Wilson's disease. Psychiatric symptoms in 195 cases

A series of 195 cases of Wilson's disease were assessed retrospectively on a range of variables, including psychiatric, neurologic, and hepatic symptoms, and biochemical data as recorded at first admission to a specialist clinic. Ninety-nine patients (51%) were rated as displaying some evidence of psychopathologic features, and 39 (20%) had seen a psychiatrist before the diagnosis of Wilson's disease. The most common psychiatric features were abnormal behavior and personality change, although depression and cognitive impairment were also rated frequently. Schizophrenialike psychoses were rare, apparently occurring at no more than chance frequency. Psychiatric symptoms were related to neurologic rather than hepatic symptoms, and certain symptoms (incongruous behavior, irritability, and personality change) had a particularly significant relationship with bulbar and dystonic disorders but not with tremor. Psychiatric manifestations are important in Wilson's disease, and many of the psychopathologic features seem to have an organic basis.     

Psychiatric manifestations in Wilson's disease: a cross-sectional analysis

Behavioral and psychiatric abnormalities in Wilson's disease (WD) have a variable frequency and spectrum. This study involved evaluation of the psychiatric comorbidities in patients of Wilson's disease, using structured clinical interview for DSM-IV Axis-I disorders (SCID). Among the 50 confirmed patients with Wilson's disease recruited for this study, 12 patients (24%) fulfilled the diagnostic criteria for syndromic psychiatric diagnosis: bipolar affective disorder (18%), major depression (4%), and dysthymia (2%). Formal assessment of psychopathology in all patients with Wilson's disease may have therapeutic significance.     

Psychosis and Wilson's disease: a case report

In this article we present a case of a 26-year-old woman with clinical picture of acute psychosis, as the first and main manifestation of Wilson's disease, who developed abnormal involuntary choreoathetoid limb movements, few days after initiation of neuroleptic therapy. At the first movement neurological symptoms were misinterpreted as side effect of haloperidol, but consulted neurologist suggested additional diagnostic procedure which confirmed Wilson's disease. Psychiatric symptomatology and abnormal involuntary movements were the clinical manifestation of this disease, which improved with neuroleptic and chelating treatment. Interdisciplinary approach with good collaboration of psychiatrists and neurologists is crucial for Wilson's disease, because early diagnosis and treatment without delay is critical to the prognosis. This case serves as a reminder that involuntary movements can be side effect of antipsychotics but also the clinical manifestation of some illnesses, for example Wilson's, Huntington's and Fuhr's diseases.     

Comparison of MRI, EEG, EPs and ECD-SPECT in Wilson's disease

OBJECTIVES: The purpose of this study is to evaluate the efficiency of a few methodologies in detecting anatomo-functional brain abnormalities in patients with Wilson's disease. MATERIALS AND METHODS: Twenty-three patients with Wilson's disease underwent almost simultaneously brain magnetic resonance imaging (MRI), computerized electroencephalography (EEG), multimodal evoked potentials (EPs) and ECD single photon computerized tomography (SPECT) evaluation. The clinical picture was of the neurologic type in 8 patients and of the hepatic type in 15. RESULTS: MRI was abnormal in 7 patients with neurological manifestations. The EPs proved pathologic in 7 neurologically symptomatic patients and in 4 cases with hepatic form. These results agree with those reported in other case studies. The EEG records were abnormal only in 3 cases. Nevertheless, the most interesting finding of this study is the particular frequency (86%) of diffuse or focal decrease of ECD uptake shown by brain SPECT. CONCLUSION: We highlight the use of this interesting procedure in the therapeutic monitoring of this disease.     

The psychiatric presentations of Wilson's disease.

We reviewed the records of 42 patients with Wilson's disease participating in a zinc acetate treatment protocol and interviewed 17 of them. Five of the patients studied were asymptomatic. A significant number of symptomatic patients (64.8%) reported psychiatric symptoms at the time of initial presentation. These symptoms were severe enough to warrant psychiatric intervention in almost half of all symptomatic patients before the diagnosis of Wilson's disease was made. Personality changes, particularly irritability and aggression, were most commonly described (45.9%), followed by depression (27%). Cognitive changes, anxiety, psychosis, and catatonia, while less frequent, also occurred. These data underscore the need to include Wilson's disease in the differential diagnosis of psychiatric disorders.     

Wilson's disease: a longitudinal study of psychiatric symptoms

One hundred and twenty-nine cases of Wilson's disease (WD) were assessed at index admission and two follow-ups (F1 and F2) on a range of clinical and biochemical variables. The commonest psychiatric symptoms throughout were incongruous behavior, irritability, depression, and cognitive impairment. Among psychiatric cases, most improvements occurred in the interval index-F1, with subsequent leveling off. Significant improvement occurred only with incongruous behavior and cognitive impairment. Psychiatric cases whose psychiatric symptoms persisted to F2 differed from those who responded, in particular showing more dysarthria, incongruous behavior, and hepatic symptoms. Neuropsychiatric cases displayed more dysarthria and incongruous behavior than patients with neurological symptoms alone. Further evidence for associations between dysarthria and abnormal behavior emerged from this study.     

Wilson's disease and psychiatry. Apropos of a case

This work is based on the case of a 24 year old young man sent to a psychiatry department for behaviour troubles, hysterical demonstrations and a neurological syndrome atypical. The first part develops his familial and medical background, the clinical schemes and, finally, the biological elements leading to the Wilson's disease diagnosis. The second part is a clinical and biological summary. Comparing to our case, we can see that it is a relatively typical form. This work ends with the difficulty of determining such a diagnosis regarding a patient whose personal and familial background allowed for a consistent psychopathological explanation and who had been already treated in this sense, with the risk of neglecting the biological check up. But can this Wilson's disease diagnosis be enough to sum up all the psychiatric pathology of this patient? The question remains to be resolved in the absence of any future studies.     

Plasma and erythrocyte copper, zinc, manganese and magnesium concentrations in Wilson's disease

Plasma copper was significantly reduced in Wilson's disease with decreased ceruloplasmin levels, while there was no significant difference in erythrocyte copper levels between Wilson's disease and controls. Mean zinc and manganese levels in plasma were increased in Wilson's disease, but these differences were not significant. Mean magnesium level in plasma was normal. The levels of these metals in erythrocytes showed no difference between Wilson's disease and controls. Our results suggest that the abnormal copper level in plasma is not due to the primary metabolic defects, but is probanly due to the level of the binding proteins in plasma to this metal, ceruloplasmin, in Wilson's disease.     

Abnormal copper metabolism: another "non-Wilson's" case

We describe a patient with extrapyramidal neurologic disease and an abnormal copper profile with hepatic copper accumulation, but no cirrhosis histologically, thus excluding a diagnosis of Wilson's disease (WD). We compared and highlighted the differences between similar previously reported cases of abnormal copper metabolism and true WD and suggest a spectrum of disease due to abnormal copper metabolism resulting in varied histochemical expression.     

肝豆状核变性的早期临床表现及误诊分析

目的:探讨肝豆状核变性(wilson’s disease WD)的早期临床表现及早期诊断,旨在提高临床医生对本病的 认识,减少误诊。方法:回顾性分析50例WD病的早期临床表现、实验室及特殊检查、首次误诊情况。结果:50例患者 中,神经、精神异常者35例,肝炎、肝硬化13例,伴消化道出血2例。关节痛2例。K-F环阳性49例。血清铜蓝蛋白、血 清铜均降低。误诊最常见的依次为各种类型肝炎、肝硬化、精神疾患、关节炎、脱髓鞘脑病、胶质瘤、肌营养不良、肾炎、癫 痫、贫血、消化道大出血和Leigh、脊髓病等,误诊率达34％。结论:WD多见于青少年,神经系统及肝损害为主要临床表 现,常伴有肾脏损害,K-F角膜环是重要阳性体征,头颅CT或MRI可作为辅助诊断手段。本病易被长期误诊或诊断不 明,早期治疗对预后至关重要。建议对具有上述易被误诊疾病症状的患者常规行角膜K-F环及铜代谢检查,以免误诊误 治。     

The interaction of motor, memory, and emotional dysfunction in Wilson's disease.

Measures of the degree of motor, psychiatric, and declarative memory disability were made in neurologically impaired and neurologically asymptomatic patients with Wilson's disease. All three types of disability were significantly greater in the neurologically impaired than in the asymptomatic patients. There was no significant interaction between these disabilities in the impaired patients suggesting that motor, psychiatric, and memory symptoms are three relatively independent sequelae of the copper-induced central nervous system (CNS) damage that underlies Wilson's disease.     

Psychosis and epileptic seizures in Wilson's disease with predominantly white matter lesions in the frontal lobe

Although psychiatric symptoms are not rare in Wilson's disease (WD), their association with epileptic seizures has not been reported. We describe three patients with such clinical manifestations who had predominantly cerebral white matter lesions in the frontal lobe. There were two men and one woman with ages ranging from 20 to 26 yr. The early presentations were psychiatric symptoms and epileptic seizures with or without secondary generalization. The psychiatric features were usually misinterpreted as schizophrenia-like disease and the diagnosis was delayed. The cerebral white matter lesions on magnetic resonance imaging (MRI) were usually asymmetric and mainly restricted to the frontal lobes. The present observation suggests that early onset of psychiatric manifestations and seizures commonly occur in WD with frontal white matter lesions.     

Correlation of clinical aspects as well as genotype and phenotype in Wilson's disease on the basis of epidemiologic, clinical and cranial MRI findings

Wilson's disease, a rare autosomal recessive disorder of hepatic copper transport, is characterized by a varying pattern of hepatic, neurologic and psychiatric symptoms. Currently, about 250 causative mutations of the ATP 7B gene are known. However, a correlation between genotype and phenotype according to these mutations is not yet clear. To elucidate a possible correlation in this study 39 patients with Wilson's disease were subdivided into three groups according to the underlying mutation in group I for homocygote respectively group II for compound heterocygote mutation in H1069Q and group III for other mutations. Clinical subtype and extent of neurologic disturbance as well as epidemiologic aspects, presence of psychiatric symptoms, results of acustically evoked potentials (Wave III, interpeak latency III-V) and findings of cranial MRI were considered. While psychopathological symptoms, the results of acustically evoked potentials and cranial MRI show a correlation to the clinical subtype of Wilson's disease there was no genotype-phenotype correlation on the basis of the mutation in H1069Q. The qualitative and quantitative pattern of results do not show any significant differences in the three groups of genotype. Thus, the time of treatment onset still has most influence on the extent of clinical manifestation and reversibility of the toxic copper accumulation.     

Schizophrenia and Wilson's disease]

An 18 year-old male first presented a clinical picture of acute psychosis with two recurrences at ages 22 and 23. The diagnosis made at that time was paranoid schizophrenia. Twelve years after his first psychiatric hospitalization, it was discovered that he was suffering from Wilson's disease. In retrospect, the clinical picture was atypical, notably with an important neurologic involvement mainly parkinsonism almost uncontrollable and aggravated with neuroleptics. The chelating treatment with d-penicillamine resulted in partial improvement of the neurological involvement because the extrapyramidal and neurovegetative symptoms persisted. The psychiatric symptoms improved with fewer neuroleptics than during the 12 previous years. However, neuroleptics had to be continued because of the delay in diagnosing the illness, which diminished the efficiency of the single chelating treatment. The clinical presentation and therapeutic response of this patient strongly suggest a link between the cerebral intoxication by copper and the psychiatric symptoms.     

Mania as the first manifestation of Wilson's disease

Background:  Although mental changes are frequent in Wilson's disease, severe psychiatric disorders occur uncommonly and usually accompany the neurological picture. There are few reports in the literature of Wilson's disease patients with typical bipolar affective disorder (BPAD).
Case report:  The authors report the case of a patient with Wilson's disease whose initial manifestation was a manic episode followed by depression. Tremor in the upper limbs appeared one year after the onset of symptoms. The diagnosis of Wilson's disease was established three years after the first symptoms appeared, based on the neuropsychiatric picture, the detection of Kayser–Fleischer rings and the results of diagnostic tests indicating chronic liver disease and copper excess. ATP7B genotyping and magnetic resonance imaging of the brain with proton spectroscopy study were also performed. The patient became asymptomatic two years after starting treatment with penicillamine and remained non-symptomatic controlled during the eight-year follow-up period, without any specific treatment for the BPAD.
Conclusions:  To our knowledge, this is a singular report of a case of Wilson's disease in which a manic episode preceded the onset of neurological symptoms. The association between Wilson's disease and bipolar disorder is discussed.     

Wilson's Disease

Wilson's disease is an autosomal-recessive disorder caused by mutation in the ATP7B gene, with resultant impairment of biliary excretion of copper. Subsequent copper accumulation, first in the liver but ultimately in the brain and other tissues, produces protean clinical manifestations that may include hepatic, neurological, psychiatric, ophthalmological, and other derangements. Genetic testing is impractical because of the multitude of mutations that have been identified, so accurate diagnosis relies on judicious use of a battery of laboratory and other diagnostic tests. Lifelong palliative treatment with a growing stable of medications, or with liver transplantation if needed, can successfully ameliorate or prevent the progressive deterioration and eventual death that would otherwise inevitably ensue. This article discusses the epidemiology, genetics, pathophysiology, clinical features, diagnostic testing, and treatment of Wilson's disease.     

Dominant psychiatric manifestations in Wilson's disease: a diagnostic and therapeutic challenge!

INTRODUCTION: Recognition of psychiatric manifestations of Wilson's disease (WD) has diagnostic and therapeutic implications. OBJECTIVE: To describe the clinical features and psychopathology of patients with WD who had initial or predominant psychiatric manifestations. PATIENT AND METHODS: Records of 15 patients with WD (M:F: 11:4), from a large cohort of 350 patients, with predominant psychiatric manifestations at onset were reviewed. Their initial diagnosis, demographic profile, family history, pre-morbid personality, clinical manifestations, treatment and outcome were recorded. RESULTS: Their mean age at diagnosis was 19.8+/-5.8 years. Six patients were born to consanguineous parentage and two patients each had family history of WD and past history of psychiatric illness. Diagnosis of WD was suspected by detection of KF rings (all), observing sensitivity to neuroleptics (n=2), history of jaundice (n=2) and family history suggestive of WD (n=9). Psychiatric manifestations could be classified as affective disorder spectrum (n=11) and schizophreniform-illness (n=3). While the psychiatric symptoms improved in five patients with de-coppering therapy, seven patients needed symptomatic treatment as well. Three of the four patients who responded to de-coppering therapy were sensitive to neuroleptics. Long-term follow up of 10 patients revealed variable recovery. CONCLUSIONS: Young patient with psychiatric manifestations with clues like history of jaundice, family history of neuropsychiatric manifestations and sensitivity to neuroleptics should be evaluated for WD to avoid delay in diagnosis and associated morbidity. SIGNIFICANT OUTCOMES: The study reemphasizes the importance of behavioral manifestations in Wilson disease in terms of diagnosis and management difficulties. LIMITATIONS: Retrospective nature of the study.     

Wilson's disease associated with olfactory paranoid syndrome and idiopathic thrombocytopenic purpura]

In this study we report an individual of Wilson's disease associated with olfactory paranoid syndrome and idiopathic thrombocytopenic purpura. The initial symptom of this female patient was olfactory paranoia at age 17. Although that psychiatric symptom was well controlled under pharmacological treatment for two years, she developed olfactory paranoia as well as sialorrhea, dysarthria and finger tremor at age 20. A year later rigidity was also present in the extremities. At age 23, idiopathic thrombocytopenic purpura was found based on hematological examinations. Because her extrapyramidal symptoms were progressive, she was referred to our department to evaluate her neurologic condition. She was diagnosed as having Wilson's disease based on (1) the presence of Kayser-Fleischer rings, (2) extrapyramidal signs, and (3) a decreased level of serum copper and ceruloplasmin. T2 and FLAIR images of brain MRI showed hyperintense lesions in the putamen, thalamus and pontine tegmentum. Diffusion-weighted images also showed hyperintense lesions in the thalamus and pontine tegmentum. The biopsy specimen of the liver revealed chronic hepatitis with copper accumulation. Since D-penicillamine treatment was initiated, she has shown no olfactory paranoia and exacerbation of ITP. Her gait disturbance has also improved. Olfactory paranoia and ITP are rare clinical complications of Wilson's disease. Further analysis may warrant consideration of the pathophysiological mechanism of the psychiatric, hematological and neuroradiological condition seen in Wilson's disease.     

Effects of long-term treatment in Wilson's disease withd-penicillamine and zinc sulphate

The results of treatment withd-penicillamine (d-P) or zinc sulphate (Zn) in 67 newly diagnosed cases of Wilson's disease have been compared. All patients (7 with hepatic, 1 with psychiatric and 59 with neurological or preclinical forms) were fully compliant. During 12 years of observation, 34 patients receivedd-P and 33 Zn as the primary treatment. Fifteen patients (44%) discontinuedd-P, in 10 cases owing to side effects. Four (12%) patients discontinued Zn, in 2 cases because of side-effects. One patient who received Zn deteriorated during the first few months after the initiation of therapy. The effectiveness of longterm treatment withd-P and Zn was similar in those patients who were able to continue the initial therapy. Zn was tolerated better thand-P; we suggest, therefore, that it may be recommended as an initial therapy for patients in the preclinical stage of Wilson's disease or with neurological presentation of the disease. More observation is needed for patients with the hepatic and psychiatric forms of the disease.