Paraneoplastic Neurologic Syndromes
Summary of Key Points
• The paraneoplastic neurologic syndromes include an extensive group of disorders that can affect any part of the central or peripheral nervous system.
• Evidence indicates that many of these syndromes have an immunopathogenesis.
• Patients with paraneoplastic neurologic syndromes may have serum and cerebrospinal fluid antibodies that are highly specific for the presence of a cancer. The detection of these antibodies serves as a marker of paraneoplasia. Other antibodies associate with specific neurologic syndromes that occur with or without cancer. In these cases, the antibodies serve as markers for the neurologic syndrome but do not distinguish between a paraneoplastic or nonparaneoplastic etiology.
• Antibodies directly mediate some disorders such as the Lambert-Eaton myasthenic syndrome, myasthenia gravis, and neuromyotonia and likely mediate other disorders such as anti-N-methyl-d-aspartate receptor encephalitis. In these disorders the antibodies target neuronal cell surface proteins (e.g., receptors and ion channels), and immunotherapy along with tumor treatment often result in substantial neurologic improvement.
• For paraneoplastic neurologic syndromes in which T-cell mechanisms are predominant, the associated antibodies target intracellular neuronal proteins. In this group of disorders, the response to therapy is, in general, disappointing. The physician’s main concern should be to rule out other diagnostic entities and to uncover the presence of the associated neoplasm. For these syndromes the treatment approach should be aimed at the tumor, because stabilization and, less often, improvement of neurologic symptoms after tumor treatment have been reported for almost all syndromes. In a few cases, depending on the syndrome and whether the patient is in the early stages of the neurologic disease, treatment with immunosuppression may have some effect on the paraneoplastic neurologic syndrome.
1. The diagnosis of a paraneoplastic disorder takes all of the following factors into consideration except:
A The type of neurologic syndrome
B The detection of the underlying tumor
2. Which of the following statements regarding paraneoplastic neurologic disorders is not correct?
A In more than two thirds of patients, the neurologic symptoms develop before the cancer is detected.
B In more than two thirds of patients, the neurologic symptoms develop after the cancer is detected.
C Disorders similar to the paraneoplastic neurologic disorders also occur in patients without cancer.
D The specificity of some anti-neuronal antibodies for specific paraneoplastic neurologic syndromes makes them useful diagnostic tools.
3. Neuroimaging studies are often not useful in the diagnosis of paraneoplastic neurologic disorders except for which of the following disorders?
4. Which of the following statements is not correct when describing paraneoplastic neurologic syndromes associated with antibodies to neuronal cell surface or synaptic proteins?
1. Answer: D. Criteria have been proposed to facilitate the diagnosis of paraneoplastic disorders that take into consideration the type of neurologic syndrome, the detection of an associated tumor, and the presence or absence of paraneoplastic antibodies.
2. Answer: B. Identification of the paraneoplastic origin of a patient’s symptoms is important because in more than two thirds of patients, the neurologic symptoms develop before the cancer is detected. Because similar disorders may occur without cancer, the diagnosis of the paraneoplastic origin of a disorder depends heavily on the index of suspicion. The specificity of some paraneoplastic antineuronal antibodies for paraneoplastic neurologic syndromes or some types of cancer makes them useful diagnostic tools.
3. Answer: C. Paraneoplastic limbic encephalitis is one of the few paraneoplastic neurologic disorders in which neuroimaging may be useful. Typical magnetic resonance imaging findings include unilateral or bilateral mesial temporal lobe abnormalities best seen on T2-weighted and fluid-attenuated inversion recovery images. On T1-weighted sequences, the temporal-limbic regions may be hypointense and sometimes enhance with contrast injection.
4. Answer: A. Neurologic syndromes associated with antibodies that target cell surface or synaptic receptors (e.g., myasthenia gravis and anti–N-methyl d-aspartate (NMDA) receptor encephalitis among others) occur with or without a cancer association. In some disorders the antibodies have been proven to be pathogenic, and in others, strong evidence supports a pathogenic role. Therefore immunotherapies are often effective. Some of these disorders (e.g., anti-NMDA receptor encephalitis) preferentially affect younger patients and children.
