Degeneración hepatocerebral adquirida reporte de caso y revisión de la literatura / Acquired hepatocerebral degeneration. case report and literature review

Acquired hepatocerebral degeneration also termed acquired hepatolenticular degeneration, cirrhosis-related Parkinsonism o pseudo-Wilson is a rare, progressive and chronic neurological syndrome that occurs in patients with chronic liver disease, particularly in those with surgically or spontaneously induced portosystemic shunts. The clinical features of this pathological entity include extrapyramidal signs, ataxia, cognitive decline and neuropsychiatric changes, such as delirium, apathy, lethargy and emotional instability. Brain Magnetic Resonance Imaging classically shows symmetrical T1-weighted hyperintensities in the globus pallidus, substantia nigra and periaqueductal gray matter. Although its pathogenesis is not completely elucidated, it is postulated that the excess manganese accumulation and deposition in the basal ganglia, leading to dysfunctional dopaminergic system in this anatomical location, would have a key role in triggering the disease. Orthotopic liver transplantation is the mainstay of treatment and is considered effective by reducing motor and cognitive alterations. Other therapeutic alternatives that have reported symptomatic improvement are the use of bromocriptine or levodopa and portosystemic shunts occlusion. In this article, we report a case of a 63-year-old woman with clinical manifestations over the course of one year, characterized by cognitive decline, chorea, gait and language disturbances. She was examined with plasma levels of copper and ceruloplasmin, which excluded the possibility of Wilson´s Disease, its main differential diagnosis. Neuroimaging revealed T1-weighted hyperintensity in the pallidum, confirming suspected diagnosis of acquired hepatocerebral degeneration.

Wilson?s disease presenting as rapid eye movement sleep behavior disorder: a possible window to early treatment / Doença de Wilson apresentando-se com transtorno comportamental do sono REM: uma janela possível para instituição de tratamento precoce

Objective To describe characteristics of REM sleep behavior disorder in Wilson’s disease. Method Questionnaire-based interviews (patients and relatives), neurological examinations, two-week prospective dream-diary, video-polysomnography, transcranial sonography, MRI. Results Four Wilson’s disease cases with REM sleep behavior disorder were described; three had REM sleep behavior disorder as initial symptom. All showed mesencephalic tegmental/tectal sonographic hyperechogenicities and two presented ponto-mesencephalic tegmental MRI hyperintensities. Conclusion This first description of REM sleep behavior disorder in Wilson’s disease in literature documents REM sleep behavior disorder as a possible presenting symptom of Wilson’s disease and adds further evidence to the parallelism of Parkinson’s disease and Wilson’s disease in phenotype and brainstem topography, which ought to be further studied. REM sleep behavior disorder has prognostic relevance for neurodegeneration in α-synucleinopathies. In Wilson’s disease, usefulness of early diagnosis and treatment are already well established. REM sleep behavior disorder in Wilson’s disease offers a possible theoretical model for potential early treatment in this extrapyramidal and brainstem paradigm syndrome, previewing the possibility of neuroprotective treatment for REM sleep behavior disorder in “pre-clinical” Parkinson’s disease. .

Objetivo Descrever características do transtorno comportamental do sono REM (TCSR) na doença de Wilson (DW). Método Aplicação de entrevistas, vídeo-polissonografia, sonografia transcraniana (STC), ressonância magnética (RM), diário de sonhos. Resultados Descrevemos quatro casos de DW com TCSR. Três apresentaram o TCSR como primeira manifestação. Todos mostraram hiperecogenicidades mesencefálicas na STC, dois apresentaram hiperintensidades ponto-mesencefálicas na RM. Conclusão Esta é a primeira descrição do TCSR na DW. Relatamos o TCSR como um sintoma inicial da DW. Acrescentamos prova para o paralelismo entre a doença de Parkinson e DW, com relação aos fenótipos e localização das lesões cerebrais. Nas alfa-sinucleinopatias, o TCSR tem relevância prognóstica quanto à neurodegeneração. Na DW, já conhecemos a importância de diagnóstico e tratamento precoces. O TCSR na DW oferece um modelo para antecipar o tratamento desta síndrome de acometimento dos núcleos basais e tronco, vislumbrando a possibilidade de tratamento neuroprotetor para a fase “pré-clínica” da DP. .

Small fiber dysfunction in patients with Wilson's disease / Disfunção de fibras finas em pacientes com doença de Wilson

Objective: Patients with Wilson’s disease (WD) may develop a wide variety of neuropsychiatric symptoms, but there are few reports of autonomic dysfunction. Here, we described evidence of small fiber and/or autonomic dysfunction in 4 patients with WD and levodopa-responsive parkinsonism. Method: We reviewed the charts of 4 patients with WD who underwent evaluation for the presence of neuromuscular dysfunction and water-induced skin wrinkling test (SWT). Results: Two men and 2 women (33±3.5 years) with WD were evaluated. They all had parkinsonism at some point during their disease course. Parkinsonism on patient 4 almost completely subsided with treatment of WD. Two patients had significant sensory and 2 significant autonomic complaints, including syncopal spells. NCS/EMG was normal in all but SWT was abnormal in half of them (mean 4-digit wrinkling of 0.25 and 1). Discussion: A subset of patients with WD exhibit evidence of abnormal skin wrinkling test (small fiber neuropathy). .

Objetivo: Pacientes com doença de Wilson (DW) podem desenvolver uma ampla variedade de sintomas neuropsiquiátricos, mas existem poucos relatos de disfunção autonômica. Aqui, nós descrevemos evidência de disfunção de fibras finas/autonômica em 4 pacientes com DW e parkinsonismo responsivo à levodopa. Método: Nós revisamos os prontuários de 4 pacientes com DW que foram submetidos a avaliação neuromuscular e ao teste de quantificação do enrugamento cutâneo (TEC). Resultados: Dois homens e 2 mulheres (33±3,5 anos) com DW foram avaliados. Todos apresentaram parkinsonismo durante o curso de sua doença. Parkinsonismo no paciente 4 quase completamente desapareceu com tratamento da DW. Dois pacientes apresentaram queixas sensitivas e 2 apresentaram queixas autonômicas significativas incluindo episódios de síncope. Eletroneuromiografia foi normal em todos e TEC foi anormal em metade deles (score do TEC nos 4 dedos de 0,25 e 1). Discussão: Um subgrupo de pacientes com DW apresenta evidência de TEC anormal (neuropatia de fibras finas). .

Analysis of clinical and biochemical spectrum of Wilson Disease patients.

Background and Aims: Wilson disease (WD) is autosomal recessive disorder of copper metabolism. Wilson disease patients usually suffer from hepatic or neuropsychiatric complications. The symptoms appear between ages five to 35 but it can vary from two years to 72 years. Materials and Methods : Study was carried out from June 2008 to November 2010. This study included nine families with eleven cases of WD to determine clinical presentation, diagnostic findings (including laboratory results) and liver histology. It included 11 patients who presented with hepatic manifestations and/or Neuropsychiatric manifestations and/or family history suggesting features of WD. Patients with hepatitis B and C and those with history of taking antipsychotic drugs were excluded from the study. Patient's data was included in a well designed performa. Liver function test, serum ceruloplasmin, serum copper, 24 hour urinary copper, blood complete picture were analyzed. Quantitative data such as age, hemoglobin etc were expressed as mean with ± SD and quantitative variables such as sex, movement disorders, hepatic involvement etc were expressed as frequency and percentage. Results: There were five male and six female patients with evidence of various manifestations here (i) hepatic in which they had only liver dysfunction (ii) hepatic and neurological (iii) neurological. The mean age of presentation was 8.7±3.92 years (range 4-19 years) and 45% were male patients. Decreased serum ceruloplasmin, enhanced 24-h urinary copper excretion and signs of chronic liver damage were confirmed in all patients and Kayser-Fleischer rings (KF rings) in 72% of patients. In severe WD patients, serum prothrombin activity was less than 50%, serum ceruloplasmin were low and serum copper levels were high than those in non-severe WD patients. High degree of suspicion leads to early treatment with good outcome. Conclusions: The WD is rare but important cause of chronic liver disease. Clinical and biochemical analysis in cases of patients with unexplained liver disease with high degree of suspicion can lead to early treatment with good outcome.

Acquired hepatocerebral degeneration and hepatic encephalopathy: correlations and variety of clinical presentations in overt and subclinical liver disease / Degeneração hepatocerebral adquirida e encefalopatia hepática: correlações e variedade de apresentações clínicas na doença hepática evidente e subclínica

Acquired hepatocerebral degeneration (AHD) and hepatolenticular degeneration can have similar clinical presentations, but when a chronic liver disease and atypical motor findings coexist, the distinction between AHD and hepatic encephalopathy (HE) can be even more complicated. We describe three cases of AHD (two having HE) with different neuroimaging findings, distinct hepatic diseases and similar motor presentations, all presenting chronic arterial hypertension and weight loss before the disease manifestations. The diagnosis and physiopathology are commented upon and compared with previous reports. In conclusion, there are many correlations among HE, hepatolenticular degeneration and AHD, but the overlapping of AHD and HE could be more common depending on the clinical knowledge and diagnostic criteria adopted for each condition. Since AHD is not considered a priority that affects the liver transplant list, the prognosis in AHD patients remains poor, and flow interruption in portosystemic shunts must always be taken into account.

A degeneração hepatocerebral adquirida (AHD) e a degeneração hepatolenticular podem ter apresentações clínicas semelhantes, mas quando uma doença hepática crônica e achados motores atípicos coexistem, a distinção entre AHD e encefalopatia hepática (HE) pode ser ainda mais complicada. Descrevemos três casos de AHD (dois tendo HE) com diferentes achados em neuroimagem, doenças hepáticas distintas e apresentações motoras semelhantes, todos com hipertensão arterial e perda de peso antes das manifestações motoras. O diagnóstico e a fisiopatologia são comentados e comparados com relatos prévios. Concluímos que existem muitas correlações entre HE, degeneração hepatolenticular e AHD, mas a sobreposição de HE e AHD pode ser mais comum dependendo do conhecimento clínico e da acurácia dos critérios diagnósticos adotados para cada enfermidade. Como a AHD não é considerada prioridade na lista de transplante hepático, o prognóstico dos pacientes com AHD permanece ruim, e a interrupção do fluxo nos shunts portossistêmicos deve ser sempre considerada.

Doença de Wilson: apresentação clínica, diagnóstico e tratamento / Wilson's disease: clinical presentation, diagnosis and treatment

A doença de Wilson é um erro inato do metabolismo do cobre causado por uma mutação no gene ATP7B, responsável por seu transporte. É uma doença de herança autossômica recessiva, caracterizada pela deposição excessiva de cobre principalmente no fígado e no cérebro. Clinicamente, os pacientes apresentam manifestações hepáticas, neurológicas e psiquiátricas. O diagnóstico pode ser feito quando as seguintes características estiverem presentes: anéis de Kayser-Fleischer na córnea, diminuição dos níveis plasmáticos de ceruloplasmina e sintomas neurológicos típicos. A prevenção de danos permanentemente severos depende do reconhecimento e diagnóstico precoces pelo médico, seguidos de tratamento apropriado. A doença de Wilson pode ter prognóstico excelente, desqe que o tratamento seja feito durante toda a vida.

Wilson's disease is an inborn error of copper metabolismo caused by a mutation to the cooper-transporting gene ATP7B. This disease has an autosomal recessive mode of inheritance, and is characterized by excessive cooper deposition, predominantly in the liver and brain. Clinically, patients usually present hepatic, neurologic or psychiatric manifestations. The diagnosis can be done when these symptoms are present: Kayser-Fleischer rings, low serum ceruloplasmin levels and typical neurological symptoms. The prevention of severe permanente damage depends upon early recognition and diagnosis by the physician, followed by appropriate anticopper treatment. Wilson's disease it can have an excellent prognosis since that treatment either for all the life.

Doença de Wilson com sinal da face do panda gigante na ressonância magnética de encéfalo / WilsonÆs disease with the face of giant panda sign on magnetic resonance imaging

A Doença de Wilson (DW), é uma desordem hereditária de transmissão genética autossômica recessiva, que altera o metabolismo hepático do cobre e ocasiona seu acúmulo em órgãos e tecidos. Embora alterações na Ressonância Magnética de Encéfalo (RM) não façam parte dos critérios diagnósticos as mesmas podem ser sensíveis para detectar alterações em pacientes com a doença. Os autores descrevem o caso de uma paciente de 22 anos com manifestações neurológicas progressivas cujo diagnóstico de DW foi suspeitado pelas manifestações clínicas associadas as anormalidades na RM. Paciente apresentava alterações no putamen, caudato e tálamo além do chamado sinal do face do panda gigante no mesencéfalo. Um sinal considerado característico da DW

Wilson disease and its clinical manifestation in childhood

Wilson disease is a rare autosomal recessive inherited disorder of copper metabolism. The condition is characterized by excessive deposition of copper in the liver, brain, and other tissues. The major physiologic aberration is excessive absorption of copper from the small intestine and decreased excretion of copper by the liver. The genetic defect, localized to chromosome arm l3q, has been shown to affect the copper-transporting adenosine triphosphatase [ATPase] gene [ATP7B] in the liver. Patients with Wilson disease usually present with liver disease during the first decade of life or with neuropsychiatric illness during the third decade. The diagnosis is made by measurement of serum ceruloplasmin, urinary copper excretion, and hepatic copper content, as well as the detection of Kayser-Fleischer rings. Wilson's disease requires lifelong treatment. If the disorder is detected early and treated correctly, a person with Wilson's disease can enjoy completely normal health. Or hepatolenticular degeneration is a neurodegenerative disease of copper metabolism. In 1912, Wilson first described it as a familial disorder associated with neurological symptoms and cirrhosis. In 1956, Walshe first treated patients with the chelating agent penicillamine. Neurological signs:, Parkinsonian symptoms-Rigidity, bradykinesia. Dysarthria Tremor at rest or with action Dystonia mainly of the face Dysdiadochokinesia Poor handwriting, Incoordination, Abnormal eye movements. Psychiatric signs:, Hyperkinetic behavior Irritability or anger Emotional lability Psychosis Mania Difficulty concentrating Abnormal behavior Personality changes Depression Schizophrenia. Skeletal abnormalities Osteoporosis Osteomalacia Chondrocalcinosis Osteoarthritis, Joint hypermobility Ophthalmic findings:, Kayser-FIeischer rings are greenish-yellow or brown rings seen at the lirnbus of the cornea. They are best seen by slit-lamp examination and usually progress from just the superior pole to both the superior and inferior poles and then finally to a full circle. Sunflower cataracts are brilliantly multicolored and are visible only by slit-lamp examination. They do not impair vision. Other less common findings may include exotropic strabismus, optic neuritis or optic disc pallor, or night blindness. Other physical findings:Azure lunulae of the fingernails. Arthropathy. The study has been done in Aleppo University hospital and Alkindy hospital between 2001-2004. The ale cases were 16 cases. There was an increase in cases diagnosed in Idleb and its country because of consanguinity. Wilson disease is more common in male [62.25%]. Hepatic disease is the most common initial manifestation in children [68.25%]. Three cases has been discovered by screening tests. Liver symptoms was noticed in 81.25% of cases and neurological symptoms in 12.5%. Jaundice was the most common symptom [62.5%], bleeding in 25%, musculoskeletal symptoms in 12.5%. Hepatomegaly is the most common sign in 50%, spleenomegaly in 43.75%. Neurological signes in 12.25% and tremor was the most common sign. Kayser-Fleisher ring are observed in 100% of individuals with neurological symptomes, and in 84.6%of those with hepatic symptoms Sunflower cataracts are observed in 12.5% of cases. Low serum cereloplasmin level is observed in 93.75%. Low serum copper level is noticed in 87.5%. Increasing urinary copper level in[100%] of cases and the values between [151-681]mkg/24h. Low serum protein in 40% of cases. Increasing gammaglobulin levels in [60%] of cases. There was disturbance in liver function in 87.5% [prothrombine time prolongation in 87.5%]. Increasing serum bilirubin level is found in 75%. Low hemoglubine value is found in 56.25%. Nitropenia in one case also thrombocytopenia in the same one There was disturbance in kidney function in two cases [12.5%]. Proteinuria in 50%, hematuria in 37.5. Penicillamin has been used in treatment in 81.25%. The initial dose was between 105-19 Rapidly progressive liver failure occurred in 3 cases and death was found in 25% of cases Consanguinity is observed in 68.75%

La apoptosis en las enfermedades hepáticas / Apoptosis and liver diseases

La apoptosis es una forma de muerte celular que ocurre en una amplia variedad de enfermedades hepáticas. En ésta revisión se presentan generalidades del proceso y métodos de detección; la apoptosis como generadora de enfermedad en la hepatitis alcohólica, hepatitis virales, hepatocarcinoma, colestasis, rechazo de transplantes, enfermedad de Wilson y consideraciones sobre la posible implementación de terapéuticas que modulen la apoptosis en las enfermedades hepáticas

Correlación imagenológica por resonancia magnética cerebral de manifestaciones neurológicas y oculares en la enfermedade de Wilson / Cerebral MR imaging correlation of neurological and ocular disorders in Wilson's disease

La enfermedad de Wilson o degeneración hepatolenticular es un defecto en el metabolismo del cobre que ocasiona su acumulación en diferentes tejidos, siendo el hígado, cerebro, riñón, ojo, y esqueleto óseo los más afectados. Los signos oftalmológicos de esta entidad consisten en un anillo corneal (Kayser-Fleischer) y cataratas floriformes. Se presenta el caso de un paciente femenina de 35 años en quien se manifestaron alteraciones motoras, cambios oculares como el anillo corneal y modificación en la amplitud de convergencia, hipercupremia e imágenes obtenidas por resonancia magnética cerebral que explican las manifestaciones clínicas. La enfermedad de Wilson debe de ser conisderada como una posibilidad diagnóstica en sujetos con signología motora e hipercupremia, siendo la exploración oftalmológica del segmento anterior útil para documentar la afección ocular y la resonancia magnética cerebral para correlacionar el cuadro clínico neurológico

Doença de Wilson: apresentaçäo com hepatite aguda

Apresentam-se dois casos de doença de Wilson que se manifestaram por hepatite aguda. No primeiro caso, o quadro clínico foi acompanhado por anemia hemolítica, hipofosfatasia com fosfatase alcalina que atingiu o mínimo de 7U/dl (normal para a idade: 57-303U/dl) e síndrome de Fanconi com hiperfosfatúria, hiperuricosúria e eliminaçäo aumentada de glicinina, glutamina, alanina e lisina. O segundo caso apresentava já quadro histológico de cirrose hepática e evoluiu para hepatite fulminante complicada por infecçäo do líquido ascítico. Nos dois casos foi iniciada terapêutica com penicilamina, imediatamente após o diagnóstico, verificando-se a regressäo das principais mainifestaçöes no primeiro caso. No segundo caso a evoluçäo foi desfavorável, verificando-se o aparecimento de sepse e insuficiência renal que näo respondeu à terapêutica com hemofiltraçäo, vindo a falecer três semanas após o início da terapêutica. Discutem-se os problemas de diagnóstico diferencial da terapêutica e prognóstico desta forma de apresentaçäo, com mençäo especial das indicaçöes atuais para transplante

Degeneracion hepatolenticular (Enfermedad de Wilson) / Hepatolenticular degeneration (Wilson's Disease)

Se presenta el caso de una nina de 13 anos con Enfermedad de Wilson y se hace un resumen de los aspectos mas importantes de la enfermedad hepatolenticular una de las afecciones "degenerativas", cuyo trastorno del metabolismo del cobre se origina en defectos enzimaticos de la ceruloplasmina. Un hallazgo importante en este caso fueron los depositos de cobre en las encias. La escanografia mostro atrofia cerebral y cavitaciones paraventriculares.