RESUMEN
AIM: Brain magnetic resonance imaging (MRI) motor development score (MDS) correlations were used to analyze the natural time-course of hypomyelinating PLP1-related disorders (Pelizaeus-Merzbacher disease [PMD] and spastic paraplegia type 2). METHOD: Thirty-five male patients (ranging from 0.7-43.5y at the first MRI) with PLP1-related disorder were prospectively followed over 7 years. Patients were classified according to best motor function acquired before 5 years (MDS) into five categories (from PMD0 without motor acquisition to PMD4 with autonomous walking). We determined myelination and atrophy scores and measured corpus callosum area, volume of cerebellum, white matter and grey matter on 63 MRI. RESULTS: Age-adjusted multivariate analysis revealed that patients with PMD0-1 had higher-severity atrophy scores and smaller corpus callosum area than did patients with PMD2 and PMD3-4. Myelination score increased until 12 years. There was evidence that the mean myelination differed in frontal white matter, arcuate fibres, and internal capsules among the groups. Most patients showed worsening atrophy (brain, cerebellum, corpus callosum), whereas grey matter and white matter proportions did not change. INTERPRETATION: Brain atrophy and myelination of anterior cerebral regions appear to be pertinent biomarkers of motor development. The time-course of inter- and intra-individual cerebral white matter and grey matter atrophy suggests that both oligodendrocytes and neurons are involved in the physiopathology of PLP1-related disorders.
Asunto(s)
Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Trastornos del Movimiento/etiología , Vaina de Mielina/patología , Enfermedad de Pelizaeus-Merzbacher/complicaciones , Enfermedad de Pelizaeus-Merzbacher/diagnóstico por imagen , Adolescente , Adulto , Factores de Edad , Atrofia/diagnóstico por imagen , Atrofia/etiología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Niño , Preescolar , Estudios de Cohortes , Progresión de la Enfermedad , Humanos , Procesamiento de Imagen Asistido por Computador , Lactante , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Trastornos del Movimiento/diagnóstico por imagen , Enfermedad de Pelizaeus-Merzbacher/clasificación , Índice de Severidad de la Enfermedad , Estadísticas no Paramétricas , Adulto JovenRESUMEN
We report the successful management of general anesthesia for a patient with Pelizaeus-Merzbacher disease (PMD). PMD is one of a group of progressive, degenerative disorders of the cerebral white matter. The typical clinical manifestations of PMD include psychomotor retardation, nystagmus, abnormal muscle tone, seizures, and cognitive impairment. General anesthesia for a patient with PMD may be difficult mainly because of seizures and airway complications related to poor pharyngeal muscle control. In addition, the possibility of exacerbation of spasticity should be considered. A 20-year-old man with PMD required removal of impacted wisdom teeth under general anesthesia. General anesthesia was induced with thiamylal, fentanyl, and desflurane. Anesthesia was maintained with desflurane and continuous intravenous remifentanil under bispectral index and train-of-4 monitoring. Anesthesia lasted 1 hour 20 minutes and was completed uneventfully. Airway complications, seizures, and exacerbation of spasticity did not occur postoperatively. Preoperatively, our patient had no history of epilepsy attacks or aspiration pneumonia, and no clinical symptoms of gastroesophageal reflux disease. Therefore, exacerbation of spasticity was one of the most likely potential complications. Identification of these associated conditions and evaluation of risk factors during preoperative examination is important for performing safe anesthesia in these patients.
Asunto(s)
Anestesia Dental/métodos , Anestesia General/métodos , Enfermedad de Pelizaeus-Merzbacher/complicaciones , Anestésicos por Inhalación/administración & dosificación , Anestésicos Intravenosos/administración & dosificación , Monitores de Conciencia , Desflurano , Fentanilo/administración & dosificación , Humanos , Isoflurano/administración & dosificación , Isoflurano/análogos & derivados , Masculino , Tercer Molar/cirugía , Espasticidad Muscular/prevención & control , Monitoreo Neuromuscular/métodos , Piperidinas/administración & dosificación , Remifentanilo , Tiamilal/administración & dosificación , Extracción Dental/métodos , Diente Impactado/cirugía , Adulto JovenRESUMEN
CASE: We present a 20-year-old man who suffered anaphylactic shock during posterior spinal fusion for neuromuscular scoliosis with the offending agent later identified via intradermal testing to be tranexamic acid (TXA). CONCLUSION: TXA, although an increasingly common drug, can be the cause of sudden anaphylactic shock intraoperatively. This now represents the fifth reported case in the literature of patients ranging from 15 years to 80 years old with no previous exposure to the drug.
Asunto(s)
Anafilaxia/inducido químicamente , Antifibrinolíticos/inmunología , Complicaciones Intraoperatorias/inducido químicamente , Escoliosis/cirugía , Ácido Tranexámico/inmunología , Adulto , Antifibrinolíticos/efectos adversos , Humanos , Masculino , Enfermedad de Pelizaeus-Merzbacher/complicaciones , Escoliosis/etiología , Fusión Vertebral , Ácido Tranexámico/efectos adversosAsunto(s)
Anemia/etiología , Huesos/diagnóstico por imagen , Cobre/deficiencia , Niños con Discapacidad , Neutropenia/etiología , Osteoporosis/diagnóstico por imagen , Osteoporosis/etiología , Nutrición Parenteral Total/efectos adversos , Biomarcadores/sangre , Niño , Enfermedad Crónica , Cobre/sangre , Humanos , Enfermedad de Pelizaeus-Merzbacher/complicaciones , Tomografía Computarizada por Rayos XRESUMEN
A 3-year-old pediatric patient with previously diagnosed Pelizaeus-Merzbacher syndrome presented for outpatient dental restoration. Given the infrequency of this demyelinating disorder, an anesthetic plan was tailored to address the patient's hypotonia and aspiration risk, as well as minimize potential complications including seizures, hemodynamic instability, and postoperative respiratory support. Multimodal analgesia, along with an appropriate ventilation strategy and normothermia, allowed the patient to successfully undergo a general anesthetic and be safely discharged home the same day.
Asunto(s)
Anestesia General/métodos , Reparación de Restauración Dental/métodos , Enfermedad de Pelizaeus-Merzbacher/complicaciones , Anestesia Dental/métodos , Preescolar , Terapia Combinada , Humanos , Masculino , Resultado del TratamientoRESUMEN
Pelizaeus Merzbacher Disease is a rare X-linked central nervous system disease involving the proteolipid protein 1 gene. Patients exhibit signs for instance nystagmus, hypotonia, ataxia. We report a three-year-old female patient with chief compliant of developmental delay. On physical examination, patient was alert but had poor eye contact while sitting in a stroller. Since no chromosomal evaluation was performed, a chromosomal microarray testing was performed. Review of geneticist report indicated that patient carries a deletion of at least 2.26 Mb within cytogenetic band Xq22.1 to Xq22.2 which is known to contain 39 genes. Out of the 39 genes, proteolipid protein 1 is associated with known clinical disorder; Pelizaeus Merzbacher Disease. Our case highlights the second only known female with Pelizaeus Merzbacher Disease due to deletions of proteolipid protein 1 gene. For a patient with developmental delay, the importance of performing genetic testing and/or radiological imaging early on is strongly recommended. Keywords: deletion; female; Genetic testing; Pelizaeus Merzbacher Disease; Proteolipid Protein 1.
Asunto(s)
Proteína Proteolipídica de la Mielina/genética , Enfermedad de Pelizaeus-Merzbacher/genética , Preescolar , Discapacidades del Desarrollo/etiología , Femenino , Pruebas Genéticas , Humanos , Enfermedad de Pelizaeus-Merzbacher/complicaciones , Enfermedad de Pelizaeus-Merzbacher/diagnóstico , Eliminación de SecuenciaRESUMEN
Pelizaeus-Merzbacher disease (PMD; MIM 312080), an inherited defect of central nervous system myelin formation, affects individuals in many ways, including their hearing and language abilities. The aim of this study was to assess the auditory abilities in 18 patients with PMD by examining the functional processes along the central auditory pathways using auditory brainstem responses (ABR) and cortical auditory evoked potentials (CAEP) in response to speech sounds. The significant ABR anomalies confirm the existence of dyssynchrony previously described at the level of the brainstem in patients with PMD. Despite the significant auditory dyssynchrony observed at the level of the brainstem, CAEPs were present in most patients, albeit somehow abnormal in terms of morphology and latency, resembling a type of auditory neuropathy spectrum disorder.
Asunto(s)
Enfermedades Auditivas Centrales/etiología , Potenciales Evocados Auditivos del Tronco Encefálico/fisiología , Enfermedad de Pelizaeus-Merzbacher/complicaciones , Pruebas de Impedancia Acústica , Estimulación Acústica , Adolescente , Adulto , Enfermedades Auditivas Centrales/diagnóstico , Enfermedades Auditivas Centrales/patología , Vías Auditivas/fisiopatología , Niño , Preescolar , Electroencefalografía , Femenino , Humanos , Lactante , Masculino , Emisiones Otoacústicas Espontáneas , Otoscopía , Adulto JovenRESUMEN
Pelizaeus-Merzbacher disease is a rare X-linked disease characterized by defective central nervous system myelination owing to a mutation in the proteolipid protein 1 gene. Few studies report detailed clinical findings in children with genetic confirmation of mutations in the proteolipid protein 1 gene. We reviewed the records of 10 boys with Pelizaeus-Merzbacher disease and one symptomatic carrier girl. Their median age was 2 1/2 years (range 10 months to 20 years). Nine had proteolipid protein 1 gene duplications, one had a point mutation, and one had a single codon deletion. The families of eight patients reported perinatal complications, including maternal hypertension (three patients) and meconium aspiration (three patients). All of the patients were social and interactive, but all had difficulty with expressive speech. All patients presented with nystagmus and had hypotonia that progressed to spasticity, affecting the legs more than the arms; ataxia also contributed to motor impairment. Additional problems reported regarded feeding (eight patients) and sleep (three patients). Further work is needed to clarify the variations in disease course and the relationship of genotype to phenotype.
Asunto(s)
Trastornos del Conocimiento/etiología , Epilepsia/etiología , Trastornos de la Destreza Motora/etiología , Enfermedad de Pelizaeus-Merzbacher/complicaciones , Trastornos del Habla/etiología , Adolescente , Adulto , Niño , Preescolar , Enfermedades del Sistema Digestivo/etiología , Femenino , Humanos , Lactante , Masculino , Enfermedad de Pelizaeus-Merzbacher/fisiopatología , Enfermedad de Pelizaeus-Merzbacher/cirugía , Trastornos Respiratorios/etiología , Escoliosis/etiología , Trastornos del Sueño-Vigilia/etiologíaRESUMEN
OBJECTIVE: To determine whether quantitative measure of magnetic resonance imaging data from patients with the inherited leukodystrophy, Pelizaeus-Merzbacher disease (PMD) correlates with clinical severity or progression. METHODS: In our current work we have analyzed the clinical phenotypes and MRI scans of 51 male patients with PMD and 10 female carriers for whom the PLP1 genotype had been determined. In addition, we developed a 32-point functional disability scoring (FDS) system for PMD, and validated it for inter-rater reliability. Using conventional T1- and T2-weighted MRI images of the whole brain, we measured white matter and total brain volume (WMV and TBV), inter-caudate ratio (ICR), and corpus callosum area. RESULTS: There was a significant positive correlation of FDS with white matter fraction (WMV/TBV) and corpus callosum area. Also, when applying a median split based on FDS, patients with lower FDS showed reduced white matter fraction and corpus callosum area, and increased ICR compared to patients with relatively higher FDS, regardless of age. CONCLUSION: Although this patient population is heterogeneous, with multiple genetic and molecular mechanisms causing PMD, these data imply that white matter atrophy is a major pathological determinant of the clinical disability in most patients. Development of reliable non-invasive quantitative biomarkers of disease activity would be useful not only for following the natural history of the disease, but also raising the potential for evaluating future therapies.
Asunto(s)
Personas con Discapacidad , Enfermedades del Sistema Nervioso/etiología , Enfermedad de Pelizaeus-Merzbacher/complicaciones , Adolescente , Adulto , Encéfalo/patología , Niño , Preescolar , Cuerpo Calloso/patología , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Lactante , Masculino , Persona de Mediana Edad , Mutación/genética , Proteína Proteolipídica de la Mielina/genética , Fibras Nerviosas Mielínicas/patología , Enfermedad de Pelizaeus-Merzbacher/genética , Adulto JovenRESUMEN
Tracheo-innominate artery fistula (TIF) is a serious, life-threatening complication following tracheostomy. We report a fatal TIF in a 15-year-old girl with Pelizaeus-Merzbacher disease. She received a tracheostomy for prolonged translaryngeal intubation due to acute respiratory failure without a trial of noninvasive ventilatory support before intubation. Severe hemorrhage from the TIF occurred 6 months after tracheostomy; immediate resuscitation failed. Antemortem fiberoptic bronchoscopy showed tracheal stenosis accompanied by granulation tissue, and postmortem examination revealed TIF with ulcerative granulation. Preventive intervention is required to avoid catastrophic TIF due to its high mortality rate. Moreover, to avoid prolonged translaryngeal intubation leading to tracheostomy, noninvasive ventilatory support before translaryngeal intubation, if applicable, is beneficial.
Asunto(s)
Tronco Braquiocefálico/cirugía , Enfermedad de Pelizaeus-Merzbacher/complicaciones , Tráquea/irrigación sanguínea , Tráquea/cirugía , Traqueostomía/efectos adversos , Fístula Vascular/etiología , Adolescente , Tronco Braquiocefálico/diagnóstico por imagen , Broncoscopía , Resultado Fatal , Femenino , Tejido de Granulación/patología , Humanos , Lactante , Enfermedad de Pelizaeus-Merzbacher/diagnóstico por imagen , Enfermedad de Pelizaeus-Merzbacher/cirugía , Radiografía Torácica , Tomografía Computarizada por Rayos X , Tráquea/diagnóstico por imagen , Tráquea/patología , Fístula Vascular/diagnóstico por imagenAsunto(s)
Enfermedad de Pelizaeus-Merzbacher , Encéfalo/patología , Preescolar , Proteínas de Unión al ADN/genética , Diagnóstico Diferencial , Duplicación de Gen , Predisposición Genética a la Enfermedad , Humanos , Hibridación Fluorescente in Situ , Imagen por Resonancia Magnética , Masculino , Enfermedad de Pelizaeus-Merzbacher/complicaciones , Enfermedad de Pelizaeus-Merzbacher/diagnóstico , Enfermedad de Pelizaeus-Merzbacher/genética , Fenotipo , Valor Predictivo de las Pruebas , Pronóstico , Factores de Transcripción/genéticaAsunto(s)
Enfermedad de Pelizaeus-Merzbacher/diagnóstico , Trastorno de la Conducta del Sueño REM/diagnóstico , Ondas Encefálicas/fisiología , Humanos , Imagen por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/psicología , Masculino , Persona de Mediana Edad , Enfermedad de Pelizaeus-Merzbacher/complicaciones , Enfermedad de Pelizaeus-Merzbacher/fisiopatología , Polisomnografía/métodos , Polisomnografía/psicología , Trastorno de la Conducta del Sueño REM/complicaciones , Trastorno de la Conducta del Sueño REM/fisiopatologíaAsunto(s)
Enfermedades Desmielinizantes/genética , Proteína Proteolipídica de la Mielina/genética , Paraplejía/genética , Enfermedad de Pelizaeus-Merzbacher/genética , Polineuropatías/genética , Adulto , Enfermedades Desmielinizantes/complicaciones , Humanos , Masculino , Paraplejía/complicaciones , Enfermedad de Pelizaeus-Merzbacher/complicaciones , Polineuropatías/complicaciones , EspañaRESUMEN
OBJECTIVE: To report an association between spastic paraplegia type 2 with axonal peripheral neuropathy and apparent proteolipid protein gene (PLP1) silencing in a family. METHODS: Pulsed-field gel electrophoresis, custom array comparative genomic hybridization, and semi-quantitative multiplex polymerase chain reaction analyses were used to examine the PLP1 genomic region. RESULTS: Electrodiagnostic studies and a sural nerve biopsy showed features of a dystrophic axonal neuropathy. Molecular studies identified a small duplication downstream of PLP1. INTERPRETATION: We propose the duplication to result in PLP1 gene silencing by virtue of a position effect. Our observations suggest that genomic rearrangements that do not include PLP1 coding sequences should be considered as yet another potential mutational mechanism underlying PLP1-related dysmyelinating disorders.
Asunto(s)
Proteínas de la Membrana/genética , Mutación , Enfermedad de Pelizaeus-Merzbacher/genética , Enfermedades del Sistema Nervioso Periférico/genética , Análisis Mutacional de ADN/métodos , Electroforesis en Gel de Poliacrilamida/métodos , Humanos , Proteínas con Dominio MARVEL , Imagen por Resonancia Magnética/métodos , Masculino , Microscopía Electrónica de Transmisión/métodos , Conducción Nerviosa/fisiología , Hibridación de Ácido Nucleico/métodos , Enfermedad de Pelizaeus-Merzbacher/complicaciones , Enfermedad de Pelizaeus-Merzbacher/patología , Enfermedades del Sistema Nervioso Periférico/complicaciones , Enfermedades del Sistema Nervioso Periférico/patología , Proteolípidos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Nervio Sural/metabolismo , Nervio Sural/patología , Nervio Sural/ultraestructuraRESUMEN
Ascended testis is a rare clinical entity. The mechanism involved in testicular ascent is still not understood completely. Spasticity of cremaster muscle may cause secondary ascent of testis. The authors present 3 brothers with Pelizaeus Merzbacher syndrome, a rare, x-linked leukodystrophy in whom the testes bilaterally ascended from the normal scrotal position to an undescended position after onset of spasticity.