Chapter 097. Paraneoplastic Neurologic Syndromes (Part 4)

PND of the Central Nervous System and Dorsal Root GangliaWhen symptoms involve brain, spinal cord, or dorsal root ganglia, the suspicion of PND is usually based on a combination of clinical, radiologic, and CSF findings. In these cases, a biopsy of the affected tissue is often difficult to obtain, and although useful to rule out other disorders (e.g., metastasis, infection), neuropathologic findings are not specific for PND. Furthermore, there are no specific radiologic or electrophysiologic tests that are diagnostic of PND. ...
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Chapter 097. Paraneoplastic Neurologic Syndromes (Part 4) Chapter 097. Paraneoplastic Neurologic Syndromes (Part 4) PND of the Central Nervous System and Dorsal Root Ganglia When symptoms involve brain, spinal cord, or dorsal root ganglia, thesuspicion of PND is usually based on a combination of clinical, radiologic, andCSF findings. In these cases, a biopsy of the affected tissue is often difficult toobtain, and although useful to rule out other disorders (e.g., metastasis, infection),neuropathologic findings are not specific for PND. Furthermore, there are nospecific radiologic or electrophysiologic tests that are diagnostic of PND. Thepresence of antineuronal antibodies (Table 97-2) may help in the diagnosis withthe following caveats: (1) antibodies are detected in only 60–70% of PNDs of theCNS; (2) antibodies may be present in both the serum and CSF, but in somepatients only the CSF is positive (especially with antibodies to Tr and Maproteins); (3) antibodies (usually at low titer) are present in a variable proportionof cancer patients without PND; (4) there is an imperfect correlation betweenantibody titers and the course of the neurologic disorder; (5) several antibodiesmay associate with a similar syndrome, with the antibody specificity oftencorrelating with the tumor type (e.g., cerebellar degeneration is associated withanti-Tr antibodies if the tumor is Hodgkins disease but with anti-Yo antibodies ifthe tumor is ovarian or breast cancer); and (6) several antibodies may be present inthe serum or CSF of the same patient (e.g., anti-Hu and anti-CV2/CRMP5). MRI and CSF studies are important to rule out neurologic complicationsdue to the direct spread of cancer, particularly metastatic and leptomeningealdisease. In most PNDs the MRI findings are nonspecific. Paraneoplastic limbicencephalitis is usually associated with characteristic MRI abnormalities in themesial temporal lobes (see below), but similar findings can occur with otherdisorders [e.g., nonparaneoplastic limbic encephalitis with antibodies to VGKC,human herpesvirus (HHV) 6 encephalitis] (Fig. 97-2). The CSF profile of patientswith PND of the CNS or dorsal root ganglia typically consists of mild to moderatepleocytosis ( Figure 97-2 Fluid-attenuated inversion recovery sequence MRI of a patient with limbicencephalitis and voltage-gated potassium channel antibodies. Note the abnormalhyperintensity involving the medial aspect of the temporal lobes. PND of Nerve and Muscle If symptoms involve peripheral nerve, neuromuscular junction, or muscle,the diagnosis of a specific PND is usually established on clinical,electrophysiologic, and pathologic grounds. The clinical history, accompanyingsymptoms (e.g., anorexia, weight loss), and type of syndrome dictate the studiesand degree of effort needed to demonstrate a neoplasm. For example, the frequentassociation of LEMS with SCLC should lead to a chest and abdomen CT or bodypositron emission tomography (PET) scan and, if negative, periodic tumorscreening for at least 3 years after the neurologic diagnosis. In contrast, the weakassociation of polymyositis with cancer calls into question the need for repeatedcancer screenings in this situation. Serum and urine immunofixation studiesshould be considered in patients with peripheral neuropathy of unknown cause;detection of a monoclonal gammopathy suggests the need for additional studies touncover a B cell or plasma cell malignancy. In paraneoplastic neuropathies,diagnostically useful antineuronal antibodies are limited to anti-CV2/CRMP5 andanti-Hu. For any type of PND, if antineuronal antibodies are negative, the diagnosisrelies on the demonstration of cancer and the exclusion of other cancer-related orindependent neurologic disorders. Body PET scans often uncover tumorsundetected by other tests.