肝豆状核变性精神症状特点、影响因素及排铜治疗的临床研究

目的研究肝豆状核变性（Wilson disease,WD）精神症状的特点、影响因素及排铜治疗对精神症状的治疗效果。方法选取WD患者80例（脑型60例,肝型20例）,正常对照20例,用症状自评量表（SCL-90）、简易智能量表（MMSE）、汉密尔顿焦虑量表（HAMA）、汉密尔顿抑郁量表（HAMD）进行精神症状评估。脑型WD患者神经症状用改良Young量表进行评估。所有患者进行脑脊液铜、血清铜、尿铜、头部核磁共振检查。二巯基丙磺钠排铜治疗后,进行上述量表评分,复查铜代谢指标,对结果进行统计学分析。结果WD患者SCL-90显著高于正常对照者。精神症状依次是：行为障碍、情感障碍、智能障碍、记忆力下降、思维障碍、感知障碍。改良Young评分与精神量表评分无相关（P〉0．05）。改良Young量表震颤项目评分与SCL-90量表中躯体化、焦虑、敌对项目评分呈正相关（P〈0．05）;咽喉肌张力障碍、肢体肌张力增高、步态异常项目评分与抑郁项目评分呈正相关（P〈0．05）。基底节、丘脑病变是出现情感障碍的影响因素（P〈0．05）。脑脊液铜、血清铜、尿铜与精神量表评分无相关性（P〉0．05）。排铜治疗后,40％患者SCL-90量表总分降低,其中躯体化、焦虑、敌对项目评分明显下降（P〈0．05）。结论WD患者出现精神症状比例高。基底节、丘脑病变可能涉及WD患者异常情绪产生的病理机制。单独排铜治疗对精神症状的治疗效果不佳。精神症状的治疗应以排铜为基础,结合抗精神病药物。     

Wilson's disease with depression and parkinsonism.

Wilson's disease (WD) is an autosomal recessive disorder with reduced biliary excretion of copper plus impaired formation of ceruloplasmin, leading to copper accumulation in the liver, brain, kidney, and cornea. Clinical manifestations include liver damage, psychiatric symptoms, and neurological features. We report a 35-year-old woman with a history of deranged liver functions who had severe depression several years later and eventually presented with parkinsonian features. The underlying diagnosis is WD and family screening revealed WD in 2 other siblings. She could not tolerate penicillamine because of fever and leucopenia. While taking trientine hydrochloride and zinc sulphate, her parkinsonism improved and her depression remained in remission. WD should be considered in patients with unexplained liver function derangement or psychiatric symptoms. Early diagnosis and initiation of specific treatment are crucial in minimising any further cerebral and hepatic damage as well as securing possible improvement in organ functions.     

Wilson's disease: a great masquerader

BACKGROUND: Wilson's disease (WD) is a treatable autosomal recessive metabolic disorder which could lead to protean hepatic or neurologic manifestations. WD could mimic many neurologic disorders and is often diagnosed with a long delay. This study describes central nervous system manifestations of a group of Iranian patients with neurologic WD. METHODS: Data from case records of patients with neurologic WD presenting at a referral university hospital and a private clinic in Tehran from 1984 to 2004 were analyzed. RESULTS: Fifty patients from 44 unrelated families with WD were identified, whose mean duration of follow-up was 51.8 (+/-58.5) months. The median age of onset of neurologic symptoms in 37 patients with primary neurologic or simultaneous hepatic-neurologic presentation was 16 (10-38) years, whereas in 13 patients with prior hepatic damage, this was 18.5 (11-34) years. The 6 most common manifestations were dysarthria (80%), drooling (48%), tremor in limbs (44%), abnormal gait (44%), psychiatric and/or sleep symptoms (44%), and dystonia in limbs (42%). CONCLUSION: Neurologic WD has heterogeneous manifestations and should be considered in young patients presenting with dysarthria, drooling, any kind of movement disorders or psychiatric symptoms.     

A growth in bipolar disorder?

OBJECTIVE: This case report suggests that screening of patients with psychiatric symptoms using modern neuroimaging can help identify organic causes of mental illness. METHOD: A single case study was reported. RESULTS: We report the case of a 25-year-old woman with a recent diagnosis of bipolar II disorder having an magnetic resonance imaging (MRI) scan as part of a research project that reveals an intraventricular brain tumour. The latter is most likely the cause of her irritability and 'hypomanic' symptoms and is defined anatomically using diffusion tensor imaging and structural and functional imaging using MRI and positron emission tomography. CONCLUSION: The lesion in this individual case most probably produces mood symptoms by impinging upon the fornix, a component of the limbic system. However, more generally, the increase in diagnosis of bipolar disorder has to be tempered against alternate causes of similar symptoms and necessitates vigilance of potential organic mechanisms.     

Whipple's disease with isolated central nervous system symptomatology diagnosed by molecular identification of Tropheryma whippelii in peripheral blood

We report a new case of Whipple's disease (WD) confined to the central nervous system. The patient presented with ataxia, ophthalmoplegia, hypersomnia, hemiparesis and generalized myorhythmia. The diagnosis was confirmed by identification of specific sequences of the causal agent of WD, the actinobacteria Tropheryma whippelii (TW), by PCR of DNA extracted from peripheral blood. An epidemiological survey of TW in patients with dementia suggests that WD is an uncommon cause of dementia in our population. Molecular methods may allow rapid identification of TW in peripheral fluids, and non-invasive diagnosis of this disorder.     

Organic delusional disorder in psychiatric in-patients: comparison with delusional disorder

Organic delusional disorder (ODD) is rarely diagnosed in psychiatric in-patients, and may be misdiagnosed as delusional disorder (DD) from a similar clinical presentation. The aim of the present study was to investigate the characteristics of ODD and to make a comparison with those of DD patients. Patients who conformed to DSM-III-R criteria for ODD were recruited from an 8-year psychiatric in-patient database. Matching controls were DD patients admitted over the same time period. The prevalence of ODD according to DSM-III-R criteria was 0.4% of total admissions and 2.9% of organic mental disorders. Compared to DD patients, ODD patients less often had a family psychiatric history, and had an older age of onset of psychiatric disorder, longer hospital stays and lower treatment dosage of antipsychotic drugs. It is suggested that a detailed medical history and examination are needed in patients with delusion, especially in patients with a late onset of psychiatric symptoms and no family psychiatric history.     

Obstructive sleep apnoea syndrome as the cause of atypical depression

Sleep apnoea is a common disorder presenting with somatic comorbidities and psychiatric symptoms. This case report describes a 43-year-old man with an organic depressive disorder due to obstructive sleep apnoea. Initially, an atypical depressive episode or schizophrenic residual syndrome had been considered likely diagnoses; subsequent polysomnography results, however, suggested obstructive sleep apnoea instead. Upon nasal continuous positive airway pressure (nCPAP), the respiratory distress symptoms improved. The case report highlights the association between sleep disturbances and depressive symptoms. In patients presenting with symptoms of atypical depression and excess body weight sleep apnoea should be considered.     

Video documented follow-up of liver transplantation in Wilson's disease with predominant neurological manifestation.

Wilson's disease (WD) is a rare autosomal-recessive disorder of copper metabolism with predominantly hepatic and extrapyramidal motor symptoms. Copper chelating therapy has proven to be an effective treatment for WD. Yet, if conservative treatment fails, liver transplantation (LT) often is the only remaining therapeutic option. The indication for LT especially in patients with stable liver function but severe neurological manifestation is debated controversially. In this case report, we document the follow up of neurological symptoms in WD after LT for the first time on video.     

Psychogenic movement disorders

All varieties of movement disorders may be mimicked by a psychogenic disorder, most commonly tremor, dystonia, and myoclonus. Approximately 3% of patients seen in specialty clinics have a psychogenic movement disorder (PMD). The diagnosis of a PMD depends on not just ruling out an organic movement disorder, but moreover, recognizing features from the history and examination that are inconsistent or incongruous with an organic movement disorder. Most PMDs represent a conversion disorder, sometimes as part of a somatoform disorder; less common diagnoses include a factitious disorder or malingering. Co-morbid psychiatric illness is prevalent in patients with PMD including depression, anxiety, and personality disorders. Many PMDs remain chronic, but a multidisciplinary approach centering on psychiatric intervention can be successful. A shorter duration of symptoms and a co-existent treatable psychiatric disorder portend a better prognosis, whereas compensation and pending litigation are associated with a poorer prognosis.     

Psychiatric aspects of Wilson disease: a review

Objective

To review the current evidence about psychiatric symptoms in Wilson's disease (WD).

Method

We searched Ovid, PsychInfo, CINHAL and PubMed databases from May 1946 to May 2012 using the key words Wilson('s) disease in combination with psychiatry, psychiatric, psychosis, schizophrenia, depression, mania, bipolar, mood, anxiety, personality and behavior.

Results

Psychiatric symptoms occur before, concurrent with or after the diagnosis and treatment for WD. Thirty to forty percent of patients have psychiatric manifestations at the time of diagnosis, and 20% had seen a psychiatrist prior to their WD diagnosis. When psychiatric symptoms preceded neurological or hepatic involvement, the average time between the psychiatric symptoms and the diagnosis of WD was 864.3 days. The prevalence of psychiatric disorders in WD patients varies wildly (major depressive disorder, 4–47%; psychosis, 1.4–11.3%). Certain gene mutations of ATP7B may correlate with specific personality traits.

Conclusions

Psychiatric manifestations represent a significant part of the clinical presentation of WD and can present at any point in the course of the illness. Psychiatric manifestations occurring without overt hepatic or neurologic involvement may lead to misdiagnosis. A better understanding of the psychiatric presentations in WD may provide insights into the underlying mechanisms of psychiatric disorders.     

Different windows on executive functions

Wilson’s Disease (WD) (also known as hepatolenticular degeneration) is a rare inherited autosomal recessive disorder of abnormal copper metabolism, with an estimated prevalence of approximately 1 in 30,000. The clinical features associated with WD are highly varied. However, subtypes generally reflect neurological, hepatic, and psychiatric symptoms. The present case study reports two brothers with a recent diagnosis of WD. Neurological symptoms and cognitive deficits were exhibited in one brother (BL) in the form of extrapyramidal features, while the other brother (AL) only exhibited hepatic symptoms. Extensive neuropsychological testing was conducted on both siblings to compare cognitive profiles. Results for BL indicated significantly impaired motor functioning and information processing speed, which impacted him significantly at school. Aspects of executive dysfunction were also apparent in addition to reduced visual and verbal memory, working memory, and attention. Results for AL revealed evidence of verbal memory difficulties and aspects of executive dysfunction. Comparison is made of the distinct and common cognitive characteristics of the cases presented in terms of implications for early intervention and management of cognitive difficulties.     

Somatization and illness behaviour in a neurology ward

One hundred and thirty-three female patients admitted to a neurological ward were fully investigated for the presence of organic neurological disease, and assessed for psychiatric disorder and illness behaviour, using the Clinical Interview Schedule (CIS) and the Illness Behaviour Questionnaire (IBQ). The likelihood of the presenting symptoms being due to organic disease was expressed by the neurologists on a visual analogue scale and the psychiatrists used a similar technique to describe whether the symptoms could be the result of psychiatric disorder. Many patients either had clear organic disease or somatic presentation of psychiatric disorder 'somatization', but one-third fell between these two extremes and either had a complex mixture of the two types of illness or could not be accurately diagnosed. The IBQ scores were raised in those with psychiatric disorder but did not help to explain why some patients present to the neurologists with symptoms that are unexplained by either organic disease or psychiatric disorder. Close liaison between neurologists and psychiatrists increases the detection of psychiatric disorder but some patients would require long-term follow-up to understand the true nature of the underlying disorder.     

肝豆状核变性23例临床分析

目的 总结肝豆状核变性的临床特点,以减少误诊、漏诊.方法 回顾性分析23例肝豆状核变性患者的临床表现及诊治过程.结果 平均发病年龄21.5岁,首发症状以神经系统和肝损害症状为主,分别占69.6%(16/23)及26.1%(6/23),其中神经系统症状以肢体震颤、精神异常多见;18例患者临床分型为混合型,占78.3%(18/23),5例为脑型;所有患者均出现角膜色素环(K-F环);所有患者进行了铜代谢的实验室检查,血浆铜蓝蛋白水平降低及24 h尿铜增高常见.青霉胺与硫酸锌联合治疗对78.3%(18/23)的患者有效.结论 肝豆状核变性青少年多发,以神经系统和肝损害症状为主要表现,K-F环阳性率高.青霉胺与硫酸锌联合治疗对大部分肝豆状核变性患者有效.     

Impaired functional default mode network in patients with mild neurological Wilson’s disease

Wilson’s disease (WD) is an autosomal recessive metabolic disorder characterized by cognitive, psychiatric and motor signs and symptoms that are associated with structural and pathological brain abnormalities, in addition to liver changes. However, functional brain connectivity pattern of WD patients remains largely unknown. In the present study, we investigated functional brain connectivity pattern of WD patients using resting state functional magnetic resonance imaging. Particularly, we studied default mode network (DMN) using posterior cingulate cortex (PCC) based seed functional connectivity analysis and graph theoretic functional brain network analysis tools, and investigated the relationship between the DMN’s functional connectivity pattern of WD patients and their attention functions examined using the attention network test (ANT). Our results demonstrated that WD patients had altered DMN’s functional connectivity and lower local and global network efficiency compared with normal controls (NCs). In addition, the functional connectivity between left inferior temporal cortex and right lateral parietal cortex was correlated with altering function, one of the attention functions, across WD and NC subjects. These findings indicated that the DMN’s functional connectivity was altered in WD patients, which might be correlated with their attention dysfunction.     

Undulating tongue in Wilson's disease

We report an unusual occurrence of involuntary movement involving the tongue in a patient with confirmed Wilson''s disease (WD). She manifested with slow, hypophonic speech and dysphagia of 4 months duration, associated with pseudobulbar affect, apathy, drooling and dystonia of upper extremities of 1 month duration. Our patient had an uncommon tongue movement which was arrhythmic. There was no feature to suggest tremor, chorea or dystonia. It might be described as athetoid as there was a writhing quality, but of lesser amplitude. Thus, the phenomenology was uncommon in clinical practice and the surface of the tongue was seen to “ripple” like a liquid surface agitated by an object or breeze. Isolated lingual dyskinesias are rare in WD. It is important to evaluate them for WD, a potentially treatable disorder.     

Organic syndromes diagnosed as conversion disorder: identification and frequency in a study of 85 patients

BACKGROUND: The percentage of patients initially diagnosed with a conversion disorder and later identified as having an organic disorder has been decreasing in recent studies. METHOD: Consecutive patients with a diagnosis of conversion disorder were referred for psychiatric diagnosis and treatment. Research questions were: (1) What incidence of neurological disorder is revealed by neurological reassessment and by which diagnostic technique is the final diagnosis established? (2) What differences can be observed between true-positive and the false-positive results? RESULTS: Ten (11.8%) of the 85 patients examined appeared to suffer from a neurological disorder. In this sample, variables discriminating between the true positives and false positives were: (1) prior suspicion of neurological disorder; (2) older age at referral; (3) older age at onset of symptoms; (4) longer duration of symptoms; and (5) use of medication. Three variables contributed significantly to the prediction of organic disorder: prior suspicion of neurological disorder; age at onset of symptoms; and duration of symptoms. CONCLUSIONS: Although our results are in line with those of other recent studies, the percentage of false positives was still high. The data further emphasize the dangers of making a diagnosis of conversion disorder in the absence of positive evidence. It is important to continue to provide follow up for patients with a diagnosis of conversion disorder. Unfortunately, unreliable psychiatric indications, like certain behavioral characteristics, are still used in the diagnostic process. The results show that a general neurological examination is still a valuable diagnostic instrument in addition to modern diagnostic techniques.     

Organic brain syndrome in three cases of acquired immune deficiency syndrome

A triad of psychiatric symptoms involving mood disturbance, thought disorder with grandiose delusions, and severe memory deficits is described for three male homosexual patients suffering from acquired immume deficiency syndrome. The evidence suggests that the last two of these symptoms are inexplicable on the basis of previous psychiatric history or as a reaction to medical illness. Rather, an organic brain syndrome may be part of the natural history of AIDS for some patients.     

Evaluation of the Unified Wilson's Disease Rating Scale (UWDRS) in German patients with treated Wilson's disease

Wilson's disease (WD) is an inherited autosomal‐recessive disorder of copper metabolism characterized by a wide variety of neurological, hepatic, and psychiatric symptoms. The aim of the present study was the development and evaluation of a clinical rating scale, termed Unified Wilson's Disease Rating Scale (UWDRS), to assess the whole spectrum of clinical symptoms in WD. Altogether 107 patients (mean age 37.6 ± 11.9 years; 46 male, 61 female) with treated WD participated in the study. Cronbach's alpha as a measure of the internal consistency for the entire scale was 0.92, whereas the intraclass correlation coefficient (ICC) was 0.98 (confidence interval (CI_95%) 0.97–0.99), indicating an excellent interrater reliability as determined in 32 patients. Besides the total score was significantly correlated with the earning capacity of the patients as indicated by an estimated Spearman's ρ ≈ 0.54 (CI_95% 0.40–0.69, P < 0.001). In summary, the UWDRS appears to be a promising tool to assess the disease severity in WD. Its usefulness in clinical research and drug trials should be further addressed. © 2007 Movement Disorder Society     

Does brain degeneration in Wilson disease involve not only copper but also iron accumulation?

Background and purposeWilson disease (WD) is an autosomal recessive inherited disorder of hepatic copper metabolism. Clinical manifestations of WD include neurologic, hepatic and psychiatric symptoms. Most WD patients with the neuropsychiatric form, and some with the hepatic and presymptomatic forms have both hypointense and hyperintense lesions in basal ganglia on T2-weighted magnetic resonance imaging (MRI), which can be iron and copper accumulation. It has been established that T2* and susceptibility-weighted imaging (SWI) are highly sensitive in demonstrating brain iron accumulation, showing decreased signal intensity. Hypointense globus pallidus (GP) signal has been described on T2-, T2*-weighted images and on SWI as typical MRI lesion for patients with neurodegeneration with brain iron accumulation (NBIA). We investigated whether WD patients have MRI changes suggesting iron accumulation using T2*-weighted and VEN_BOLD SWI imaging protocols.Material and methodsStandard MRI with additional sequences (T2*-weighted and VEN_BOLD SWI) was performed in consecutively admitted, clinically stable, and treated patients.ResultsTwenty-eight patients entered the study. Hypointensity in the GP was observed on T2*-weighted images in 10 patients. Using the VEN_BOLD SWI technique, we found hypointense signal in GP in 20 patients.ConclusionsMRI data suggest not only copper but also iron accumulation in GP in WD patients.     

Psychiatric status of patients with primary fibromyalgia, patients with rheumatoid arthritis, and subjects without pain: a blind comparison of DSM-III diagnoses

OBJECTIVE: The major purpose of this study was to compare the frequency of the occurrence of DSM-III diagnoses in patients with primary fibromyalgia syndrome, patients with rheumatoid arthritis, and subjects without pain. METHOD: Thirty-five patients with primary fibromyalgia, 33 patients with rheumatoid arthritis, and 31 nonpatients without pain were blindly assessed for psychiatric diagnoses with the Psychiatric Diagnostic Interview. RESULTS: Data from this interview revealed no group differences in terms of lifetime history of any psychiatric disorders, including major depression, somatization disorder, or anxiety-based disorders. Analysis of the auxiliary symptoms of depression on the Psychiatric Diagnostic Interview revealed that the patients with fibromyalgia did not report a higher frequency of vegetative signs of depression. However, analysis of the somatization scale revealed an interaction between medical and psychiatric diagnoses: patients with primary fibromyalgia syndrome and a psychiatric history endorsed significantly more somatic symptoms than did patients with rheumatoid arthritis or subjects without pain, and fibromyalgia patients without a psychiatric history were no more likely to endorse somatic symptoms than were arthritis patients or subjects without pain. CONCLUSIONS: The Psychiatric Diagnostic Interview data failed to discriminate in any major way between primary fibromyalgia syndrome (a disorder with no known organic etiology) and rheumatoid arthritis (a disorder with a known organic etiology). Therefore, these data do not support a psychopathology model as a primary explanation of the symptoms of primary fibromyalgia syndrome.