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Neurological Emergencies in Cancer Patients

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Presentation on theme: "Neurological Emergencies in Cancer Patients"— Presentation transcript:

1 Neurological Emergencies in Cancer Patients
Pete Kang

2 Neurologic Emergencies in Cancer Patients
Neurologic sx’s present in 38% of oncology-related ED visits Most common neurologic dx’s among cancer 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 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

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”: 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 Todd’s 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 g/kg over 15-20min; w/in minutes, for several hours) 3. diuretics (with mannitol) 4. IV dexamethasone, mg 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 (>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)

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 dx’d 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-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

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) % 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

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
cGy in fractions over 2-4 weeks Importance of early detection: % 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:
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

25 Leptomeningeal Metastases (LMM): Epidemiology
Definition: Tumor cells seeding the meninges along the CSF pathways % 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 - >70% of pts - common in the lumbrosacral region - pain and sphincter dysfunction are less common Cranial nerve involvement % 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 (>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%)

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 (< 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

31 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

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 (> 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 Lhermitte’s sign: electric sensation produced by neck flexion - resolves spontaneously (transient demyelination of posterior columns)

37 Complications of Treatments: chemotherapy
Intrathecal methotrexate: aseptic meningitis % of pts - 2-4 hours after injection, last for 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

39 Complications of Treatments: chemotherapy
Carboplatin - acute: strokes, retinopathy Cisplatin - acute: vestibulopathy, Lhermitte’s 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, 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

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 - Hodgkin’s 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 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, 16:449, 1998

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