Updates in the Diagnosis and Treatment of Paraneoplastic Neurologic Syndromes.

The disorders of the central nervous system associated with cancer by remote immune-mediated mechanisms are a heterogeneous group. These disorders encompass the classic paraneoplastic disorders and the recently recognized autoimmune encephalitis associated with antibodies against neuronal cell surface or synaptic proteins that occur with or without cancer association. In the last decade, the new surge of interest in neuronal diseases associated with anti-neuronal antibodies led to the rapid discovery of new forms of disease that have different manifestations and were not previously suspected to be immune mediated. The recognition of these syndromes is important because it may lead to early detection of an underlying malignancy and prompt initiation of treatment, improving chances for a better outcome.

Autoimmune and paraneoplastic movement disorders: An update.

Movement disorders (MDs) are common in patients with autoimmune disorders affecting the central and peripheral nervous system. They may be observed in autoimmune disorders triggered by an infectious agent, such as streptococcus in Sydenham's chorea, or in basal ganglia encephalitis with antibodies against the dopamine-D2 receptors. In these patients chorea or dystonia are usually the most prominent hyperkinetic MDs. MDs are also observed in patients with diffuse or limbic encephalitis with antibodies directed against neuronal cell-surface antigens. Anti-NMDA receptor encephalitis is one of the most common and may present with a variety of MDs, including: chorea, stereotypies, dystonia and myorhythmia. The recognition of other abnormal motor phenomena such as "faciobrachial dystonic seizures" and neuromyotonia, observed in patients with LGI1 and Caspr-2 antibodies, is important because they may herald the onset of overt limbic encephalitis. Autoimmunity directed against the intracellular enzyme glutamic acid decarboxylase usually presents with MDs, most commonly stiff-person syndrome or cerebellar ataxia. Chorea may be observed in rheumatologic disorders such as systemic lupus erythematosus or antiphospholipid syndrome. Disorders with uncertain autoimmune mechanisms such as Hashimoto's encephalitis and idiopathic opsoclonus-myoclonus syndrome commonly present with tremor, myoclonus and ataxia. A rapid diagnosis of an autoimmune disorder, which typically presents with subacute onset, is critical as early therapeutic intervention improves long-term prognosis and may be life-saving. Treatment usually involves some form of immunotherapy and symptomatic therapy of the abnormal movements with dopamine depleters, dopamine receptor antagonists, or GABAergic drugs. Detection and removal of an underlying tumor is essential for optimal outcome.

Cáncer de mama metastásico oculto: a propósito de un caso / Hidden Metastatic Breast Cancer: A Case Report

El cáncer de mama triple negativo es un tumor agresivo que, muy pocas veces en la clínica, se presenta con un síndrome neurológico paraneoplásico asociado a un carcinoma metastásico de origen desconocido. Este artículo reporta una paciente con tal asociación y que su caso fue discutida en Clínica Patológica Institucional(AU)

Triple negative breast cancer is an aggressive tumor that, in the clinic, rarely presents with a paraneoplastic neurological syndrome associated with a metastatic carcinoma of unknown origin. This article reports a patient with such an association and that was discussed in Institutional Pathological Clinic(AU)

Limbic encephalitis associated with immature teratoma.

Paraneoplastic neurological syndrome (PNS) includes rare manifestations of different forms of cancer, in which the specific syndrome of limbic encephalitis can be found. This report describes a case of a previously healthy young lady who developed severe limbic encephalitis associated with an immature teratoma. After surgical treatment, the patient showed rapid progressive neurological improvement with complete regression of the symptoms during follow-up. Although rare, correct recognition and management of PNS is of great importance especially considering the fact that PNS can carry the risk of permanent disability or even death, even when associated with tumors in which high cure rates are expected.

Progressive encephalomyelitis with rigidity: a paraneoplastic presentation of oat cell carcinoma of the lung. Case report

A encefalomielite progressiva com rigidez e mioclonia (PEWR) é doença neurológica rara, caracterizada por rigidez muscular, espasmos dolorosos, mioclonia e evidência de envolvimento de tronco cerebral e medula espinhal. Um paciente branco de 73 anos foi admitido com história de 10 dias de espasmos musculares dolorosos e rigidez muscular contínua no membro inferior esquerdo. Apresentava espasmos involuntários em membros inferiores e evoluiu com encefalopatia associada a sinais de nervos cranianos e sintomatologia de trato longo de medula espinhal. A tomografia computadorizada de crânio e a ressonância magnética de coluna foram normais. O LCR evidenciou pleocitose linfocítica, sem outras alterações. A EMG mostrou atividade muscular involuntária, de duração de 2-6 segundos, intervalo de 30-50 ms e uma freqüência de 2/segundo no membro inferior esquerdo. Foram detectados anticorpos anti-GAD no sangue. Na evolução, foram observados sinais radiográficos de neoplasia pulmonar, sendo posteriormente diagnosticado carcinoma de pequenas células de pulmão. O paciente faleceu duas semanas após o diagnóstico de câncer.

Long-term neurobehavioral outcomes in children with neuroblastoma and opsoclonus-myoclonus-ataxia syndrome: relationship to MRI findings and anti-neuronal antibodies.

OBJECTIVES: Opsoclonus-myoclonus-ataxia (OMA) syndrome affects 2% to 3% of patients with neuroblastoma. This study examined relationships between long-term neurobehavioral outcomes and potential biologic markers of OMA, including chronic changes on magnetic resonance imaging (MRI) brain scanning and prevalence of late antineuronal antibodies. STUDY DESIGN: Children with neuroblastoma and OMA were identified through medical record review of patients treated at the University of California at San Francisco Medical Center from 1979 to 1999. Eleven patients with a mean follow-up time of 7.6 years underwent standard neurologic, neurocognitive, developmental/behavioral, and academic assessments. Consenting patients underwent MRI brain scanning and a blood draw. Sera were analyzed for the presence of antineuronal immunoreactivity. RESULTS: Two (18%) patients had no observed neurologic abnormalities, 7 (64%) demonstrated mild deficits, and 2 (18%) had severe neurologic deficits. However, on neurocognitive, behavioral, and academic assessments, 6 (55%) children performed within the average range, 1 (9%) was moderately below average and 4 (36%) had severe cognitive and behavioral deficiencies. Brain MRI in 5 of 5 patients was notable for cerebellar atrophy without supratentorial involvement. Antineuronal activity was detected in sera of 0 of 10 children at follow-up. CONCLUSIONS: Certain patients with neuroblastoma associated OMA may achieve average-range neurobehavioral function in spite of residual neurologic abnormalities, with suggestion of continued improvement over time. Late cerebellar atrophy appears to be a common finding regardless of neurologic outcome, whereas antineuronal immune reactivity does not appear to be a long-term feature of OMA.