The Prevalence and Impact of Neurological Disease in Cancer

 

Number of patients
Percentage of consults
Chief complaint
Back pain
385
18
Headache
192
9
Other pain
160
7
Altered mental status
521
24
Weakness
395
18
Sensory deficit
173
8
Ataxia/gait instability
156
7
Seizures
156
7
Vision deficit
54
2
Speech deficit
52
2
Neurologic diagnosis
Parenchymal brain metastasis
407
19
Epidural metastasis
298
14
Leptomeningeal metastasis
224
10
Other metastasis
407
19
Toxic metabolic encephalopathy
275
12
Cerebrovascular disease
169
8
Headache
67
3
Syncope
45
2
Peripheral neuropathy
40
1
Epilepsy
34
1
Paraneoplastic syndrome
7
0.3
Other
246
12
Patients may have more than one chief complaint or neurologic diagnosis
Used with permission of Oxford University Press from DeAngelis and Posner [5]
An estimated 1.7 million Americans will be diagnosed with cancer in 2015, of whom 68% will be alive at 5 years [7]. Many of these 1.2 million cancer survivors will have a neurologic symptom or disability and would benefit from neurologic expertise. This book seeks to address the broad scope of these issues and the large unmet clinical needs of these patients.

Management of the Neurologic Complications of Cancer

Neurooncology is the subspecialty of neurology that deals with the neurologic complications of cancer. Neurologic symptoms may arise from primary malignancies of the brain, and for that reason, one focus of neurooncology is the management of gliomas and other primary tumors of the CNS. A second, equally important focus is the diagnosis and management of neurologic complications of systemic cancer and its treatment which is the core of this book. This second focus extends far beyond brain metastases, a problem that is already ten times more common than malignant gliomas [3, 7].
The first step in managing a neurologic complication of cancer is the correct identification of the underlying problem. A cancer patient with a change in gait may have loss of proprioception from prior chemotherapy, disease within the CNS, or severe pain that limits function. Correct diagnosis and treatment of the patient’s complaint is contingent upon the same principles of neurology that apply to the non-cancer population. A careful history and detailed exam localizes the deficit in the nervous system to a focal, multifocal, or diffuse process. From that localization, a neurologic differential diagnosis can be developed that is based on specialized knowledge of the characteristic propensities of each cancer, the off-target effects of a wide array of conventional cytotoxic, novel small molecule and biologic therapeutics, and the complications of radiotherapy and surgical treatments. The most common neurologic complications of cancer and their association with different malignancies and treatment are provided in Table 1.2.
Table 1.2
Neurologic complications of cancer
Location
Complication
Cancer or treatment related causes
Brain
Direct complications
Brain metastasis
Lung, melanoma, renal, breast, and colon cancer
Primary brain tumor
Meningioma, glioma, pituitary adenoma, and schwannoma
Leptomeningeal metastasis
Breast, lung, melanoma, and gastrointestinal cancer
Complications associated with cancer
Epilepsy/status epilepticus
Brain metastasis, primary brain tumor, paraneoplastic limbic encephalitis, and meningitis/encephalitis
Paraneoplastic limbic encephalitis
Anti-VGKC
SCLC and thymoma
Anti-NMDA
Ovarian teratoma
Anti-Hu
SCLC and gynecological cancer
Anti-Ma2
Testicular germ cell
Paraneoplastic cerebellar degeneration
Anti-Yo
Ovarian and breast cancer
Anti-Tr
Hodgkin lymphoma
Anti-Hu
SCLC and gynecological cancer
Meningitis/encephalitis
Cancer-mediated immunosuppression
Hodgkin lymphoma, CLL, multiple myeloma, and Waldenstrom macroglobulinemia
Ischemic stroke
Hyperviscosity
Multiple myeloma, Waldenstrom macroglobulinemia, and leukemia
Cancer-mediated hypercoagulability
Pancreatic cancer, adenocarcinomas
Tumor emboli
Rhabdomyosarcoma
DIC
Sepsis from cancer-mediated immunosuppression
Vasculopathy
Intravascular lymphoma
Infectious vasculopathy (VZV) from cancer-mediated immunosuppression
Hemorrhagic stroke
Coagulopathy/DIC
APL
Sepsis from cancer-mediated immunosuppression
Liver metastases
Thrombocytopenia
Leukemia, lymphoma, and multiple myeloma
Hemorrhage from a metastasis
Renal cell carcinoma, melanoma, choriocarcinoma, and papillary thyroid cancer
Treatment complications
Encephalopathy
Methotrexate, ifosfamide, and 5-FU
PRES
Bevacizumab, sorafenib, cyclophosphamide, high-dose corticosteroids, l-asparaginase, cisplatin, gemcitabine, and tacrolimus
Ischemic stroke
Bevacizumab, sunitinib, sorafenib, and cisplatin
Radiation-induced vasculopathy from treatment of head and neck cancers
Infectious vasculopathy and DIC from treatment-induced immunosuppression
Hemorrhagic stroke
Chemotherapy-induced thrombocytopia
Bevacizumab
Hemorrhage due to vascular changes secondary to radiotherapy
Venous sinus thrombosis
l-asparaginase
Pseudoprogression
Radiation to a primary or metastatic brain tumor
Radiation necrosis
Radiation to the head and neck; SRS to brain metastases
Bacterial meningitis/abscess/empyema
Neurosurgical procedure
VP shunt, burr hole, craniotomy, transsphenoidal resection, and laminectomy
Treatment-induced immune suppression
Cytotoxic chemotherapy, hematopoietic stem cell transplant, and immune-modulating biologics
Spinal cord
 
Leptomeningeal Metastasis
Breast, lung, melanoma, and gastrointestinal cancers
Cord compression/cauda equina syndrome
Lung, breast, prostate, renal, colorectal, and hematologic malignancies
Paraneoplastic myelopathy
Anti-amphiphysin
Breast cancer
Anti-CRMP5
SCLC and thymoma
Anti-Hu
SCLC and gynecological cancer
Anti-ANNA-3
SCLC
Anti-NMO
Carcinoma and lymphoma
Radiation myelopathy
Radiation to the vertebral column, thorax, abdomen, or neck
Radiculomyelitis
Cancer-mediated and treatment-induced immunosuppression
Plexus
 
Neoplastic infiltration
Brachial
Breast and lung cancer
Lumbosacral
Prostate, colorectal, cervical, bladder cancers, and retroperitoneal sarcoma
Radiation plexopathy
Radiation near the plexus
Peripheral nerve
 
Neoplastic infiltration
Leukemia, lymphoma, Waldenstrom macroglobulinemia, prostate cancer, and squamous cell of head and neck (to cranial nerves)
Drug-associated neuropathy
Platinum agents, vinca alkaloids, thalidomide, bortezomib, and ipilimumab
Immune-mediated neuropathy
POEMS syndrome, MGUS, and multiple myeloma
Paraneoplastic neuronopathy
Anti-Hu
SCLC and gynecological cancer
Peripheral nerve hyper-excitability
Anti-VGKC
SCLC and thymoma
Neuromuscular junction
 
Myasthenia gravis
Anti-acetylcholine receptor
Thymoma
Lambert–Eaton myasthenic syndrome
Anti-Ca channel
SCLC
Muscle
 
Steroid myopathy
Pituitary adenomas/carcinomas, adrenal adenomas/adrenocortical carcinomas, and exogenous steroids
Dermatomyositis/polymyositis
Cervical, lung, ovarian, pancreatic, bladder, and gastric cancer
Abbreviations APL acute promyelocytic leukemia, CLL chronic lymphocytic leukemia; DIC disseminated intravascular coagulation, MGUS monoclonal gammopathy of unknown significance, POEMS polyneuropathy organomegaly endocrinopathy M-protein skin-changes, PRES posterior reversible encephalopathy syndrome, SCLC small cell lung cancer, SRS stereotactic radiosurgery, VP shunt ventriculoperitoneal shunt, VZV varicella zoster virus, 5-FU 5-flurouracil

Direct Effects of Cancer on the Nervous System

Cancer frequently metastasizes to the nervous system, primarily to the brain, dura, subarachnoid space, spinal cord, and plexus. Considered together, the direct complications of cancer on the nervous system are responsible for a major burden of disability and death. Ironically, enhanced therapeutics and longer systemic disease control may be responsible for increasing the incidence of these complications, making the need for better therapeutics for CNS disease ever more pressing.

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Dec 24, 2017 | Posted by in NEUROLOGY | Comments Off on The Prevalence and Impact of Neurological Disease in Cancer

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