Beecher Grayson, Shelly Shahar, Dyck P James B, Mauermann Michelle L, Martinez-Thompson Jennifer M, Berini Sarah E, Naddaf Elie, Shouman Kamal, Taylor Bruce V, Dyck Peter James, Engelstad JaNean, Howe Benjamin M, Mills John R, Dubey Divyanshu, Spinner Robert J, Klein Christopher J
From the Departments of Neurology (G.B., S.S., P. James B. Dyck, M.L.M., J.M.M.-T., S.E.B., E.N., K.S., Peter James B. Dyck, D.D., C.J.K.), Radiology (B.M.H.), Laboratory Medicine and Pathology (P. James B. Dyck, Peter James B. Dyck, J.E., J.R.M., D.D., C.J.K.), and Neurosurgery (R.J.S.), Mayo Clinic, Rochester, MN; and Menzies Institute for Medical Research (B.V.T.), University of Tasmania, Australia.
Neurology. 2021 Oct 4;97(14):e1392-e1403. doi: 10.1212/WNL.0000000000012618.
To longitudinally investigate patients with multifocal acquired demyelinating sensory and motor neuropathy (MADSAM), quantifying timing and location of sensory involvements in motor onset patients, along with clinicohistopathologic and electrophysiologic findings to ascertain differences in patients with and without monoclonal gammopathy of uncertain significance (MGUS).
Patients with MADSAM seen at Mayo Clinic and tested for monoclonal gammopathy and ganglioside antibodies were retrospectively reviewed (January 1, 2007-December 31, 2018).
Of 76 patients with MADSAM, 53% had pure motor, 16% pure sensory, 30% sensorimotor, and 1% cranial nerve onsets. Motor-onset patients were initially diagnosed with multifocal motor neuropathy (MMN). MGUS occurred in 25% (89% immunoglobulin M [IgM] subtype), associating with ganglioside autoantibodies ( < 0.001) and higher IgM titers ( < 0.04). Median time to sensory involvements (confirmed by electrophysiology) in motor onset patients was 18 months (range 6-180). Compared to initial motor nerve involvements, subsequent sensory findings were within the same territory in 35% (14/40), outside in 20% (8/40), or both in 45% (18/40). Brachial and lumbosacral plexus MRI was abnormal in 87% (34/39) and 84% (21/25), respectively, identifying hypertrophy and increased T2 signal predominantly in brachial plexus trunks (64%), divisions (69%), and cords (69%), and intrapelvic sciatic (64%) and femoral (44%) nerves. Proximal fascicular nerve biopsies (n = 9) more frequently demonstrated onion-bulb pathology ( = 0.001) and endoneurial inflammation ( = 0.01) than distal biopsies (n = 17). MRI and biopsy findings were similar among patient subgroups. Initial Inflammatory Neuropathy Cause and Treatment (INCAT) disability scores were higher in patients with MGUS relative to without ( = 0.02). Long-term treatment responsiveness by INCAT score reduction ≥1 or motor Neuropathy Impairment Score (mNIS) >8-point reduction occurred in 75% (49/65) irrespective of MGUS or motor onsets. Most required ongoing immunotherapy (86%). Patients with MGUS more commonly required dual-agent immunotherapy for stability ( = 0.02).
Pure motor onsets are the most common MADSAM presentation. Long-term follow-up, repeat electrophysiology, and nerve pathology help distinguish motor onset MADSAM from MMN. Better long-term immunotherapy responsiveness occurs in motor onset MADSAM compared to MMN reports. Patients with MGUS commonly require dual immunotherapy.
This study provides Class II evidence that most clinical, electrophysiologic, and histopathologic findings were similar between patients with MADSAM with and without MGUS.
纵向研究多灶性获得性脱髓鞘感觉运动神经病（MADSAM）患者，量化运动起病患者感觉受累的时间和部位，并结合临床组织病理学和电生理检查结果，以确定意义未明的单克隆丙种球蛋白病（MGUS）患者与非MGUS患者之间的差异。
对梅奥诊所就诊并接受单克隆丙种球蛋白病和神经节苷脂抗体检测的MADSAM患者进行回顾性研究（2007年1月1日至2018年12月31日）。
76例MADSAM患者中，53%为单纯运动起病，16%为单纯感觉起病，30%为感觉运动起病，1%为颅神经起病。运动起病患者最初被诊断为多灶性运动神经病（MMN）。MGUS发生率为25%（89%为免疫球蛋白M [IgM]亚型），与神经节苷脂自身抗体相关（<0.001）且IgM滴度较高（<0.04）。运动起病患者感觉受累（经电生理证实）的中位时间为18个月（范围6 - 180个月）。与最初的运动神经受累相比，随后的感觉检查结果在同一区域的占35%（14/40），在区域外的占20%（8/40），两者皆有的占45%（18/40）。臂丛和腰骶丛MRI异常率分别为87%（34/39）和84%（21/25），主要表现为臂丛干（64%）、分支（69%）和束（69%）以及盆腔内坐骨神经（64%）和股神经（44%）的肥大和T2信号增强。与远端活检（n = 17）相比，近端束状神经活检（n = 9）更常显示洋葱球样病理改变（= 0.001）和神经内膜炎症（= 0.01）。MRI和活检结果在各患者亚组中相似。MGUS患者的初始炎症性神经病病因与治疗（INCAT）残疾评分高于非MGUS患者（= 0.02）。无论有无MGUS或运动起病情况，75%（49/65）的患者通过INCAT评分降低≥1或运动神经病损害评分（mNIS）降低>8分实现长期治疗反应。大多数患者需要持续免疫治疗（86%）。MGUS患者更常需要联合免疫治疗以维持病情稳定（= 0.02）。
单纯运动起病是MADSAM最常见的表现形式。长期随访、重复电生理检查和神经病理学检查有助于将运动起病的MADSAM与MMN区分开来。与MMN报道相比，运动起病的MADSAM患者长期免疫治疗反应更好。MGUS患者通常需要联合免疫治疗。
本研究提供II级证据表明，有MGUS和无MGUS的MADSAM患者在大多数临床、电生理和组织病理学检查结果方面相似。
