RESUMO
Complementary DNAs (cDNAs) encoding portions of the amyloid beta protein were used to investigate possible amyloid gene duplication in sporadic Alzheimer's disease. A strategy employing two Eco RI restriction fragment length polymorphisms (RFLPs) detected by the amyloid cDNAs was used. RFLPs allow the detection of a 2:1 gene dosage in the DNA of any individual who is heterozygous for a particular RFLP. The amyloid gene regions homologous to the cDNAs used were not duplicated in the DNA from brains of individuals with sporadic Alzheimer's disease. Similar results were also obtained with a strategy employing a test for 3:2 gene dosage.
Assuntos
Doença de Alzheimer/genética , Amiloide/genética , Alelos , Peptídeos beta-Amiloides , Cromossomos Humanos Par 17 , Cromossomos Humanos Par 21 , DNA/genética , Genes , Humanos , Proteínas Associadas aos Microtúbulos/genética , Polimorfismo de Fragmento de Restrição , Proteínas tauRESUMO
In the brains of deceased schizophrenics who underwent long-term treatment with antipsychotic drugs, the concentration of homovanillic acid (a dopamine metabolite) was significantly increased in the orbital frontal, cingulate, and temporal tip areas of the cortex, but not in the putamen or the nucleus accumbens. The concentration of homovanillic acid was normal in the brains of schizophrenics who were not treated with drugs.
Assuntos
Encéfalo/metabolismo , Dopamina/metabolismo , Esquizofrenia/tratamento farmacológico , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Antipsicóticos/uso terapêutico , Córtex Cerebral/metabolismo , Ácido Homovanílico/metabolismo , Humanos , Núcleo Accumbens/metabolismo , Putamen/metabolismo , Esquizofrenia/metabolismo , Fatores de TempoRESUMO
A distinct subpopulation of striatal aspiny neurons, containing the enzyme nicotinamide adenine dinucleotide phosphate diaphorase, is preserved in the caudate nucleus in Huntington's disease. Biochemical assays confirmed a significant increase in the activity of this enzyme in both the caudate nucleus and putamen in postmortem brain tissue from patients with this disease. The resistance of these neurons suggests that the gene defect in Huntington's disease may be modifiable by the local biochemical environment. This finding may provide insight into the nature of the genetically programmed cell death that is a characteristic of the disease.
Assuntos
Corpo Estriado/patologia , Doença de Huntington/patologia , Neurônios/patologia , Adulto , Idoso , Núcleo Caudado/enzimologia , Núcleo Caudado/patologia , Corpo Estriado/enzimologia , Humanos , Doença de Huntington/enzimologia , Pessoa de Meia-Idade , NADPH Desidrogenase/análise , Proteínas do Tecido Nervoso/análise , Neurônios/enzimologia , Neuropeptídeo YRESUMO
Somatostatin receptor concentrations were measured in patients with Alzheimer's disease and controls. In the frontal cortex (Brodmann areas 6, 9, and 10) and temporal cortex (Brodmann area 21), the concentrations of somatostatin in receptors in the patients were reduced to approximately 50 percent of control values. A 40 percent reduction was seen in the hippocampus, while no significant changes were found in the cingulate cortex, postcentral gyrus, temporal pole, and superior temporal gyrus. Scatchard analysis showed a reduction in receptor number rather than a change in affinity. Somatostatin-like immunoreactivity was significantly reduced in both the frontal and temporal cortex. Somatostatin-like immunoreactivity was linearly related to somatostatin-receptor binding in the cortices of Alzheimer's patients. These findings may reflect degeneration of postsynaptic neurons or cortical afferents in the patients' cerebral cortices. Alternatively, decreased somatostatin-like immunoreactivity in Alzheimer's disease might indicate increased release of somatostatin and down regulation of postsynaptic receptors.
Assuntos
Doença de Alzheimer/metabolismo , Córtex Cerebral/análise , Receptores de Superfície Celular/análise , Adulto , Idoso , Cromatografia Líquida de Alta Pressão , Feminino , Lobo Frontal/análise , Humanos , Masculino , Pessoa de Meia-Idade , Neurônios/metabolismo , Neurônios/fisiologia , Radioimunoensaio , Receptores de Somatostatina , Somatostatina/metabolismo , Somatostatina/fisiologia , Lobo Temporal/análiseRESUMO
A series of computer-assisted stereomorphometric analyses of the spatial arrangements of neurons and glia in postmortem cerebral cortex specimens has been developed and applied to both control subjects and schizophrenic patients. The data suggest that the anterior cingulate cortex of schizophrenic patients may contain domains or aggregates of neurons, particularly in layer II, which are smaller in size and separated by wider distances than those observed in the control group. Verification of the inferences made from the computer-generated data has been obtained by direct microscopic visualization and measurement of neuronal aggregates of layer II in Nissl-stained cingulate specimens from the control and schizophrenic groups. Statistical correction of the data, using multivariate statistics, for effects of age, hypoxia, postmortem interval, fixation, and neuroleptic exposure does not eliminate the differences in size and separation of neuronal aggregates in layer II of schizophrenic patients. The possible relevance of these findings to our understanding of schizophrenic symptomatology is discussed.
Assuntos
Córtex Cerebral/patologia , Giro do Cíngulo/patologia , Esquizofrenia/patologia , Idoso , Contagem de Células , Computadores , Humanos , Pessoa de Meia-Idade , Córtex Motor/patologia , Vias Neurais/patologia , Neuroglia/patologia , Neurônios/patologiaRESUMO
Quantitative morphometric determinations of neuronal and glial density, neuron-glia ratios, and neuronal size were performed in the prefrontal, anterior cingulate, and primary motor cortex of ten controls and ten schizophrenics diagnosed by Feighner criteria under blind conditions to assess whether neuronal degeneration had occurred. Stepwise multiple regression and multiple classification analyses were used to evaluate the effect of potential confounding variables such as age, postmortem interval, fixation, hypoxia, and neuroleptic exposure on the measures studied. The neuronal density was significantly lower in layer VI of the prefrontal, layer V of the cingulate, and layer III of motor cortex. There was also a trend toward fewer neurons in most layers of both prefrontal and motor cortex, although by discriminant analysis this generalized pattern was significant only for the prefrontal area. The glial density also tended to be lower throughout most layers of all three cortical regions. There were no differences in the neuron-glia ratios or neuronal size between the two groups. The data do not support the presence of neuronal degeneration in schizophrenic cortex as it is conventionally described by neuropathologists, but do suggest the possibility that cytoarchitectural variations in cortical structure might exist in this group of schizophrenics.
Assuntos
Córtex Cerebral/patologia , Esquizofrenia/patologia , Idoso , Contagem de Células , Humanos , Pessoa de Meia-Idade , Córtex Motor/patologia , Neuroglia/patologia , Neurônios/patologiaRESUMO
Data generated from an earlier study have suggested a model in which greater numbers of long, vertical, associative axons may occur in the anterior cingulate cortex of schizophrenic patients relative to control subjects. This hypothesis has now been tested using neuron-specific antibodies raised against the 200-kilodalton neurofilament subunit, a component of neuronal cytoskeleton, to immunostain axons of human postmortem cingulate cortex. A manual method for counting axons in the region of layer II and sublamina IIIA has been designed and applied blindly to parallel control and schizophrenic immunoprocessed specimens. The results show that there are 25% more vertical axons in the schizophrenic than in the control specimens. Preferentially higher numbers of both long vertical axons (62%) and axons associated with blood vessels (52%) have also been noted in the schizophrenic specimens. By contrast, the number of large-caliber horizontal axons was the same in the two groups; therefore, the greater number of vertical axons in schizophrenic specimens does not appear to represent a nonspecific effect. When these data are corrected for the effects of several confounding variables using analysis of covariance, the overall pattern of the results persists. These findings suggest the possibility that there might be an increase of associative inputs into the anterior cingulate cortex of schizophrenic patients, although it is not clear at present whether the differences noted, if replicative, may be primarily or perhaps only secondarily related to the disorder.
Assuntos
Axônios/ultraestrutura , Giro do Cíngulo/ultraestrutura , Esquizofrenia/patologia , Axônios/metabolismo , Giro do Cíngulo/metabolismo , Humanos , Imuno-Histoquímica , Proteínas de Filamentos Intermediários/metabolismo , Proteínas de Neurofilamentos , Esquizofrenia/imunologia , Esquizofrenia/metabolismo , Coloração e RotulagemRESUMO
A recent report suggested that neurons in the prefrontal, anterior cingulate, and primary motor cortex of the brains of schizophrenic subjects may be less dense than those in the brains of nonschizophrenic subjects. We have determined whether pyramidal neurons and/or interneurons are preferentially reduced in schizophrenic subjects. Twelve control subjects and 18 schizophrenic subjects were studied in a blind, quantitative analysis of the density of pyramidal cells, interneurons, and glial cells in each of the six layers of the anterior cingulate and prefrontal cortex. The results showed that numbers of small neurons (interneurons) were reduced in most layers of the cingulate cortex in schizophrenic subjects compared with nonschizophrenic subjects, with the differences being greatest in layer II. In the prefrontal area, interneuronal density was also lower in layer II and, to a lesser extent, in layer I in schizophrenic subjects compared with control subjects. In most cases, the differences were similar, although more significant, in schizophrenic subjects who had had superimposed mood disturbances than in schizophrenic subjects who had not had such comorbidity. Numbers of pyramidal neurons generally were not different between control and schizophrenic subjects, except in layer V of the prefrontal area, where schizophrenic subjects showed higher densities of these neurons. Glial numbers did not differ between the control and schizophrenic subjects, suggesting that a neurodegenerative process did not cause the reduced interneuronal density observed. Using multiple regression analysis and analysis of covariance, decreases in the density of layer II interneurons could not be adequately explained by the effects of various confounding variables, such as age, postmortem interval, duration of specimen fixation, or administration of neuroleptic agents.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Lobo Frontal/citologia , Giro do Cíngulo/citologia , Transtornos Psicóticos/diagnóstico , Esquizofrenia/diagnóstico , Contagem de Células , Lobo Frontal/fisiopatologia , Giro do Cíngulo/fisiopatologia , Humanos , Interneurônios/citologia , Vias Neurais/citologia , Vias Neurais/fisiopatologia , Neuroglia/citologia , Transtornos Psicóticos/fisiopatologia , Esquizofrenia/fisiopatologiaRESUMO
We have previously found that a biochemically distinct subset of neurons, containing nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), is selectively resistant to the degenerative process that affects the striatum in Huntington's disease (HD). We report the morphologic and histochemical characteristics of these striatal neurons and their distribution with respect to the histochemical compartments as defined by acetylcholinesterase (AChE) activity. Sections of striatum were stained histochemically for NADPH-d and AChE and immunocytochemically for somatostatin and neuropeptide Y-like immunoreactivity. The diaphorase end-product was contained within medium-sized neurons which corresponded morphologically to a category of aspiny interneurons. Combined techniques showed that NADPH-d, somatostatin, and neuropeptide Y coexisted within the same neurons in controls and patients with HD. The density of these neurons was greater in the ventral putamen and the nucleus accumbens than in the remainder of the striatum. The distinctive AChE pattern of high and low enzyme activity was altered in HD. The AChE-rich matrix zone was markedly reduced in size, while the total area of zones of low enzyme activity was not different from that found in control striatum. The relation between these AChE chemical compartments and the distribution of preserved diaphorase neurons remained intact; NADPH-d neurons were predominantly observed in the matrix zone.
Assuntos
Corpo Estriado/patologia , Doença de Huntington/patologia , Acetilcolinesterase/metabolismo , Idoso , Corpo Estriado/metabolismo , Corpo Estriado/ultraestrutura , Histocitoquímica , Humanos , Doença de Huntington/metabolismo , NADPH Desidrogenase/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Neurônios/ultraestrutura , Neuropeptídeo Y/metabolismoRESUMO
Decreased density of neurons was found throughout the head of the caudate nucleus in Huntington's disease (HD), with the most severe neuronal loss early in the disease in the medial region. The density of reactive astrocytes is inversely proportional to the neuronal loss. In cases of mild Huntington's disease which had no identifiable abnormality on conventional neuropathologic evaluation (grade 0), there is a reduction in neuron density without an accompanying reactive astrocytosis. The pattern for decrease in neurons and accompanying astrocytosis suggests that the earliest changes occur in the most medial portion of the head of the caudate nucleus and subsequently sweep laterally across the caudate nucleus to the internal capsule. An increased density of oligodendrocytes is observed in the head of the caudate nucleus for the lower grades (0, 1 and 2). The decreased neuronal and increased oligodendroglial densities may be of significance in understanding the pathogenesis of HD. These altered densities, observed in the absence of reactive astrocytosis, suggest that these changes may not represent recent effects of disease, but rather that HD gene expression may influence brain cell densities from early in the life of the gene carrier.
Assuntos
Núcleo Caudado/patologia , Doença de Huntington/patologia , Neurônios/patologia , Oligodendroglia/patologia , Idoso , Astrócitos/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
We describe two protocols for preparing human brains collected for research and diagnosis. In both protocols, one half brain is processed for research and the other for neuropathological evaluation. Clinical, neuropathological and tissue mRNA retention data are used for sample categorization. In protocol 1, coronal, whole hemisphere slices cut at standardized landmarks are frozen with a cooling device at -90 degrees C, which yields discrete anatomical structures. In selected instances, small blocks of brain are frozen at -160 degrees C in liquid nitrogen vapor. Cooling device or liquid nitrogen vapor frozen samples are suitable for in situ hybridization, protein blotting or immunohistochemistry. Morphological freezing artifacts are minimal. In protocol 2, one half brain is frozen en bloc on dry ice; this tissue is suitable for regional evaluation of gene expression or neurochemistry. Morphological freezing artifacts are severe. In both protocols, the other half brain is fixed in formalin prior to sectioning and diagnostic evaluation. The standardized selection of paraffin blocks from each brain allows precise diagnoses to be established, including identification of dangerous infectious processes; moreover, it makes it possible to produce a set of uniformly selected blocks and slides for comparative studies. These protocols lead to standardized tissue preparation for research and reduce variables impairing interpretation and comparison of data.
Assuntos
Encéfalo , Técnicas Histológicas , Pesquisa , Manejo de Espécimes , Encéfalo/metabolismo , Encéfalo/patologia , Cadáver , Criopreservação/instrumentação , Desenho de Equipamento , Humanos , Hibridização In Situ , RNA Mensageiro/metabolismo , Bancos de TecidosRESUMO
In postmortem brain specimens from 163 clinically diagnosed cases of Huntington's disease (HD) the striatum exhibited marked variation in the severity of neuropathological involvement. A system for grading this severity was established by macroscopic and microscopic criteria, resulting in five grades (0-4) designated in ascending order of severity. The grade correlates closely with the extent of clinical disability as assessed by a rating scale. In five cases of clinically diagnosed HD there were no discernible neuropathological abnormalities (grade 0), suggesting that the anatomical changes lag behind the development of clinical abnormalities. In eight cases, neuropathological changes could only be recognized microscopically (grade 1). The earliest changes were seen in the medial paraventricular portions of the caudate nucleus (CN), in the tail of the CN, and in the dorsal part of the putamen. Counts of neurons in the CN reveal that 50% are lost in grade 1 and that 95% are lost in grade 4; astrocytes are greatly increased in grades 2-4. These studies indicate that analyses of the CN in grade 4 would reflect mainly its astrocytic composition with a component of remote neurons projecting to the striatum. Because of the relative preservation of the lateral half of the head of the CN in grades 1-2, these regions would reflect early cellular and biochemical changes in HD.
Assuntos
Doença de Huntington/patologia , Núcleo Caudado/patologia , Globo Pálido/patologia , Humanos , Doença de Huntington/classificação , Neurônios/patologiaRESUMO
The specific binding of (3H)kainic acid (KA) to high- and low-affinity receptor sites was assayed in postmortem samples from the brains of patients affected with Huntington's disease (HD) and age-matched controls. Treatment of rat brain with conditions that closely mimic the temperature gradient occurring in postmortem human brain only slightly but not significantly decreased receptor binding by 12 hr after death. In HD brains, total specific binding of (3H)KA was reduced in the caudate nucleus by 51%, putamen by 77%, and frontal cortex by 47%. Specific binding to the high-affinity site was virtually undetectable in the caudate nucleus and was reduced by 90% in the putamen from HD brains. No significant alterations in specific binding of (3H)KA were noted in the insular or temporal cortex, hippocampus, or cerebellum. Thus, losses of KA receptor binding were mainly localized to those regions of the HD brain that are most severely affected by neuronal degeneration, and the high-affinity receptor site appeared more affected.
Assuntos
Química Encefálica , Doença de Huntington/metabolismo , Ácido Caínico/metabolismo , Pirrolidinas/metabolismo , Receptores de Droga/análise , Adulto , Animais , Sítios de Ligação , Núcleo Caudado/análise , Feminino , Lobo Frontal/análise , Humanos , Masculino , Pessoa de Meia-Idade , Mudanças Depois da Morte , Putamen/análise , RatosRESUMO
OBJECTIVE: To evaluate the hypothesis that patients with schizophrenia who have been treated with neuroleptics have a high rate of Alzheimer's disease-like neuropathology. METHOD: Neuropathological studies indicating the presence or absence of Alzheimer's disease-like neuropathology in the postmortem brains of patients with schizophrenia, normal comparison subjects, and comparison subjects who had affective disorder were evaluated with Mantel-Haenszel chi-square and odds ratio analyses. RESULTS: Ten studies with relevant data were reviewed; none of eight with comparisons indicated that Alzheimer's disease-like neuropathology was more likely to be found in the brains of patients with schizophrenia than in the brains of comparison subjects. CONCLUSIONS: Suggestions that cerebral plaques and neurofibrillary tangles are more common in schizophrenia in association with neuroleptic treatment were not supported.
Assuntos
Doença de Alzheimer/patologia , Antipsicóticos/uso terapêutico , Encéfalo/patologia , Esquizofrenia/patologia , Idoso , Autopsia , Distribuição de Qui-Quadrado , Intervalos de Confiança , Humanos , Pessoa de Meia-Idade , Emaranhados Neurofibrilares/patologia , Razão de Chances , Esquizofrenia/tratamento farmacológicoRESUMO
Gangliosides GM1, GD1a, GD1b, and GT1b were measured in nine brain regions of five patients, clinically and neuropathologically diagnosed as having dementia of the Alzheimer type (DAT), and of three control patients. Analysis of variance revealed that mean concentrations of all gangliosides analyzed were significantly lower in DAT than in control brains. The areas affected in DAT included the nucleus basalis, and entorhinal, posterior cingulate, visual, and prefrontal cortices. A significant interaction between ganglioside type and brain area indicated unequal ganglioside concentrations. Individual gangliosides had significantly different concentrations in the hippocampal, entorhinal, posterior cingulate, visual, and prefrontal cortices. Analysis of ratios of "a"-ganglioside (GM1 and GD1a) and "b"-ganglioside (GD1b and GT1b) subtypes indicated that DAT preferentially affected "b"-gangliosides. Ganglioside concentrations in nucleus basalis did not correlate with age at disease onset, age at death, or postmortem interval. Changes in gangliosides, observed in this study, were not correlated with classic DAT neuropathology.
Assuntos
Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Gangliosídeos/metabolismo , Idoso , Análise de Variância , Gangliosídeos/classificação , Humanos , Pessoa de Meia-Idade , Concentração OsmolarRESUMO
Serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels were measured in the sixth, 13th, and 20th milliliters of CSF in patients with dementia of the Alzheimer's type (DAT) and Parkinson's disease (PD), and in an aliquot of CSF in controls. In patients with PD there was a positive correlation between 5-HT and 5-HIAA levels in the 20th milliliter of CSF, while in patients with DAT there was a negative correlation of these levels in this CSF fraction. In patients with the senile form of DAT the 5-HIAA levels in the 20th milliliter of CSF were higher than in patients with PD. These results indicate differential involvement of the serotoninergic system in DAT and PD, and may lead to the development of a chemical marker for DAT.
Assuntos
Doença de Alzheimer/líquido cefalorraquidiano , Demência/líquido cefalorraquidiano , Ácido Hidroxi-Indolacético/líquido cefalorraquidiano , Doença de Parkinson/líquido cefalorraquidiano , Serotonina/líquido cefalorraquidiano , Idoso , HumanosRESUMO
The rate of disease progression was assessed for 42 persons affected by Huntington's disease who had been neurologically examined at least six times and followed up for at least 3 years. Disease progression was assessed by a disability rating scale administered at each examination. Slow progression was associated with older age at onset of disease and with heavier weight (body mass index) at the first examination. Men tended to have a slower disease progression than did women, and this was particularly evident among men inheriting Huntington's disease from affected mothers. Neither the butyrophenone haloperidol nor the tricyclic antidepressant imipramine were related to rate of progression. Assessments of depression, hostility, and tobacco use were also unrelated to rate of progression. Clinical trials in Huntington's disease should consider these factors when designing therapeutic studies.
Assuntos
Doença de Huntington/fisiopatologia , Adolescente , Adulto , Fatores Etários , Idoso , Consumo de Bebidas Alcoólicas , Peso Corporal , Feminino , Hostilidade , Humanos , Doença de Huntington/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Plantas Tóxicas , Fatores Sexuais , Fumar , NicotianaRESUMO
We estimated dopamine release postmortem in the neostriatum of patients with Huntington disease (HD) and in controls. In HD, dopamine levels were unchanged in caudate and elevated in putamen, but homovanillic acid (HVA) and the ratio HVA:dopamine were unaltered in both nuclei. When rats were injected with kainic acid (an experimental model of HD), dopamine levels in striatum remained unchanged 2 to 30 days postoperatively; HVA and 3,4-dihydroxyphenylacetic acid (DOPAC) increased significantly from 2 to 18 days after injections but returned to normal levels later. These findings suggest that the nigrostriatal projection adapts to loss of striatal neurons that normally influence dopamine release and is not hyperactive in HD chorea.
Assuntos
Corpo Estriado/metabolismo , Dopamina/metabolismo , Doença de Huntington/metabolismo , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Animais , Encefalopatias/induzido quimicamente , Feminino , Ácido Homovanílico/metabolismo , Humanos , Ácido Caínico , Masculino , Pessoa de Meia-Idade , Neurônios/metabolismo , Ratos , Ratos EndogâmicosRESUMO
Variability of expression of the Huntington's disease (HD) gene is illustrated in 2 families with linkage of DNA restriction fragment length polymorphism to the short arm of chromosome 4. In 1 family, affected persons from 3 generations show 50-year variation of onset age. The member with the latest onset age (67) died at 91 with autopsy-confirmed HD. The next generation had hypotonic chorea beginning in the 4th decade with death in the 5th. In the 3rd generation, a rigid patient, inheriting the illness from an affected father, had a much earlier onset at 16, while her siblings had chorea beginning in the 3rd decade. In the 2nd family, several members had cerebellar signs, chorea, and dementia. MRI and CT revealed olivoponto-cerebellar and striatal atrophy. These phenotypes may be the result of different allelic genes at the HD locus or unlinked autosomal modifying loci influencing the expression of the HD gene.
Assuntos
Cromossomos Humanos Par 4 , Ligação Genética , Doença de Huntington/genética , Adolescente , Adulto , Atrofia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Núcleo Caudado/diagnóstico por imagem , Núcleo Caudado/patologia , Humanos , Doença de Huntington/complicações , Doença de Huntington/diagnóstico , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Atrofias Olivopontocerebelares/etiologia , Linhagem , Fenótipo , Tomografia Computadorizada por Raios XRESUMO
We studied a 68-year-old man who died after 13 years of progressive dementia, rigidity, bradykinesia, mild tremor, stooped posture, slow and shuffling gait, dystonia, blepharospasm, apraxia of eyelid opening, anarthria, aphonia, and incontinence. At autopsy, he had generalized brain atrophy with large deposits of iron pigment in the globus pallidus, caudate, and substantia nigra. Axonal spheroids were found in the globus pallidus, substantia nigra, medulla, and spinal cord. The neurochemical analysis of the brain revealed marked loss of dopamine in the nigral-striatal areas, with relative preservation of dopamine in the limbic areas. This is the oldest case of familial Hallervorden-Spatz disease reported and the first with neurochemical analysis of the brain.