Prevalencia y etiopatogenia del dolor oncológico neuropático en el anciano / Prevalence and aetiopathogenesis of neuropathic pain in elderly cancer patients

Es muy difícil estimar la prevalencia del dolor neuropático ya que la mayoría de los estudios que evalúan el dolor crónico no diferencian el nociceptivo del neuropático. Aún más complicado es obtener información de estudios que aborden específicamente el dolor neuropático en ancianos y más concretamente en población oncológica. En esta revisión no sistemática se analizan los artículos más relevantes acerca de la prevalencia y etiopatogenia del dolor oncológico neuropático en el anciano (AU)

The prevalence of neuropathic pain is difficult to estimate as most studies evaluating chronic pain do not differentiate neuropathic from nociceptive pain. There are only a few studies of neuropathic pain in the elderly, specifically in the oncology population. This article is a non-systematic review of the relevant evidence on the prevalence and aetiopathogenesis of neuropathic cancer pain in the elderly (AU)

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.

Poorly differentiated hepatocellular carcinoma accompanied by anti-Hu antibody-positive paraneoplastic peripheral neuropathy.

The anti-Hu antibody is one of the most famous onco-neural antibodies related to paraneoplastic neurological syndrome, and is associated with small cell lung carcinoma in most cases. Here, we report a case of poorly differentiated hepatocellular carcinoma accompanied by paraneoplastic peripheral neuropathy positive for the anti-Hu antibody. Image inspection before operation revealed that no tumors were found in organs other than the liver, including lung, and that the liver tumor had no metastatic lesion. The liver tumor showed histological appearance of poorly differentiated carcinoma with cartilaginous metaplasia and partial blastoid cell appearance. Most tumor cells presented trabecular-like structure lined by sinusoidal vessels. Immunohistochemically, the tumor cells were positive for low molecular weight cytokeratin and vimentin, partially positive for cytokeratin 19 and CD56, but negative for synaptophysin, chromogranin A and alpha-fetoprotein. Based on the trabecular-like morphology and the results of immunohistochemical staining, we concluded that the tumor was diagnosed as poorly differentiated hepatocellular carcinoma. Anti-Hu antibody-positive paraneoplastic peripheral neuropathy accompanied with liver tumor is extremely rare as far as is known. The presented case indicates that poorly differentiated carcinoma has the potential to be the responsible lesion of anti-Hu antibody-positive paraneoplastic neurological syndrome and systemic work-up is important for the management of this neurological disorder.

Magnetic resonance neurography of peripheral nerve tumors and tumorlike conditions.

Peripheral nerve enlargement may be seen in multiple conditions including hereditary or inflammatory neuropathies, sporadic or syndromic peripheral nerve sheath tumors, perineurioma, posttraumatic neuroma, and intraneural ganglion. Malignancies such as neurolymphoma, intraneural metastases, or sarcomas may also affect the peripheral nervous system and result in nerve enlargement. The imaging appearance and differentiating factors become especially relevant in the setting of tumor syndromes such as neurofibromatosis type 1, neurofibromatosis type 2, and schwannomatosis. This article reviews the typical magnetic resonance neurography imaging appearances of neurogenic as well as nonneurogenic neoplasms and tumorlike lesions of peripheral nerves, with emphasis on distinguishing factors.

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.

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.

Paraneoplastic subacute sensory neuronopathy in association with adenocarcinoma of the prostate.

Paraneoplastic syndromes arise infrequently in prostate cancer and paraneoplastic subacute sensory neuronopathy has not previously been reported in association with prostate cancer. When paraneoplastic syndromes occur, it is usually in the setting of small-cell carcinoma of the prostate or advanced, hormone-resistant disease. Here the authors report a 64- year-old man who developed a progressive, severe, sensory neuronopathy in the setting of a recently diagnosed stage T4 hormone-responsive prostate adenocarcinoma. Anti-Hu antibodies were positive and screening for a concurrent neoplasm at another site was negative. Sensory neuronopathy progressed, despite hormone responsiveness of his prostate adenocarcinoma, and resulted in a severe level of disability. His symptoms did not respond to intravenous corticosteroid therapy but there was a partial response to intravenous immunoglobulin.

[Is it optic neuritis? Differential diagnosis]. / Névrite optique. Diagnostics différentiels.

Optic neuritis is clinically suspected when painful, rapidly progressive central visual loss occurs in a young patient who has a relative afferent pupillary defect. Ophthalmoscopy is normal in the majority of cases but papillitis or optic disc palor can occur. Several other diseases can mimic optic neuritis, such as ophthalmological conditions or other diseases affecting the visual pathways. Their appropriate clinical diagnosis is of paramount importance in order to avoid unnecessary or invasive procedures or treatments.

[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.

Supraclavicular extraskeletal myxoid chondrosarcoma presenting with a sensorimotor polyneuropathy associated with anti-Hu antibodies.

Extraskeletal myxoid chondrosarcomas usually arise deep in the proximal extremities and limb girdles. Patients with this type of sarcoma have high rates of local recurrence and metastases, but do not typically have paraneoplastic syndromes. We report an unusual case of a 49-year-old man with anti-Hu syndrome in the setting of an extraskeletal myxoid chondrosarcoma. This case shows the importance of searching for antineural antibodies in oncologic patients with new neurologic deficits, and of having a judicious workup for occult malignancies in patients with known antineural antibodies.

Paraneoplastic sensory neuropathy associated with small cell carcinoma of the gallbladder.

A small number of patients with carcinoma of the gallbladder can present with a variety of paraneoplastic syndromes, including the Cushing syndrome, hypercalcemia, acanthosis nigricans, bullous pemphigoid, dermatomyositis, and the Leser-Trélat sign. We report on what appears to be the first case of a patient, a 48-year-old woman, with anti-Hu paraneoplastic sensory neuropathy and small cell carcinoma of the gallbladder. The patient's neurologic symptoms preceded the diagnosis of small cell carcinoma by 11 months. These symptoms improved after surgical removal of the tumor and chemotherapy. The small cell carcinoma was relatively small and was not associated with gallstones. In spite of the small size of the tumor, it metastasized to a celiac lymph node and probably to the liver. Anti-Hu paraneoplastic sensory neuropathy should be added to the list of paraneoplastic syndromes associated with small cell carcinoma of the gallbladder.

Paraneoplastic neurological syndromes in patients with carcinoid.

BACKGROUND: Paraneoplastic neurological syndromes (PNS) are mainly associated with small-cell lung cancer, gynaecological tumours and lymphomas. Few studies report the association of neurological syndromes with a carcinoid, the majority being a serotonin-related myopathy. We report four patients with a PNS associated with carcinoid. PATIENTS AND RESULTS: The clinical syndromes were sensory neuropathy, limbic encephalitis, myelopathy and brain stem encephalitis. Two patients had antineuronal autoantibodies (one anti-Hu, one anti-Yo), one patient had antinuclear antibodies, and one patient had no autoantibodies. For two of the carcinoids, expression of HuD in the tumour could be demonstrated. CONCLUSION: This study demonstrates that carcinoids can also be associated with classical antineuronal antibody-associated PNS.

Autoimmune and paraneoplastic channelopathies.

Thirty years ago, antibodies against the muscle acetylcholine receptor (AChR) were recognized as the cause of myasthenia gravis. Since then, there has been great interest in identifying other neurological disorders associated with autoantibodies. Several other antibody-mediated neuromuscular disorders have been identified, each associated with an antibody against a ligand- or voltage-gated ion channel. The Lambert-Eaton syndrome is caused by antibodies against voltage-gated calcium channels and often occurs in patients with small cell lung cancer. Acquired neuromyotonia is caused by voltage-gated potassium channel antibodies, and autoimmune autonomic ganglionopathy is caused by antibodies against the neuronal AChR in autonomic ganglia. There is good evidence that antibodies in these disorders cause changes in synaptic function or neuronal excitability by directly inhibiting ion channel function. More recently, studies have identified ion channel antibodies in patients with certain CNS disorders, such as steroid-responsive encephalitis and paraneoplastic cerebellar ataxia. It remains unclear if antibodies can gain access to the CNS and directly cause ion channel dysfunction. Treatment of autoimmune channelopathies includes drugs that help restore normal neuronal function and treatments to remove pathogenic antibodies (plasma exchange) or modulate the immune response (steroids or immunosuppressants). These disabling neurological disorders may be dramatically responsive to immunomodulatory therapy. Future studies will likely lead to identification of other ion channel antibodies and other autoimmune channelopathies.

Acute motor and sensory neuronopathy associated with small-cell lung cancer: a clinicopathological study.

A 48-year-old Chinese woman developed ascending motor paralysis while visiting Japan, leading to tetraplegia and respiratory failure over 2 weeks. The patient's course was complicated by anoxic encephalopathy. Nerve conduction studies revealed a severely decreased amplitude of compound muscle action potentials and a sural nerve biopsy specimen showed findings consistent with axonal-form Guillain-Barr6 syndrome. An autopsy, excluding the brain, demonstrated small-cell lung cancer that was not detected clinically, axonal-dominant degeneration in the nerve roots and distal peripheral nerves, and the loss of both myelin and axons in the dorsal spinal column. The spinal anterior horn cells were severely decreased and were accompanied by astrocytic reaction in all spinal segments with lymphocytic infiltration. A limited examination of the dorsal root ganglia did not show Nageotte nodules, but the infiltration of T cells was observed. Although the clinical course mimicked axonal-form Guillain-Barré syndrome, the autopsy demonstrated both sensory and motor neuronal involvement, as well as small-cell lung cancer. Although anti-Hu and antiganglioside antibodies were negative in the patient's serum, the para-neoplastic mechanism might have damaged the anterior horn and dorsal root ganglia cells, which subsequently led to secondary axonal degeneration. There has been a report on a case of paraneoplastic subacute motor neuronopathy, but the acute course described here has not been reported before.