目的 分析麻痹性痴呆(general paresis of insane,GPI)患者治疗前后认知功能变化和精神行为症状的变化特点以及预测因素.方法 入组GPI患者31例,给予青霉素G(2400万U/d)治疗14 d,再用苄星青霉素(240万U/周)治疗3周,治疗后7个月复诊;完成随访30例,因搬家失访1例.采用临床痴呆评估量表(Clinical Dementia Rating Scale,CDR)、简易精神状态检查(Mini Mental State Examination,MMSE)、阿尔茨海默病评定量表认知部分(Alzheimer's Disease Assessment Scale-cognitive Subscale,ADAS-Cog)、工具性日常生活活动量表(Instrumental Activities of Daily Living Scale,IADL)、躯体生活自理量表(Physical Self maintenance Scale,PSMS)与神经精神问卷(Neuropsychiatric Inventory,NPI)对患者进行评估;并比较CDR不同评分(CDR=0.5分、CDR=1.0分、CDR>1.0分)患者治疗前后各量表评分的变化;采用相关分析、多元线性逐步回归分析GPI患者预后相关的因素.结果 (1)GPI患者MMSE总分[(14.4±6.9)分比(17.1±9.1)分]、IADL评分[4.0(2.0,5.0)分比6.0(2.0,7.3)分]、ADAS-Cog注意力因子分[1.5(0.7,3.0)分比1.5(0,2.3)分]、NPI总分[(46.0±27.1)分比(17.6±15.4)分]治疗前后比较差异有统计学意义(t=5.820,Z=3.710、-2.680、-4.940;均P<0.01);NPI中的幻觉、妄想、激越、抑郁、欣快、脱抑制、易激惹因子分与治疗前比较差异有统计学意义(Z=-2.381、2.504、-3.095、-2.492、-3.097、-2.527、-3.715,均P<0.05).(2)CDR=0.5分组MMSE评分(t=8.488,P<0.01)、IADL评分(Z=2.593,P<0.05)有显著改善,CDR=1.0分组除PSMS外的各量表评分均显著改善(MMSE总分:t=5.409,ADAS-Cog总分:Z=-2.366,IADL总分:Z=2.546,NPI总分:Z=-3.558;均P<0.05或P<0.01),CDR>1.0分组仅NPI总分明显改善(t=-3.772,P<0.05).(3)单因素与多因素分析显示,治疗前MMSE与IADL评分越高,治疗前后的MMSE评分差值越大(β=0.541,P=0.004;β=0.364,P=0.044).结论 GPI患者在治疗后认知功能障碍与精神行为症状未全面彻底恢复,其中中重度痴呆、焦虑、睡眠与淡漠症状的预后不佳.
Objective To investigate the characteristics of cognitive impairment and psychotic symptoms in general paresis of insane (GPI) before and after penicillin therapy, and explore factors that may predict the clinical outcomes. Methods Thirty patients with GPI were recruited. All GPI patients underwent a comprehensive neuropsychological assessment before receiving penicillin therapy, and returned for follow-up visits after 7 months. The severity of dementia was determined by Clinical Dementia Rating Scale (CDR), cognitive functions were assessed by Mini Mental State Examination (MMSE) and Alzheimer 's Disease Assessment Scale-cognitive subscale (ADAS-Cog), ability of daily living was assessed by Instrumental Activities of Daily Living Scale (IALD) and Physical Self maintenance Scale(PSMS), behavioral and psychological symptoms were assessed by Neuropsychiatric Inventory (NPI). Aqueous crystalline penicillin G 24 million units per day was administered as continuous infusion for 14 days, followed by benzathine penicillin 2.4 million units IM once per week for 3 weeks. Patients returned for follow-up visits after 7 months. Clinical outcomes were determined by the improvement of neuropsychological test scores at the end of the treatment. Grouped by CDR scores, changes in neuropsychological tests scores among different GPI groups were used to explore the correlation between severity of dementia and clinical outcomes. Univariate analysis and multivariate linear regression analysis were used to identify factors that may predict the clinical outcomes. Results (1)After penicillin therapy, GPI patients' MMSE scores(14.4± 6.9 vs.17.1 ± 9.1)and IADL scores(4.0(2.0, 5.0)vs.6.0(2.0, 7.3))both improved significantly(t=5.820, Z=3.710, P<0.01),while in ADAS-Cog, only factor scores of attention(1.5(0.7, 3.0)vs.1.5(0, 2.3))reduced significantly(Z=- 2.680, P<0.01). NPI's total scores(46.0 ± 27.1 vs.17.6 ± 15.4)and subscores of hallucination, delusion, agitation, depression, euphoria, disinhibition and irritability reduced significantly (Z=-4.940,-2.381,-2.504,-3.095,-2.492,-3.097,-2.527,-3.715, all P<0.05).(2) Grouped by the CDR scores, MMSE scores and IADL scores in very mild GPI group with CDR=0.5 improved significantly. In mild GPI group with CDR=1, significant changes were also found in all neuropsychological tests scores(MMSE,t=5.409, P<0.01), total scores of ADAS-Cog (Z=-2.366,P<0.05), IADL (Z=2.546, P<0.05), total scores of NPI (Z=-3.558,P<0.01), but except for PSMS. In moderate to severe GPI group with CDR>1,significant change was found only in total scores of NPI (t=-3.772,P<0.05). (3) Univariate analysis and multivariate linear regression analysis showed that improvement of MMSE scores after the treatment was significantly correlated with IADL scores and MMSE scores at baseline(β=0.541,P=0.004;β=0.364,P=0.044). Conclusions After penicillin treatment, GPI patients may improve in both cognitive function and psychotic symptoms but not in all the domains. Symptoms of anxiety, sleep/nigh-time behavior change, and apathy, as well as moderate to severe GPI patients may not benefit much from the treatment.