São descritos três casos d© degeneração hepatolenticular (DHL.) em que o efeito nefrotóxico da D-penicilina (DP) levou à substituição dessa droga por zinco, com resultados satisfatórios. O tempo médio de tratamento com zinco nos casos descritos foi de 2 anos e 7 meses. Com base nos dados de literatura e na experiência com esses pacientes, os autores consideram que os sais de zinco podem ser uma alternativa para o tratamento da DHL quando a DP determina o aparecimento de efeitos colaterais graves que levam à sua retirada definitiva.

Three patients with symptoms and signs of hepatolenticular degeneration (HLD) who developed serious renal side effects of D-penicillamine (DP) had their therapeutic schedule changed to zinc. Patient 1, a 55 year-old man had been well until 12 years old, when skeletal changes (osteomalacia) due to tubular renal disturbance began. His diagnosis of HLD had first been established at age of 32 when he presented with «wing-beat» tremor. He was then begun on DP and his neurological symptons resolved within one year of initiating therapy but skeletal abnormalities remained unchanged as a sequel. During the next 22 years the patient was continued on DP therapy but with poor compliance. Then the reapperance of his neurological manifestations occurred several times. By the age of 53, after one year without therapy, his neurological status has worse. DP was reinstituted but some weeks later his renal laboratorial parameters became serevely affected. DP was discontinued and zinc sulfate (220mg three times daily) was introduced. On this therapeutic regimen his renal laboratorial parameters returned to previous level after one month. Within one year on this therapeutic regimen neurological manifestations were resolved. After 31 months on zinc treatment he remains neurologically asymptomatic and his renal function is satisfactory. Patient 2, a 41 years old woman had been her diagnosis of HLD at age of 20, when following the diagnosis of the disease in her old brother, she was found to have the laboratorial features of HLD and bilateral Kayser-Fleischer rings. DP treatment was recommended at that time but she quitted the follow-up. When she. was 23, an esophageal variceal bleeding occurred. At the age of 30 she started DP treatment. During 9 years the patient, under regular use of the drug remained assymptomatic. At the age of 39 she developed acute renal failure due to penicillamine-induced immune complex nephropathy. DP was then stopped and prednisone introduced. After 4 months, as renal function returned to normal, prednisone was discontinued and zinc sulphate (220mg three times daily) introduced. She remained asymptomatic for 38 months. By the age of 41 a relapse of renal manifestations occurred, and she died months later. Patient 3, a 20 year-old man developed hemolytic anemia as the single manifestation of HLD at 16. DP was introduced with excellent results. Neverthless, 4 months later, with the appearance of severe renal side--effects, this drug was replaced by zinc sulphate (220mg three times daily). After 11 months under this therapeutic schedule he was hematologically asymptomatic but an epigastric distress appeared. Zinc sulphate was discontinued and zinc acetate (170mg three times daily) was introduced. Since that time, after 30 months of treatment with zinc, he remains asymptomatic and Kayser-Fleisher rings disappeared. A review of zinc salts therapy of HLD is presented and discussed.

Distúrbios do movimento, geralmente de tipo distónico, têm sido relatados em heterozigotos para doença de Wilson (DW). O presente relato assinala a presença em uma mesma família de heterozigoto para DW com quadro distónico e sua sobrinha com quadro clássico de DW. Discutem-se as peculiaridades dessa família, comparando-se aos dados da literatura, bem como os possíveis mecanismos etiopatrogênicos envolvidos.

Movement disorders, mostly dystonia, sometimes occur in heterozygotes for Wilson's disease (WD). A patient with metabolic abnormalities suggestive of heterozigose for WD and dystonia is reported. His niece showed the typical neurological and metabolic abnormalities of WD. This rare coincidence and the etiopathogenic mechanisms involved are discussed .

O estudo ultra-sonográfico de 33 pacientes com degeneração hepatolenticular revelou as seguintes alterações princpais: desordens da ecotextura hepática (29 casos), alterações das dimensões esplénicas (21), contração do fígado (10), colelitíase (8), hepatomegalia e ascite (1). As desordens da ecotextura hepática se apresentaram sob diversas formas, desde leves até graves alterações da ecogênese hepática, associadas com distorções anatômicas do fígado, tais como modificações do perfil e redução das dimensões. A contração hepática sempre se acompanhou de esplenomegalia. A raridade da hepatomegalia pode ser explicada pelo fato de que a ultra-sonografia foi realizada após o início do tratamento com penicilamina, ou por outros fatores ainda desconhecidos, como a possibilidade de que o cobre possua uma ação fibrogênica maior do que a de outros agentes hepatotóxicos. A colelitíase foi muito freqüente no sexo teminino (6 de 13 pacientes) e sua incidência tendeu a crescer com a idade. Quanto aos doentes do sexo masculino, não se notou aumento da incidência em relação à freqüência na população geral. Os dois únicos pacientes do sexo masculino eram jovens, fato raramente observado nos homens normais.

The ultrasonographic study of 33 patientes with hepatolenticular degeneration showed the following main changes: disorders of the hepatic echotexture (29 cases), changes of the splenic dimensions (21), liver shrinkage (10), cholelithiasis (8), hepatomegaly and ascitis (1). The disorders of liver echotexture exhibited different patterns, from slight to severe changes of the hepatic echogenicity, associated with anatomic distortions of the liver, such as alterations of outline and decrease of dimensions. Liver shrinkage was always accompanied by splenomegaly. The scarcity of hepatomegaly may be explained by the fact that the ultrasonography was performed after the onset of treatment with penicillamine, or by other factors still unknown, copper perhaps possessing a stronger fibrogenetic action than other hepatotoxic agents. Cholelithiasis was very frequent in females (6 of 13 patients), its incidence tending to increase with age. Regarding males there was no increase when the incidence was compared to the general population. The two sole males were young, an unusual finding in normal men.

O autor descreve as características clínicas e laboratoriais de 102 casos de degeneração hepatolenticular (DHL) acompanhados no Departamento de Neurologia da Faculdade de Medicina da Universidade de São Paulo desde 1946. É analisado o problema do diagnóstico precoce dos familiares, a anatomia patológica da moléstia de Wilson é revista, e são examinadas as relações entre a DHL e outras moléstias hepatocerebrais. A etiopatogenia é discutida à luz das pesquisas mais recentes, sendo destacado o papel da redução da excreção biliar de cobre. A seguir são expostos os resultados do tratamento com D-penicilamina em 84 casos.

The author reports the clinical and laboratory findings in 102 patients of hepatolenticular degeneration (HLD) followed up in the Department of Neurology, University of São Paulo Medical School, since 1946. The problem of the early diagnosis of the relatives is analysed, the pathology of Wilson's disease is reviewed, and the relationship of HLD with other hepatocerebral diseases is examined. Etiopathogenesis is discussed according to current researches, the role of the decreased biliary copper excretion being emphasized. The results of treatment with D-penicillamine in 84 cases are commented.

É relatado um caso de síndrome de Menkes, que acreditamos ser o primeiro descrito no Brasil. O paciente, menino de 15 meses, apresentava, desde o quinto mês de vida, pili torti, grave involução do desenvolvimento neuropsicomotor e síndrome convulsiva. Os exames complementares evidenciaram ceruloplasmina e cobre séricos baixos, alterações arteriais e intensa atrofia cerebral difusa. O exame necroscópico confirmou este último aspecto, observando-se despopulação neuronal nas camadas mediocorticais do cérebro, no tálamo e sobretudo no cerebelo, sede de lesões intensas e particulares em nível cortical. Acredita-se que a síndrome de Menkes, de herança recessiva ligada ao sexo, seja devida a um erro inato do metabolismo do cobre, primário ou secundário a alterações variáveis das proteínas que permitem o transporte de cobre aos diferentes tecidos. Os autores revisam os principais aspectos etiopatogênicos referidos na literatura.

The authors report a case of Menkes' syndrome, probably the first one described in Brazil. The patient, a 15-month-old boy, showed pili torti, early progressive psychomotor deterioration and seizures. Serum levels of ceruloplasmin and copper were very low. Neuroradiological and roentgenological examinations revealed diffuse cerebral atrophy, arterial changes and bone abnormalities. At the post-mortem examination the more consistent findings were cerebral atrophy, neuronal loss in the thalamus and above all cerebellar cortical lesions. The disease has a sex-linked recessive inheritance and is believed to be caused by an inborn error of copper metabolism, perhaps subordinated to changes of proteins which carry copper to different tissues. The relevant literature in relation to the pathogenesis is reviewed.

Os autores apresentam uma revisão de 21 pacientes com diagnóstico de neuropatia amilóide tipo I, firmado sobre os dados epidemiológicos, a evolução clínica e os achados histopatológicos. Chamam a atenção para a possibilidade de comprometimento de vários nervos cranianos, para a gravidade do quadro digestivo, a precocidade dos distúrbios neurovegetativos e a incidência relativamente alta de sintomatologia cardíaca. Constituem contribuição para o melhor conhecimento da afecção, os estudos sobre a síndrome digestiva feitos através de exames radiológicos e dos testes de absorção de vitamina B12 e trioleína radioativas.

The authors present a review of 21 cases with the diagnosis of type I amyloid neuropathy based on epidemiological data, clinical evolution and histopathological findings. They call attention to the possibility of cranial nerves involvement (hyposmia, diplopia, masseterian hypotrophy, peripheral facial paralysis, hypoacusis, dysphonia, laryngeal paralysis, dysphagia, and trapezium muscle hypotrophy), to the severeness of the digestive symptoms, to the precocity of the autonomic disorders, and to the rather high incidence (6 cases) of heart involvement. The electromyography showed anterior horn involvement in 3 cases. The electrocardiography showed repolarization disorders in 11 cases, left ventricular overload in 6 cases and atrioventricular block in 5 cases. The serum proteins electrophoresis showed frequent abnormalities, but no typical curve could be obtained. The barium-contrasted X-rays of the gastrointestinal tract showed no anatomical lesions, but functional abnormalities (hypo or hypermotility) were found in 14 examinations. The Schilling test showed impairment of vitamin B12 absorption in 50% of the cases. However, with the concomitant administration of intrinsic factor (3 cases) there was improvement of its absorption. This proves that the gastric mucosa plays an important role in the disease malabsorption. The test with labeled-triolein showed slow absorption in 2 cases and steatorrhea in 3 (6 tests). For the confirmation of the amyloid deposits, the best histopathological procedure was nerve biopsy. In men, when the nerve biopsy was negative, testicular biopsy has shown to be a good option.

Foi estudado, mediante eletroforese e imunoeletroforese do soro sanguíneo, o metabolismo protêico em 4 casos de neuropatia radicular sensitiva hereditária. Em todos os casos foi encontrado discreto aumento do teor de gamaglobulina. A imunoeletroforese evidenciou ausência de imunoglobulina A em um caso, discreto aumento de imunoglobulina G em todos os casos, ausência de imunoglobulina M em dois casos e acentuada diminuição desta macroglobulina nos dois outros casos, assim como nos outros membros da família aparentemente sadios. Somente em dois pacientes foi assinalado aumento de hipoproteina beta1.

The protein metabolism in four cases of hereditary sensory radicular neuropathy was studied through the electrophoresis and immunoelectrophoresis of the blood serum. A slight increase of the gammaglobulin content was found in all cases. The immunoelectrophoresis showed an absense of IgA in a case, a slight increase of IgG in all cases, and an absence of IgM in two cases and a marked decrease of this macroglobulin in two cases of the disease and in their healthy parents. Only two patients showed an increase of beta1 lipoprotein.

Foram estudados os balanços metabólicos do enxôfre em dois pacientes com degeneração hepatolenticular. Em ambos foi comprovado um balanço positivo; em um paciente submetido a dieta geral, a média foi significantemente superior à normal. A administração de D-penicilamina promoveu acentuado aumento da excreção urinária do enxôfre, levando a um balanço fortemente negativo. As concentrações de enxôfre no soro sangüíneo, que eram normais no período de contrôle, sofreram progressivo incremento após a instituição do tratamento com D-penicilamina.

The metabolic balances of sulfur in two cases of hepatolenticular degeneration were studied. A positive balance was found in both cases; in one patient submitted to mixed diet, the average was significantly higher than the normal mean. The administration of D-penicillamine promoted a marked increase in the urinary excretion of sulfur, leading to a strongly negative balance. The blood sulfur contents, which were normal in the control periods, showed a progressive increment after D-penicillamine was started.

Foram determinadas as concentrações de água, sódio, potássio, cálcio, fósforo, magnésio, cobre, ferro, enxôfre e nitrogênio de espécimes de dura máter aparentemente normal retirados de 18 indivíduos recentemente falecidos em conseqüência de traumatismo crânio-encefálico. As concentrações médias, expressas em peso seco, foram as seguintes: água 79,55 g/100 g ± 2,52; sódio 1,63 mequiv/100 g ± 0,27; potássio 3,68 mequiv/100 g ± 0,66; cálcio 119,84 mg/100 g ± 107,40; fósforo 68,2 mg/100 g ± 34,5; magnésio 0,61 mequiv/100 g ± 0,37; cobre 249,8 mg/100 ± 109,4; ferro 0,82 mg/100 g ± 0,28; enxôfre 490,7 mg/100 g ± 22,5; nitrogênio 3,33 g/100 g ± 0,17.

The concentrations of water, sodium, potassium, calcium, phosphorus, magnesium, copper, iron, sulfur, and nitrogen were determined in samples of apparently normal dura mater removed from 18 subjects recently dead by craniocerebral trauma. The average concentrations expressed in dry weight were: water 79.55 g/100 g ± 2.52; sodium 1.63 mequiv/100 g ±0.27; potassium 3.68 mequiv/100 g ± 0.66; calcium 119.84 mg/100 g ± 107.40; phosphorus 68.2 mg/100 g ± 34.5; magnesium 0.61 mequiv/100 g ± 0.37; copper 249.8 /xg/100 g ± 109.4; iron 0.82 mg/100 g ± 0.28; sulfur 490.7 mg/100 g ± 22.5; nitrogen 3.33 g/100 g ± 0.17.

Foram revistos 12 casos de tumores da região pineal, sob os aspectos clínico, laboratorial e neurorradiológico. Em 6 doentes o diagnóstico baseou-se apenas nos dados clínicos e neurorradiológicos (particularmente ventriculográficos) e, nos restantes 6 casos, foi confirmado por exame histopatológico. A sobrevida de 3 a 9 anos, verificada em 4 casos submetidos a tratamento conservador mediante operações de derivação seguidas de irradiação pela bomba de cobalto, constitui índice em favor da conduta adotada.

Twelve cases of tumours of the pineal region were analysed under the clinical, laboratorial and radiological viewpoints. In 6 cases the diagnosis was based only on the clinical and radiological (particularly ventriculogramortem examination. The survival from 3 to 9 years, in 4 cases submitted to the conservative treatment including intra or extracranial shunts follow by cobalto-therapy, supports the indication of the procedure adopted.

Foram estudados os balanços metabólicos do enxofre em dois pacientes com a forma juvenil da leucodistrofia metacromática. Foi verificado, em ambos os casos, um balanço positivo desse metaloide, aparentemente não influenciado pelo tipo de dieta (geral ou vegetal). Este resultado está de acordo com a atual concepção patogênica dessa moléstia, que consiste, essencialmente, em uma sulfatidose com diminuição da atividade das sulfatases.

The metabolic balances of sulfur in two cases of the late juvenile form of metachromatic leucodystrophy were studied. A positive balance of sulfur was found in both patients, apparently not influenced by the type of diet (either mixed or vegetarian). This finding is in accordance with the current views on the pathogenesis of the disease, namely a sulfatidosis with low sulfatase activity.

Em 10 casos de mielose funicular foram estudadas a absorção, a depuração e a utilização de lípides radioativos. Em 4 dêsses casos foram verificadas alterações do metabolismo lipídico. Embora não significantemente, as síndromes periférica e funicular dorsal mostraram-se mais intensas nos 4 casos com distúrbios do metabolismo lipídico que nos demais, enquanto a síndrome piramidal foi aproximadamente semelhante nos dois grupos de pacientes. A sintomatologia neurológica global também se apresentou mais intensa nos 4 casos com alterações do metabolismo lipídico. Estes resultados parecem indicar que as alterações do metabolismo das gorduras demonstradas nesses casos não se vinculam diretamente ao processo desmielinizante em geral, parecendo antes refletir uma carência de metabólitos (provavelmente vitaminas do complexo B) diversos da vitamina B12, que desempenhariam papel mais importante na preservação dos nervos periféricos.

In 10 cases of subacute combined degeneration of the spinal cord the absorption, clearance and utilization of labeled fat was studied. In 4 cases disorders of the lipid metabolism were found. Although not significantly, the peripheral and dorsal funiculi syndromes were more severe in the 4 cases with impaired fat metabolism than in the normal cases, while the pyramidal syndrome was almost the same in the two groups. The whole neurological picture was also more severe in the 4 cases with disorders of fat metabolism. These results seem to indicate that the impairment of lipid metabolism evidenced in such cases bears no direct relationship with the demyelinating process in general, and would rather attend a deficiency of metabolites (probably B-complex vitamins) other than vitamin B12, which play a more significant role in the preservation of the peripheral nerves.

Foi estudada a absorção da vitamina B12 radioativa em 29 casos de mielose funicular. O diagnóstico baseou-se na clássica sintomatologia neu- rológica e na presença de acloridria gástrica e eventuais alterações hemato-lógicas. As manifestações neurológicas foram avaliadas de modo semiquan-titativo e correlacionadas com os resultados do teste de excreção urinária da vitamina B12. Não foi verificada correlação significante da absorção da vitamina B12, quer com a sintomatologia nuerológica total, quer com as síndromes periférica e funicular dorsal. Contudo, foi encontrada significante correlação negativa entre a síndrome piramidal e a absorção da vitamina B12. Os resultados são confrontados com o papel desempenhado pela vitamina B12 na síntese das bainhas de mielina e do ácido ribonuclêico, sendo salientada a importância dêste último para a vida das células nervosas e dos longos axônios.

The absorption of labeled vitamin B12 in 29 cases of subacute combined degeneration of the spinal cord was studied. The diagnosis was based on the classical neurologic picture and on the presence of gastric achlorhydria and eventual blood or bone marrow changes. The neurologic manifestations were evaluated in a semiquantitative way and were correlated to the results of the urinary excretion test of vitamin B12. The absorption of vitamin B12 was not significantly correlated to the neurologic picture as a whole, or to the peripheral and dorsal funiculi syndromes. However, a significant negative correlation was found between the pyramidal syndrome and the absorption of vitamin B12. The results are confronted with the significance of vitamin B12 in the synthesis of myelin sheaths and ribonucleic acid, the essential role of RNA for the life of the nerve cells and the long axons being emphasized.