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Neurologic complications associated with CAR T-cell therapy

Introduction Immune-based therapies have revolutionized cancer treatment. These agents enhance the immune system’s ability to seek out and attack tumor cells. One such treatment, CAR T-cells or chimeric antigen receptor T-cells, are a type of adoptive cell transfer therapy where a patient’s own T-cells are collected, genetically modified to treat their cancer, and reinfused. CAR T-cell therapy starts with collecting autologous T lymphocytes from a patient…

Neurologic complications of immune checkpoint inhibitors

Brief introduction to immunotherapy Immune-based therapies have emerged as a promising modality in cancer treatment. These therapies use the body’s immune system to fight cancer by harnessing the antitumor properties of the host immune system to eliminate the cancer. Several types of immunotherapy exist and can be broadly categorized into: 1. Cancer vaccines 2. Adoptive cell transfer therapies such as those using chimeric antigen receptor T-cells…

Approach to chemotherapy-induced peripheral neuropathy

Introduction Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common side effects of cytotoxic chemotherapy and presents as a distal, symmetric polyneuropathy ( Table 28.1 ). Rates of CIPN depend on the agent being used but tend to occur in 60–70% of patients who receive neurotoxic agents. , According to one metaanalysis, the aggregate prevalence of CIPN is estimated to be 48%. Incidence is highest…

Approach to the patient with a delayed posttreatment CNS neurotoxicity

Introduction With significant advances in cancer treatment, both the number of long-term cancer survivors and the complications to which these patients are vulnerable have grown. These complications can involve the peripheral and/or central nervous systems, significantly impairing quality of life (QOL) and not infrequently affecting overall survival. This chapter complements other chapters’ discussion of treatment-related complications, concentrating on those that occur after the acute phase of…

Uncommon radiation-induced neurological syndromes

Introduction Cranial irradiation is used in settings ranging from definitive treatment of primary brain and head and neck cancers to palliation of metastatic disease and prophylaxis, as a single modality or in combination with surgery or systemic therapy. Common side-effect considerations include neurocognitive and inflammatory effects as well as damage to critical brain structures, which are discussed elsewhere in this text (see Chapter 24 for a…

Neurological complications of radiation

Introduction Cognitive abilities in glioma patients are influenced by a myriad of factors: the tumor itself, depression and anxiety, fatigue, sleep dysfunction, pre–brain tumor cognitive baseline (e.g., premorbid functioning), pain, and brain tumor treatments themselves (e.g., surgery, chemotherapy, and radiation). Most often, attention, working memory, and information processing speed are affected in brain tumor patients but a wide array of cognitive symptoms can be seen. Roughly…

Approach to the patient with radiation necrosis

Introduction Cerebral radiation necrosis is a challenging and potentially devastating complication of cranial irradiation. Based on the temporal relationship to radiation therapy (RT), it can be classified as pseudoprogression (a form of early subacute injury) or radiation necrosis (a form of delayed injury). Pseudoprogression typically occurs within 3 months of fractionated RT and usually reverses spontaneously after a few weeks. Delayed radiation necrosis typically develops months…

Cancer complications in patients with hematologic malignancies

Acknowledgments We thank Dr. Andrew McKeon (Departments of Laboratory Medicine and Pathology and Neurology, Mayo Clinic, Rochester, Minnesota) for providing Case 23.6: Paraneoplastic neurological syndrome. Introduction Malignant cells of both B-cell and T-cell origin have a predilection for infiltrating into the cerebrospinal fluid (CSF) and the meningeal membranes surrounding the brain and the spinal cord. Central nervous system (CNS) involvement can occur at presentation, with systemic…

Cancer-associated plexopathy

Introduction Despite the development of new therapies and related neurological complications, the two main considerations in patients with a history of cancer presenting with a brachial or lumbar plexopathy is neoplastic plexopathy or radiation-induced plexopathy. A focused cancer history and neurological examination can aid in localization and in narrowing down the differential diagnosis. Cancer-related plexopathies are more common, tend to be painful, and have a more…

Perineural spread of cancer

Introduction Perineural invasion (PNI) refers to a rare type of contiguous spread of neoplastic cells from their primary site along the potential space between or beneath the layers of perineurium. This entity is best described in cancers of the head and neck but is also well described in other solid tumors. Exact pathogenesis remains unclear, but proximity of the primary tumor to major nerves and plexus…

Paraneoplastic neurological disorder syndromes

Introduction Paraneoplastic neurological disorder (PND) syndromes are immune-mediated disorders that affect the central, peripheral, or autonomic nervous system in the setting of a cancer. These disorders are not caused by a direct tissue invasion of cancer; instead, they are associated with cancer-induced immune responses directed toward neuronal proteins. They are extremely rare, estimated to affect less than 0.1% of patients with cancer. This, however, is likely…

Neurologic complications of cancer

Introduction to medical complications of brain tumors Patients with brain tumors are at risk of many complications from their cancer. Complications may result from direct effects of the tumor itself due to infiltration of the brain parenchyma or mass effect, often manifesting as focal neurologic deficits. Non-focal symptoms such as headache, nausea, vomiting, and mental status changes may occur as a result of increased intracranial pressure…

Approach to von Hippel Lindau, Cowden disease, and other inherited conditions

Introduction Although neurofibromatosis and tuberous sclerosis comprise some of the most common inherited tumor syndromes in neuro-oncology, clinicians will encounter patients with other, less common syndromes who could present with a range of neurologic and extranervous manifestations of their disease. Awareness of these syndromes, understanding of the common neurological manifestations, and familiarity of the associated nonnervous features will aid the clinician in evaluating, managing, and counseling…

Approach to the patient with tuberous sclerosis

Introduction Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous condition characterized by a predisposition to hamartomas in the brain, heart, kidney, skin, eye, and other organs. TSC is the second most common neurogenetic tumor syndrome affecting approximately 1 in 5500 to 10,000 live births, making it less common than neurofibromatosis (NF) 1 but more common than NF2. There is no racial, ethnic, or sex predilection.…

Approach to patients with the neoplasms associated with neurofibromatosis type 1, neurofibromatosis type 2, and schwannomatosis

Introduction Neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN) are rare tumor suppressor conditions with estimated incidences of 1:3,000, 1:60,000, and 1:100,000, respectively. Although all three conditions are autosomal dominant and predispose to tumors throughout the central and peripheral nervous systems, the natural history for all of these conditions is highly variable both across and within families ( Table 16.1 ). For example,…

Approach to the patient with leptomeningeal metastases

Introduction Leptomeningeal spread occurs in both solid tumors and hematologic malignancies. Leptomeningeal disease (LMD) for all primary cancer types portends a very poor prognosis, with survival measured in weeks if left untreated and an average of only 3.5 months with maximal therapy. The gold standard for diagnosing LMD is the presence of malignant cells observed on cerebrospinal fluid (CSF) cytology, though in a patient with known…

Approach to a patient with brain metastasis

Introduction Brain metastases are a frequent occurrence in patients with solid malignancies. Up to 40% of patients with solid tumors will develop brain metastases at some point in their disease course, and 170,000 patients are diagnosed with brain metastases each year. The most common solid tumors that metastasize to the brain are lung, breast, melanoma, renal cell carcinoma, and gastrointestinal (GI) malignancies. The incidence of brain…

Approach to the patient with CNS lymphoma

Introduction Primary central nervous system lymphoma (PCNSL) is defined as lymphoma confined to the central nervous system (CNS) at presentation. By contrast, secondary CNS lymphoma represents a systemic lymphoma (i.e., outside the CNS) that has metastasized to the CNS (e.g., secondary site) either as part of the initial presentation or at relapse. Secondary CNS lymphoma can also manifest as isolated CNS relapse despite systemic remission. Although…

Approach to the high-grade glioma patient

Introduction The broad definition of high-grade glioma encompasses all central nervous system neoplasms that are derived from glial components of the brain and show anaplasia (i.e., poor cellular differentiation, atypia, pleomorphism, and loss of normal cellular organization). This chapter focuses on the high-grade diffuse gliomas including anaplastic oligodendrogliomas and astrocytomas, glioblastomas, and the recently added histone-3 K27M mutated diffuse midline gliomas. These tumors were classically labeled…

Approach to the low-grade glioma patient

Introduction The understanding of low-grade gliomas has significantly changed over the past 10 years. Genomic and epigenetic discoveries have revolutionized our understanding of these cancers. For the first time, the 2016 WHO classification of central nervous system tumors integrated molecular information with histologic classification to more precisely differentiate types of brain and spinal cord tumors. Previous histologic systems classified low-grade gliomas as astrocytomas, oligodendrogliomas, or mixed…