Movement disorders in hereditary spastic paraplegias / Distúrbios de movimento em paraplegia espástica hereditária

Abstract Background Hereditary or familial spastic paraplegias (SPG) comprise a group of genetically and phenotypically heterogeneous diseases characterized by progressive degeneration of the corticospinal tracts. The complicated forms evolve with other various neurological signs and symptoms, including movement disorders and ataxia. Objective To summarize the clinical descriptions of SPG that manifest with movement disorders or ataxias to assist the clinician in the task of diagnosing these diseases. Methods We conducted a narrative review of the literature, including case reports, case series, review articles and observational studies published in English until December 2022. Results Juvenile or early-onset parkinsonism with variable levodopa-responsiveness have been reported, mainly in SPG7 and SPG11. Dystonia can be observed in patients with SPG7, SPG11, SPG22, SPG26, SPG35, SPG48, SPG49, SPG58, SPG64 and SPG76. Tremor is not a frequent finding in patients with SPG, but it is described in different types of SPG, including SPG7, SPG9, SPG11, SPG15, and SPG76. Myoclonus is rarely described in SPG, affecting patients with SPG4, SPG7, SPG35, SPG48, and SPOAN (spastic paraplegia, optic atrophy, and neuropathy). SPG4, SPG6, SPG10, SPG27, SPG30 and SPG31 may rarely present with ataxia with cerebellar atrophy. And autosomal recessive SPG such as SPG7 and SPG11 can also present with ataxia. Conclusion Patients with SPG may present with different forms of movement disorders such as parkinsonism, dystonia, tremor, myoclonus and ataxia. The specific movement disorder in the clinical manifestation of a patient with SPG may be a clinical clue for the diagnosis.

Resumo Antecedentes As paraplegias espásticas hereditárias ou familiares (SPG) compreendem um grupo de doenças geneticamente e fenotipicamente heterogêneas caracterizadas por degeneração progressiva dos tratos corticospinais. As formas complicadas evoluem com vários outros sinais e sintomas neurológicos, incluindo distúrbios do movimento e ataxia. Objetivo Resumir as descrições clínicas de SPG que se manifestam com distúrbios do movimento ou ataxias para auxiliar o clínico na tarefa de diagnosticar essas doenças. Métodos Realizamos uma revisão da literatura, incluindo relatos de casos, séries de casos, artigos de revisão e estudos observacionais publicados em inglês até dezembro de 2022. Resultados O parkinsonismo juvenil ou de início precoce com resposta variável à levodopa foi relatado principalmente em SPG7 e SPG11. A distonia pode ser observada em pacientes com SPG7, SPG11, SPG22, SPG26, SPG35, SPG48, SPG49, SPG58, SPG64 e SPG76. O tremor não é um achado frequente em pacientes com SPG, mas é descrito em diferentes tipos de SPG, incluindo SPG7, SPG9, SPG11, SPG15 e SPG76. A mioclonia é raramente descrita em SPG, afetando pacientes com SPG4, SPG7, SPG35, SPG48 e SPOAN (paraplegia espástica, atrofia óptica e neuropatia). SPG4, SPG6, SPG10, SPG27, SPG30 e SPG31 podem raramente apresentar ataxia com atrofia cerebelar. E SPG autossômico recessivo, como SPG7 e SPG11, também pode apresentar ataxia. Conclusão Indivíduos com SPG podem apresentar diferentes formas de distúrbios do movimento, como parkinsonismo, distonia, tremor, mioclonia e ataxia. O distúrbio específico do movimento na manifestação clínica de um paciente com SPG pode ser uma pista clínica para o diagnóstico.

Discapacidad física, una valoración bajo dos perspectivas para la inserción laboral en Perú / Physical disability, an assessment under two perspectives for labor market insertion in Peru / Deficiência física, uma avaliação sob duas perspectivas para a inserção no mercado de trabalho no Peru

Las normativas legales peruanas como es la Ley 29973, busca la promoción, protección de las personas con discapacidad en el ámbito laboral logrando así el desarrollo, igualdad e inclusión social, política que actualmente aplicado en las instituciones públicas ni privadas en Perú. Objetivo. Analizar la influencia de la discapacidad física en la inserción laboral en Perú. Materiales y Métodos. La metodología que se utilizó estuvo enmarcada en el enfoque cuantitativo, el tipo de investigación fue básica causal explicativo, el método hipotético deductivo, el diseño de la investigación fue no experimental de corte transeccional. La población fue de 61 usuarios, la técnica utilizada para la recolección de datos fue la encuesta y como instrumento el cuestionario, los datos se analizaron mediante el software estadístico SPSS. El procesamiento estadístico fue no paramétrico de Chi-Cuadrada. Resultados. Como resultado de la investigación fue que el 31,1% de los usuarios manifestaron que no están insertados en el mercado laboral ya que la discapacidad física que poseen es de tipo paraplejia, es decir, que, ambas piernas carecen de movilidad lo cual es una restricción para su desarrollo y dificulta su integración en el mercado laboral. Conclusiones. La discapacidad influye significativamente en la inserción laboral de los usuarios de la Oficina Municipal de Atención a las Personas con Discapacidad.

Peruvian legal regulations such as Law 29973, seeks the promotion and protection of people with disabilities in the workplace, thus achieving development, equality and social inclusion, a policy that is currently applied in public and private institutions in Peru. Objective. To analyze the influence of physical disability on labor market insertion in Peru. Materials and Methods. The methodology used was framed in the quantitative approach, the type of research was basic causal explanatory, the method was hypothetical deductive, the research design was non-experimental of transectional cut. The population consisted of 61 users, the technique used for data collection was the survey and the instrument was the questionnaire; the data were analyzed using SPSS statistical software. The statistical processing was nonparametric Chi-Square. Results. As a result of the research, 31.1% of the users stated that they are not inserted in the labor market since the physical disability they have is paraplegia, that is, both legs lack mobility, which is a restriction for their development and hinders their integration in the labor market. Conclusions. Disability has a significant influence on the labor market insertion of the users of the Municipal Office of Attention to People with Disabilities.

As normas legais peruanas, como a Lei 29973, buscam a promoção e a proteção de pessoas com deficiência no local de trabalho, alcançando assim o desenvolvimento, a igualdade e a inclusão social, uma política que atualmente é aplicada em instituições públicas e privadas no Peru. Objetivo. Analisar a influência da deficiência física na inserção laboral no Peru. Materiais e métodos. A metodologia utilizada foi enquadrada no enfoque quantitativo, o tipo de pesquisa foi causal explicativa básica, o método foi hipotético dedutivo, o desenho da pesquisa foi de corte transeccional não experimental. A população foi de 61 usuários, a técnica utilizada para a coleta de dados foi a pesquisa e como instrumento o questionário, os dados foram analisados com o uso do software estatístico SPSS. O processamento estatístico foi o qui-quadrado não paramétrico. Resultados. Como resultado da pesquisa, 31,1% dos usuários afirmaram que não estão inseridos no mercado de trabalho porque a deficiência física que possuem é a paraplegia, ou seja, falta mobilidade nas duas pernas, o que é uma restrição para o seu desenvolvimento e dificulta a sua integração no mercado de trabalho. Conclusões. A deficiência tem uma influência significativa na inserção no mercado de trabalho dos usuários da Secretaria Municipal de Atenção às Pessoas com Deficiência.

The Neuroprotective Effects of Ginsenoside Rd Pretreatment in a Rat Model of Spinal Cord Ischemia-Reperfusion Injury

ABSTRACT Introduction: Paraplegia may develop as a result of spinal cord ischemia-reperfusion injury in patients who underwent thoracoabdominal aortic surgery. The objective of this research is to determine the neuroprotective effects of ginsenoside Rd pretreatment in a rat model of spinal cord ischemia-reperfusion injury. Methods: Sprague-Dawley rats (n=36) were randomly assigned to three groups. The sham (n=12) and control (n=12) groups received normal saline orally. The Rd group (n=12) received ginsenoside Rd (100 mg/kg) orally 48 hours before the induction of spinal cord ischemia. Spinal cord ischemia was induced by aortic occlusion using a Fogarty balloon catheter in the Rd and control groups. A neurological assessment according to the motor deficit index and a histological evaluation of the spinal cord were performed. To evaluate the antioxidant activity of ginsenoside Rd, malondialdehyde levels and superoxide dismutase activity were determined. Further, the tissue levels of tumor necrosis factor-alpha and interleukin-1 beta were measured. Results: The Rd group showed significantly lower motor deficit index scores than did the control group throughout the entire experimental period (P<0.001). The Rd group demonstrated significantly greater numbers of normal motor neurons than did the control group (P=0.039). The Rd group exhibited decreased malondialdehyde levels (P<0.001) and increased superoxide dismutase activity (P=0.029) compared to the control group. Tumor necrosis factor-alpha and interleukin-1 beta tissue levels were significantly decreased in the Rd group (P<0.001). Conclusion: Ginsenoside Rd pretreatment may be a promising treatment to prevent ischemia-reperfusion injury in patients who undergo thoracoabdominal aortic surgery.

Treating Neurogenic Heterotopic Ossification around a Femur Following Paraplegia after an Open Surgery for Thoracoabdominal Aortic Aneurysm / 日本心臓血管外科学会雑誌

A 59-year-old man who was diagnosed with hypertension and a large thoracoabdominal aortic aneurysm was referred to our hospital for surgical treatment. He underwent open surgery and thoracic endovascular aneurysm repair in three stages. He developed paraplegia after the third surgery. Despite acute postoperative treatment and rehabilitation, his lower extremity motor function and bladder and bowel dysfunction did not improve. He was transferred to a recovery hospital 67 days after the third surgery. However, he was readmitted to our hospital about four months later for management of a refractory decubitus ulcer and recurrent urinary tract infections. Computed tomography revealed hematoma and calcification around the femur. Based on the clinical course and imaging findings, we diagnosed neurogenic heterotopic ossification associated with postoperative paraplegia in this patient. He had flap reconstruction for the ulcer. Finally, he was discharged 79 days after readmission. To date, no study has reported neurogenic heterotopic ossification associated with postoperative aortic aneurysm paraplegia. The mechanism underlying this condition is similar to the widely accepted process associated with traumatic spinal cord injury, and conservative treatment comprising pressure ulcer treatment and antibiotics was continued. Although acute rehabilitation is important after highly invasive aortic aneurysm surgery, rehabilitation is limited by the risk of neurogenic heterotopic ossification in patients with postoperative paraplegia, and recovery and maintenance of activities of daily living are challenging. To our knowledge, early diagnosis and prompt treatment for these complications are important considering neurogenic heterotopic ossification.

Paraplejia funcional que imita una mielopatía aguda durante el embarazo: reporte de un caso

Introducción: Los trastornos funcionales son un reto clínico en la atención de pacientes con déficits neurológicos. Pueden generar manifestaciones clínicas típicas y gran discapacidad. Para su diagnóstico se requiere de una alta sospecha inicial asociado a una batería de examen físico completa. Hallazgos clínicos: Presentamos el caso de una paciente indígena embarazada de 19 años, con pérdida de la fuerza en sus extremidades inferiores, un nivel sensitivo y pérdida del control de los esfínteres. Luego de una evolución estacionaria con estudios imagenológicos e infectocontagiosos dentro de la normalidad. Se sospechó el diagnóstico de un trastorno neurológico funcional por lo que se realizó la prueba del Spinal Injuries Center (SIC) el cual fue positivo. Tratamiento y evolución: Realizamos una intervención multidisciplinar, incluyendo el servicio de rehabilitación, neurología, psiquiatría y psicología. Se utilizaron intervenciones con movimientos articulares, fortalecimiento muscular, estimulación eléctrica y psicoterapia. Posteriormente se obtuvo la recuperación completa de la paciente antes del alta hospitalaria, con la exigencia de seguimiento ambulatorio, además de una inserción satisfactoria en las actividades sociales y familiares. Conclusiones: Este caso refleja la importancia de un análisis neurológico detallado, el conocimiento de diferentes herramientas de semiología y el reto diagnóstico de los trastornos funcionales en neurológicos. La intervención de un equipo multidisciplinar favorece abordajes multidimensionales y resultados clínicos favorables.

Introduction: Functional disorders pose a clinical challenge in the care of patients with neurological deficits. They can generate typical clinical manifestations and great disability. Diagnosis requires a high initial suspicion together with comprehensive physical examination. Clinical Findings: We present the case of a 19-year-old pregnant indigenous patient, with loss of strength in her lower extremities, with a sensitive level and loss of sphincter control. After a stationary evolution with imaging and infectious studies within normal limits, a diagnosis of a functional neurological disorder was suspected; thus, the Spinal Injuries Center (SIC) test was performed, showing positive results. Treatment and evolution: A multidisciplinary intervention was carried out, including the neurology, psychiatry and psychology rehabilitation. Interventions amied towards joint movements, muscle strengthening, electrical stimulation and psychotherapy were used. Eventually, the patient's complete recovery was achieved before hospital discharge, in addition to a satisfactory integration into social and family activities, with a outpatient follow-up requirement. Conclusions: This case reflects the importance of a detailed neurological analysis, knowledge of different semiology tools and the diagnostic challenge of functional neurological disorders. The intervention of a multidisciplinary team favors multidimensional approaches and favorable clinical results.

Epidemiology of post-traumatic spinal cord injury in a tertiary hospital / Epidemiologia do lesado medular pós-traumático em um hospital terciário

ABSTRACT Objective: to outline the profile of risk groups for spinal cord injury (SCI) at the Hospital de Clinicas de Campinas by an epidemiological survey of 41 patients with SCI. Methods: Data from patients with SCI were collected and analyzed: demographic data, level of neurological injury, visual analogue scale (VAS), and the current American Spinal Injury Association (ASIA) impairment scale (AIS), using questionnaires, medical records, and imaging tests. Fisher's exact test was used to assess the relationship between categorical variables, Spearman's correlation coefficient was used for numerical variables, and the Mann-Whitney and Kruskal-Wallis tests were used to analyze the relationship between categorical and numerical variables, with significance level of 5%. Results: There was a prevalence of 82.9% of men, a mean age of 26.5 years, and traffic accidents as the cause of SCI in 56.1% of cases. Conclusion: Results suggest the importance of SCI prevention campaigns directed at this population. Level of Evidence II, Retrospective Study.

RESUMO Objetivo: Traçar o perfil dos grupos de risco para trauma raquimedular (TRM) do Hospital das Clínicas de Campinas através de levantamento epidemiológico de 41 pacientes vítimas de TRM. Métodos: Foram coletados e analisados dados demográficos, nível da lesão neurológica, escala visual analógica (EVA) e American Spinal Injury Association impairment scale (AIS) atuais, através da aplicação de questionários, análise de prontuários e de exames de imagem. Para avaliar a relação entre as variáveis categóricas foi utilizado o teste exato de Fisher; para as variáveis numéricas foi utilizado o coeficiente de correlação de Spearman; e para a análise da relação entre variáveis categóricas e numéricas foram utilizados os testes de Mann-Whitney e Kruskal-Wallis, adotando nível de significância de 5%. Resultados: Houve prevalência de 82,9% do sexo masculino, média de idade de 26,5 anos e de 56,1% casos de TRM causados por acidente automobilístico. Conclusão: Os resultados sugerem a importância da realização de campanhas de prevenção ao TRM voltadas para essa população. Nível de Evidência II, Estudo Retrospectivo.

Dysarthria in hereditary spastic paraplegia type 4

Abstract Objective: To describe the speech pattern of patients with hereditary Spastic Paraplegia type 4 (SPG4) and correlated it with their clinical data. Methods: Cross-sectional study was carried out in two university hospitals in Brazil. Two groups participated in the study: the case group (n = 28) with a confirmed genetic diagnosis for SPG4 and a control group (n = 17) matched for sex and age. The speech assessment of both groups included: speech task recording, acoustic analysis, and auditory-perceptual analysis. In addition, disease severity was assessed with the Spastic Paraplegia Rating Scale (SPRS). Results: In the auditory-perceptual analysis, 53.5% (n = 15) of individuals with SPG4 were dysarthric, with mild to moderate changes in the subsystems of phonation and articulation. On acoustic analysis, SPG4 subjects' performances were worse in measurements related to breathing (maximum phonation time) and articulation (speech rate, articulation rate). The articulation variables (speech rate, articulation rate) are related to the age of onset of the first motor symptom. Conclusion: Dysarthria in SPG4 is frequent and mild, and it did not evolve in conjunction with more advanced motor diseases. This data suggest that diagnosed patients should be screened and referred for speech therapy evaluation and those pathophysiological mechanisms of speech involvement may differ from the length-dependent degeneration of the corticospinal tract.

Post-thoracotomy paraplegia after oxidized cellulose spinal compression

ABSTRACT Post-thoracotomy paraplegia after non-aortic surgery is an extremely uncommon complication. A 56-year-old woman presented with a 1-year history of progressive shortness of breath. Computed tomography revealed a locally advanced posterior mediastinal mass involving the ribs and the left neural foramina. Tumor excision with a left pneumonectomy was performed. Post-resection, bleeding was noted in the vicinity of the T4-T5 vertebral body, and the bleeding point was packed with oxidized cellulose gauze (Surgicel®). Postoperatively, the patient complained of bilateral leg numbness extending up to the T5 level, with bilateral paraplegia. An urgent laminectomy was performed, and we noted that the spinal cord was compressed by two masses of Surgicel® with blood clots measuring 1.5 × 1.5cm at T4 and T5 levels. The paraplegia did not improve despite the removal of the mass, sufficient decompression, and aggressive postoperative physiotherapy. Surgeons operating in fields close to the intervertebral foramen should be aware of the possible threat to the adjacent spinal canal as helpful hemostatic agents can become a preventable threat.

Acute Paraplegia Result from Spinal Ischemia Nine Years After Hybrid Total Arch Repair with Frozen Elephant Trunk: A Case Report

ABSTRACT Spinal cord ischemia due to decreased cord perfusion is a devastating complication in patients with thoracoabdominal dissection following frozen elephant trunk (FET) repair surgery. However, rare occurrence of spinal cord ischemia leading to paraplegia after long-term follow-up of FET repair has been reported. Here, we describe a case of spinal cord ischemia resulting in paraplegia nine years after hybrid total arch repair with FET. Cerebrospinal fluid drainage and serial treatment were utilized to decrease intraspinal pressure and increase blood flow to the spinal cord. Three months after the onset of paraplegia and with treatment and rehabilitation, the patient recovered to walk.

Clinical analysis of a family with autosomal recessive spastic paraplegia caused by IBA57 gene mutations / 中华神经科杂志

Objective:To investigate the clinical, imaging and gene variation characteristics of hereditary spastic paraplegia type 74 caused by mutations in IBA57 gene. Methods:A retrospective analysis was performed on 2 cases of autosomal recessive spastic paraplegia caused by mutations in IBA57 gene who visited the Department of Neurology, the Affiliated Wuxi Children′s Hospital of Nanjing Medical University in 2010 and 2021, and the patients′ clinical data were collected. Results:The 2 patients were siblings with onset age of 4 years and 7 months, 1 year and 3 months, respectively. The same compound heterozygous mutations in IBA57 gene were found in the sibling patients [c.473G>C (p.R158P) and c.697C>T (p.R233X)]. Both patients were diagnosed as spastic paraplegia type 74. They had mild to moderate gait abnormalities, optic atrophy, decreased vision, and leukodystrophy with periventricular white matter abnormality, but no obvious growth and mental retardation in developmental assessment. Conclusions:Cases of spastic paraplegia type 74 caused by compound heterozygous mutations in IBA57 gene mainly manifested as childhood onset and slowly progressive inferior spasmodic weakness. The patients did not display significant cognitive impairment, and imaging examinations showed obvious leukodystrophy.

Hereditary spastic paraplegia due to nipa1 gene mutation: case report

ABSTRACT Introduction: Hereditary spastic paraplegia (HSP) is the term for a group of neurological disorders characterized by progressive spasticity and muscle weakness in the lower limbs. Its etiology is genetic and has been associated with mutations in more than 60 genes. HSP is rare and may be useful in the differential diagnosis of cerebral palsy. Case presentation: 16-year-old male with a diagnosis of HSP due to mutation of the NIPAi gene:c.316G>A (p. Gly106arg), which corresponds to HSP type 6 (SPG6). The patient presented with clinical signs of progressive upper motor neuron syndrome in the lower limbs, such as spasticity, hyperreflexia and paraparesis, associated with focal onset seizures diagnosed at age 11 and successfully treated with valproic acid. Spasticity treatment was complex and included oral baclofen, intraoperative botulinum toxin, physical therapy, and multilevel orthopedic surgery for the management of musculoskeletal deformities. Conclusion: This is a rare case of complex HSP, associated with epilepsy, due to the mutation of the NIPAi gene (SPG6), the most common pathogenic variant within this type of mutation. The present case demonstrates the importance of making an early diagnosis of GSP6 to perform timely interventions in these patients, prevent complications, and avoid a higher level of disability.

RESUMEN Introducción. La paraplejía espástica hereditaria (PEH) es un grupo de trastornos neurológicos caracterizados por espasticidad progresiva y debilidad muscular de miembros inferiores. Su etiología es genética y se ha asociado con mutaciones en más de 60 genes. La PEH es poco frecuente y puede ser útil en el diagnóstico diferencial de la parálisis cerebral. Presentación de caso. Adolescente masculino de 16 años con diagnóstico de PEH por mutación del gen NIPAi: c. 316G>A (p. Gly106arg), correspondiente a una PEH tipo 6 (SPG6). El paciente presentó signos clínicos de síndrome de motoneurona superior progresivos en miembros inferiores como espasticidad, hiperreflexia y paraparesia, asociados a epilepsia de inicio focal diagnosticada a los 11 años y tratada satisfactoriamente con ácido valproico. El manejo de la espasticidad fue complejo e incluyó baclofeno oral, toxina botulínica intraoperatoria, terapia física y cirugía ortopédica multinivel para manejo de deformidades musculoesqueléticas en miembros inferiores. Conclusión. El presente caso demuestra la importancia de realizar un diagnóstico temprano de la SPG6 (variante más común de la PEH) para realizar intervenciones oportunas en estos pacientes, prevenir complicaciones y evitar un mayor nivel de discapacidad.

Espondiloartropatía destructiva no infecciosa en un paciente en hemodiálisis / Destructive noninfectious spondyloarthropathy in a hemodialysis patient

Resumen La espondiloartropatía destructiva es una patología osteoarticular presente en algunos pacientes con enfermedad crónica que puede afectar varios niveles de la columna vertebral y puede ser asintomática, generar dolor o causar complicaciones que ponen en peligro la integridad de la médula espinal y/o la vida. Presentamos el caso de un hombre de 70 años con enfermedad renal crónica terminal en hemodiálisis quien consultó por dolor dorsal y paraplejia, en quien se diagnosticó espondiloartropatía destructiva no infecciosa por imágenes y estudio histopatológico. Este caso nos muestra la importancia de pensar en esta patología y la necesidad de un enfoque multidisciplinario en el diagnóstico y manejo. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2193).

Abstract Destructive spondyloarthropathy is a bone and joint disease which presents in some patients with chronic illnesses and may affect various levels of the spinal column. It may be asymptomatic, cause pain, or produce spinal cord and/or life-endangering complications. We present the case of a 70-year-old man with end-stage renal disease on hemodialysis who consulted due to back pain and paraplegia. He was diagnosed with destructive noninfectious spondyloarthropathy through imaging and histopathological studies. This case shows us the importance of considering this disease and the need for a multidisciplinary approach in its diagnosis and management. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2193).

Advances in treatment of hereditary spastic paraplegia / 国际儿科学杂志

Hereditary spastic paraplegia (HSP) is a neurodegenerative disease with clinical manifestations of increased muscle tone, enhanced tendon reflex and positive pathological reflex of both lower limbs.Currently, the pathological mechanism of HSP is considered as bilateral corticospinal axonal degeneration.So far, more than 80 pathogenic genes have been reported to be associated with the pathogenesis of HSP, among which spastic paraplegia type 4 (SPG4) caused by SPAST mutation is the most common.Genetic testing is crucial for diagnosing and typing HSP.The incidence of this disease is low.Although it is not a short-term fatal disease, it will seriously affect the patient′s self-care ability and cause seriously psychological burden to the patient with the progress of the disease.There is no effective cure for the disease at present.In this paper, the therapeutic methods of HSP are reviewed from different aspects: small molecular compounds, gene therapy, rehabilitation therapy and surgical treatment.

Research on clinical and molecular genetics of hereditary spastic paraplegia 11 patients in China / 中南大学学报(医学版)

The hereditary spastic paraplegia (HSP) is a rare hereditary disease in nervous system due to the damage of corticospinal tract. HSP has various inheritance modes, including autosomal dominant inheritance, autosomal recessive inheritance, X-linked inheritance, and mitochondrial inheritance in some cases. At present, there are at least 80 subtypes of HSP. Hereditary spastic paraplegia type 11 (SPG11) is the most common subtype in autosomal recessive inheritance, and its pathogenic factor is KIAA1840 gene, which encodes spatacsin protein. A total of 52 SPG11 patients aged from 4-24 years old have been reported. Their initial symptoms were gait disturbance and/or mental retardation. As the disease develops, they may present with mental retardation, sphincter disturbance, decreased vision, ataxia, amyotrophy, pes arcuatus, ophthalmoplegia, peripheral neuropathy, and others. Except agenesis of the corpus callosum and periventricular white matter changes, patients might show cortical atrophy, ventricular dilation, and cerebellar atrophy, and so on. Chinese SPG11 patients manifested significant clinical and genetical heterogeneity and no obvious gender difference. Of them, 37 pathogenic mutations of KIAA1840 gene were detected, which all introduced truncated mutation of spatacsin protein. KIAA1840 gene frameshift mutation is the most common type of mutation.

A case report of hereditary spastic paraplegia type 58 / 中华神经科杂志

Hereditary spastic paraplegia type 58 is rare, caused by pathogenic variations in KIF1C gene. Here, a case diagnosed in Qilu Hospital, Shandong University, was reported. The 15-year-old female suffered tremor in bilateral upper limbs which was aggravated gradually since age 8. Cerebellar ataxia, positive pyramidal tract sign and dystonic tremor were prominent on physical examination. The brain magnetic resonance imaging showed T 2-hyperintense signals in bilateral pyramidal tracts, optic radiations and superior cerebellar peduncles, with mild cerebellar atrophy. Whole exon sequencing revealed the unreported homozygous c.425_426delTG (p.V142Gfs*10) mutation which was presumed pathogenic.

A Case of Paraplegia after Total Arch Replacement with Frozen Elephant Trunk for Acute Type A Aortic Dissection / 日本心臓血管外科学会雑誌

The frozen elephant trunk technique (FET) for the treatment of acute aortic dissection is associated with more favorable remodeling in the descending aorta compared to those patients without FET, but it may also be associated with postoperative spinal cord injury (SCI) and actually,some postoperative SCI cases after FET are reported. Several risk factors for SCI are known and one of them is due to the occlusion of intercostal arteries from false lumen. A 71-year-old woman underwent total arch replacement with FET, but after surgery, she noticed decreased movement in both lower extremities and was suspected of postoperative paraplegia. She went through cerebrospinal fluid drainage but didn't get better at all. According to the preoperative contrast computed tomography images, seven out of ten intercostal arteries were originating from the false lumen and six of them were occluded after surgery. When most of intercostal arteries are originating from the false lumen and there is no entry inside the descending and abdominal aorta, the intercostal arteries may be occluded due to thrombosis of the false lumen and it may cause spinal cord ischemia after surgery.

Clinical phenotype and genotype analysis of hereditary spastic paraplegia type 35 / 中华神经科杂志

Objective:To report 8 cases of hereditary spastic paraplegia type 35 (SPG35) in Chinese mainland, summarize the clinical and genetic features of this disease.Methods:Eight probands with SPG35, admitted in Shanghai Jiao Tong University Affiliated Sixth People′s Hospital and Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from September 2006 to June 2021, were collected in detail. Physical examination, cranial imaging examination and whole exome sequencing were conducted, followed by Sanger sequencing and family co-segregation. In addition, the recent advances in clinical, genetic and pathogenesis studies of the disease were also reviewed.Results:Among all of the 8 patients, 7 had juvenile-onset and 1 was adult-onset. The clinical phenotype of 2 cases was pure spastic paraplegia. The other 6 cases presented with complicated form, which was characterized by not only motor dysfunction, but also cognitive impairment and dysphagia, etc. Genetic testing revealed a total of 13 fatty acid 2-hydroxylase (FA2H) gene (NM_024306) mutations, of which 6 were reported and 7 were newly reported in this study.Conclusions:SPG35 is an autosomal recessive neurodegenerative disease with highly phenotypic heterogeneity, with the causative gene as FA2H. The genotype-phenotype correlations in SPG35 are not clear.

Analysis of pathogenic genes in two cases of Sj?gren-Larsson syndrome / 中华皮肤科杂志

Objective:To detect pathogenic mutations in 2 patients with Sj?gren-Larsson syndrome.Methods:Clinical data were collected from 2 children with Sj?gren-Larsson syndrome, who were diagnosed and treated in Department of Dermatology, Capital Institute of Pediatrics, and genetic testing was performed to clarify their pathogenic mutations.Results:Both the 2 patients presented with typical ichthyosis-like skin manifestations, accompanied by a certain degree of intellectual disorder and growth, development and motor retardation. A previously reported homozygous mutation c.1157A>G was identified in the ALDH3A2 gene in case 1; compound heterozygous mutations c.1157A>G and c.1309A>T were identified in the ALDH3A2 gene in case 2, which were considered as novel pathogenic mutations.Conclusion:Genetic testing should be performed as early as possible in patients with suspected Sj?gren-Larsson syndrome, in order to facilitate early definite diagnosis.

A novel mutation of SPAST gene in a hereditary spastic paraplegia type 4 family / 中华内科杂志

Objective:To clarify the pathogenicity and further explore the association between genotype and clinical phenotype of this variant, analyzing a novel variation of SPAST gene in hereditary spastic paraplegia (HSP) family from Changzhi city, Shanxi Province.Methods:A family with HSP was tracked and collected in Neurology Department of Heping Hospital Affiliated to Changzhi Medical College in October 2019. Peripheral venous blood of 2 ml was extracted from the proband and 8 other members of the family, genomic DNA was extracted from the blood samples, and the genes of spastic paraplegia were screened by next-generation sequencing (NGS). HGMD, 1000G, OMIM databases and PolyPhen2, SIFT and other software were used for bioinformatics analysis of suspected mutations. Multiplex ligation-dependent probe amplification (MLPA) was used to further screen for total deletions/duplications in patients who remained negative after targeting NGS, and Sanger sequencing was performed to verify the suspected pathogenic mutation sites in the family to determine co-isolation of the mutation sites in the family members. Finally, it is necessary to refer to the latest version of The American College of Medical Genetics and Genomics (ACMG) sequence variation interpretation guidelines to interpret the mutation sites to determine pathogenicity.Results:The HSP family consist 47 members of 4 generations and 10 patients, with onset ages ranging from 2 to 44 years. The proband′s daughter only showed positive bilateral Babbitt signs on physical examination, and the rest of the patients showed spasticity and weakness of lower limbs with varying severity on this basis. Preliminary screening by next-generation sequencing technology showed that the proband had frame-shift variation of SPAST gene c.1057_1058insCC (p.Leu354HisfsTer11) and missense variation of DCTN1 gene c.2213A>G (p.Gln738Arg). Then, Sanger sequencing was used for in-family verification, which showed SPAST gene c.1057_1058insCC (p.Leu354HisfsTer11) was detected in the affected members include father, brother, son and daughter, and not detected in the unaffected normal members, the proband′s wife, mother, sister and sister-in-law. However, the unaffected of mother detected missense variation of DCTN1 gene c.2213A>G (p.Gln738Arg), while the remaining members did not detect this variation. The results of MLPA showed that no large fragment variation was found.Conclusions:The genetic pattern of the HSP family was autosomal dominant, and the clinical characteristics were consistent with hereditary spastic paraplegia type 4 (SPG4). Co-segregation of SPAST gene c.1057_1058insCC (p.Leu354HisfsTer11) was found in the HSP family and was the pathogenicity cause of this SPG4 family, and it was a newly discovered mutation locus.

Cirugía convencional del aneurisma tóraco-abdominal

Background: Thoracoabdominal aortic aneurysm (TAAA) is an infrequent disease and demands a highly specialized and experienced management. Open repair (OR) is the gold standard but it is associated with significant morbidity and mortality. Paraplegia and renal failure are the most important complications. Aim: To report our results with OR treatment of TAAA. Material and Methods: Descriptive study including all patients with TAAA operated electively and consecutively by OR between 1983 and 2019. Main outcomes are operative mortality, renal and neurological morbidity, and long-term survival. Results: We report 45 operated patients aged 33 to 84 years, 74% males. Aneurysm extension according to Crawford classification was I in 18%, II in 18 %, III in 36% and IV in 29%. Operative mortality was 4%. The frequency of paraplegia or paraparesis at discharge was 9%. No patient was discharged on hemodialysis. Survival at 5 and 10 years were 60% and 40% respectively. Conclusions: OR of TAAA is a complex procedure. Our results show perioperative mortality rates comparable to highly experienced centers. Although being a major procedure, OR remains an alternative to treat this serious condition.