Paraneoplastic and Other Autoimmune Neurologic Disorders

A paraneoplastic disorder arises from remote effects of malignancy, rather than direct tumor invasion. Paraneoplastic neurologic disorders occur because of the vigorous immune responses directed against antigens expressed in tumors. The vigor of the immune response usually ensures that neoplasm is confined to the primary organ and regional lymph nodes. However, in the clinical setting of paraneoplastic disease, the immune response may attack any part of the nervous system (brain, spinal cord, nerve, neuromuscular junction, or muscle), and antibodies are either directed at intracellular neuronal proteins or against neuronal cell surface or synaptic proteins. Treatment is often aimed at the cancer and suppression of the abnormal immune response.

Erythema Nodosum Revealing Metastatic Lung Cancer

Erythema nodosum (EN) is an inflammatory condition of the subcutaneous fat and has been reported in patients with haematological malignancies (lymphomas) or solid tumours. Lung cancer is the most common cause of paraneoplastic syndrome. We report a case of EN occurring as a paraneoplastic disease. A 48-year-old Tunisian woman, a non-smoker with no relevant medical history, presented with painful, erythematous, firm nodules on her legs with ankle swelling. The patient did not report any other symptoms. There were no abnormalities on examination except for moderate fever. An extensive infectious and immunological investigation was negative. Antistreptolysin antibodies were undetectable. Chest radiography showed a focal opacity in the right lung and a CT scan revealed a mass in the lower right pulmonary lobe with hilar and mediastinal lymphadenopathies, a nodule in the right adrenal gland, condensation in the iliac bone and multiple bilateral nodular cerebral expansive processes. Bronchial biopsies revealed a primitive and moderately differentiated adenocarcinoma. No argument for tuberculosis or sarcoidosis was found.

Paraneoplastic pemphigus caused by pre-existing stroma-rich variant of Castleman disease: from a pathologist’s point of view

A young woman presented with mucocutaneous blisters and ulcerating lesions, and was diagnosed with erythrodermic pemphigus complicated by bronchiolitis obliterans. Her clinical condition did not improve on immunosuppressive therapy. She had a history of an asymptomatic retroperitoneal mass, presumed to be a dermoid cyst, followed up clinically. Due to the pre-existing nature of the retroperitoneal mass, the paraneoplastic nature of the pemphigus was initially not recognised, but after a multidisciplinary team meeting a biopsy was performed. Histology revealed a rare stroma-rich variant of Castleman disease with a prominent stroma demonstrating a myoid phenotype. Resection of the retroperitoneal tumour resulted in resolution of the cutaneous blisters. This emphasises the importance to consider paraneoplastic disease in treatment-resistant pemphigus as surgical removal of the tumour forms the mainstay of therapy. The differential diagnosis should include Castleman disease and careful evaluation of histology is essential with the awareness of this rare stroma-rich variant.

Nicotinic ganglionic acetylcholine receptor autoantibodies associated with paraneoplastic disease in a neuropsychiatric patient

Nicotinic ganglionic acetylcholine receptor autoantibodies (alpha-3-AChR Ab) are associated with paraneoplastic syndromes when present in low elevations. These antibodies can be tested for as part of an autoimmune encephalopathy panel in neuropsychiatric patients; a mildly elevated titre of alpha-3-AChR Ab that may start as an incidental finding can lead to the diagnosis of a previously undetected cancer. While alpha-3-AChR Ab are most typically associated with thymomas and small cell lung cancer, the presence of these antibodies can suggest a diverse range of other cancers. This case presents a patient with longstanding neuropsychiatric symptoms and possible functional hypothyroidism for whom a low elevation in alpha-3-AChR Ab led to the finding of papillary thyroid carcinoma.

Trismus as a Presenting Symptom in a Case of Progressive Encephalopathy with Rigidity and Myoclonus

In this report we present a clinical case of trismus. The patient in question showed symptoms of trismus for 3 days, rapidly leading to respiratory insufficiency. Afterwards she developed myoclonus and progressive encephalopathy. Neurological workup showed no relevant abnormalities. A CT of the abdomen revealed a mass in the lower abdomen, which turned out to be an ovarian teratoma. Progressive encephalopathy with rigidity and myoclonus (PERM) was diagnosed clinically. Treatment with corticosteroids, benzodiazepines, and levetiracetam did not ameliorate the patient’s condition. Only after the introduction of plasmapheresis was there a spectacular improvement in her clinical state. In this case we could not detect associated antibodies. The most likely cause of PERM is paraneoplastic disease secondary to ovarian teratoma. This type of tumor has been associated with multiple paraneoplastic neurological conditions, but this is the first case associated with PERM. To date there is only one publication on trismus as a sole presenting sign, with a quite similar disease course.

Autoimmune Dementia

Dementia refers to an acquired syndrome of intraindividual cognitive decline that ultimately interferes with an individual's ability to manage their usual duties at work or home. As experience with the diagnosis and management of patients with autoimmune and paraneoplastic encephalitis (AE) has expanded, it has become increasingly apparent that dementia may arise as a subacute or chronic complication of immune-mediated injury to the central nervous system. Progressive memory and thinking problems may represent the first (or only) sign of an underlying autoimmune or paraneoplastic disease. Accordingly, there is a need to routinely consider the diagnosis of AE in patients with dementia, and to evaluate patients recovering from AE for clinically meaningful cognitive impairment. We review and summarize the available evidence concerning the diagnosis and care of AE patients with associated cognitive impairment, herein referred to as autoimmune dementia (AiD). Relevant information is used to propose a novel diagnostic framework that may be applied to improve recognition, and facilitate the expedited evaluation and treatment of patients with AiD.