| Objective:Amyloid peripheral neuropathy of amyloidosis is a relatively rare type of peripheral neuropathy,the nonspecificity and heterogeneity of the clinical manifestations of amyloid peripheral neuropathy make the diagnose of the disease difficult and confusing.In order to provide help for the diagnosis of this disease,this study was conducted to analyze the clinical,electrophysiological and pathological characteristics of patients with amyloid peripheral neuropathy.Methods:Retrospective analysis of 14 patients diagnosed of amyloid peripheral neuropathy through peripheral nerve biopathy performed by muscle and peripheral nerve pathology laboratory in Qilu hospital of Shandong University from December 2017 to January 2020.Clinical presentation,laboratory examination,electrophysiological examination,neuropathology,genetic testing of the patients were concerned and a follow-up for patients was performed.Results:Clinical characteristic of 14 patients:There are 12 males and 2 females,aged 30-69 years,with an average age of 56.36±10.62 years.The time from onset to pathological diagnosis was 0.5-15 years,with a median of 2.5 years.All patients presented chronic onset,the first symptom of onset was weakness in 5 patients and was paresthesia in another 5 patients.A first involvement of lower limbs was observed in 6 patients and that of upper limbs was observed in 3,1 patient had all limbs involved at the time of onset.There was a symmetrical bilateral onset in 7 patients and a unilateral onset in 3 patients.4 patients started with dysautonomia(including 3 patients of digestive tract dysfunction and 1 case of postural hypotension).At the time of nerve biopsy,there were limbs weakness in 13 patients,all patients showed weakness in lower limbs and 12 showed weakness in upper limbs.12 patients exist muscular atrophy,including 9 patients with lower limbs atrophy and 6 patients with upper limbs atrophy.Muscle hypertrophy and macroglossia were found in 1 patient respectively.Tendon reflexes decreased or disappeared in 12 patients.Among the 14 patients,13 had sensory disorders with lower limbs involved in all these patients and 10 patents combined with sensory disorders in upper limbs;9 patients had disorders of proprioceptive and superficial sensory and 4 had only superficial sensory disorders.11 of the 14 patients had autonomic nerve dysfunction,including 7 patients with digestive system symptoms,7 patients with abnormal sweat secretion,4 patients with postural hypotension,and 2 male patients with erectile dysfunction.Weight loss occurred in 8 patients,and the range of weight loss within 2 years was 5-10kg.Laboratory examination:Serum immunofixation electrophoresis was performed in 12 patients,a monoclonal λ chain was showed in 2 and κ chain was showed in 1.Quantification of serum light chain was performed in 10 patients,1 case showed elevated λ,chain and 1 case showed ratio reduction of κ/λ.Monoclonal λ chain was showed in 5 patients and κ chain in 4 with quantification of urine light chain was performed in 8 patients,5 patients showed abnormal κ/λ ratio.Bone marrow aspiration was performed in 5 patients,4 of which showed abnormal monoclonal plasma cells.Cerebrospinal fluid examination:the examination was performed in 8 patients,and 6 patients had increased cerebrospinal fluid protein.There were no obvious abnormalities in blood routine,coagulation function,liver and kidney function,HIV antibody,serum syphilis antibody,serum vitamin,urine routine and rheumatism series in 14 patients.Electrophysiological examination:Nerve conduction and needle electromyography were performed in 13 patients,which showed a character of predominant axonal damage,nerve conduction was significantly abnormal at sites prone to entrapment in 3 patients,4 patients showed demyelinating characters.Skin sympathetic reaction was performed in 6 patients,and the latency was prolonged in 3,but the conduct wave could not be educed in 2 patients.All the 14 patients received sural nerve biopsy,with 4 patients of mild reduction of myelinated fibers,6 patients of moderate reduction,and 4 patients of severe reduction.Fluorescence microscopy(red fluorescence)was used to observe Congo red stained nerve sections of 14 patients,all showed amyloid diposition with significant flourescence.Among the 14 patients,muscle biopsy was performed in 2 patients with amyloid deposition was observed in 1 patient.Echocardiography was performed in 8 patients,left ventricular hypertrophy was reported in 5 patients of,diastolic dysfunction and abnormal filling of left ventricle were reported in 8 patients.Decreased ejection fraction of left ventricle was reported in 1 patient.Genetic examination:TTR gene detection was completed in 7 patients,and 5 patients were found carrying pathogenic mutations:3 patients with V50M mutation and 2 patients with E62G mutation,all of which were simple heterozygous mutations.4 of the 5 patients were of late-onset TTR-FAP.Treatment and follow-up:Among the 14 patients,2 were lost to follow-up,among which 1 patient was an WM patient and the other patient belongs to the group that was difficult to been classified.3 patients with hereditary TTR peripheral neuropathy received oral drug treatment with diflunisal,1 patient get improved with decreased body surface of numbness and hypodydrosis,2 showed no changes.2 patients received doxycycline and tauroursodeoxycholic acid,1 case showed improvement in autonomic nerve function,1 case showed no changes.Among the patients suspected to be AL,2 patients received chemotherapy,among which 1 patient showed aggravation of lower limbs sensation,limbs movement and gastrointestinal dysfunction.One patient died of refractory shock about 1 month after diagnosis.Conclusion:1.The 14 patients with amyloid peripheral neuropathy in this group were mainly males,and the onset was mostly after middle age and there was a common delayed diagnosis.Most patients showed symmetrical onset of bilateral lower limbs and manifestation of motor and sensory disorders companied by autonomic dysfunction.Macroglossia and weight loss suggested a possibility of amyloid peripheral neuropathy.2.Electrophysiological examination of the patients suggested peripheral neuropathy with predominant axonal damage.The abnormal skin sympathetic response and the abnormal nerve conduction at carpal or cubital tunnel suggested the possibility of amyloidosis peripheral neuropathy.3.Abnormal blood immunofixation electrophoresis,blood or urine light chain quantification or abnormal plasma cells cloning population in bone marrow may suggested a possibility of amyloid peripheral neuropathy.4.Combined fluorescence microscopy examination can increase the sensitivity of neuropathologic diagnosis,and most patients have a moderate or severe decrease in myelinated fiber density,indicating a sereve damage of nerve fibers.5.8 patients underwent echocardiography,all of whom had left ventricular diastolic dysfunction or abnormal filling.This suggests that amyloid peripheral neuropathy is a systemic disease that would have other organs involvement.6.Treatment with diflonilius or combined doxycycline with tauroursodeoxycholic acid could partially improve the symptoms of TTR-FAP patients,which means certain clinical significance. |
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