Maubert A, Hanon C, Sedel F
EPS Érasme, 92160 Antony, France.
EPS Érasme, 92160 Antony, France.
Encephale. 2016 Jun;42(3):208-13. doi: 10.1016/j.encep.2015.11.003. Epub 2015 Dec 23.
Niemann-Pick type C disease (NPC) is a rare genetic disease with an extremely heterogeneous clinical presentation. The adult form of this disease is usually expressed with neurological symptoms; however, non-specific psychiatric disorders are often associated. This article presents a retrospective study on a cohort of NPC patients diagnosed in France with the objectives of researching the presence of psychiatric disorders and qualifying these disorders.
After carrying out a research within hospital records, a questionnaire was sent to patients or their relatives and their doctors.
The cohort was made up of 22 patients. Fifty-two questionnaires were sent to 47 different doctors. We received 67% of answers from the doctors, with 42% of positive answers. The answer rate of the families was 27%. Among the 22 patients, we found the presence of psychiatric disorders in 86% of cases. Seventy-three percent of the patients presented behavior disorders. Among them, 27% exhibited psychomotor excitation or agitation, 23% aggressiveness, 18% intolerance to frustration, 27% sleep disorders and 23% apathy, listlessness and/or clinophilia. Fifty-five percent of patients presented psychotic symptoms, with 45% with delusions and 36% with hallucinations. Seventy-seven percent of patients presented with mood disorders: 36% suffered from depression and 27% from emotional lability or mood swings. Of the 22 patients, a diagnosis of psychiatric disease was made in 50% of cases. The main diagnoses were schizophrenia (27%) and depression (23%). The other diagnoses identified were acute delirium, dysthymia, infantile psychosis, intellectual disharmonic disability and personality disorder. The average age of emergence of the troubles was 17.1 years old for neurological symptoms and 20.9 years old for psychiatric symptoms. The median age was 18 years old for neurological symptoms and 20 years old for psychiatric ones. In 45% of cases, psychiatric occurred after neurological symptoms; in 27%, they occurred before and they were concomitant in 9%. In 50% of cases, psychiatric symptoms existed before the early diagnosis of NPC; in 9%, they occurred after and in 5%, they occurred during the diagnostic process. Fifty-five percent of the patients were followed by a psychiatrist, 50% of patients had been hospitalized at least once in a psychiatric department. Fifty-five percent of the patients received neuroleptics or antipsychotics, 41% received antidepressants, 41% received mood stabilizers or anticonvulsants, 45% received anxiolytics and 23% hypnotics.
Whilst a small cohort, the low incidence of NPC (1/120,000 to 1/150,000) and the scale of a single-center study make the findings important. In our cohort, we found psychiatric disorders in most of the patients. The symptoms were varied and non-specific, and mainly found in late-onset forms of the disease. This incidence of disorder is much higher than the literature suggests, generally describing psychiatric disorders in approximately one third of NPC adult form. On the other hand, our results on schizophrenia are consistent with the updated recommendations for the diagnosis and management of NPC. According to our results, a retrospective study to develop a suspicion index to aid diagnosis of NPC suggests that psychotic symptoms are underestimated in this disease. In our cohort, we also found a significant rate of psychiatric hospitalizations and psychotropic drugs prescription that had not been previously described in the international literature. We did not have sufficient data on the effectiveness of symptomatic treatment in NPC; the literature was contradictory. It should be noted that despite the high rate of psychiatric patients in our cohort, only half of patients consulted a psychiatrist and a few of them have regular follow-up. To conclude, our study is in line with the current literature that suggests an under-estimation of psychiatric disorders in NPC, but also a likely under-diagnosis of NPC in psychiatric departments. All this data encourage us to keep alerting psychiatrists to identifying this disease in order to promote early and optimal care.
尼曼-皮克C型病（NPC）是一种罕见的遗传性疾病，临床表现极为多样。该疾病的成人形式通常表现为神经症状；然而，非特异性精神障碍也常常与之相关。本文对一组在法国确诊的NPC患者进行了回顾性研究，旨在研究精神障碍的存在情况并对这些障碍进行定性。
在医院记录中进行研究后，向患者或其亲属以及他们的医生发送了一份问卷。
该队列由22名患者组成。向47名不同的医生发送了52份问卷。我们收到了67%的医生回复，其中42%为肯定答复。家属的回复率为27%。在22名患者中，我们发现86%的病例存在精神障碍。73%的患者出现行为障碍。其中，27%表现为精神运动性兴奋或激动，23%表现为攻击性，18%表现为不耐挫折，27%表现为睡眠障碍，23%表现为冷漠、无精打采和/或亲床症。55%的患者出现精神病性症状，45%有妄想，36%有幻觉。77%的患者出现情绪障碍：36%患有抑郁症，27%有情绪不稳定或情绪波动。在22名患者中，50%的病例被诊断为精神疾病。主要诊断为精神分裂症（27%）和抑郁症（23%）。其他确诊的诊断包括急性谵妄、心境恶劣、婴儿期精神病、智力不协调残疾和人格障碍。神经症状出现的平均年龄为17.1岁，精神症状出现的平均年龄为20.9岁。神经症状的中位年龄为18岁，精神症状的中位年龄为20岁。在45%的病例中，精神症状出现在神经症状之后；在27%的病例中，精神症状出现在神经症状之前，9%的病例中两者同时出现。在50%的病例中，精神症状在NPC早期诊断之前就已存在；在9%的病例中，精神症状在诊断之后出现，5%的病例中精神症状在诊断过程中出现。55%的患者接受精神科医生的随访，50%的患者至少在精神科住院一次。55%的患者接受抗精神病药物治疗，41%接受抗抑郁药物治疗，41%接受心境稳定剂或抗惊厥药物治疗，45%接受抗焦虑药物治疗，23%接受催眠药物治疗。
尽管该队列规模较小，但NPC的低发病率（1/120,000至1/150,000）以及单中心研究的规模使得这些发现具有重要意义。在我们的队列中，我们发现大多数患者存在精神障碍。症状多样且不具特异性，主要出现在该疾病的晚发型形式中。这种障碍的发生率远高于文献报道，文献通常描述NPC成人形式中约三分之一的患者存在精神障碍。另一方面，我们关于精神分裂症的结果与NPC诊断和管理的最新建议一致。根据我们的结果，一项旨在建立怀疑指数以辅助NPC诊断的回顾性研究表明，该疾病中精神病性症状被低估了。在我们的队列中，我们还发现了精神科住院和精神药物处方的显著比例，这在国际文献中此前未曾描述。我们没有关于NPC对症治疗有效性的足够数据；文献存在矛盾。应当指出的是，尽管我们队列中的精神科患者比例很高，但只有一半的患者咨询过精神科医生，其中很少有人接受定期随访。总之，我们的研究与当前文献一致，表明NPC中的精神障碍被低估，而且精神科可能对NPC诊断不足。所有这些数据促使我们继续提醒精神科医生识别这种疾病，以促进早期和最佳治疗。
