Clinicopathological features of adult-onset neuronal intranuclear inclusion disease.
Clinicopathological features of adult-onset neuronal intranuclear inclusion disease.
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DOI：
10.1093/brain/aww249
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发表时间：
2016-12
期刊：
影响因子：
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通讯作者：
Sobue G
中科院分区：
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作者：
Sone J;Mori K;Inagaki T;Katsumata R;Takagi S;Yokoi S;Araki K;Kato T;Nakamura T;Koike H;Takashima H;Hashiguchi A;Kohno Y;Kurashige T;Kuriyama M;Takiyama Y;Tsuchiya M;Kitagawa N;Kawamoto M;Yoshimura H;Suto Y;Nakayasu H;Uehara N;Sugiyama H;Takahashi M;Kokubun N;Konno T;Katsuno M;Tanaka F;Iwasaki Y;Yoshida M;Sobue G
神经元核内包涵病（NIID）的临床表现变化很大。Sone等人描述了57例通过死后解剖/死前皮肤活检诊断的成人发病病例的临床和病理特征。他们报告了“痴呆显性”和“肢体无力”亚型，并建议在白质脑病和神经病变的鉴别诊断中考虑NIID。神经元核内包涵体病（NIID）是一种缓慢进展的神经退行性疾病，以中枢和周围神经系统以及内脏器官的嗜酸性透明蛋白核内包涵体为特征。由于临床表现多变，NIID一直被认为是一种异质性疾病，且尸检诊断困难。然而，自从我们报道了皮肤活检诊断NIID的有效性以来，NIID诊断的数量有所增加，特别是成人发病的NIID。在这项研究中，我们研究了57例成人发病的NIID，并描述了他们的临床和病理特征。我们分析了死后解剖和死前皮肤活检诊断的NIID病例，这些病例基于特征性嗜酸性粒细胞、透明蛋白和泛素阳性核包涵的存在：38例散发病例和19例家族性病例，来自6个家庭。在51 ~ 76岁的散发性NIID病例中，痴呆是最突出的首发症状（94.7%），被称为“痴呆优势组”，其次是缩小、共济失调和意识不清。肌肉无力和感觉障碍也被观察到。我们观察到，在发病年龄小于40岁的家族性NIID病例中，最常见的是肌肉无力（100%），被称为“肢体无力组”，其次是感觉障碍、瞳孔缩小、膀胱功能障碍和痴呆。在发病年龄超过40岁的家族性病例中，痴呆最为突出（100%）。脑脊液蛋白升高和神经传导异常在散发性和家族性NIID病例中都很常见。散发性和家族性NIID患者的头部磁共振成像弥散加权像均显示皮质-髓交界处高强度信号，为诊断提供有力线索。所有痴呆的主要病例在头部磁共振成像上表现为这种类型的脑白质病。散发性和家族性NIID病例均表现为最小精神状态检查和正面评估电池得分下降。基于这些临床病理特征，我们提出了成人发病NIID的诊断流程图。我们的研究表明，成人发病的NIID患病率可能比以前认为的要高，并且NIID可能未被充分诊断。在白质脑病和神经病变的鉴别诊断中应考虑到NIID。
Neuronal intranuclear inclusion disease (NIID) has highly variable clinical manifestations. Sone et al. describe the clinical and pathological features of 57 adult-onset cases diagnosed by postmortem dissection/antemortem skin biopsy. They report ‘dementia dominant’ and ‘limb weakness’ subtypes, and recommend consideration of NIID in the differential diagnosis of leukoencephalopathy and neuropathy. Neuronal intranuclear inclusion disease (NIID) is a slowly progressive neurodegenerative disease characterized by eosinophilic hyaline intranuclear inclusions in the central and peripheral nervous system, and also in the visceral organs. NIID has been considered to be a heterogeneous disease because of the highly variable clinical manifestations, and ante-mortem diagnosis has been difficult. However, since we reported the usefulness of skin biopsy for the diagnosis of NIID, the number of NIID diagnoses has increased, in particular adult-onset NIID. In this study, we studied 57 cases of adult-onset NIID and described their clinical and pathological features. We analysed both NIID cases diagnosed by post-mortem dissection and by ante-mortem skin biopsy based on the presence of characteristic eosinophilic, hyaline and ubiquitin-positive intanuclear inclusion: 38 sporadic cases and 19 familial cases, from six families. In the sporadic NIID cases with onset age from 51 to 76, dementia was the most prominent initial symptom (94.7%) as designated ‘dementia dominant group’, followed by miosis, ataxia and unconsciousness. Muscle weakness and sensory disturbance were also observed. It was observed that, in familial NIID cases with onset age less than 40 years, muscle weakness was seen most frequently (100%), as designated ‘limb weakness group’, followed by sensory disturbance, miosis, bladder dysfunction, and dementia. In familial cases with more than 40 years of onset age, dementia was most prominent (100%). Elevated cerebrospinal fluid protein and abnormal nerve conduction were frequently observed in both sporadic and familial NIID cases. Head magnetic resonance imaging showed high intensity signal in corticomedullary junction in diffusion-weighted image in both sporadic and familial NIID cases, a strong clue to the diagnosis. All of the dementia dominant cases presented with this type of leukoencephalopathy on head magnetic resonance imaging. Both sporadic and familial NIID cases presented with a decline in Mini-Mental State Examination and Frontal Assessment Battery scores. Based on these clinicopathological features, we proposed a diagnosis flow chart of adult-onset NIID. Our study suggested that the prevalence rate of adult-onset NIID may be higher than previously thought, and that NIID may be underdiagnosed. We should take NIID into account for differential diagnosis of leukoencephalopathy and neuropathy.