A Case Report of Pediatric Paraneoplastic Dysautonomia.

We present the case of a 16-year-old girl who presented with severe refractory orthostatic hypotension secondary to pandysautonomia. Initially, she was treated for Guillain-Barré syndrome given clinical symptoms and increased protein on cerebrospinal fluid, but the severity of symptoms and lack of response to intravenous immunoglobulin prompted further evaluation for an autoimmune etiology. She was ultimately diagnosed with paraneoplastic neuropathy secondary to Hodgkin lymphoma. Paraneoplastic neurologic phenomena are rare, occurring in just 0.01% of cancers, and prompt recognition is crucial for initiating appropriate therapy. Rapid progression of severe disabling symptoms should raise suspicion for an underlying malignancy. The patient had limited response to splanchnic vasoconstrictors in addition to α-agonists, anticholinergics, and mineralocorticoids until initiation of modified Hodgkin lymphoma directed chemotherapy plus rituximab.

Breast Cancer with Paraneoplastic Syndrome in a 72 Year Old Male Patient.

Breast cancer in male is rare which accounts about 1% of all malignant breast neoplasm cases. Since paraneoplastic syndrome is unusual with male breast cancer, very few reported cases are found. A72- year-old gentleman presented with proximal myopathy in all four limbs was referred to Dr. Sirajul Islam Medical College and Hospital in April 2017. He had generalized wasting with reduced tone and reflexes. Planter responses were normal with intact sensory. There were typical Heliotrope rash bilaterally. In background, he had history of radical mastectomy due to stage IIA ductal carcinoma of left breast 7 years back. Three years later, he was found to have multiple metastases in lung and liver, however, deliberately discontinued chemotherapy after first dose. Currently he is on Tamoxifen. Two months back, he was diagnosed to have brain metastasis. Also his serum sodium level was low with low urine osmolality. Considering his background, we diagnosed him dermatomyositis with peripheal neuropathy & SIADH as paraneoplastic presentation of breast malignancy. Despite of normal CPK and NCV, we treated him with steroid as dermatomyositis can present with normal CPK. His myopathy improved after 2 weeks of steroid treatment. Fluid restriction increased his serum sodium level. The aim of reporting this case is to aware physicians about the aggressive nature of male breast cancer, its orthodox paraneoplastic presentation and to differentiate neuropathy from myopathy so that early treatment can improve the outcome.

Retrospective study of paraneoplastic neurological syndromes in a Chinese Han population from Shandong, East China.

OBJECTIVE: To analyze the clinical features, diagnostic strategies and therapeutic methods associated with paraneoplastic neurological syndromes. METHODS: A retrospective study of paraneoplastic neurological syndromes was performed at a single center in Shandong, East China. The medical records and follow-up data of 28 patients were intensively reviewed between February 2011 and December 2014. RESULTS: Twenty-four (85.7%) patients experienced subacute or chronic onset of disease, and the most common symptoms reported were mild myasthenia and paresthesias. Twenty-five (89.3%) patients presented nervous system lesions prior to occult tumors, and the median time frame between paraneoplastic neurological syndromes onset and the diagnosis of a tumor was 15 weeks. Sensorimotor neuropathy, Lambert-Eaton myasthenic syndrome and limbic encephalitis were the three most common neurological syndromes reported. Elevated serum tumor markers were observed in 44.0% of patients, while 40.7% of patients were positive for onconeural antibodies. Tumors were detected in 21 (75.0%) patients after repeated whole-body screening, and lung carcinomas were the most common primary tumor detected. Seventeen patients received anti-tumor or immunological therapy, and clinical symptoms were relieved in 13 (76.5%) of these patients. CONCLUSIONS: In the majority of paraneoplastic neurological syndromes patients, the onset of disease is subacute or chronic with mild clinical symptoms. Nervous system lesions usually occur prior to occult tumors with complicated and various clinical manifestations. Neither tumor markers nor onconeural antibodies exhibit a high rate of occurrence, while repeated whole-body screening is helpful in identifying occult tumors. Early diagnosis and treatment are crucial to these patients.

Endoneurial edema in sural nerve may indicate recent onset inflammatory neuropathy.

INTRODUCTION: Sural nerve biopsy is an important means of establishing the diagnosis of inflammatory neuropathies. We investigated the diagnostic value of endoneurial edema. METHODS: Diagnostic sural nerve biopsies from 42 patients with inflammatory and 28 patients with noninflammatory neuropathies were re-evaluated for the presence of endoneurial edema. Edema was assessed on hematoxylin-eosin stained paraffin and frozen sections and on azure II-methylene blue stained semithin sections. We determined the area of endoneurial edema on digitized images in relation to the entire endoneurial area of each fascicle. RESULTS: Edema was more extensive in neuropathies with short disease duration (≤12 months) as compared to long duration (>12 months; P < 0.01). Edema in inflammatory neuropathies of ≤12 months duration covered a larger area than in noninflammatory neuropathies (P < 0.01), and the extent of edema correlated negatively with disease duration (P < 0.05). CONCLUSIONS: Endoneurial edema may be a useful additional disease marker in inflammatory neuropathies of recent onset.

Small Cell Lung Cancer Accompanied by Tonsillar Metastasis and Anti-Hu Antibody-Associated Paraneoplastic Neuropathy: A Rare Case Report With Long-Term Survival.

Tonsillar metastatic small cell lung cancer (SCLC) is rare, while anti-Hu antibodies are frequently found in SCLC. A 66-year-old man was admitted to our hospital with painful dysesthesia and muscle weakness in the distal extremities for over 1 year, progressive dysphagia for over 1 month, and severe cough and dyspnea for over 1 week. He was diagnosed with SCLC accompanied by tonsillar metastasis and anti-Hu antibody-associated paraneoplastic sensory neuropathy (PSN). The patient tolerated 6 cycles of sequential chemoradiotherapy and gradually recovered. The patient's disease remained in remission 2 years after the diagnosis with a remarkable reduction of tumor burden and a persisting high titer of anti-Hu antibodies. To our knowledge, this is the first case of tonsillar metastatic SCLC accompanied by anti-Hu antibody-associated PSN, whereby the anticancer immune response was presumed to play a vital role in disease control. Unilateral tonsillar metastasis of SCLC accompanied by anti-Hu antibody-associated PSN can occur and in certain circumstances, may have a favorable prognosis.

Meningeal carcinomatosis in a patient with Crohn's disease.

Leptomeningeal carcinomatosis, also known as carcinomatous meningitis, is defined by spreading of neoplastic cells to the meninges and ventricles, and is a form of cancer dissemination. In this case, a patient with inflammatory bowel disease had developed a neoplastic process that spread to the meninges. A 49-year-old woman developed an abdominal pain, and was diagnosed the same month with Crohn's disease, complicated with intestinal perforation, for which she was hospitalized. Pathological examination revealed acute phase-terminal ileitis. She undergone many hospitalizations during which she was suspected to have celiac disease, inflammatory bowel disease, and tuberculous meningitis, as well as femoral head necrosis after she had been unsuccessfully treated with Prednisone for Crohn's disease. After she developed peripheral bilateral facial paresis, bilateral hypoacusia, hypotonia, tetraparesis and diminished osteotendinous reflexes at the legs, the patient was admitted in our department. Several lumbar punctures were performed but no specific disease could be detected. The MRI performed showed pachymeningeal and leptomeningeal inflammation. Tuberculous meningitis was taken into consideration and the patient was transferred into an Infectious Disease Department where this diagnostic was infirmed. The patient was retransferred into the Department of Neurology where after an episode of hematemesis she had a cardiac arrest and deceased. Inflammatory bowel disease may involve different segments of the intestine, and may be accompanied by a variety of conditions, such as neurologic findings, osteoarticular manifestations and also may be the starting point of a neoplastic process. The patient had an inflammatory bowel condition, which by the time it was appropriately diagnosed as being Crohn's disease, a neoplastic process spread to the meninges, causing multiple cranial nerve palsy, tetraparesis, along other neurological manifestations.

Paraneoplastic lower motor neuronopathy associated with Hodgkin lymphoma.

INTRODUCTION: Paraneoplastic lower motor neuronopathies have been reported rarely with Hodgkin lymphoma. METHODS: We report a case of rapidly progressive motor neuronopathy preceding the diagnosis of Hodgkin lymphoma. RESULTS: A 31-year-old woman developed subacute rapidly progressive quadriparesis. Electrodiagnostic studies revealed a severe diffuse disorder of motor neurons and their axons. Symmetric enhancement of the cauda equina motor nerve roots was notable on magnetic resonance imaging scan. Further imaging demonstrated an enlarged supraclavicular lymph node, and biopsy revealed Hodgkin lymphoma. A final diagnosis of paraneoplastic motor neuronopathy was made after investigations for alternative causes of motor neuronopathy were unrevealing. Neurological improvement was seen with combined treatment of the underlying malignancy and intravenous immunoglobulin. CONCLUSIONS: Paraneoplastic causes should be considered in the differential diagnosis of subacute motor neuronopathy, as the neurological presentation may precede cancer detection. Combinations of lymphoma treatment and immunotherapy may result in a favorable outcome.

Narcolepsy, REM sleep behavior disorder, and supranuclear gaze palsy associated with Ma1 and Ma2 antibodies and tonsillar carcinoma.

OBJECTIVE: To describe a patient with diencephalic and mesencephalic presentation of a Ma1 and Ma2 antibody-associated paraneoplastic neurological disorder. DESIGN: Case report. SETTING: The Colorado Neurological Institute Movement Disorders Center in Englewood, Colorado, and the Mayo Clinic in Rochester, Minnesota. PATIENT: A 55-year-old man with a paraneoplastic neurological disorder characterized by rapid eye movement sleep behavior disorder, narcolepsy, and a progressive supranuclear palsy-like syndrome in the setting of tonsillar carcinoma. INTERVENTION: Immunotherapy for paraneoplastic neurological disorder, surgery and radiotherapy for cancer, and symptomatic treatment for parkinsonism and sleep disorders. MAIN OUTCOME MEASURES: Polysomnography, multiple sleep latency test, and neurological examination. RESULTS: The cancer was detected at a limited stage and treatable. After oncological therapy and immunotherapy, symptoms stabilized. Treatment with modafinil improved daytime somnolence. CONCLUSIONS: Rapid onset and progression of multifocal deficits may be a clue to paraneoplastic etiology. Early treatment of a limited stage cancer (with or without immunotherapy) may possibly slow progression of neurological symptoms. Symptomatic treatment may be beneficial.

Paraneoplastic neurological disorders.

The article provides an overview on the diagnosis and pathogenesis of paraneoplastic neurological disorders (PNDs), and subsequently the current therapeutic strategies in these patients. PNDs are nervous system dysfunctions in cancer patients, which are not due to a local effect of the tumor or its metastases. Most of these clinically defined syndromes in adults are associated with lung cancer, especially small-cell lung cancer, lymphoma and gynecological tumors. In a part of the PND, an overlapping of different clinical syndromes can be observed. Highly specific autoantibodies directed against onconeuronal antigens led to the current hypothesis of an autoimmune pathophysiology. Whereas the most central nervous PNDs are more T-cell-mediated, limbic encephalitis can be caused by pathogenic receptor autoantibodies. The PND of the neuromuscular junction and paraneoplastic autonomic neuropathy are mainly associated with receptor or ion channel autoantibodies. The childhood opsoclonus-myoclonus syndrome and the PNDs associated with receptor/ion channel autoantibodies often respond to immunosuppressive therapies, plasmapheresis and intravenous immunoglobulins. By contrast, most CNS PNDs associated with defined antineuronal antibodies directed against intracellular antigens only stabilize after tumor treatment.

Glutamic acid decarboxylase antibody-positive paraneoplastic stiff limb syndrome associated with carcinoma of the breast.

Stiff limb syndrome (SLS) is a rare "focal" variant of stiff person syndrome which presents with rigidity and painful spasms of a distal limb, and abnormal fixed foot or hand postures. Anti-glutamic acid decarboxylase antibodies (GAD-Ab) are variably present in most cases. Most reported cases of SLS are unassociated with cancer. We describe a patient with SLS as a paraneoplastic manifestation of breast carcinoma, in whom GAD-Ab was present. The patient responded very well to oral diazepam, baclofen and steroids.This is the third reported case of SLS as a paraneoplastic accompaniment to cancer.

[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.

Thymoma associated with myasthenia and autonomic anti-Hu paraneoplastic neuropathy.

Along with myasthenia, other paraneoplastic neurological syndromes (PNS) may occur in thymoma. Anti-Hu antibodies and a clinical "anti-Hu syndrome" characterized by encephalitis and/or painful neuropathies have been reported in only three patients at the time of the diagnosis of thymoma. We describe a severe anti-Hu-related autonomic neuropathy with gastrointestinal paresis and intestinal pseudo-obstruction with malabsorption that occurred concomitantly with the worsening of myasthenic symptoms long after the initial diagnosis of thymoma in a young patient. The clinical anti-Hu syndrome preceded the radiological diagnosis of thymoma recurrence. Treatment with plasma exchange led to a transient improvement of neurological symptoms.

A rare case of anti-Hu paraneoplastic neurologic syndrome in association with cervical cancer.

Anti-Hu antibodies, also known as ANNA-1, are well characterized in paraneoplastic neuropathies. We present here the first known case of anti-Hu seropositivity, cerebellar ataxia, and sensory neuropathy in association with cervical cancer.