KIF1A-related autosomal dominant spastic paraplegias (SPG30) in Russian families.

BACKGROUND: Spastic paraplegia type 30 (SPG30) caused by KIF1A mutations was first reported in 2011 and was initially considered a very rare autosomal recessive (AR) form. In the last years, thanks to the development of massive parallel sequencing, SPG30 proved to be a rather common autosomal dominant (AD) form of familial or sporadic spastic paraplegia (SPG),, with a wide range of phenotypes: pure and complicated. The aim of our study is to detect AD SPG30 cases and to examine their molecular and clinical characteristics for the first time in the Russian population. METHODS: Clinical, genealogical and molecular methods were used. Molecular methods included massive parallel sequencing (MPS) of custom panel 'spastic paraplegias' with 62 target genes complemented by familial Sanger sequencing. One case was detected by the whole -exome sequencing. RESULTS: AD SPG30 was detected in 10 unrelated families, making it the 3rd (8.4%) most common SPG form in the cohort of 118 families. No AR SPG30 cases were detected. In total, 9 heterozygous KIF1A mutations were detected, with 4 novel and 5 known mutations. All the mutations were located within KIF1A motor domain. Six cases had pure phenotypes, of which 5 were familial, where 2 familial cases demonstrated incomplete penetrance, early onset and slow relatively benign SPG course. All 4 complicated cases were caused by novel mutations without familial history. The phenotypes varied from severe in two patients (e.g. lack of walking, pronounced mental retardation) to relatively mild non-disabling symptoms in two others. CONCLUSION: AD SPG30 is one of the most common forms of SPG in Russia, the disorder has pronounced clinical variability while pure familial cases represent a significant part.

Hereditary spastic paraplegia caused by compound heterozygous mutations outside the motor domain of the KIF1A gene.

BACKGROUND AND PURPOSE: Hereditary spastic paraplegia is a clinically and genetically heterogeneous group of rare, inherited disorders causing an upper motor neuron syndrome with (complex) or without (pure) additional neurological symptoms. Mutations in the KIF1A gene have already been associated with recessive and dominant forms of hereditary spastic paraplegia (SPG30) in a few cases. METHODS: All family members included in the study were examined neurologically. Whole-exome sequencing was used in affected individuals to identify the responsible candidate gene. Conventional Sanger sequencing was conducted to validate familial segregation. RESULTS: A family of Macedonian origin with two affected siblings, one with slowly progressive and the other one with a more complex and rapidly progressing hereditary spastic paraplegia is reported. In both affected individuals, two novel pathogenic mutations outside the motor domain of the KIF1A gene were found (NM_001244008.1:c.2909G>A, p.Arg970His and c.1214dup, p.Asn405Lysfs*40) that segregate with the disease within the family establishing the diagnosis of autosomal recessive SPG30. CONCLUSIONS: This report provides the first evidence that mutations outside the motor domain of the gene can cause (recessive) SPG30 and extends the genotype-phenotype association for KIF1A-related diseases.

Walking dreams in congenital and acquired paraplegia.

To test if dreams contain remote or never-experienced motor skills, we collected during 6 weeks dream reports from 15 paraplegics and 15 healthy subjects. In 9/10 subjects with spinal cord injury and in 5/5 with congenital paraplegia, voluntary leg movements were reported during dream, including feelings of walking (46%), running (8.6%), dancing (8%), standing up (6.3%), bicycling (6.3%), and practicing sports (skiing, playing basketball, swimming). Paraplegia patients experienced walking dreams (38.2%) just as often as controls (28.7%). There was no correlation between the frequency of walking dreams and the duration of paraplegia. In contrast, patients were rarely paraplegic in dreams. Subjects who had never walked or stopped walking 4-64 years prior to this study still experience walking in their dreams, suggesting that a cerebral walking program, either genetic or more probably developed via mirror neurons (activated when observing others performing an action) is reactivated during sleep.

Hemicorporectomia associada à colostomia úmida: procedimento de exceção / Hemicorporectomy with double barreled wet colostomy: an extremely rare procedure

Por ser um procedimento de alta complexidade, a Hemicorporectomia associada a Colostomia úmida em alça deve ser empregada como procedimento de exceção. Por ser uma medida heróica trata-se do último recurso utilizado para tratamento de doenças pélvicas localmente avançadas e sem evidências de metástases à distância. Analisamos retrospectivamente os detalhes da técnica cirúrgica utilizada em um caso de carcinoma epidermóide desenvolvido em ulcera de pressão de região sacra e os resultados da primeira Hemicorporectomia associada a colostomia úmida em alça em um único tempo.

The Hemicorporectomy associated to Double-barreled wet colostomy is a high complex and heroic procedure and is to be used only exceptionally, when it is the last resource for treating locally advanced pelvic diseases in the absence of evidences of distant metastasis. We retrospectively analyzed the surgical technical details and the results from a hemicorporectomy with double-barreled wet colostomy in a single surgical time in a case of epidermoide carcinoma from a coetaneous pressure ulcer.

[Hemicorporectomy with double barreled wet colostomy: an extremely rare procedure]. / Hemicorporectomia associada à colostomia úmida: procedimento de exceção.

The Hemicorporectomy associated to Double-barreled wet colostomy is a high complex and heroic procedure and is to be used only exceptionally, when it is the last resource for treating locally advanced pelvic diseases in the absence of evidences of distant metastasis. We retrospectively analyzed the surgical technical details and the results from a hemicorporectomy with double-barreled wet colostomy in a single surgical time in a case of epidermoide carcinoma from a coetaneous pressure ulcer.

Diffusion tensor imaging in familial spastic paraplegia with mental impairment and thin corpus callosum.

We investigated 2 Japanese siblings with a complicated form of familial spastic paraplegia. Cranial magnetic resonance (MR) imaging revealed marked thinning of the corpus callosum. Diffusion tensor imaging (DTI) showed microstructural changes in the thalamus, basal ganglia, and cerebral white matter, and single photon emission computed tomography (SPECT) using 99mTc-ethylcysteinate dimer showed very similar findings. DTI and SPECT effectively revealed global changes not revealed by conventional MR imaging.

Chemotherapy as a therapeutic option for congenital neuroblastoma complicated by paraplegia.

BACKGROUND: Spinal compression can be a complication of neuroblastoma (NBL). Delayed or insufficient treatment of this condition may lead to permanent neurological sequelae. Therefore, appropriate treatment should be introduced promptly. Therapeutic options include neurosurgery, chemotherapy, and radiation therapy. CASE REPORT: We report on a newborn male with congenital NBL who presented with complete paraplegia of the legs at birth. Tumor size diminished quickly and neurological symptoms partly recovered after the patient received chemotherapy consisting of vincristine, doxorubicine, and cyclophosphamide. CONCLUSION: Rapid initiation of chemotherapy was safe and effective in a neonate with NBL complicated by spinal cord compression.

Ataxia, autism, and the cerebellum: a clinical study of 32 individuals with congenital ataxia.

The suggested link between autism and cerebellar dysfunction formed the background for a Swedish clinical study in 2001. Thirty-two children (17 females, 15 males; mean age 12y, SD 3y 10mo; range 6 to 21y) with a clinical suspicion of non-progressive congenital ataxia were examined, and parents were interviewed about the presence of neuropsychiatric problems in the child. Twelve children had simple ataxia, eight had ataxic diplegia, and 12 had 'borderline' ataxia. All but one of the 32 children had a mild to moderate gross motor disability according to Gross Motor Function Classification System (15 were categorized as level I, 16 as level II, and one child as level IV). Neuroimaging and neuropsychological testing were achieved in most cases. There was a strong association between learning disability* and autism spectrum disorder (often combined with hyperactivity disorder) on the one hand, and both simple and borderline 'ataxia' on the other, but a weaker link between ataxic diplegia and neuropsychiatric disorders. A correlation between cerebellar macropathology on neuroimaging and neuropsychiatric disorders was not supported. Congenital ataxia might not be a clear-cut syndrome of cerebellar disease, but one of many signs of prenatal events or syndromes, leading to a complex neurodevelopmental disorder including autism and learning disability.

La paraplejia como causa de desintegración familiar / The paraplegia as cause of family desintegration

La discapacidad es una traba en el contexto social, familiar, incluso a nivel personal que los margina, discrimina y desintegra, en este caso el parapléjico que en su situación de discapacitado olvida que es una persona y se ve como minusválido, sintiendo que perdió gra parte de sus capacidades y habilidades para poder enfrentar sus problemas, tropezando con muchas dificulatades que bloquean su integración familiar, traducidos en la falta de aceptación, lo cual produce efectos psicológicos importantes en todos los casos. En el presente trabajo se efectua un estudio de intervención, un total de personas parapléjicas, teniendo en cuenta la prevalencia de estas patologias en nuestro medio, tomando en cuenta las complicaciones muy severas; de tipo físico, psicológico, de adpatación e integración, que actualmente son manejados en el ámbito intrahospitalario, en una primera etapa de sock medular, pero no se considera la etapa de adaptación domiciliaria, en el que se presentan mayores complicaciones, debiendo orientar y capacitar al paciente parapléjico, para su autouidado, por esta razón tiene gran significado el establecer las causas que llevan a una desintegración a la vida familiar...

Congenital paraplegia following maternal hypotension.

Congenital paraplegia, with partial improvement over the first months of life, occurred in a female neonate born at 35 weeks' gestation, whose mother had suffered hypotension and hypoxaemia due to anaphylaxis 12 weeks earlier. Our patient subsequently had an acute encephalopathy during a respiratory illness with later developmental delay. We speculate that the baby's paraplegia resulted from spinal-cord ischaemia in utero. The aim of this report is to describe the spinal presentation.

Spinal canal involvement in infantile myofibromatosis: case report and review of the literature.

PURPOSE: An unusual case of infantile myofibromatosis with spinal canal involvement is reported and the literature is reviewed. PATIENT AND METHODS: A female neonate had bladder and bowel dysfunction and paresis of the lower extremities. RESULTS: Intrapelvic and paravertebral masses with extension into the spinal canal were detected by imaging studies. In addition, radiologic examination showed multiple metaphyseal radiolucent lesions of the long bones and pathologic fracture of the left femur. The histopathologic diagnosis of the paravertebral tumor and bone lesions was infantile myofibromatosis. Surgical resection of the paravertebral and intrapelvic masses was performed to improve her neurologic impairments. Paresis of the lower limbs gradually improved, whereas bladder and bowel dysfunction remained unchanged. CONCLUSIONS: Only six cases of infantile myofibromatosis associated with spinal canal involvement have been reported. Three patients with flaccid paresis of extremities and respiratory distress died in the newborn period. The other three patients showed improvement of the paresis. The prognosis of infantile myofibromatosis without visceral complication is generally good, but neurologic impairment may occur at birth if the spinal cord is compressed.

A case of congenital intraspinal neuroblastoma.

A case of congenital intraspinal neuroblastoma with paraplegia in a newborn is described, and a review of previously reported cases is presented. Calcification within the spinal canal and abdominal mass was noted. At age 75 days, the patient underwent a resection of almost the entire retroperitonial tumor. A magnetic resonance scan showed hepatic metastasis, and chemotherapy was changed to a more intensive regimen. The liver metastasis disappeared; however, neurological signs persisted. A literature review of 38 cases showed 26 patients had a laminectomy and 12 patients did not. Treatment with or without laminectomy was associated with a poor prognosis for neurological recovery, suggesting cord compression must occur antenatally, and irreversible damage occurs before birth. Congenital intraspinal neuroblastoma has a relatively good prognosis (survival rate, 91.9%), although complete neurological recovery is highly unusual. Based on these findings, the authors conclude that a laminectomy is not indicated for those patients.

Medial spinal aplasia--a rare manifestation of congenital paraplegia: report of six cases and review of the literature.

Medial aplasia of the spine is a rarely recognized malformation characterized by isolated absence of spinal segments, with vertebrae present cranially and caudally. We analyzed six patients and the five cases described in the relevant literature. The extent of defect ranges from one to 11 segments and leads to spinal instability with resulting kyphosis. All patients have a thoracic or high lumbar level of paralysis and, in varying degrees, typical contractures of hips, knees, and feet. The differentiation between medial aplasia of the spine and the syndrome of caudal regression is discussed.

Energetics of paraplegic walking.

A group of 35 paraplegic subjects using reciprocating walking orthoses have been examined in order to gain an insight into the potential functional benefits of using such devices. Measurements have been made of walking speeds and of the energy costs of ambulation using an established technique based on heart rate recordings. It was found that orthotically aided walking for paraplegics was slow and energy costly compared with both normal walking and wheelchair propulsion and, as it additionally requires the use of a walking aid in both hands, cannot be considered to confer the functional benefits frequently claimed for it. Nevertheless, the majority of the subjects studied liked their orthosis and did well in it, with many subjectively reporting improvements in mobility and independence.

Congenital neuroblastoma presenting with paraplegia.

A girl presented with paraplegia at birth. A magnetic resonance scan showed an abdominal neuroblastoma with intraspinal extension. Treatment by chemotherapy did not produce any improvement in the neurological signs. Review of previously reported cases suggests the outlook for neurological recovery is poor regardless of treatment.