Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polyneuropathy associated with IgM monoclonal gammopathy has been documented first for Waldenstrom's disease, then for IgM monoclonal gammopathy of undetermined significance (MGUS). The usual clinical aspect is a chronic symmetric predominantly sensory polyneuropathy, occurring insidiously in elderly patients. Tremor and ataxia are characteristic findings, but their mechanism is unclear. The electrophysiological and pathological features are consistent with a primary demyelination with secondary axonal loss. Monoclonal IgM level is frequently low in MGUS cases and the light chain is Kappa in most of the cases. The IgM M-protein is shown to bind to myelin-associated-glycoprotein (MAG) and/or other antigens of the peripheral nerve myelin in most of the cases. The course of the polyneuropathy is usually slowly progressive. Some other clinical aspects of peripheral neuropathy associated to IgM monoclonal gammopathy have been reported. Recently the attention has been directed towards motor neuron diseases (MND) associated to IgM MGUS, but the significance of this association remains unclear.
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PMID:Polyneuropathy associated with IgM monoclonal gammopathy: a review. Clinical, electrophysiological and pathological features. 196 90

Recent papers underline the possible involvement of the central nervous system when an acquired peripheral demyelinating disease occurs and vice-versa. We describe five patients with chronic polyneuropathy and "benign" gammopathy, monoclonal (IgM-K, IgA-k, IgG-k) in three cases and polyclonal (IgG, IgM) in two cases; the monoclonal gammopathies were detected in cases of peripheral nerve disease. Three patients showed tremor and signs of pyramidal system impairment when the peripheral damage had improved or was stable. All cases underwent a longitudinal assessment according to clinical, CSF, EMG-ENG, neuroradiological and pathological criteria. The MRI finding always showed multiple alterations of encephalic white matter. When related to neurophysiological and pathological data supporting a chronic demyelinating neuropathy, such results point to possible encephalic involvement in chronic polyneuropathies due to a pathogenetic mechanism common to both.
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PMID:Evidence of central nervous system involvement in chronic demyelinating neuropathies associated with "benign" gammopathies. 254 77

Monoclonal gammopathies are frequently associated with peripheral neuropathies of which clinical, electrophysiological, pathological and possibly pathogenetical aspects are heterogeneous. Nevertheless some clinico-biological entities, which account for the majority of cases, have been recently recognized: 1) The IgM neuropathy is a chronic demyelinating sensori-motor polyneuropathy with tremor and ataxia as prominent features. It can be either associated with MGUS or Waldenstrom macroglobulinemia. The light chain of the gammopathy is kappa in a majority of cases. Numerous reports have demonstrated specific antibody activities supported by the M-protein and directed against various peripheral nerve antigens, usually myelin components such as the myelin associated glycoprotein (MAG). The ultrastructural evidence of widely spaced myelin is suggestive of the diagnosis but is not consistent. Treatment directed towards the gammopathy is occasionally associated with improvement of the symptoms. 2) The neuropathy of the osteosclerotic myelomas and solitary plasmacytomas present as a chronic sensori-motor polyradiculoneuropathy with conspicuous demyelination and may be associated with one or more of the systemic clinical features of the Crow-Fukase or POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, Skin changes). The POEMS syndrome may also be associated with "benign" monoclonal or even polyclonal dysproteinemias. The M-proteins are almost all IgG or IgA with lambda light chains. There are some relations between POEMS syndrome and Castleman's disease. The pathogenesis of both disorders remains obscure. Treatment is most favorable in case of solitary plasmacytomas, which may be completely removed. 3) The neuropathy observed in patients with primary AL amyloidosis or amylosis associated with malignant plasma-cell dyscrasias is rare. Sensory deficit and autonomic dysfunction are related to a prominent involvement of small myelinated and unmyelinated fibers. A clinical and/or electro-physiological carpal tunnel syndrome is frequent. In a majority of cases the light chain of the M-protein is lambda. Amyloid deposits are observed on nerve biopsy. Treatment is inefficient. 4) The neuropathy associated with cryoglobulinemias may be asymmetric, painful, cryosensitive and associated with cutaneous purpura and neuromuscular vasculitis. In fact, in a majority of cases the symptoms are less suggestive raising the problem of an incidental laboratory finding. 5) A motoneuron disease-like syndrome may develop in patients with various types of monoclonal gammopathies.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Dysglobulinemic neuropathies]. 284 76

A 49-year-old man was admitted with the chief complaints of muscle weakness and gait disturbance. His neurological examination was compatible with peripheral neuropathy, and laboratory tests revealed IgA monoclonal gammopathy, increased protein content in the cerebrospinal fluid (CSF) without pleocytosis, and slow motor and sensory nerve conduction velocity. He was diagnosed as having chronic inflammatory demyelinating polyneuropathy with IgA monoclonal gammopathy of undetermined significance. The patient was treated with steroid, and plasmapheresis. He became so restless that antidepressant and haloperidol were administered. Then, he became unresponsive, and developed high fever, sweating, tachycardia, and tremor. Examination of CSF showed increased 3-methoxy-4-hydroxy-phenylglycol and decreased homovanillic acid. He was diagnosed as having neuroleptic malignant syndrome (NMS). However, his muscle tonus was still flaccid in his lower extremities that had been suffered from chronic polyneuropathy. Interestingly, his serum creatine kinase (CK) content was only slightly elevated. We suppose that the pathophysiological location of NMS might be primarily central, and that muscle rigidity and elevation of serum CK might not occur, if the peripheral nerves were completely impaired.
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PMID:[Neuroleptic malignant syndrome in a patient with polyneuropathy: mechanism of muscle rigidity and elevated serum creatine kinase levels]. 1020 83

Many data point to a pathogenetic role for IgM antibodies to the myelin-associated glycoprotein (MAG) in the neuropathy associated with IgM monoclonal gammopathy, supporting the use of immune therapies in affected patients. Almost 50% of patients have been reported to improve with these therapies, but the effect of treatment on the long-term prognosis of the neuropathy remains unclear. We analysed the outcome of 25 of the 26 patients (mean age at entry 65 years, range 45-85 years) with neuropathy and high anti-MAG IgM, first examined by us between 1984 and 1994. By January 1999, after a mean follow-up of 8.5 years (range 2-13 years) and a mean duration of neuropathy symptoms of 11.8 years (range 3-18, >10 years in 16), 17 patients (68%) (aged 58-84 years, mean 73.4) were alive, while eight (32%) (aged 69-78 years, mean 73.1) had died 3-15 years (mean 10.6) after neuropathy onset; in none of them was death caused by the neuropathy, although in three it was possibly related to the therapy for the neuropathy. By the time of last follow-up or patients' death, 11 patients (44%) were disabled by severe hand tremor, gait ataxia or both. The disability rates at 5, 10 and 15 years from neuropathy onset were 16, 24 and 50%, respectively. Of the 19 patients treated during the follow-up for 0.5-11 years (mean 4 years) with various immune therapies, five reported a consistent and four a slight improvement in the neuropathy (total 47%) after one treatment or more, but in only one patient was improvement persistent throughout, to the end of follow-up. In 10 patients (53%), severe adverse events, possibly related to therapy, occurred during treatment and were considered responsible for the patient's death in three. The neurological impairment did not differ between treated and untreated patients at the end of a similar follow-up. Our findings indicate that (i) the majority of patients with neuropathy and anti-MAG IgM have a favourable prognosis even after several years, and (ii) current immune therapies, though temporarily effective in half of the patients, are associated with considerable side effects which limit their prolonged use and efficacy, suggesting that until more effective or safer therapies become available, they should probably be reserved for patients impaired in their daily life or in a progressive phase of the disease.
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PMID:Long-term prognosis of neuropathy associated with anti-MAG IgM M-proteins and its relationship to immune therapies. 1073 2

We demonstrate the effect of deep brain stimulation of the ventral intermediate thalamic nucleus on intractable action tremor, in a 72-year-old man suffering from neuropathy associated with monoclonal gammopathy.
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PMID:VIM thalamic stimulation for tremor in a patient with IgM paraproteinaemic demyelinating neuropathy. 1453 27

Schnitzler syndrome is a rare idiopathic disease characterized by chronic urtica, presence of monoclonal IgM immunoglobuline and further, less common symptoms. This case report describes another case of this disease affecting a male adult born in 1963. The first symptoms, eruptions of non-pruritic urticarial rash, appeared in this patient at the age of 43. In addition, bone pains (mainly tibias) and joint pains (mainly knees) were present. Later on however, severe attacks of fever, chills and shaking together with bone and joint pains were added to during which new urticarial eruptions appeared. Primarily, the man was followed up without any substantial therapeutic results at a department of dermatovenerology, subsequently, due to a finding of monoclonal IgM kappa immunoglobulin (serum concentration 1.9 g/l) he was referred to our department for the reason of gammopathy being a differential diagnosis. On a CT scan hyperostosis in claviculae and pelvic bones was identified. Also on the CT, an increase in cortical thickness was described in the long bones of the lower extremities, where areas of technetium pyrophosphate accumulation were identified on a bone scintigraphy. These areas were found in the chest and sacral regions as well. From the blood exams, the proinflammatory status of the organism was apparent (CRP 35.9 mg/l, erythrocyte sedimentation rate 92 mm/h, leukocytes 12.4 x 10(9)/l). After excluding other differential diagnoses, the patient was diagnosed with Schnitzler syndrome. As regards therapy, we made initial use of the effect of corticoids which abated the symptoms, however, these were causing serious adverse reactions in the form of iatrogenous Cushing's syndrome. The therapy took a turn only after biologic therapy with anakinra (interleukin-1 receptor antagonist) had started, which minimized the Schnitzler symptoms with very good drug tolerance. In the work we measured serum levels of interleukins for disease activity monitoring. The most sensitive were interleukins IL-6 and especially IL-18 the levels of which were the highest at the time of clinical exacerbation of the disease, whereas the levels of IL-1beta and TNF-alpha (tumour necrosis factor) were during all measurements below the limit of detection. Concerning the growing numbers of the reports on successful biological therapy with anakinra and our positive experience, we propose that the therapeutic response to anakinra should be included within the diagnostic criteria of Schnitzler syndrome, which is significant above all in differential diagnosis thereof.
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PMID:[Schnitzler syndrome: case report, the experience with glucocorticoid and anakinra (Kineret) therapies and monitoring of systemic cytokine response]. 2135 69

At age 35, a man with a genetic diagnosis of Charcot-Marie-Tooth disease type 1A (CMT1A) but no family history of neuropathy and no clinical symptoms developed rapidly progressive loss of balance, distal limb numbness, loss of manual dexterity, and hand tremor. Five years later, he walked with support and had mild pes cavus, marked sensory ataxia, severe leg and hand weakness, absent deep tendon reflexes (DTRs), severe sensory loss, and hand tremor. He had dramatically reduced motor nerve conduction velocity (MNCV), strikingly prolonged motor distal latencies, absent sensory action potentials and lower limb compound muscle action potentials. CMT1A duplication was reconfirmed but the dramatic change in his clinical course suggested a superimposed acquired neuropathy. An IgM-kappa monoclonal gammopathy of uncertain significance (MGUS) with high titer anti-myelin associated glycoprotein (anti-MAG) activity was found. Nerve biopsy showed severe loss of myelinated fibers with onion bulbs, no evidence of uncompacted myelin, and few IgM deposits. Rituximab was given and he improved. It is very likely that this is a chance association of two rare and slowly progressive neuropathies; rapidly worsening course may have been due to a "double hit". Interestingly, there are reports of possible superimposition of dysimmune neuropathies on hereditary ones, and the influence of the immune system on inherited neuropathies is matter for debate.
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PMID:Coexistence of Charcot-Marie-Tooth disease type 1A and anti-MAG neuropathy. 2378 67