Roberta Vitaliani

Paraneoplastic neurologic syndrome in the PNS Euronetwork database: a European study from 20 centers.

BACKGROUND Paraneoplastic neurologic syndrome (PNS) represents the remote effects of cancer on the nervous system. Diagnostic criteria for the syndrome were published by the PNS Euronetwork and form the basis of a database to collect standardized clinical data from patients with PNS. OBJECTIVES To analyze various types of PNS, frequent tumor and antibody associations, clinical characteristics of individual syndromes, and possible therapeutic and prognostic strategies. DESIGN Prospective case series and database study. SETTING Twenty European centers. Patients Patients were recruited from January 1, 2000, to December 31, 2008. MAIN OUTCOME MEASURES Based on diagnostic criteria published by the PNS Euronetwork consortium, clinical characteristics of classic PNS and several other less well-characterized syndromes associated with cancer were assessed. RESULTS Data from 979 patients were analyzed, representing the largest PNS investigation to date. The findings elucidate the clinical evolution of paraneoplastic cerebellar syndrome according to the onconeural antibodies present, the heterogeneity and prognosis of dysautonomic disorders, and the clinical variability of paraneoplastic limbic encephalitis. CONCLUSION The study results confirm that PNS influences oncologic patient survival. Tumors are the main cause of death, but some types of PNS (such as dysautonomia) have a poorer prognosis than malignant neoplasms.

Spectrum of paraneoplastic disease associated with lymphoma

Objective: To define the frequency and clinical and immunologic characteristics of patients affected by paraneoplastic neurologic syndromes (PNS) and lymphoma. Methods: Patients fulfilling the criteria for PNS associated with lymphoma collected from the European Commission-funded PNS Euronetwork group database were analyzed. Results: Fifty-three patients with Hodgkin lymphoma (HL) (24 patients, mean age 51, range 16–84) or non-Hodgkin lymphoma (NHL) (29 patients, mean age 64, range 31–82) and PNS were analyzed. The most commonly associated PNS was paraneoplastic cerebellar degeneration, present in 21 cases, with a higher prevalence in HL (16/24 cases). Peripheral nervous system (mainly demyelinating polyradiculopathies) and motor neuron involvement were more common in NHL. Onconeural antibodies were more frequent in patients with paraneoplastic cerebellar degeneration, most commonly against the Tr antigen. Fifty percent of the patients with PNS and HL responded to chemotherapy, whereas neurologic improvement was less frequent (24%) in patients with PNS and NHL. In both groups, the survival rate was good. Overall, 10 out of 53 patients eventually died, with only 2 patients (1 with HL, 1 with NHL) dying from PNS. Conclusions: PNS in patients with lymphoma are relatively rare. Paraneoplastic cerebellar degeneration, mainly associated with anti-Tr antibodies, is more prevalent in HL and NHL, followed in our study by motor neuron disease in patients with NHL. Involvement of the peripheral nervous system is heterogeneous, with a prevalence of polyradiculoneuritis in patients with NHL.

Spontaneous pain, pain threshold, and pain tolerance in Parkinson’s disease

The mechanisms underlying pain in Parkinson’s disease (PD) are unclear. Although a few studies have reported that PD patients may have low pain threshold and tolerance, none could accurately assess whether there was a correlation between sensory thresholds and demographic/clinical features of PD patients. Thus, tactile threshold, pain threshold, and pain tolerance to electrical stimuli in the hands and feet were assessed in 106 parkinsonian patients (of whom 66 reported chronic pain) and 51 age- and sex-matched healthy subjects. Linear regression models determined relationships between psychophysical parameters and demographic/clinical features. Female gender, severity of disease, medical disease associated with painful symptoms, and dyskinesia were more frequently observed in PD patients experiencing pain, even though dyskinesia did not reach significance. Pain threshold and pain tolerance were significantly lower in PD patients than in control subjects, whereas the tactile threshold yielded comparable values in both groups. Multivariable linear regression analyses yielded significant inverse correlations of pain threshold and pain tolerance with motor symptom severity and Beck depression inventory. Pain threshold and pain tolerance did not differ between PD patients with and without pain. In the former group, there was no relationship between pain threshold and the intensity/type of pain, and number of painful body parts. These findings suggest that pain threshold and pain tolerance tend to decrease as PD progresses, which can predispose to pain development. Female gender, dyskinesia, medical conditions associated with painful symptoms, and postural abnormalities secondary to rigidity/bradikinesia may contribute to the appearance of spontaneous pain in predisposed subjects.

Current approaches to the treatment of paraneoplastic encephalitis

Paraneoplastic neurological syndromes (PNSs) cover a wide range of diseases and involve both the central nervous system (CNS) and peripheral nervous system. Paraneoplastic encephalitis comprises several diseases such as paraneoplastic cerebellar degeneration (PCD), limbic encephalitis (LE), paraneoplastic encephalomyelitis (PEM), brainstem encephalitis, opsomyoclonus syndrome, in addition to other even less frequently occurring entities. LE was the first historically identified CNS PNS, and similarities between other temporal lobe diseases such as herpes encephalitis have been elucidated. In the past few decades several autoantibodies have been described in association with LE. These encompass the classical ‘onconeuronal’ antibodies (abs) such as Hu, Yo, Ri and others, and now additionally abs towards either ion channels or surface antigens. The clinical core findings in LE are various mental changes such as amnesia or confusion, often associated with seizures. Careful characterization of psychiatric manifestations and/or associated neurological signs can help to characterize the syndrome and type of ab. The treatment options in LE depend on the aetiology. In LE caused by onconeuronal abs, the treatment options are poor. In two types of abs associated with LE, abs against ion channels and surface antigens (e.g. NMDA), immunomodulatory treatments seem effective, making these types of LE treatable conditions. However, LE can also occur without being associated with cancer, in which case only immunomodulation is required. Despite effective treatments, some patients’ residual deficits remain, and recurrences have also been described.