Prostate cancer, Hu antibodies and paraneoplastic neurological syndromes.

Prostate cancer is the most common cancer among American and European men. Nervous system affection caused by local tumor growth or osseous metastases are the main causes of neurological symptoms in prostate cancer patients. Prostate cancer is rarely reported in association with paraneoplastic neurological syndromes (PNS). We have, therefore, studied clinical and paraclinical findings of a series of patients with prostate cancer and PNS, and reviewed cases reported in the literature. Case histories of 14 patients with definite PNS from the PNS Euronetwork database and from the authors' databases were reviewed. A PubMed literature search identified 23 patients with prostate cancer and PNS. Thus, a total of 37 case histories were reviewed with respect to syndrome type, cancer evolution, paraclinical investigations, antibody status, treatment and outcome. The three most frequent isolated PNS were paraneoplastic cerebellar degeneration, paraneoplastic encephalomyelitis (PEM)/limbic encephalitis and subacute sensory neuronopathy (SSN). Onconeural antibodies were detected in 23 patients, in most cases the Hu antibody (17 patients, 74 % of all antibody-positive cases). Other well-characterized onconeural antibodies (Yo, CV2/CRMP5, amphiphysin, VGCC antibodies) were found in a minority. PNS was diagnosed prior to prostate cancer diagnosis in 50 % of the cases. The association of PNS with prostate cancer is quite infrequent, but clinically important. PNS often heralds prostate cancer diagnosis. Syndromes associated with Hu antibodies predominate. Another tumor more prone to associate with PNS should always be excluded.

A rare case of paraneoplastic cerebellar degeneration discovered by whole-body F-18 FDG PET.

A rare case of paraneoplastic cerebellar degeneration (PCD) in a 36-year-old woman is reported. She developed hyposthenia of the inferior limbs, diplopia, and disequilibrium in July 2001. Routine blood tests, tumoral markers, brain MRI, evoked potentials, and cerebrospinal fluid (CSF) examination were substantially normal. The clinical syndrome rapidly worsened in the following 2 months; she was wheelchair-bound with marked limb ataxia. CSF showed an increase of the IgG index with oligoclonal bands; brain MRI remained negative. The patient's serum and CSF were analyzed to detect antineuronal antibodies; anti-Yo antibodies were found that is typical of PCD. No tumor was found until April 2003; repeated CT scan, ultrasound, and mammographic examinations were negative. A further worsening in clinical symptoms was observed with a complete loss of autonomy (Rankin score 5) despite the performance of immunosuppressive therapy. In April 2003, an F-18 FDG PET scan visualized an area of abnormal uptake in the upper outer quadrant of the left breast. Interestingly, brain F-18 FDG uptake was normal. Suspicious microcalcifications were found on a new mammography and malignant cells were disclosed at cytology. The patient was operated on and final histologic examination revealed an infiltrating ductal breast cancer. In the reported case, F-18 FDG PET played a crucial role in detecting the unknown primary tumor in a young patient with PCD.

The spectrum of antineuronal autoantibodies in a series of neurological patients.

The aim of the present study is to identify the range of neurological disorders expressing antineuronal antibodies, evaluate the number of different patterns of reactivity that can be detected, and analyse the contribution of these studies to the identification of subgroups of patients. The records of 882 patients were reviewed and their sera and cerebrospinal fluids tested for antineuronal antibodies. Patients were initially divided into four groups according to suspected clinical diagnosis. Autoantibodies were detected by immunohistochemistry, Western blot of gradient-separated neuronal and recombinant proteins and by RIA. Cerebellar degeneration and sensory neuropathies were the most common neurological disorders in which paraneoplastic-related anti-neuronal antibodies were detected. However, in addition to PCA1/anti-Yo and ANNA1/anti-Hu antibodies, we found other reactivities in six patients with cerebellar degeneration: anti-GAD in three females and atypical in the other cases. The widest range of different anti-neuronal antibodies was detected in patients with peripheral sensory neuropathy. Few patients with Stiff-Person syndrome, temporal lobe epilepsy and myoclonus harboured anti-GAD antibodies. Atypical antibodies were detected in single cases with motor neuron disorder and multiple system atrophy. No anti-neuronal antibodies were detected in patients with neurological complications of connective tissue disorders other than Sjögren's syndrome, or in neurological diseases other than motor neuron disease and multiple system atrophy. Our study shows that the spectrum of neurological disorders in which anti-neuronal antibodies can be detected is wider than previously thought. In addition, we found patterns of neuronal staining and Western blot reactivity that differed from those so far reported. This may permit identification of subgroups of patients in whom strategies directed at removing and/or suppressing antibody production could be of some benefit.

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.

Neuronal loss in Onuf's nucleus in three patients with progressive supranuclear palsy.

Disorders of micturition have been reported only sporadically in patients with progressive supranuclear palsy (PSP). We report the results of a clinicopathological study of 3 patients with a definite diagnosis of PSP at various stages of their illness with sphincter abnormalities. Electromyography of the sphincter muscles was performed in all 3 patients and was abnormal in 2. Morphological and morphometric evaluation of Onuf's nucleus in the sacral spinal cord, which is involved in sphincter control, showed severe cell loss, presence of neurofibrillary tangles, neuropil threads, and glial inclusions. We conclude that bladder dysfunction and abnormal sphincter electromyographic results are due to pathological changes in Onuf's nucleus, and we propose that sphincter abnormalities should be included in the list of possible symptoms of PSP.