survival among cancer patients
Brain Tumors: mechanism
Direct tissue destruction
 Displacement of brain tissues
(tumor/edema)
 Compression of vasculature (ischemia)
 Compression of CSF pathways
(hydrocephalus)
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Brain Tumors: clinical features
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Headache
- presenting sx in 35% of patients
- 70% of patients will have a headache at some point
- “classic”: mild @ onset, worse in morning, improves
after rising
- usually: dull, non-throbbing headache, gradually
increases, chronic
- accompanied by impaired MS, nausea/vomiting
Focal deficits
Cognitive disturbances
- presenting sx in 30% of patients
Brain Tumors: clinical features
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Seizure
- presenting sx in 33% of pts with gliomas
- presenting sx in 15-20% of pts with brain mets
- postictal deficits or Todd’s paralysis
Papilledema
- older studies: present in 70%
- now: 8%
Acute presentations: hydrocephalus, intratumoral
hemorrhage, seizures
Brain tumors: management
Symptomatic Treatments
 cerebral edema
- emergency management
1. hyperventilation (w/in 30sec, for 15-20min)
2. hyperosmolar agents (mannitol 20-25% @ 0.5-2.0g/kg
over 15-20min; w/in minutes, for several hours)
3. diuretics (with mannitol)
4. IV dexamethasone, 40-100mg bolus + same/day
5. barbiturates/hypothermia
- non-emergency management
dexamethasone (10mg po q6hrs)
Brain tumors: management
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seizures
symptomatic treatment: anticonvulsants
prophylactic treatment: controversial
- two randomized prospective studies (>170 pts with both
primary and metastatic brain tumors) showed no significant
benefit with prophylactic treatment
- possible exceptions: melanoma brain mets, pts w/ both
brain mets and leptomeningeal mets (both groups 50-60% risk
of seizures)
Brain tumors: management
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venous thromboembolism
19-37% of brain tumor pts will develop VT
IVC filters vs. anticoagulation
- several retrospective studies showed lower risk of
complications with anticoagulation compared to IVC filters
- possible exceptions include:
post-operative patients
pts with choriocarcinomas or melanomas
other contraindications to anticoagulation (e.g. GI
bleeds)
Brain tumors: management
Definitive Treatments
 Curative surgical resections
e.g., meningiomas, vestibular schwannomas, pituitary
adenomas, certain glial tumors
 Palliative surgical resections: malignant tumors
relieve neurologic symptoms
allow safer delivery of radiation treatments
 External beam irradiation
post-op focal EBI: single brain lesion
whole brain EBI: best for multiple mets & pts with
single brain mets & widespread systemic spread
Brain tumors: management
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Brachytherapy
Stereotactic surgery
New modalities:
implantation of chemotherapy-filled biodegradable
polymers
immunotherapy
gene therapy
Epidural Spinal Cord Compression
(ESCC): epidemiology
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Definition: compression of the thecal sac by tumor in
the epidural space, either at the level of the spinal
cord or the cauda equina
Occurs in approximately 5% of cancer patients
R/O cord compression is the most common reason
for neuro-oncologic consultation at Memorial SloanKettering
Treatability when dx’d early & poor outcome once
neurologic function deteriorates
ESCC: mechanism
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Hematogenous spread of tumor cells to bone marrow of
vertebral bodies
Compresses thecal sac by:
1) Direct growth posteriorly
2) Produce vertebral collapse
15-20% of pts: spread of paraspinal tumors through the
neuroforamen to compress the thecal sac
Common in: lymphomas, renal cell carcinoma, Pancoast tumor
of the lung
Enlarging epidural tumor compresses epidural venous plexus,
causing vasogenic edema, with eventual spinal cord infarction
Slowly progressive lesions much more likely to be reversible
than rapidly progressive lesions
ESCC: clinical features
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Underlying malignancies:
~20% prostate
~20% lung
~20% breast
~10% non-Hodgkin’s lymphoma
~10% multiple myeloma
~10% renal cell carcinoma
~10% virtually every other primary tumor
Pediatric: sarcomas, neuroblastoma
20% of ESCC cases occur as initial presentations of the
underlying malignancies
Location: 60% in thoracic, 30% in lumbar, 10% cervical
ESCC: clinical features
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Pain
- 95% of ESCC patients as initial symptom
- precedes other symptoms of ESCC by 1-2 mos
- worsens with recumbency (vs. pain of disc prolapse
or OA, which improves when pt lies down)
- thoracic localization
- percussion tenderness
- acute worsening may be sign of pathologic fx
- radicular pain almost always bilateral
ESCC: clinical features
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Weakness
- present in 75% of pts who have ESCC
- usually symmetric
Sensory complaints
- ascending numbness and paresthesias
ESCC: neuroimaging
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Plain spinal radiographs
- False-negatives in 10-17% (paraspinal invasion)
- 30-35% of bone must be destroyed before radiography turns
positive
- In cancer pts w/ back pain alone, major vertebral body collapse
associated with >75% chance of ESCC
- If both plain films and bone scans are negative for pt w/ back
pain alone, the risk of ESCC may be as low as 2%
Modality of choice: MRI and CT myelography
- CT myelography allows for simultaneous CSF collection
ESCC: neuroimaging
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37-year-old patient with
breast cancer who
presented with acute
low back pain. T1weighted sagittal MR
image of the lumbar
spine showing
metastases in the body
of L3 with extension into
the posterior elements.
ESCC: differential diagnosis
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Must consider benign conditions such as:
- disc herniation
- suppurative bacterial infections
- TB
- hemorrhage
- chordoma
- vertebral hemangioma
Other malignant conditions:
- vertebral metastases w/o epidural extension
- leptomenigeal diseases (co-exist in 25%)
- intramedullary spinal metastases (lung cancer)
- chronic progressive radiation myelopathy
ESCC: management
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Pain
- corticosteroids (alleviate vasogenic edema)
- appropriate analgesics (e.g., opiates)
DVT prophylaxis for paraparetic pts
Corticosteroids
- randomized trial showed significantly higher percentage of pts
receiving DXM remained ambulatory over time
Laminectomy
- small randomized trial showed no difference in outcome
between laminectomy & radiotherapy vs. radiotherapy alone
- poor access to anterior tumor & further destabilization of spine
ESCC: management
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Fractionated external beam radiotherapy
2500-4000 cGy in 10-20 fractions over 2-4 weeks
Importance of early detection:
- 80-100% of pts who were ambulatory at start of treatment
remain ambulatory.
- 33% of pts who were non-ambulatory will regain their ability to
walk.
- 2-6% of paraplegic pts will regain their ability to walk.
Medial survival following onset of ESCC is ~6 months.
50% of the patients who are still alive at 1 year will be
ambulatory.
ESCC: management
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Vertebrectomy
gross total tumor resection followed by spinal reconstruction
with bone grafting
Recent series:
- 82% of pts post-op improved
- 67% of non-ambulatory pts were able to walk post-op
Strongly considered in:
- pts w/ spinal instability or bone w/in spinal canal
- local recurrence post-RT
- known radioresistant tumor
Mortality: 6-10%
Complication rate: 48%
wound breakdown (rel. to steroids), stabilization failure,
infection, hemorrhage
ESCC: management
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Chemotherapy
For chemo-sensitive tumors:
Hodgkin’s disease, NHL, neuroblastoma, germ-cell tumors,
breast cancer
Bisphosphonates
Reduce the incidence of pathologic fx’s & bone pain in pts with
multiple myeloma or breast cancer
Recurrence
10% of all irradiated pts will experience local recurrence
Chemotherapy and surgery (vertebrectomy) should be
considered
Leptomeningeal Metastases
(LMM): Epidemiology
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Definition: Tumor cells seeding the meninges along the CSF
pathways
0.8-8.0% of all cases of cancer
LMM is especially likely with:
- leukemia
- NHL
- breast cancer
- small-cell lung cancer (SCLC)
LMM: clinical features
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Spinal signs
- involvement of tumor cells with the nerve roots
- asymmetric weakness, sensory loss, parasthesias, depressed
reflexes
- >70% of pts
- common in the lumbrosacral region
- pain and sphincter dysfunction are less common
Cranial nerve involvement
- 30-50% of pts will have cranial nerve symptoms/signs
- oculomotor nerves (III, IV, VI) are most commonly involved
LMM: diagnostic tests/imaging
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Lumbar puncture/CSF
- elevated opening pressure (>50%), elevated WBC (>70%),
elevated protein (>75%), reduced glucose (25-30%)
- positive cytology after 1 LP: 50%; after 3 LPs: 90%
- future use of biochemical markers
Brain MRI
- meningeal enhancement (50%)
- hydrocephalus (<40%)
Spine MRI
- meningeal enhancement (>50%)
Myelogram
- subarachnoid masses (<25%)
LMM: management
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Intrathecal chemotherapy
- via dural puncture or indwelling ventricular reservoir
- multiple drug therapy does not confer advantage over a singleagent therapy with methotrexate
- leucovorin po bid X 4d reduces systemic toxicity from
methotrexate
- alternatives: cytosine arabinoside, thiotepa
Localized cranial or spinal irradiation
- for pts with focal symptoms or CSF block only
Median survival: 3-6 months with treatment
15-25% of pts survive more than one year
Stroke: epidemiology
7% of cancer patients experience
symptomatic stroke during their lifetime
 Cause equally divided between cerebral
infarctions and hemorrhages
 Hematologic vs. Non-hematologic
malignancies
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Stroke: in hematologic
malignancies
Leukemias
 Mostly hemorrhagic strokes
 At autopsy: 18% of AML and 8% of ALL had hemorrhagic
strokes
 Risk factors for hemorrhagic strokes:
1) Thrombocytopenia (< 20,000/mul)
2) DIC (found in APML)
3) Hyperleukocytosis
- 10% of AML pts w/ WBC > 100,000/mul will die w/in 10 days of
starting therapy due to intracerebral or pulmonary hemorrhage
- less often in ALL (inc. risk w/ >400,000/mul
Stroke: in hematologic
malignancies
Cerebral infarction occurs less frequently (septic emboli or DIC)
 Cerebral venous thrombosis in L-asparaginase-treated ALL pts
(presents with headaches & seizures)
Lymphomas
 Substantially less common
 Cerebral infarction ocurs more commonly (septic emboli,
nonbacterial thrombotic endocarditis, DIC)
 Intracerebral hemorrhage occurs less commonly
Waldenstrom’s macroglobulinemia & multiple myeloma
 Hyperviscosity: headache, visual complaints, lethargy -->
seizures, focal deficits, coma
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Stroke: in non-hematologic
malignancies
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Intracranial hemorrhages
- ~50% of strokes in pts w/ non-hematologic tumors
- mechanism: bleeding into the intracerebral mets
- common underlying cancers: melanoma, germ-cell tumors,
non-SCLC
- 67% presents w/ stroke-like symptoms, while remaining will
have more gradual deterioration
- management: corticosteroids, surgical evacuation,
surgery/radiation
Stroke: in non-hematologic
malignancies
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Ischemic infarcts
- majority of ischemic infarcts are due to atherosclerotic disease
unrelated to the malignancy
- hypercoagulability of cancer may contribute
- non-bacterial thrombotic endocarditis fairly common
- management:
evaluate cardiovascular causes
treat underlying malignancy
heparin?
Rare causes:
- tumor embolization
- direct compression of superior sagittal sinus causing venous
infarction
Complications of Treatments:
radiation
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Mechanism:
- direct injury to neural structures
- damaging blood vessels that supply neural structures
- damaging endocrine organs
- producing tumors
Acute reaction
- relatively uncommon
- occur w/ large doses (> 300 cGy) given to pts w/ cerebral
edema and increased ICP
- increased edema w/in neural structures
Complications of Treatments:
radiation
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Early delayed reaction
- weeks to months post-RT
- mechanism: transient demyelination
- most recover spontaneously w/in 6-8 weeks
Late delayed reaction
- early as 3 months, usually 1-2 years post-RT
- mechanism: radiation necrosis
- often progressive and irreversible
- risk much higher in pts post-brachytherapy or stereotactic
radiosurgery
- steroids & surgery
Cerebral atrophy & leukoencephalopathy
- cognitive problems
Complications of Treatments:
radiation
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Cranial neuropathy
- optic neuropathy
occurs months to years post-RT
pain-less, progressive visual loss w/ optic atrophy
- radiation-induced otitis media & conductive hearing loss
Lhermitte’s sign: electric sensation produced by neck flexion
- resolves spontaneously (transient demyelination of posterior
columns)
Complications of Treatments:
chemotherapy
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Intrathecal methotrexate: aseptic meningitis
- 10-40% of pts
- 2-4 hours after injection, last for 12-72 hours
- CSF shows granulocytic pleocytosis, elevated protein
- self-limited; no treatment required
Cytosine arabinoside: cerebellar syndrome
- high doses (3 g/m2/12 hours), 25% of pts
- somnolence, confusion to ataxia in 2-5 days post-CT
- some resolve spontaneously, some permanent
Corticosteroids
- acute: psychosis, hallucinations, blurred vision, tremor,
seizures, myelopathy
- chronic: myopathy, cerebral atrophy
Complications of Treatments:
chemotherapy
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5-Fluorouracil
- acute: cerebellar syndrome, encephalopathy
- chronic: cerebellar syndrome, Parkinsonian syndrome
Taxol/taxotere
- acute: arthralgias, myalgis (common)
- chronic: neuropathy (common)
Vincristine
- acute: encephalopathy, seizures, cortical blindness,
extrapyramidal syndrome
- chronic: neuropathy (common)
Complications of Treatments:
chemotherapy
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Carboplatin
- acute: strokes, retinopathy
Cisplatin
- acute: vestibulopathy, Lhermitte’s sign, encephalopathy,
seizures, focal deficits, strokes
- neuropathy (common), ototoxicity (common)
Complications of Treatments:
bone marrow transplantation
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Allogeneic BMT pts: 50-70%, smaller proportions in autologous
BMT pts
Toxic-metabolic encephalopathy (37% of pts)
Seizures (12-16% of pts)
CNS infections (7-14% of pts)
GBS following BMT unrelated to GVHD (case reports)
Cerebrovascular complications (4-13% of pts)
Complications of Treatments:
bone marrow transplantation
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Acute GVHD not associated with neurologic complications
Chronic GVHD
- occurs in 40% of HLA-matched, 75% of HLA-mismatched
transplants
- “auto”-immune disorders of PNS (DDx of “weakness”):
myasthenia gravis
polymyositis
chronic inflammatory demyelinating polyneuropathy
Paraneoplastic Syndromes
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Very rare
Autoimmune etiology
Account for a high-percentage of patients who have these
particular syndromes
e.g., 50% of pts w/ subacute cerebellar degeneration have an
underlying neoplasm
Frequently develop before the diagnosis of tumor
Run a course independent of underlying tumor
Paraneoplastic Syndromes
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Paraneoplastic cerebellar degeneration
- most common
- progresses over weeks to months
- severe truncal and appendicular ataxia and dysarthria
- small-cell lung cancer, gynecologic cancers, breast cancer,
Hodgkin’s disease
- CSF: elevated protein, mild pleocytosis, oligoclonal bands
- MRI: early shows normal scan; later may show cerebellar
atrophy
- anti-Yo IgG (anti-Purkinje cell cytoplasmic antibody type I)
- generally do not improve after antineoplastic or
immunosuppressive therapy
Paraneoplastic Syndromes
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Paraneoplastic Opsoclonus-Myoclonus
- involuntary, multidirectional, high-amplitude, conjugate, chaotic
saccades
- neuroblastoma in children, small-cell lung cancer, breast
cancer
- anti-Ri (antineuronal nuclear antibody type II)
- prognosis better than PCD; remissions occur spontaneously
post-cancer treatment
Paraneoplastic Encephalomyelitis/Sensory neuronopathy
- one or more of: dementia, brain-stem encephalitis, cerebellar
degeneration, myelopathy, autonomic neuropathy, subacute
sensory neuronopathy
- most pts have SCLC
Paraneoplastic Syndromes
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Necrotizing myelopathy
- rapidly ascending myelopathy
- flaccid paraplegia and death
- lymphoma, leukemia, lung cancer
Peripheral nerve disorders
- Hodgkin’s disease & GBS and branchial neuritis
Paraneoplastic Syndromes
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Lambert-Eaton Myasthenic Syndrome
- autoimmune IgG to voltage-gated Ca++ channels on
presynaptic nerve terminals
- weakness, fatigability, pain, esp. of proximal muscles, with
reduced or absent reflexes
- may be improvement in strength w/ repeated muscle
contractions
- 75% of male and 25% of female pts have underlying
neoplasm, usually SCLC
- NCS: low amp muscle action potentials that increase
significantly after exercising for 10-15 sec
- autoantibodies that bind solubilized Ca++ channel w-conotoxin
complexes
Source
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Schiff D, Batchelor T, Wen PY. Neurologic Emergencies in
Cancer Patients. Neurologic Clinics, 16:449, 1998