Paraneoplastic Demyelinating Neuropathy, a Multifactorial Disease and Approach to Management.

We report a 53-year-old male with demyelinating polyneuropathy due to a paraneo- plastic syndrome from lymphoplasmacytic lymphoma. This syndrome is an immune-mediated event via plasma cell dyscrasia. The patient suffered near quadriplegia requiring prolonged ventilation. He was treatedwith systemic therapyforhis malignancy, as well as immunemodulating therapy with a recovery near his baseline. We propose it is important to not only control malignant plasma cell dyscrasia, but also target peripheral antibodies carrying out the attack in order to prevent further damage to the nervous system.

Case report of severe Cushing's syndrome in medullary thyroid cancer complicated by functional diabetes insipidus, aortic dissection, jejunal intussusception, and paraneoplastic dysautonomia: remission with sorafenib without reduction in cortisol concentration.

BACKGROUND: Normalization of cortisol concentration by multikinase inhibitors have been reported in three patients with medullary thyroid cancer-related Cushing's syndrome. Aortic dissection has been reported in three patients with Cushing's syndrome. Diabetes insipidus without intrasellar metastasis, intestinal intussusception, and paraneoplastic dysautonomia have not been reported in medullary thyroid cancer. CASE PRESENTATION: An adult male with metastatic medullary thyroid cancer presented with hyperglycemia, hypernatremia, hypokalemia, hypertension, acne-like rash, and diabetes insipidus (urine volume >8 L/d, osmolality 190 mOsm/kg). Serum cortisol, adrenocorticoitropic hormone, dehydroepiandrostenedione sulfate, and urinary free cortisol were elevated 8, 20, 4.4, and 340 folds, respectively. Pituitary imaging was normal. Computed tomography scan revealed jejunal intussusception and incidental abdominal aortic dissection. Sorafenib treatment was associated with Cushing's syndrome remission, elevated progesterone (>10 fold), normalization of dehydroepiandrostenedione sulfate, but persistently elevated cortisol concentration. Newly-developed proximal lower limb weakness and decreased salivation were associated with elevated ganglionic neuronal acetylcholine receptor (alpha-3) and borderline P/Q type calcium channel antibodies. CONCLUSION: Extreme cortisol concentration may have contributed to aortic dissection and suppressed antidiuretic hormone secretion; which combined with hypokalemia due cortisol activation of mineralocorticoid receptors, manifested as diabetes insipidus. This is the first report of paraneoplastic dysautonomia and jejunal intussusception in medullary thyroid cancer, they may be related to medullary thyroid cancer's neuroendocrine origin and metastasis, respectively. Remission of Cushing's syndrome without measurable reduction in cortisol concentration suggests a novel cortisol-independent mechanism of action or assay cross-reactivity. Normalization of dehydroepiandrostenedione sulfate and elevation of progesterone suggest inhibition of 17-hydroxylase and 21-hydroxylase activities by sorafenib.

Cytokines as Mediators of Pain-Related Process in Breast Cancer.

Pain is a clinical sign of inflammation found in a wide variety of chronic pathologies, including cancer. The occurrence of pain in patients carrying breast tumors is reported and is associated with aspects concerning disease spreading, treatment, and surgical intervention. The persistence of pain in patients submitted to breast surgery is estimated in a range from 21% to 55% and may affect patients before and after surgery. Beyond the physical compression exerted by the metastatic mass expansion and tissue injury found in breast cancer, inflammatory components that are significantly produced by the host-tumor interaction can significantly contribute to the generation of pain. In this context, cytokines have been studied aiming to establish a cause-effect relationship in cancer pain-related syndromes, especially the proinflammatory ones. Few reports have investigated the relationship between pain and cytokines in women carrying advanced breast cancer. In this scenario, the present review analyzes the main cytokines produced in breast cancer and discusses the evidences from literature regarding its role in specific clinical features related with this pathology.

Hodgkin lymphoma and hypothermia: case report and review of the literature.

We report the development of hypothermia in a patient with Hodgkin lymphoma which resolved with chemotherapy administration. A review of the literature revealed 16 previous reports of hypothermia in patients with Hodgkin lymphoma. Overall prognosis seems to be unfavorable. To the best of our knowledge this is the first report of hypothermia in a patient with Hodgkin lymphoma transforming from chronic lymphocytic leukemia (Richter's syndrome). A possible pathophysiology could be paraneoplastic autonomic neuropathy. Physicians should be aware that Hodgkin lymphoma can present with hypothermia and should carefully monitor newly diagnosed patients with advanced disease for this complication. Likewise, patients with Hodgkin lymphoma who develop hypothermia should be screened for signs of autonomic neuropathy.

Acute sensorimotor paraneoplastic neuropathy in a patient with small cell prostate cancer.

The authors describe a patient with a background of metastatic small cell prostate cancer who presented with a rapidly evolving sensorimotor neuropathy with bulbar features closely resembling Guillain-Barré syndrome, with a good initial response to intravenous immunoglobulins and platinum-based chemotherapy. This represented a likely paraneoplastic manifestation of the patient's urological malignancy.

Rare case of anti-CV2 paraneoplastic polyneuropathy associated with lung adenocarcinoma.

We describe the first case of anti-CV2 paraneoplastic polyneuropathy associated with lung adenocarcinoma. Our patient presented with progressive unsteadiness and numbness involving bilateral upper and lower limbs. He had symmetrical length-dependent lower motor neuron pattern of weakness and numbness involving both small and large fibres with prominent sensory ataxia. An extended workup for the polyneuropathy involving a serum paraneoplastic antineuronal antibody panel showed a positive reaction for anti-CV2 antibody. CT scan of the thorax, abdomen and pelvis revealed a right upper lung nodule and histopathological examination of the nodule revealed lung adenocarcinoma. He was scheduled for chemotherapy following his discharge and there was improvement of his sensorimotor polyneuropathy following his chemotherapy.

Amphiphysin-IgG autoimmune sciatic neuropathy and facial neuropathy related to primary central nervous system lymphoma: A case report.

We reported a 61-year-old man presented with 10-month progressing left sciatic neuropathy and 10-day right facial neuropathy. Serum amphiphysin-IgG was positive. 18F-FDG PET/CT of the whole body showed no signs of malignancy. Treatment with plasma exchange and oral prednisone relieved the symptoms. Nine months later, right hemiparesis and seizure of right limbs developed. 18F-FDG and 18F-PBR06 (18 kDa translocator protein, TSPO) radioligand PET/MRI of the whole body revealed intense uptake in the intracranial lesions. Intracranial lymphoma was diagnosed by stereotactic needle brain biopsy. Mononeuropathies could be paraneoplastic syndromes. TSPO shows high uptake in intracranial lymphoma on 18F-PBR06 PET images.

A clinical pattern-based etiological diagnostic strategy for sensory neuronopathies: a French collaborative study.

Sensory neuronopathies (SNNs) encompass paraneoplastic, infectious, dysimmune, toxic, inherited, and idiopathic disorders. Recently described diagnostic criteria allow SNN to be differentiated from other forms of sensory neuropathy, but there is no validated strategy based on routine clinical investigations for the etiological diagnosis of SNN. In a multicenter study, the clinical, biological, and electrophysiological characteristics of 148 patients with SNN were analyzed. Multiple correspondence analysis and logistic regression were used to identify patterns differentiating between forms of SNNs with different etiologies. Models were constructed using a study population of 88 patients and checked using a test population of 60 cases. Four patterns were identified. Pattern A, with an acute or subacute onset in the four limbs or arms, early pain, and frequently affecting males over 60 years of age, identified mainly paraneoplastic, toxic, and infectious SNN. Pattern B identified patients with progressive SNN and was divided into patterns C and D, the former corresponding to patients with inherited or slowly progressive idiopathic SNN with severe ataxia and electrophysiological abnormalities and the latter to patients with idiopathic, dysimmune, and sometimes paraneoplastic SNN with a more rapid course than in pattern C. The diagnostic strategy based on these patterns correctly identified 84/88 and 58/60 patients in the study and test populations, respectively.

A novel approach to paraneoplastic intestinal pseudo-obstruction.

Paraneoplastic neurologic syndromes (PNS) are uncommon, affecting fewer than 1 in 10,000 patients with cancer. PNS, while rare, can cause significant morbidity and impose enormous socio-economic costs, besides severely affecting quality of life. PNS can involve any part of the nervous system and can present as limbic encephalitis, subacute cerebellar ataxias, opsoclonus-myoclonus, retinopathies, chronic intestinal pseudo-obstruction (CIPO), sensory neuronopathy, Lambert-Eaton myasthenic syndrome, stiff-person syndrome, and encephalomyelitis. The standard of care for CIPO includes the use of promotility and anti-secretory agents and the resection of the non-functioning gut segment; all of which can cause significant compromise in the quality of life. There is significant evidence that paraneoplastic neurologic syndromes are associated with antibodies directed against certain nerve antigens. We successfully treated a patient with CIPO in the setting of small cell lung cancer with a combination of rituximab and cyclophosphamide. The patient, who had failed to respond to prokinetic agents, anti-secretory therapy, and multiple resections, responded to the immunomodulatory therapy, with minimal residuals with PEG tube feeding and sustained ostomy output. The use of rituximab and cyclophosphamide should therefore be considered in patients with CIPO, especially if it can avoid complicated surgical procedures.

Chronic demyelinating polyneuropathy preceding T-cell lymphoma: differentiation between primary neurolymphomatosis and paraneoplastic neuropathy.

A 49-year-old man presented with progressive asymmetric weakness and pain. Electrodiagnostic tests and nerve biopsy suggested chronic demyelinating polyneuropathy refractory to immune-modulating therapy. The patient's symptoms were aggravated, and he was finally diagnosed with T-cell lymphoma based on the findings of the second 18F-2 fluoro-2-deoxy-glucose positron emission tomography/CT performed 16 months after symptom onset. The patient received intravenous chemotherapy, but died 2 months later because of lymphoma progression. A clinical suspicion of neurolymphomatosis and early diagnosis are important for proper management.

[Paraneoplastic sensorimotor neuropathy with anti-Hu antibody associated with gallbladder carcinoma].

A 78-year-old woman experienced gait disturbance. She became unable to walk within a month. On admission, her cranial nerves were normal. She had motor weakness in the arms and legs, dysesthesia of the peripheral extremities, impaired deep sensation in the legs, and hyporeflexia in the arms and legs. She was initially diagnosed with Guillain-Barré syndrome; therefore, she was treated with intravenous immunoglobulin therapy and steroid mini-pulse therapy, however improvements of her neurological deficits were minimal. Anti-Hu antibody was positive in serum and gallbladder carcinoma was detected. She was treated with chemotherapy but neurological symptoms worsened progressively. Gallbladder carcinoma can rarely cause anti-Hu associated paraneoplastic sensorimotor neuropathy.

A case of IVIg responsive paraneoplastic SOX1 peripheral neuropathy in a male with breast carcinoma.

BACKGROUND AND AIMS: SOX1 antibodies are generally associated with small cell lung cancer and anti-Hu antibody overlap is common. This case demonstrates isolated anti-SOX1 antibodies with an uncommon tumor type, and relapse of a paraneoplastic syndrome with recurrence of tumor. METHODS: We describe a case of a 65-year-old male with a paraneoplastic peripheral neuropathy and anti-SOX1 antibody positivity in the context of a prior male breast Grade 2 ductal carcinoma, in remission at the time of the initial neurological presentation. RESULTS: Treatment response to intravenous immunoglobulin (IVIg) was demonstrated. After period of clinical stability on IVIg in the context of remission of breast carcinoma, the patient experienced a relapse of his neuropathy. This was associated with tumor recurrence and again responded to tumor excision, radiotherapy and IVIg. INTERPRETATION: Male breast carcinoma has not previously been associated with anti-SOX1 antibody positive paraneoplastic neuropathy.

Paraneoplastic sensitive neuropathy associated with anti-hu antibodies in a neuroendocrine tumor of duodenum: a case report.

Paraneoplastic sensitive neuropathy is one of the most common presentations among a group of cancer-related disorders known as Paraneoplastic Neurological Syndromes (PNS). PNS likely have an autoimmune etiology since they have been associated with the presence of antibodies against neuronal antigens expressed by tumor cells (such as anti-Hu, anti-Ri and anti-Yo). The tumors most frequently associated with PSN and onconeural antibodies are lung cancer, lymphomas and gynaecological tumors; however, they have also been described in other tumors. We report, for the first time, a case of neuroendocrine tumor of duodenum and PNS associated with anti-Hu antibodies. Moreover, we analyze and discuss the clinical implications that PNS and anti-Hu could have in patients with tumors.

[Paraneoplastic chorea and behavioral disorders in a patient with anti-CV2/CRMP5 antibodies and two different tumors]. / Chorée paranéoplasique et troubles du comportement chez un patient présentant des anticorps anti-CV2/CRMP5 et deux cancers différents.

INTRODUCTION: Paraneoplastic movement disorders are rare. Reported cases frequently describe association with anti-CV2/CRMP5 antibodies. CASE REPORT: We report a case of an 80-year-old man who developed sensorial neuronopathy, following by movement disorders mimicking chorea and obsessive-compulsive and behavioral disorders. These manifestations were first considered to be associated with a prostatic adenocarcinoma but PET and surgical biopsy revealed a mediastinal small cell lung carcinoma classically associated with anti-CV2/CRMP5 antibodies. CONCLUSION: This case demonstrates that in a context of paraneoplastic neurological syndrome, search for a classically associated cancer is necessary in order to institute adapted treatment early, even if another tumor is obvious.

[Case of systemic myositis and subacute sensory neuropathy concomitant with signet-ring cell carcinoma].

A 72-year-old woman referred to our hospital because of slowly progressive (over 2 years) muscle weakness and paresthesias of the lower limbs. On neurological examination, weakness and muscle atrophies were noted in the distal upper limbs as well as the proximal lower limbs. She had also paresthesias of the legs. The level of creatinine phosphokinase (CK) was 126 IU/l. The magnetic resonance imaging demonstrated gadolinium enhancement of the nerve roots at the L4-S2 vertebrate levels. Nerve conduction study showed decreased compound muscle action potential and motor conduction velocity of tibial and peroneal nerves. Biopsy of the left biceps brachii muscle showed variations in fiber size, endomysial mononuclear cell infiltration and the findings like a rimmed vacuole. Although almost of her findings were in accord with clinical features of inclusion body myositis, strong inflammatory cellular influences allowed us to administer corticosteroid therapy. Because her weakness was well responded to steroid therapy, polymyositis was considered as differential diagnosis. Then, further examinations were investigated to search any occult neoplasm, and detected the early gastric cancer. Total gastrectomy was performed later, and the pathological diagnosis was made as a signet-ring cell carcinoma. To our knowledge, this is the first report of systemic myositis and subacute sensory neuropathy concomitant with signet-ring cell carcinoma. These symptoms might be occurred as a result of paraneoplastic syndrome associated with satellite effects of the signet-ring cell carcinoma.