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Neurological Emergencies in Cancer Patients

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Title: Neurological Emergencies in Cancer Patients


1
Neurological Emergencies in Cancer Patients
  • Pete Kang

2
Neurologic Emergencies in Cancer Patients
  • Neurologic sxs present in 38 of
    oncology-related ED visits
  • Most common neurologic dxs among cancer patients
    _at_ Memorial Sloan-Kettering Cancer Center
  • Brain mets 16
  • Metabolic encephalopathy 10
  • Bone mets 10
  • Epidural tumor 8

3
Neurologic Emergencies in Cancer Patients
  • Brain tumors
  • Epidural spinal cord compression (ESCC)
  • Leptomeningeal metastasis (LMM)
  • Stroke
  • Acute neurologic complications of cancer
    treatment
  • Paraneoplastic syndromes

4
Brain Tumors epidemiology
  • Each year
  • 17,500 dxd with primary brain tumors
  • 66,000 dxd 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

5
Brain Tumors mechanism
  • Direct tissue destruction
  • Displacement of brain tissues (tumor/edema)
  • Compression of vasculature (ischemia)
  • Compression of CSF pathways (hydrocephalus)

6
Brain Tumors clinical features
  • Headache
  • - presenting sx in 35 of patients
  • - 70 of patients will have a headache at some
    point
  • - classic mild _at_ 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

7
Brain Tumors clinical features
  • Seizure
  • - presenting sx in 33 of pts with gliomas
  • - presenting sx in 15-20 of pts with brain mets
  • - postictal deficits or Todds paralysis
  • Papilledema
  • - older studies present in 70
  • - now 8
  • Acute presentations hydrocephalus, intratumoral
    hemorrhage, seizures

8
Brain tumors management
  • Symptomatic Treatments
  • cerebral edema
  • - emergency management
  • 1. hyperventilation (w/in 30sec, for 15-20min)
  • 2. hyperosmolar agents (mannitol 20-25 _at_
    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)

9
Brain tumors management
  • seizures
  • symptomatic treatment anticonvulsants
  • prophylactic treatment controversial
  • - two randomized prospective studies (gt170 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)

10
Brain tumors management
  • 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)

11
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

12
Brain tumors management
  • Brachytherapy
  • Stereotactic surgery
  • New modalities
  • implantation of chemotherapy-filled
    biodegradable polymers
  • immunotherapy
  • gene therapy

13
Epidural Spinal Cord Compression (ESCC)
epidemiology
  • 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
    Sloan-Kettering
  • Treatability when dxd early poor outcome once
    neurologic function deteriorates

14
ESCC mechanism
  • 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

15
ESCC clinical features
  • Underlying malignancies
  • 20 prostate
  • 20 lung
  • 20 breast
  • 10 non-Hodgkins 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

16
ESCC clinical features
  • 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

17
ESCC clinical features
  • Weakness
  • - present in 75 of pts who have ESCC
  • - usually symmetric
  • Sensory complaints
  • - ascending numbness and paresthesias

18
ESCC neuroimaging
  • 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 gt75
    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

19
ESCC neuroimaging
  • 37-year-old patient with breast cancer who
    presented with acute low back pain. T1-weighted
    sagittal MR image of the lumbar spine showing
    metastases in the body of L3 with extension into
    the posterior elements.

20
ESCC differential diagnosis
  • 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

21
ESCC management
  • 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

22
ESCC management
  • 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.

23
ESCC management
  • 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

24
ESCC management
  • Chemotherapy
  • For chemo-sensitive tumors
  • Hodgkins disease, NHL, neuroblastoma,
    germ-cell tumors, breast cancer
  • Bisphosphonates
  • Reduce the incidence of pathologic fxs 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

25
Leptomeningeal Metastases (LMM) Epidemiology
  • 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)

26
LMM clinical features
  • Spinal signs
  • - involvement of tumor cells with the nerve
    roots
  • - asymmetric weakness, sensory loss,
    parasthesias, depressed reflexes
  • - gt70 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

27
LMM diagnostic tests/imaging
  • Lumbar puncture/CSF
  • - elevated opening pressure (gt50), elevated WBC
    (gt70), elevated protein (gt75), 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 (lt40)
  • Spine MRI
  • - meningeal enhancement (gt50)
  • Myelogram
  • - subarachnoid masses (lt25)

28
LMM management
  • Intrathecal chemotherapy
  • - via dural puncture or indwelling ventricular
    reservoir
  • - multiple drug therapy does not confer
    advantage over a single-agent 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

29
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

30
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 (lt 20,000/mul)
  • 2) DIC (found in APML)
  • 3) Hyperleukocytosis
  • - 10 of AML pts w/ WBC gt 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/ gt400,000/mul

31
Stroke in hematologic malignancies
  • Cerebral infarction occurs less frequently
    (septic emboli or DIC)
  • Cerebral venous thrombosis in L-asparaginase-treat
    ed 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
  • Waldenstroms macroglobulinemia multiple
    myeloma
  • Hyperviscosity headache, visual complaints,
    lethargy --gt seizures, focal deficits, coma

32
Stroke in non-hematologic malignancies
  • 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

33
Stroke in non-hematologic malignancies
  • 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

34
Complications of Treatments radiation
  • 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 (gt 300 cGy) given to pts
    w/ cerebral edema and increased ICP
  • - increased edema w/in neural structures

35
Complications of Treatments radiation
  • 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

36
Complications of Treatments radiation
  • 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
  • Lhermittes sign electric sensation produced by
    neck flexion
  • - resolves spontaneously (transient
    demyelination of posterior columns)

37
Complications of Treatments chemotherapy
  • 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

38
Complications of Treatments chemotherapy
  • 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)

39
Complications of Treatments chemotherapy
  • Carboplatin
  • - acute strokes, retinopathy
  • Cisplatin
  • - acute vestibulopathy, Lhermittes sign,
    encephalopathy, seizures, focal deficits, strokes
  • - neuropathy (common), ototoxicity (common)

40
Complications of Treatments bone marrow
transplantation
  • 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)

41
Complications of Treatments bone marrow
transplantation
  • 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

42
Paraneoplastic Syndromes
  • 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

43
Paraneoplastic Syndromes
  • 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, Hodgkins 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

44
Paraneoplastic Syndromes
  • 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

45
Paraneoplastic Syndromes
  • Necrotizing myelopathy
  • - rapidly ascending myelopathy
  • - flaccid paraplegia and death
  • - lymphoma, leukemia, lung cancer
  • Peripheral nerve disorders
  • - Hodgkins disease GBS and branchial neuritis

46
Paraneoplastic Syndromes
  • 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

47
Source
  • Schiff D, Batchelor T, Wen PY. Neurologic
    Emergencies in Cancer Patients. Neurologic
    Clinics, 16449, 1998
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