RESUMEN
BACKGROUND AND PURPOSE: Paraneoplastic neurological autoimmunity is well described with small-cell lung cancer, but information is limited for other neuroendocrine neoplasms (NENs). METHODS: Adult patients with histopathologically confirmed non-pulmonary NENs, neurological autoimmunity within 5 years of NEN diagnosis, and neural antibody testing performed at the Mayo Clinic Neuroimmunology Laboratory (January 2008 to March 2023) were retrospectively identified. Control sera were available from patients with NENs without neurological autoimmunity (116). RESULTS: Thirty-four patients were identified (median age 68 years, range 31-87). The most common primary tumor sites were pancreas (nine), skin (Merkel cell, eight), small bowel/duodenum (seven), and unknown (seven). Five patients received immune checkpoint inhibitor (ICI) therapy before symptom onset; symptoms preceded cancer diagnosis in 62.1% of non-ICI-treated patients. The most frequent neurological phenotypes (non-ICI-treated) were movement disorders (12; cerebellar ataxia in 10), dysautonomia (six), peripheral neuropathy (eight), encephalitis (four), and neuromuscular junction disorders (four). Neural antibodies were detected in 55.9% of patients studied (most common specificities: P/Q-type voltage-gated calcium channel [seven], muscle-type acetylcholine receptor [three], anti-neuronal nuclear antibody type 1 [three], and neuronal intermediate filaments [two]), but in only 6.9% of controls. Amongst patients receiving cancer or immunosuppressive therapy, 51.6% had partial or complete recovery. Outcomes were unfavorable in 48.3% (non-ICI-treated) and neural autoantibody positivity was associated with poor neurological outcome. DISCUSSION: Neurological autoimmunity associated with non-pulmonary NENs is often multifocal and can be treatment responsive, underscoring the importance of rapid recognition and early treatment.
Asunto(s)
Autoanticuerpos , Tumores Neuroendocrinos , Humanos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Tumores Neuroendocrinos/inmunología , Tumores Neuroendocrinos/complicaciones , Adulto , Anciano de 80 o más Años , Estudios Retrospectivos , Autoinmunidad/inmunología , Síndromes Paraneoplásicos del Sistema Nervioso/inmunología , Síndromes Paraneoplásicos del Sistema Nervioso/sangre , Enfermedades Autoinmunes del Sistema Nervioso/inmunología , Enfermedades Autoinmunes del Sistema Nervioso/sangreRESUMEN
Evaluation of rapidly progressive dementia (RPD) is usually challenging. In most cases, patients progress to dementia in weeks to months, and the differential diagnosis is broad. In this case, a woman in her 60s presented with a 1-month history of episodic vertigo, cognitive decline, ataxia and myoclonus. Cerebrospinal fluid total tau was markedly elevated, which was helpful in establishing the diagnosis and discussing prognosis/end-of-life measures with the patient's family. This case summarises a stepwise diagnostic approach for patients with RPD and highlights recent literature on biomarkers of Creutzfeldt-Jakob disease and autoimmune encephalitis.
Asunto(s)
Disfunción Cognitiva , Síndrome de Creutzfeldt-Jakob , Encefalitis , Mioclonía , Femenino , Humanos , Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/líquido cefalorraquídeo , Encefalitis/diagnóstico , Mioclonía/diagnóstico , Biomarcadores/líquido cefalorraquídeo , Disfunción Cognitiva/diagnóstico , Diagnóstico DiferencialRESUMEN
Jaw dystonia and laryngospasm in the context of subacute brainstem dysfunction have been described in a small number of diseases, including antineuronal nuclear antibody type 2 (ANNA-2, also known as anti-Ri) paraneoplastic neurologic syndrome. Severe episodes of laryngospasms causing cyanosis are potentially fatal. Jaw dystonia can also cause eating difficulty, resulting in severe weight loss and malnutrition. In this report, we highlight the multidisciplinary management of this syndrome associated with ANNA-2/anti-Ri paraneoplastic neurologic syndrome and discuss its pathogenesis.
Asunto(s)
Distonía , Laringismo , Síndromes Paraneoplásicos del Sistema Nervioso , Humanos , Laringismo/complicaciones , Laringismo/diagnóstico , Diplopía , Distonía/diagnóstico , Distonía/etiología , Anticuerpos AntinuclearesRESUMEN
BACKGROUND AND PURPOSE: Autoimmune encephalitis (AE) is a potentially treatable cause of rapidly progressive dementia that may mimic Creutzfeldt-Jakob disease (CJD). Alzheimer disease (AD) cerebrospinal fluid (CSF) biomarkers may discriminate CJD from AD, but utility in discriminating CJD and AE is unclear. This study compared AD CSF biomarkers in CJD and AE. METHODS: Patients with probable or definite CJD and probable or definite AE who underwent Roche Elecsys AD CSF biomarker testing at Mayo Clinic from March 2020 through April 2021 were included. Total-tau, phosphorylated181 tau and amyloid-ß42 levels were compared. RESULTS: Of 11 CJD cases, four were autopsy proven; the rest had positive real-time quaking-induced conversion testing. Disease-associated autoantibodies were detected in 8/15 cases of AE: leucine-rich glioma-inactivated 1 and neuronal intermediate filaments (two cases each), and N-methyl-d-aspartate receptor, contactin-associated protein-like 2, dipeptidyl-peptidase-like protein 6 and immunoglobulin-like cell adhesion molecule IgLON family member 5. Total-tau provided excellent discrimination between CJD and AE in a univariate model (odds ratio 1.46 per 100 pg/ml, 95% confidence interval 1.17-2.11, p < 0.05, c = 0.93). Total-tau was elevated in 91% of CJD cases (median > 1300, range 236->1300 pg/ml), of which 55% were above the limit of assay measurement (>1300 pg/ml). Total-tau was elevated in 20% of AE cases (median 158, range 80->1300 pg/ml). CONCLUSION: Total-tau was greater in CJD than AE. Given that amyloid-ß42 and phosphorylated181 tau were comparable, the ratio differences were probably driven by elevated total-tau in CJD. This study supports the role for AD biomarker testing in patients with rapidly progressive dementia.
Asunto(s)
Enfermedad de Alzheimer , Síndrome de Creutzfeldt-Jakob , Encefalitis , Enfermedad de Alzheimer/líquido cefalorraquídeo , Enfermedad de Alzheimer/diagnóstico , Biomarcadores/líquido cefalorraquídeo , Síndrome de Creutzfeldt-Jakob/líquido cefalorraquídeo , Síndrome de Creutzfeldt-Jakob/diagnóstico , Diagnóstico Diferencial , Encefalitis/diagnóstico , Enfermedad de Hashimoto , Humanos , Fosforilación , Proteínas tau/líquido cefalorraquídeoRESUMEN
The uncommon presentation of simultaneous brain and lung lesions in an immunocompetent adult patient with frequent travel to a mycobacterium tuberculosis (MTB) endemic area requires high clinical suspicion for central nervous system (CNS) MTB, as this disease often results in severe neurologic morbidity and mortality. Non-specific and subacute symptoms make the diagnosis of CNS MTB clinically challenging, and a workup with imaging and microbiological studies such as acid-fast bacilli staining, nucleic acid amplification testing, and tissue culture must not delay prompt treatment with anti-tuberculosis therapy. This case illustrates the complex challenges of medical diagnosis and multi-disciplinary decision-making involved in the workup of CNS MTB.