Imaging Review of Paraneoplastic Neurologic Syndromes.

Paraneoplastic syndromes are systemic reactions to neoplasms mediated by immunologic or hormonal mechanisms. The most well-recognized paraneoplastic neurologic syndrome, both clinically and on imaging, is limbic encephalitis. However, numerous additional clinically described syndromes affect the brain, spinal cord, and peripheral nerves. Many of these syndromes can have imaging findings that, though less well described, are important in making the correct diagnosis. Moreover, imaging in these syndromes frequently mimics more common pathology, which can be a diagnostic challenge for radiologists. Our goal is to review the imaging findings of paraneoplastic neurologic syndromes, including less well-known entities and atypical presentations of common entities. Specifically, we discuss limbic encephalitis, paraneoplastic cerebellar degeneration, paraneoplastic brain stem encephalitis, cranial neuropathy, myelitis, and polyneuropathy. We also demonstrate common diagnostic pitfalls that can be encountered when imaging these patients.

Isolated recurrent myelitis in a persistent MOG positive patient.

MOG-Ab positive CNS demyelination typically involves the optic nerve and spinal cord. Recurrent episodes of myelitis without optic neuritis are very rare and according to current literature review represent about 3-5% of positive MOG-Ab cases. We report a 30-year-old woman with positive serum MOG-Ab suffering two discrete episodes of transverse myelitis without ophthalmic involvement. Repeated serum MOG-Ab test after the second relapse was positive, correlating with high likelihood of relapsing disease. Of note, our patient relapsed under Rituximab therapy, which does not seem to be uncommon for MOG-Ab patients. Patients with isolated or recurrent myelitis without optic involvement should be screened for anti MOG IgG as a part of their workup.

Diagnosis and management of spinal cord emergencies.

Most spinal cord injury is seen with trauma. Nontraumatic spinal cord emergencies are discussed in this chapter. These myelopathies are rare but potentially devastating neurologic disorders. In some situations prior comorbidity (e.g., advanced cancer) provides a clue, but in others (e.g., autoimmune myelopathies) it may come with little warning. Neurologic examination helps distinguish spinal cord emergencies from peripheral nervous system emergencies (e.g., Guillain-Barré), although some features overlap. Neurologic deficits are often severe and may quickly become irreversible, highlighting the importance of early diagnosis and treatment. Emergent magnetic resonance imaging (MRI) of the entire spine is the imaging modality of choice for nontraumatic spinal cord emergencies and helps differentiate extramedullary compressive causes (e.g., epidural abscess, metastatic compression, epidural hematoma) from intramedullary etiologies (e.g., transverse myelitis, infectious myelitis, or spinal cord infarct). The MRI characteristics may give a clue to the diagnosis (e.g., flow voids dorsal to the cord in dural arteriovenous fistula). However, additional investigations (e.g., aquaporin-4-IgG) are often necessary to diagnose intramedullary etiologies and guide treatment. Emergency decompressive surgery is necessary for many extramedullary compressive causes, either alone or in combination with other treatments (e.g., radiation) and preoperative neurologic deficit is the best predictor of outcome.

Immunotherapy trial as diagnostic test in evaluating patients with presumed autoimmune gastrointestinal dysmotility.

BACKGROUND: Chronic gastrointestinal dysmotility greatly impacts the quality of life. Treatment options are limited and generally symptomatic. Neural autoimmunity is an under-recognized etiology. We evaluated immunotherapy as an aid to diagnosing autoimmune gastrointestinal dysmotility (AGID). METHODS: Twenty-three subjects evaluated at the Mayo Clinic for suspected AGID (August 2006-February 2014) fulfilled the following criteria: (1) prominent symptoms of gastrointestinal dysmotility with abnormalities on scintigraphy-manometry; (2) serological evidence or personal/family history of autoimmune disease; (3) treated by immunotherapy on a trial basis, 6-12 weeks (intravenous immune globulin, 16; or methylprednisolone, 5; or both, 2). Response was defined subjectively (symptomatic improvement) and objectively (gastrointestinal scintigraphy/manometry studies). KEY RESULTS: Symptoms at presentation: constipation, 18/23; nausea or vomiting, 18/23; weight loss, 17/23; bloating, 13/23; and early satiety, 4/23. Thirteen patients had personal/family history of autoimmunity. Sixteen had neural autoantibodies and 19 had extra-intestinal autonomic testing abnormalities. Cancer was detected in three patients. Preimmunotherapy scintigraphy revealed slowed transit (19/21 evaluated; gastric, 11; small bowel, 12; colonic, 11); manometry studies were abnormal in 7/8. Postimmunotherapy, 17 (74%) had improvement (both symptomatic and scintigraphic, five; symptomatic alone, eight; scintigraphic alone, four). Nine responders re-evaluated had scintigraphic evidence of improvement. The majority of responders who were re-evaluated had improvement in autonomic testing (six of seven) or manometry (two of two). CONCLUSIONS & INFERENCES: This proof of principle study illustrates the importance of considering an autoimmune basis for idiopathic gastrointestinal dysmotility and supports the utility of a diagnostic trial of immunotherapy.

Primary intramedullary spinal cord lymphoma.

OBJECTIVE: Among the rare causes of myelopathies is primary intramedullary spinal cord lymphoma (PISCL). As PISCL is often underrecognized, delaying appropriate treatment, we sought to describe its presentation, imaging characteristics, and outcomes. METHODS: Mayo Clinic medical records, lymphoma database, and autopsies from 1996 to 2009 were searched. Inclusion criteria were clinical myelopathic presentation, intramedullary spinal cord abnormalities, and pathologically confirmed CNS lymphoma. Exclusion criteria were extramedullary lymphoma, secondary intramedullary lymphoma, or other myelopathic etiology. Clinical features, diagnostic methods, neuroimaging, treatment, and outcomes were assessed. RESULTS: The 14 patients' median age at presentation was 62.5 years (range 41-82 years) and 10 were men (71%). Two had lymphoma risk factors (HIV infection 1; chronic immunosuppression postorgan transplant 1). Most had initial presumptive diagnoses of CNS demyelinating disease and definitive diagnosis of lymphoma was delayed a median of 8 months (range 1-22 months). CNS lymphoma was pathologically confirmed by biopsy (brain 6; spinal cord 4), CSF cytology (3), and autopsy (1). Most patients had multifocal, persistently enhancing lesions on spinal MRI and 8 had involvement of conus medullaris, cauda equina, or both. IV methotrexate was the initial treatment in 9 of 12 (75%) but lymphoma recurred in the majority. Half of the patients were wheelchair-dependent at 10 months and 2-year survival was 36%. CONCLUSIONS: PISCL mimics other causes of myelopathy. Spinal MRI demonstrating multifocal lesions, persistent gadolinium enhancement, and conus medullaris or cauda equina involvement is characteristic. Pathologic confirmation often requires CNS biopsy. Despite chemotherapy, morbidity and mortality is high.

Paraneoplastic isolated myelopathy: clinical course and neuroimaging clues.

OBJECTIVE: To report the clinical phenotype and outcome of isolated paraneoplastic myelopathy. METHODS: We systematically reviewed clinical, serologic, and MRI data for 31 patients (20 female) who presented with an isolated myelopathy and coexisting cancer: carcinoma (lung, 9; breast, 7; kidney, 2; thyroid, 2; ovary/endometrium, 2), melanoma (2), or other cancer (3), or a paraneoplastic autoantibody with strong cancer association (amphiphysin-immunoglobulin G [IgG], 9; collapsin response-mediator protein 5-IgG, 9; Purkinje-cell cytoplasmic autoantibody type 1, 2; antineuronal nuclear autoantibody [ANNA]-1, 1; ANNA-3, 1). RESULTS: Of 31 patients who presented with a progressive myelopathy, symptom onset was subacute in 16 (52%). The median age was 62 years. CSF abnormalities included elevated protein (>45 mg/dL), 22; pleocytosis, 15; excess oligoclonal bands (normal <4), 7. MRI cord abnormalities identified in 20 patients were longitudinally extensive (>3 vertebral segments), 14; symmetric tract or gray matter-specific signal abnormality, 15 (enhancing in 13). Myelopathy preceded cancer diagnosis in 18 patients (median interval 12 months; range 2-44). After myelopathy onset, 26 patients underwent oncologic treatment, immunosuppressive treatment (median delay to commencing immunotherapy 9.5 months [range 1-54]), or both; only 8 improved (31%). At last neurologic evaluation (median interval after onset 17 months; range 1-165 months), 16 patients (52%) were wheelchair-dependent (median time from onset to wheelchair 9 months [range 1-21]). Ten patients died after a median of 38 months from symptom onset (range 7-152). CONCLUSION: Symmetric, longitudinally extensive tract or gray matter-specific changes on spinal MRI should raise suspicion for a paraneoplastic myelopathy. Resulting disability is often severe. Only a minority of patients improve with treatment.

Effect of water treatment on mutagenic potential.

Enzymatic activation did not convert the compounds in the sample concentrates into mutagens. These results are in agreement with those of CHEH et al. (1979) that the mutagenic activity was two to three times greater without the activating system than with it. The dose response relationships demonstrated a low level of mutagenic activity for the concentrates of the Lake Michigan samples. The MAR increases for the completely treated potable water. The concentrates of the Calumet River water to which chlorine had been added produced more revertants per volume of concentrate than did the concentrates of water which had not been chlorinated. Chlorination of the water with no additional treatment produced the highest degree of activity. For the Calumet River samples, treatment with coagulants reduced the net number of revertants to one-third the value for the raw water. When chlorine was added as the final treatment step, the net number of revertants increased by a factor of ten.