Analysis of TUBB4A gene variant in a patient with adolescent-onset hypomyelinating leukodystrophy with atrophy of basal ganglia and cerebellum / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical characteristics and genetic etiology of a patient with adolescent-onset hypomyelinated leukodystrophy with atrophy of basal ganglia and cerebellum (H-ABC).@*METHODS@#A patient who was diagnosed with H-ABC in March 2018 at the First Affiliated Hospital of Nanjing Medical University was selected as the study subject. Clinical data was collected. Peripheral venous blood samples of the patient and his parents were collected. The patient was subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing.@*RESULTS@#The patient, a 31-year-old male, had manifested with developmental retardation, cognitive decline and abnormal gait. WES revealed that he has harbored a heterozygous c.286G>A variant of the TUBB4A gene. Sanger sequencing confirmed that neither of his parents has carried the same variant. Analysis with SIFT online software indicated the amino acid encoded by this variant is highly conserved among various species. This variant has been recorded by the Human Gene Mutation Database (HGMD) with a low population frequency. The 3D structure constructed by PyMOL software showed that the variant has a harmful effect on the structure and function of the protein. According to the guidelines formulated by the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic.@*CONCLUSION@#The c.286G>A (p.Gly96Arg) variant of the TUBB4A gene probably underlay the hypomyelinating leukodystrophy with atrophy of basal ganglia and cerebellum in this patient. Above finding has enriched the spectrum of TUBB4A gene variants and enabled early definitive diagnosis of this disorder.

Clinical analysis of 30 cases of basal ganglia germinoma in children / 北京大学学报(医学版)

OBJECTIVE@#To summarize and analyze the clinical characteristics of children with basal ganglia germinoma and to improve the level of early clinical diagnosis.@*METHODS@#The clinical data of children diagnosed with basal ganglia germinoma admitted to the Pediatric Surgery Ward of Peking University First Hospital from January 2013 to December 2020 were retrospectively analyzed, and descriptive statistics were used to analyze the clinical characteristics of children with basal ganglia germinoma.@*RESULTS@#A total of 30 patients were included in the study, 28 were male, 2 were female, the mean age at onset was (9.7±2.2) years, the median disease duration was 7 months, 27 had unilateral disease, and 3 had bilateral disease. The clinical manifestations were decreased limb muscle strength, cognitive function disorders, polydipsia, precocious puberty, intracranial hypertension, dysphonia and swallowing dysfunction. The serum and cerebrospinal fluid tumor marker alpha-fetoprotein (AFP) were normal in the 30 patients, and the serum and cerebrospinal fluid tumor marker β-human chorionic gonadotropin (β-HCG) were normal in 8 patients.The serum β-HCG was normal in 11 patients but the cerebrospinal fluid β-HCG was slightly elevated, and the serum and cerebrospinal fluid β-HCG were slightly elevated in 11 patients. A total of 33 lesions with irregular shapes were found by imaging examination, including 15 (45.5%) patchy lesions, 10 (30.3%) patchy lesions, and 8 (24.2%) round-like high-density lesions. Tumors showed obvious high-density shadows on computed tomography (CT) scan. Magnetic resonance imaging (MRI) scan of the tumors showed low or isointensity on T1WI and isointensity on T2WI, accompanied by mild peritumoral edema, hemispheric atrophy, cerebral peduncle atrophy, calcification, cystic degeneration, ventricular dilatation and wallerian degeneration. On contrast-enhanced scans, the tumor showed no enhancement or heterogeneous enhancement.@*CONCLUSION@#The main age of onset of germ cell tumors in the basal ganglia in children is about 10 years old, and males are absolutely dominant. The clinical features and imaging manifestations have certain characteristics. With both combined, the early diagnosis of germ cell tumors in the basal ganglia can be improved.

Cognitive dysfunction in corticobasal degeneration / Disfunção cognitiva na degeneração corticobasal

ABSTRACT Corticobasal degeneration (CBD) was originally described as a distinct clinicopathological entity in 1967. Since then, different phenotypic presentations have emerged as possible manifestations of CBD histopathological findings. In addition, pathophysiological findings and the molecular basis have been delineated and several aspects of its cognitive manifestations have been clarified. Thus, not only the spectrum of what is currently designated as CBD has expanded, but overlap with other degenerative and even secondary disorders has made clinical diagnostic certainty even more challenging in the absence of specific and readily-available markers. Cognitive deficits in CBD are now recognized as a frequent initial presentation and may appear up to eight years before the motor symptoms, depending on the phenotypic variant. Characteristic cognitive features of CBD involve language deficits, visuospatial and executive dysfunctions, apraxia, and behavioral disorders. Semantic and episodic memories are usually preserved, while language is often impaired in the early stages.

RESUMO A degeneração corticobasal (DCB) foi originalmente descrita como uma entidade clínico-patológica distinta em 1967. Desde então, nossa compreensão sobre DCB evoluiu substancialmente. Diferentes apresentações fenotípicas emergiram refletindo possíveis manifestações das anormalidades histopatológicos da DCB. Adicionalmente, dados fisiopatológicos e moleculares foram delineados e aspectos das manifestações cognitivas foram explorados. Assim, não só o espectro do que é atualmente designado DCB foi expandido, mas a sobreposição com outras doenças degenerativas e até mesmo secundárias tornaram o diagnóstico clínico ainda mais desafiador na ausência de marcadores específicos e prontamente disponíveis. Déficits cognitivos na DCB são agora reconhecidos frequentemente como apresentações iniciais e podem surgir até 8 anos antes dos sintomas motores, dependendo da variante fenotípica. O quadro cognitivo envolve característicamente déficits de linguagem, disfunção visuoespacial e executiva, apraxia, e distúrbios comportamentais. Anormalidades da linguagem são frequentemente descritas nos estágios iniciais da DCB.

Encefalopatía por Kernicterus. serie clínica / Kernicterus (bilirubin encephalopathy): case reports

Introducción: La ictericia es común en los recién nacidos (RN). Niveles de bilirrubina a partir de 20 mg/dL (en RN de término) pueden causar parálisis cerebral coreoatetósica, hipoacusia sensorioneural, trastornos de la mirada y displasia del esmalte dental, cuadro clínico conocido como kernicterus. Objetivo: Describir 5 casos de kernicterus controlados en una Unidad de Neurología, entre los años 2002-2012. Casos clínicos: Se presentan 5 niños con edades gestacionales entre 35 y 39 semanas, con peso de nacimiento rango 2.580 y 4.250 g y niveles de bilirrubina entre 24 y 47 mg/dL. Dos RN estaban en su domicilio cuando iniciaron la encefalopatía aguda. Todos se trataron con fototerapia y en 3 casos se realizó además exanguineotransfusión. La edad del diagnóstico de kernicterus fluctuó entre los 12 días y 10 años (3 pacientes se diagnosticaron en etapa neonatal) con una resonancia magnética que demostró impregnación de ganglios basales. Todos evolucionaron con trastornos del movimiento de severidad variable. En 3 pacientes se diagnosticó hipoacusia sensorioneural y en dos hubo trastornos de la mirada. Los test psicométricos evaluaron retraso cognitivo en 3 pacientes y desarrollo normal en los restantes. Conclusión: El kernicterus en una enfermedad devastadora que aún está presente en la realidad nacional. Es una causa de parálisis cerebral prevenible, por lo cual es necesario educar a los padres, población y equipo de salud para la detección precoz y tratamiento oportuno de la hiperbilirrubinemia neonatal.

Introduction: Jaundice is common in newborn babies (NB). Bilirubin levels of 20 mg/dL or higher may cause choreoathetoid cerebral palsy, sensorineural hearing loss, eye disorders and enamel dysplasia in term infants; clinical picture compatible with kernicterus. Objective: To describe five cases of kernicterus treated at a Neurology Unit between 2002 and 2012. Case reports: Five cases of babies with gestational ages between 35 and 39 weeks, birth-weight ranging from 2580 to 4250 grams and bilirubin levels between 24 and 47 mg/dL are presented. Two infants were at home when acute encephalopathy developed, all were treated with phototherapy and 3 of them underwent exchange transfusion. The age of diagnosis of kernicterus was between 12 days to 10 years; three patients were diagnosed in neonatal period through MRI that revealed basal ganglia impregnation. All patients evolved presenting movement disorders of varying severity. Three of them were diagnosed with sensorineural hearing impairments and two presented eye disorders. Psychometric tests showed cognitive delay in three patients and normal development in the remaining children. Conclusion: Kernicterus in a devastating disease present in the national reality. It is a preventable cause of cerebral palsy; therefore, it is necessary to educate parents, population and health care professionals about neonatal hyperbilirubinemia early detection and treatment.

Comparison on different strategies for treatments of hypertensive hemorrhage in the basal ganglia region with a volume of 25 to 35ml / Comparação de diferentes estratégias no tratamento da hemorragia hipertensiva da região dos gânglios da base com volume de 25 a 35ml

PURPOSE: To compare curative effect of different treatments for hypertensive cerebral hemorrhage of 25 to 35ml. METHODS: In this study, 595 cases were enrolled and grouped regarding treatments including conservative treatment, evacuation with microinvasive craniopuncture technique within 6h and 6-48h after the attack. RESULTS: After follow up for three months after the attack, the assessment based on the Activity of Daily Living (ADL) indicated no significant difference among conservative treatment and surgical interventions (p>0.05). However, surgical interventions showed advantages of shorter hospitalization, quick removal of hematoma and obvious reduction of cost. CONCLUSION: The microinvasive craniopuncture technique to drain the hematoma within 6-48h may be a good way in treating hypertensive hemorrhage of basal ganglia region.

OBJETIVO: Comparar o efeito curativo de diferentes tratamentos da hemorragia hipertensiva cerebral de 25 a 35ml. MÉTODOS: Foram analisados 595 casos agrupados segundo tratamento conservador e evacuação com técnica de punção transcraniana dentro de 6h ou de 6 às 48h do início do quadro clínico. RESULTADOS: O seguimento após três meses e avaliado pelo Escore de Atividade de Vida Diário, indicou que não houve diferenças significantes entre os tratamentos conservador e cirúrgico (p>0.05) O tratamento cirúrgico mostrou vantagem com hospitalização mais curta e redução de custos. CONCLUSÃO: A técnica de punção transcraniana para drenagem de hematoma dos núcleos da base pode ser uma boa alternativa de tratamento.

Creutzfeldt-Jacob disease: An autopsy case report in tertiary care hospital.

Sporadic Creutzfeldt-Jakob disease (CJD) is the most common prion disease. It is a rare, fatal neurodegenerative disease caused by an infectious protein called prion. The diagnosis can be confirmed only by histological examination of brain tissue. Because of the transmissible nature of the disease, autopsy or brain biopsy cannot be performed at many institutions. Histology shows spongiform changes, neuronal loss, reactive astrocytic proliferation, accumulation of pathologic protein occurring in three general forms: Sporadic, familial, and acquired form, including a variant form of CJD. It clinically presents as predominantly progressive dementia with a rapid onset, myoclonus, cerebellar, pyramidal, extra pyramidal and visual signs. Occurrence of periodical spikes in electro-encephalogram, observation of cortical signal alterations in magnetic resonance imaging (MRI) studies, and detection of protein 14-3-3 in cerebrospinal fluid substantiate diagnosis. Autopsy case is presented of a 50 year old woman with progressive dementia, typical neurological symptoms, MRI findings and confirmation of CJD on histology and immunostaining.

Immunohistochemical identification of plasma protein deposits in the wall of lenticulostriate arteries in patients with long-standing hypertension, with and without lipohyalinosis / Identificação imuno-histoquímica de depósitos de proteínas plasmáticas na parede das artérias lentículo-estriadas em pacientes com hipertensão arterial de longa duração, com e sem lipo-hialinose

PURPOSE: To investigate, through an immunohistochemical method, whether there is deposition of plasma proteins in the wall of lenticulostriate, cortical and leptomeningeal arteries of hypertensive patients, with and without lipohyalinosis. METHOD: Forty patients with essential hypertension were selected at random, 20 with lipohyalinosis in the lenticulostriate arteries (HH group) and 20 without lipohyalinosis (H group), matched with 20 normotensive controls (C group). RESULTS: Plasma protein deposits were identified in eight patients (40 percent) in the C group, in 15 patients (75 percent) in the H group, and in all 20 patients (100 percent) in the HH group, the difference being significant for the H group and highly significant for the HH group, as compared with the C group. In all groups, the distribution of plasma protein deposits, subendothelial in normal arteries, and diffuse, irregular in the wall of arteries with lipohyalinosis, was more frequent in the lenticulostriate arteries of the putamen. CONCLUSION: Deposition of plasma proteins in the lenticulostriate arteries seems to be relatively frequent in normotensive individuals, starting in middle age. Such process appears to be intensified by hypertension, especially in individuals with lipohyalinosis.

PROPÓSITO: Investigar, por meio de método imuno-histoquímico, a deposição de proteínas plasmáticas na parede das artérias lentículo-estriadas, corticais e leptomeníngeas em pacientes com hipertensão arterial, com e sem lipo-hialinose. MÉTODO: Quarenta pacientes com hipertensão arterial foram selecionados aleatoriamente, sendo 20 com lipo-hialinose nas artérias lentículo-estriadas (grupo HH) e 20 sem lipo-hialinose (grupo H), pareados com 20 controles normotensos (grupo C). RESULTADOS: Depósitos de proteínas plasmáticas foram identificados em oito pacientes (40 por cento) do grupo C, em 15 pacientes (75 por cento) do grupo H e em todos os 20 pacientes (100 por cento) do grupo HH, a diferença sendo significativa para o grupo H e altamente significativa para o grupo HH, quando comparada com o grupo C. Em todos os grupos, a distribuição dos depósitos de proteínas plasmáticas, subendotelial em artérias normais e difusa, irregular, na parede das artérias com lipo-hialinose, foi mais freqüente nas artérias lentículo-estriadas do putâmen. CONCLUSÃO: A deposição de proteínas plasmáticas nas artérias lentículo-estriadas parece ser um fenômeno relativamente freqüente em indivíduos normotensos, a partir da meia-idade. Tal processo parece ser intensificado pela hipertensão arterial, particularmente naqueles pacientes com lipo-hialinose.

case report of basal ganglia calcification - a rare finding of hypoparathyroidism

Physiological intracranial calcification occurs in about 0.3-1.5% of cases. It is asymptomatic and detected incidentally by neuroimaging. Pathological basal ganglia calcification is due to various causes, such as: metabolic disorders, infectious and genetic diseases. Hypoparathyroidism and pseudohypoparathyroidism are the most common causes of pathological basal ganglia calcification. Besides tetany and seizures this condition is presented by parkinsonism and dementia. Such parkinsonism does not respond to drugs containing levodopa. Infections [toxoplasmosis, rubella, cytomegalovirus, cysticercosis, AIDS] give multiple and asymmetric intracranial calcification. Inherited and neurodegenerative diseases cause symmetrical, bilateral basal ganglia calcification which is not related to metabolic disorders. Since adequate treatment of hypoparathyroidism may lead to marked clinical improvement, serum concentration of calcium, phosphorus, and parathyroid hormone [PTH] is suggested to be determined in all individuals with calcification of the basal ganglia to rule out hypoparathyroidism

Pontine and extrapontine osmotic myelinolysis after the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with fluoxetine: case report

Osmotic demyelination syndrome (ODS) may be precipitated by aggressive correction of a hypo or hyper-osmolar states. We describe the case of a 53-year-old woman that was started on fluoxetine 20 mg/day for depression and nine days later was found to have fluoxetine-induced syndrome of inappropriate secretion of antidiuretic hormone. After hyponatremia correction the mental status of the patient gradually improved, but subsequently she had intermittent difficulty in speaking, naming objects, memory deficits and psychomotor slowness. Magnetic resonance revealed bilateral symmetric hyperintense lesions in the basal ganglia, temporal lobe and hippocampal formation compatible with ODS. These symptoms gradually resolved and she was discharged home without any deficits. Two months later, a new image showed lesion in pons and the other lesions had disappeared. Fluoxetine therapy had never been related with a complication like that.

A síndrome de desmielinização osmótica (SDO) pode ser precipitada pela correção agressiva de um estado hiper ou hipoosmolar. Nós descrevemos o caso de mulher de 53 anos que havia iniciado o uso de fluoxetina 20 mg/dia para depressão e que nove dias depois foi diagnosticada como tendo síndrome da secreção inapropriada de hormônio antidiurético induzida por fluoxetina. Depois da correção da hiponatremia o estado mental da paciente gradualmente melhorou, mas subsequentemente ela apresentou dificuldade intermitente para fala e para nomear objetos, déficits de memória recente e lentidão psicomotora. Ressonância magnética revelou lesões hiperintensas bilaterais e simétricas na região dos gânglios da base, lobo temporal e hipocampo compatíveis com SDO. Estes sintomas gradualmente se resolveram e a paciente foi de alta sem qualquer déficit. Dois meses mais tarde uma nova imagem cerebral mostrou lesão na ponte e ausência das lesões antigas. Até onde sabemos a terapia com fluoxetina nunca foi relacionada a uma complicação tardia como esta.

Hypomyelination with atrophy of the basal ganglia and cerebellum: case report

Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a rare disease that has been recently described. It must be remembered as a possible etiology of leukoencephalopathies in children. We describe a typical case of H-ABC in a 11-month-old boy. He presents with global development delay, oral dyskinesia, and global dystonia and spasticity. Magnetic resonance imaging disclosed typical features of H-ABC and clinical laboratory tests were all negative. A slow neurological deterioration has been detected with worsening of involuntary movements.

A hipomielinização com atrofia dos núcleos da base e do cerebelo (H-ABC) é uma rara afecção que deve ser lembrada como possível diagnóstico das leucoencefalopatias de difícil definição etiológica. Descrevemos um típico caso de H-ABC em um menino de 11 meses, sem antecedentes de risco para lesão cerebral, que evoluiu com atraso psicomotor acompanhado de discinesia perioral, distonia e espasticidade generalizadas. A ressonância magnética do encéfalo sugere fortemente o diagnóstico de H-ABC e os exames complementares para pesquisar possíveis diagnósticos diferenciais são negativos. O curso clínico tem sido lentamente progressivo com ausência de ganhos motores e piora dos movimentos involuntários.

Co-occurrence of radiological features of progressive supranuclear palsy and corticobasal degeneration.

We report an interesting case demonstrating co-occurrence of radiological features of progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). The clinical features were typical of PSP but magnetic resonance imaging (MRI) showed both typical brainstem changes of PSP and an atypical pattern of cortical atrophy. While the MRI had markers of CBD, the clinical features were not classical of CBD.

[Risk factors of kernicterus; a study in 312 icteric neonates]

Kernicterus, also known as bilirubin encephalopathy, is a neurologic syndrome resulting from the deposition of unconjugated bilirubin in the basal ganglia and brainstem nuclei. Indirect bilirubin is toxic for brain. Neurologic dysfunction [BIND] that include acute phase [hyperbilirubin encephalopathy] and chronic phase [Kernicterus] resulting from hyperbilirubinemia and disruption of blood brain barrier. In this study, the association between bilirubin encephalopathy and risk factors was evaluated. In this retrospective study, 312 icteric neonates were admitted in the neonatal ward of Children's Hospital, Medical Center, Tehran, and 305 of these cases were evaluated. Patient histories were taken and physical examinations were performed. For each patient, the age, sex, birth weight, time of discharge from the hospital and risk factors were recorded, and a questionnaire was completed. In this study, of the 305 icteric neonates evaluated, 25 cases had kernicterus. Risk factors included acidosis, prematurity, hemolysis, hypoglycemia, sepsis, respiratory distress, low birth weight, ABO incompatibility and G6PD deficiency. The mean level of bilirubin in cases of kernicterus was 32 mg/dl and in the others was 20 mg/dl [p=0.001]. Kernicterus was most common among high risk neonates [p<0.001]. Birth weight less than 2,500 gm was also an important factor [p=0.04]. High-risk neonates need prompt treatment for hyperbilirubinemia compared to low risk neonates

Severe hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with fluoxetine: case report

A hiponatremia é complicação significativa do tratamento com inibidores seletivos da recaptação da serotonina (ISRS). Descrevemos o caso de uma paciente de 53 anos de idade que iniciou uso de fluoxetina 20 mg/dia para depressão. Nove dias depois, a paciente apresentou fraqueza, náusea, progredindo para confusão, inapetência e vômitos. Três horas depois ela tornou-se irresponsiva e teve uma crise convulsiva generalizada. Foi então trazida ao nosso serviço de emergência. Na admissão, a paciente estava normovolêmica, sem déficits motores focais, mas apresentava leve rigidez muscular generalizada e sinal de Babinski bilateralmente. O sódio sérico era 105 mmol/L, osmolaridade sérica, 220 mmol/L, e osmolaridade urinária, 400 mmol/L. Os outros exames laboratoriais, Raio-X do pulmão, líquido cefalorraqueano e tomografia do crânio eram normais. Ela foi diagnosticada como tendo SSIHAD induzida por fluoxetina sendo esta descontinuada. Nós iniciamos a correção da hiponatremia e, em 5 dias, o estado mental da paciente gradualmente retornou ao normal, paralelamente a resolução da hiponatremia. SSIHAD e hiponatremia devem ser consideradas em um paciente que apresenta deterioração de sua condição clinica quando estiver em uso de ISRS. O uso de antidepressivos ISRS deve ser lembrado no diagnóstico diferencial de hiponatremia induzida por drogas.

Secondary tics and tourettism

Tiques motores e fônicos são usualmente sintomas da síndrome de Tourette idiopática; entretanto, existem muitas causas orgânicas conhecidas para os tiques. Analisando os prontuários de 155 pacientes (101 homens/54 mulheres; idade média 40,5 ± 20,2 anos) com tiques e transtornos comórbidos encontramos que: 14 (9,0%) pacientes tinham tiques secundários a lesão dos gânglios da base, decorrentes de trauma craniano (N = 4; 2,5%), acidente vascular cerebral (N = 2; 1,2%), encefalite (N = 3; 1,9%) ou outras causas. Além disso, certas drogas, toxinas e complicações pós-infecciosas puderam ser etiologicamente associadas aos tiques. Raramente, lesões periféricas estiveram associadas a transtornos do movimento, incluindo tiques (N = 1; 0,6%). Transtornos globais do desenvolvimento, incluindo síndrome de Asperger (N = 13; 8,3%), retardo mental (N = 4; 2,5%), autismo (N = 3; 1,9%) e síndrome de Savant (N = 1; 0,6%), também podem estar associados a tiques, como observado em 21 dos 155 pacientes (13,5%). Doenças genéticas e cromossômicas, como a síndrome de Down (N = 5; 3,2%), a neuroacantocitose (N = 2; 1,2%) e a doença de Huntington (N = 1; 0,6%) estavam associadas a tiques em 16 pacientes (10,3%). Também examinamos a comorbidade de tiques com outros transtornos de movimento como distonia (N = 31; 20,0%) e tremor essencial (N = 17; 10,9%). Dezeseis (10,3%) pacientes apresentaram tiques psicogênicos e um (0,6%), tiques psicogênicos e distonia; ao contrário, síndrome de Tourette precedeu o início de distonia psicogênica (N = 1; 0,6%) e tremor psicogênico (N = 1; 0,6%) em dois pacientes. Finalmente, 12 (7,7%) pacientes tinham tiques associados a transtornos neurológicos não relacionados ao movimento, como encefalopatia estática (N = 2; 1,2%) e convulsões (N = 3; 1,9%). Para entender a fisiopatologia dos tiques e da síndrome de Tourette é importante reconhecer que esses podem ser causados por ou associados a outros transtornos.

Leigh's syndrome.

A 15-month-old female child presented with sudden onset cough and hyperventilation along with evidence of metabolic acidosis. She had past history of recurrent vomiting, episodes of abnormal posturing, difficulty in deglutition and regression of milestones since 12 months of age. CT scan of the brain revealed hypodense lesions in bilateral basal ganglia and on MRI there were T2 hyperintensities in bilateral lentiform nuclei, caudate nuclei, thalamus, red nuclei and dentate nuclei. Biochemical examination revealed persistently elevated serum lactate levels with high lactate/pyruvate ratio. Resuscitative measures were of no avail and the child succumbed to the illness on the second day of admission. Neuropathological examination at autopsy demonstrated marked spongiosis, focal necrosis, endothelial proliferation, reactive astrogliosis and extensive demyelination involving bilateral basal ganglia, midbrain and spinal cord which were typical of Leigh's sub acute necrotizing encephalomyelopathy.