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1

Genetics Home Reference: Spastic paraplegia type 4  

MedlinePLUS

... OMIM Genetic disorder catalog Conditions > Spastic paraplegia type 4 On this page: Description Genetic changes Inheritance Diagnosis ... Reviewed January 2008 What is spastic paraplegia type 4? Spastic paraplegia type 4 is part of a ...

2

Genetics Home Reference: Spastic paraplegia type 8  

MedlinePLUS

... ClinicalTrials.gov Research studies PubMed Recent literature OMIM Genetic disorder catalog Conditions > Spastic paraplegia type 8 On this ... type 8 is part of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are ...

3

Genetics Home Reference: Spastic paraplegia type 11  

MedlinePLUS

... involve the lower limbs and can affect the upper limbs to a lesser degree. Complex spastic paraplegias also ... disturbance in the nerves used for muscle movement (motor neuropathy); intellectual disability; exaggerated reflexes (hyperreflexia) of the ...

4

Mitochondrial DNA polymorphisms\\/haplogroups in hereditary spastic paraplegia  

Microsoft Academic Search

Mitochondrial dysfunction could contribute to the development of spastic paraplegia. Among others, two of the genes implicated\\u000a in hereditary spastic paraplegia encoded mitochondrial proteins and some of the clinical features frequently found in these\\u000a patients resemble those observed in patients with mitochondrial DNA (mtDNA) mutations. We investigated the association between\\u000a common mtDNA polymorphisms and spastic paraplegia. The ten mtDNA polymorphisms

Elena Sánchez-Ferrero; Eliecer Coto; Ana I. Corao; Marta Díaz; Josep Gámez; Jesús Esteban; Juan F. Gonzalo; Samuel I. Pascual-Pascual; Adolfo López De Munaín; Germán Morís; Jon Infante; Emilia Del Castillo; Celedonio Márquez; Victoria Álvarez

5

Spinal cord potentials in traumatic paraplegia and quadriplegia  

Microsoft Academic Search

Cortical, cervical and lumbar somatosensory evoked potentials were recorded following median and tibial nerve stimulation in patients with traumatic paraplegia and quadriplegia. The isolated cord was able to produce normal potentials even during spinal shock if the vertical extent of the lesion did not involve the generator mechanisms. The cervical potentials showed subtle changes in paraplegia at Th5 levels and

E M Sedgwick; E el-Negamy; H Frankel

1980-01-01

6

Some experience with paraplegia in a small hospital in Nepal  

Microsoft Academic Search

Paraplegia is a common problem in developing countries. They are the most pitiable group of cases seen, but they can all be offered some help, however limited one's resources. The main causes are Potts Disease, arachnoiditis, tropical spastic paraplegia, trauma, lathyrism and cord compression. The usual trauma is falling from trees and the use of trained monkeys to gather leaves

David Hamilton; Tikaram Rai

1978-01-01

7

Paraplegia after intercostal neurolysis with phenol  

PubMed Central

In patients with advanced stages of cancer, severe pain is commonly encountered and is very difficult to treat. It affects the quality of life of the patient and the families involved. Pain can be managed using analgesics and adjuvant therapy. However, studies have shown that at least 10%–15% of patients fail to control pain adequately and will experience severe pain. We discuss the case of a 66-year-old female with metastatic adenoid cystic carcinoma of the left submandibular gland and developed paraplegia following intercostal neurolysis with phenol. After a successful diagnostic T6 to T12 intercostal nerve block, the patient was scheduled for an intercostal neurolytic block. We injected 2 mL of 10% aqueous phenol at each level on the left from the T6 to T12 ribs. One hour after the procedure, the patient developed bilateral lower extremity weakness with difficulty moving. A physical examination showed the absence of sensation to pinpricks and vibration from T10 to S5 and an absence of anal sphincter tone and sensation. Magnetic resonance images of the thoracic and lumbar spine showed leptomeningeal metastatic disease and myelitis. We postulate that the paraplegia could be from phenol diffusing along either the spinal nerves or the paravertebral venous plexus into the subarachnoid space. This case report points to the risks involved with phenol neurolysis close to the spine, and we propose alternative methods to minimize neurological complications.

Gollapalli, Lakshman; Muppuri, Rudramanaidu

2014-01-01

8

[Japan Spastic Paraplegia Research Consortium (JASPAC)].  

PubMed

Abstract Japan Spastic Paraplegia Research Consortium (JASPAC), a nationwide clinical and genetic survey of patients with hereditary spastic paraplegia (HSP), was started in 2006 as a project of the Research Committee for Ataxic Diseases of the Ministry of Health, Labor, and Welfare, Japan. To date (April 4, 2014), 448 indexed patients with HSP have been registered from 46 prefectures in Japan. We are now performing molecular testing of the HSP patients using Sanger sequencing (SPG4, SPG11, SPG31, and ARSACS), comparative genomic hybridization (CGH) array (SPG1, 2, 3A, 4, 5, 6, 7, 8, 10, 11, 13, 15, 17, 20, 21, 31, 33, 39, 42, ABCD1, alsin, and ARSACS), and resequencing microarray (SPG1, 2, 3A, 4, 5, 6, 7, 8, 10, 11, 13, 17, 20, 21, 31, 33, and ABCD1). In 206 Japanese families with autosomal dominant HSP, SPG4 was the most common form, accounting for 38%, followed by SPG3A (5%), SPG31 (5%), SPG10 (2%), and SPG8 (1%). In 88 patients with autosomal recessive HSP, although SPG11 was the most common form, accounting for 6%, most showed significant genetic heterogeneity. The results of molecular testing will be applicable to patients in terms of improved positive diagnosis, follow-up, and genetic counseling. JASPAC will contribute to elucidating the molecular mechanisms underlying HSP, and will facilitate the development of better treatments for HSP. PMID:25296875

Takiyama, Yoshihisa

2014-10-01

9

Paraplegia due to Acute Aortic Coarctation and Occlusion  

PubMed Central

Coarctation and occlusion of the aorta is a rare condition that typically presents with hypertension or cardiac failure. However, neuropathy or myelopathy may be the presenting features of the condition when an intraspinal subarachnoid hemorrhage has compressed the spinal cord causing ischemia. We report two cases of middle-aged males who developed acute non-traumatic paraplegia. Undiagnosed congenital abnormalities, such as aortic coarctation and occlusion, should be considered for patients presenting with nontraumatic paraplegia in the absence of other identifiable causes. Our cases suggest that spinal cord ischemia resulting from acute spinal subarachnoid hemorrhage and can cause paraplegia, and that clinicians must carefully examine patients presenting with nontraumatic paraplegia because misdiagnosis can delay initiation of the appropriate treatment. PMID:24851152

Park, Chang-Bum; Kim, Min-Ki; Kim, Sang-Hyun

2014-01-01

10

An Uncommon Cause of Paraplegia: Salmonella Spondylodiskitis  

PubMed Central

Background/Objective: Salmonella spondylodiskitis is an uncommon type of vertebral infection. The aim of this study was to present a case of progressive paraplegia caused by Salmonella spondylodiskitis and epidural abscess after endoscopic cholecystectomy. Methods: The patient underwent posterior instrumentation and posterior fusion between T6 and T12, hemilaminotomies at levels T8-T9-T10, and drainage of the abscess. Through a left thoracotomy, anterior T8–T10 corpectomy, debridement, anterior stabilization, and fusion were conducted. Results: Fifteen months later, final follow-up showed no complications secondary to the vertebral and hip surgeries, and neurological status improved to Frankel grade E. Laboratory investigations showed no evidence of Salmonella infection. Conclusion: Immunocompromised patients who undergo endoscopic intervention are vulnerable to Salmonella infections. One must consider Salmonella infection in those who develop acute progressive spondylodiskitis. PMID:16859227

Ozturk, Cagatay; Tezer, Mehmet; Mirzanli, Cuneyt; Bilen, F. Erkal; Aydogan, Mehment; Hamzaoglu, Azmi

2006-01-01

11

Novel EXOSC3 mutation causes complicated hereditary spastic paraplegia.  

PubMed

We describe two pairs of siblings from a consanguineous family manifesting autosomal recessive hereditary spastic paraplegia caused by a novel mutation in the EXOSC3 gene, previously reported in pontocerebellar hypoplasia type 1. Clinical findings included delayed motor milestones, early-onset spastic paraplegia, variable cognitive disability, and cerebellar signs. Cerebral imaging demonstrated enlarged cisterna magna and mild hypoplasia and atrophy of the lower vermis with a normal pons. Genetic analysis using homozygosity mapping followed by whole exome sequencing identified homozygous c.571G>T; p.G191C mutation in the EXOSC3 gene. We suggest that EXOSC3 mutations may present not only as pontocerebellar hypoplasia type 1, but also as a complicated form of hereditary spastic paraplegia without pontine hypoplasia or atrophy. PMID:25149867

Halevy, Ayelet; Lerer, Israela; Cohen, Rony; Kornreich, Liora; Shuper, Avinoam; Gamliel, Moria; Zimerman, Bat-El; Korabi, Isam; Meiner, Vardiella; Straussberg, Rachel; Lossos, Alexander

2014-11-01

12

Spinal cord ischemia resulting in paraplegia following extrapleural pneumonectomy.  

PubMed

A patient undergoing radical extrapleural pneumonectomy for epithelioid malignant mesothelioma developed acute paraplegia postoperatively related to long-segment spinal cord ischemia. The usual area of concern for this complication is the T9 to T12 area where the artery of Adamkiewicz is most likely to originate. In this patient, there was ligation of only upper thoracic, ipsilateral segmental arteries from the T3 to T6 level, yet he still developed paraplegia. Our hypothesis is variant mid-thoracic vascular anatomy. Previously unreported, to our knowledge, this should be understood as a rare complication of this surgery. PMID:25091760

Ural, Kelly; Jakob, Kyle; Lato, Scott; Gilly, George; Landreneau, Rodney

2014-08-01

13

Spastic paraplegia associated with brachydactyly and cone shaped epiphyses  

Microsoft Academic Search

Male uniovular twins presented at the age of 20 years with spastic paraplegia which had been slowly progressing over the years. Both have skeletal anomalies of their hands and feet with brachydactyly, cone shaped epiphyses, and an abnormal metaphyseal phalangeal pattern profile. In addition, they have a non-specific dysarthria and low-normal intellectual ability.

J S Fitzsimmons; P R Guilbert

1987-01-01

14

Mediastinal enterogenic cyst presenting as paraplegia--a case report.  

PubMed

A rare case of a mediastinal enterogenic cyst with an intraspinal extension through a anterior vertebral defect presenting with paraplegia in a 10 year boy is presented. Laminectomy and the trans-thoracic excision of the cyst resulted in the complete recovery of the neural deficit. PMID:9057369

Mam, M K; Mathew, S; Prabhakar, B R; Paul, R; Jacob, S

1996-09-01

15

A case of acute paraplegia that improved with dialysis  

PubMed Central

Acute severe hyperkalemia can present as acute paraplegia independent of cardiac effects, even though cardiac muscle is more sensitive to serum potassium changes. We managed a patient with acute hyperkalemic paralysis who did not have threatening cardiac/electrocardiographic manifestations. The limb weakness became normal after hemodialysis. PMID:19826591

Rajendiran, Govarthanan; Jayabalan, Rajamahesh; Chandrahasan, Saravanan; Mani, Ashwin Kumar

2008-01-01

16

Motor and functional evaluation of patients with spastic paraplegia, optic atrophy, and neuropathy (SPOAN).  

PubMed

Spastic paraplegia, optic atrophy, and neuropathy (SPOAN) is an autosomal recessive complicated form of hereditary spastic paraplegia, which is clinically defined by congenital optic atrophy, infancy-onset progressive spastic paraplegia and peripheral neuropathy. In this study, which included 61 individuals (age 5-72 years, 42 females) affected by SPOAN, a comprehensive motor and functional evaluation was performed, using modified Barthel index, modified Ashworth scale, hand grip strength measured with a hydraulic dynamometer and two hereditary spastic paraplegia scales. Modified Barthel index, which evaluate several functional aspects, was more sensitive to disclose disease progression than the spastic paraplegia scales. Spasticity showed a bimodal distribution, with both grades 1 (minimum) and 4 (maximum). Hand grip strength showed a moderate inverse correlation with age. Combination of early onset spastic paraplegia and progressive polyneuropathy make SPOAN disability overwhelming. PMID:20339643

Graciani, Zodja; Santos, Silvana; Macedo-Souza, Lucia Inês; Monteiro, Carlos Bandeira de Mello; Veras, Maria Isabel; Amorim, Simone; Zatz, Mayana; Kok, Fernando

2010-02-01

17

Clinical features and management of hereditary spastic paraplegia.  

PubMed

Hereditary spastic paraplegia (HSP) is a group of genetically-determined disorders characterized by progressive spasticity and weakness of lower limbs. An apparently sporadic case of adult-onset spastic paraplegia is a frequent clinical problem and a significant proportion of cases are likely to be of genetic origin. HSP is clinically divided into pure and complicated forms. The later present with a wide range of additional neurological and systemic features. To date, there are up to 60 genetic subtypes described. All modes of monogenic inheritance have been described: autosomal dominant, autosomal recessive, X-linked and mitochondrial traits. Recent advances point to abnormal axonal transport as a key mechanism leading to the degeneration of the long motor neuron axons in the central nervous system in HSP. In this review we aim to address recent advances in the field, placing emphasis on key diagnostic features that will help practicing neurologists to identify and manage these conditions. PMID:24676440

Faber, Ingrid; Servelhere, Katiane R; Martinez, Alberto R M; D'Abreu, Anelyssa; Lopes-Cendes, Iscia; França-Jr, Marcondes C

2014-03-01

18

Unusual presentation of aortic dissection: post-coital acute paraplegia with renal failure.  

PubMed

We report the case of a 45-year-old chronic smoker who presented with acute paraplegia occurring during coitus and subsequently developed acute renal failure (ARF) requiring dialysis. He had absent peripheral pulses in the lower limbs with evidence of acute ischemia. Doppler study showed dissecting aneurysm of thoracic aorta, thrombotic occlusion of the distal aorta from L1 level up to bifurcation and occlusion of the right renal artery by a thrombus that was confirmed by magnetic resonance imaging of the spine. He was not subjected to any vascular intervention as his lower limbs were not salvageable due to delay in the diagnosis. Post-coital aortic dissection and aortic dissection presenting with acute paraplegia and ARF are very rare. This is probably the first case report with post-coital acute aortic dissection presenting with paraplegia and ARF. This case emphasizes the importance of a careful examination of peripheral pulses in patients presenting with ARF and paraplegia. PMID:25193908

Galabada, Dinith P; Nazar, Abdul L M

2014-09-01

19

[Paraplegia after surgical treatment of primary aorto-duodenal fistula].  

PubMed

A 68-year-old patient with chronic cirrhosis underwent surgical repair of the subrenal abdominal aorta presenting an aorto-duodenal fistula. The fistula was considered to be a primary fistula because it occurred without prior surgery and because the aorta had ruptured without formation of an aneurysm. The postoperative period was complicated by paraplegia further compromising the outcome in this severe condition. In general, there are several problems involved in the management of aorto-duodenal fistulae. Neither computed tomography of the abdomen nor gastroduodenal endoscopy are able to provide the diagnosis in all cases before surgery. Surgical treatment is most often conducted in an emergency setting requiring repair of both the digestive tract and of the vascular lesions. It is also important to recognize the risk of neurological events occurring intra-operatively. Prognosis is usually poor. PMID:8668690

Picard, E; Demaria, R; Branchereau, P; Meunier, J P; Frapier, J M; Chaptal, P A

1996-04-13

20

Fitzsimmons syndrome: spastic paraplegia, brachydactyly and cognitive impairment.  

PubMed

Fitzsimmons syndrome is an infrequently described entity comprising slowly progressive spastic paraplegia, brachydactyly, and cone-shaped epiphyses, dysarthria, and low-normal intelligence. Five patients with this syndrome have been reported. The cause remains unknown. Here we describe a 16-year-old boy with Fitzsimmons syndrome. He was noted to toe-walk at age 18 months and spasticity progressed slowly into a spastic gait with contractures. He has mild dysarthria and hypernasal speech. Brachydactyly is notable but cannot be classified into one of the recognized types. A cone-shaped epiphysis was apparent on the only available childhood radiograph. He has moderate cognitive handicap and pervasive developmental delay. A detailed comparison of this patient with the earlier described cases is presented to further delineate the condition and increase awareness of this syndrome. PMID:19760657

Armour, Christine M; Humphreys, Peter; Hennekam, Raoul C M; Boycott, Kym M

2009-10-01

21

Evaluation of activity monitors in manual wheelchair users with paraplegia  

PubMed Central

Objective The aim of this study was to evaluate the performance of SenseWear® (SW) and RT3 activity monitors (AMs) in estimating energy expenditure (EE) in manual wheelchair users (MWUs) with paraplegia for a variety of physical activities. Methods Twenty-four subjects completed four activities including resting, wheelchair propulsion, arm-ergometry exercise, and deskwork. The criterion EE was measured by a K4b2 portable metabolic cart. The EE estimated by the SW and RT3 were compared with the criterion EE by the absolute differences and absolute percentage errors. Intraclass correlations and the Bland and Altman plots were also used to assess the agreements between the two AMs and the metabolic cart. Correlations between the criterion EE and the estimated EE and sensors data from the AMs were evaluated. Results The EE estimation errors for the AMs varied from 24.4 to 125.8% for the SW and from 22.0 to 52.8% for the RT3. The intraclass correlation coefficients (ICCs) between the criterion EE and the EE estimated by the two AMs for each activity and all activities as a whole were considered poor with all the ICCs smaller than 0.75. Except for deskwork, the EE from the SW was more correlated to the criterion EE than the EE from the RT3. Conclusion The results indicate that neither of the AMs is an appropriate tool for quantifying physical activity in MWUs with paraplegia. However, the accuracy of EE estimation could be potentially improved by building new regression models based on wheelchair-related activities. PMID:21528634

Hiremath, Shivayogi V.; Ding, Dan

2011-01-01

22

Developmental and Degenerative Features in a Complicated Spastic Paraplegia  

PubMed Central

Objective We sought to explore the genetic and molecular causes of Troyer syndrome, one of several complicated hereditary spastic paraplegias (HSPs). Troyer syndrome had been thought to be restricted to the Amish; however, we identified 2 Omani families with HSP, short stature, dysarthria and developmental delay—core features of Troyer syndrome—and a novel mutation in the SPG20 gene, which is also mutated in the Amish. In addition, we analyzed SPG20 expression throughout development to infer how disruption of this gene might generate the constellation of developmental and degenerative Troyer syndrome phenotypes. Methods Clinical characterization of 2 non-Amish families with Troyer syndrome was followed by linkage and sequencing analysis. Quantitative polymerase chain reaction and in situ hybridization analysis of SPG20 expression were carried out in embryonic and adult human and mouse tissue. Results Two Omani families carrying a novel SPG20 mutation displayed clinical features remarkably similar to the Amish patients with Troyer syndrome. SPG20 mRNA is expressed broadly but at low relative levels in the adult brain; however, it is robustly and specifically expressed in the limbs, face, and brain during early morphogenesis. Interpretation Null mutations in SPG20 cause Troyer syndrome, a specific clinical entity with developmental and degenerative features. Maximal expression of SPG20 in the limb buds and forebrain during embryogenesis may explain the developmental origin of the skeletal and cognitive defects observed in this disorder. ANN NEUROL 2010;67:516–525 PMID:20437587

Manzini, M Chiara; Rajab, Anna; Maynard, Thomas M; Mochida, Ganeshwaran H; Tan, Wen-Hann; Nasir, Ramzi; Hill, R Sean; Gleason, Danielle; Al Saffar, Muna; Partlow, Jennifer N; Barry, Brenda J; Vernon, Mike; LaMantia, Anthony-Samuel; Walsh, Christopher A

2010-01-01

23

The mouse rumpshaker mutation of the proteolipid protein in human X-linked recessive spastic paraplegia  

SciTech Connect

X-linked recessive spastic paraplegia is a rare neurodegenerative disorder characterized by slowly progressive weakness and spasticity of the lower extremities. We have recently genetically analyzed the original X-linked recessive spastic paraplegia family reported by Johnston and McKusick in 1962. We employed a fluorescent multiplex CA repeat strategy using a 22 locus, 10 cM framework map of the human X chromosome and localized the gene within a 36 cM region of Xq2l.3-q24 which includes the PLP locus. Saugier-Veber et al. recently reported a point mutation (His139Tyr) in exon 3B of the PLP gene in an X-linked recessive spastic paraplegia family (SPG2). This family shows no optic atrophy, in contrast to the family we have studied. This data showed that SPG2 and Pelizaeus-Merzbacher disease were allelic disorders. We investigated the PLP gene as a candidate gene for the original X-linked recessive spastic paraplegia family using SSCP and direct sequencing methods. We found a point mutation (T to C) in exon 4 of affected males which alters the amino-acid (Ile to Thr) at residue 186. This change was absent in the unaffected males of the family and in 40 unrelated control females (80 X chromosomes). Surprisingly, this mutation is identical to the mutation previously identified in the rumpshaker mouse model. The complete homology between both the mouse and human PLP sequence, and the mouse rumpshaker mutation and human spastic paraplegia mutation in our family, permit direct parallels to be drawn with regards to pathophysiology. Our data indicates that the well-documented and striking clinical differences between Pelizaeus-Merzbacher disease and X-linked recessive spastic paraplegia is due to the specific effect of different mutations of the human PLP gene on oligodendrocyte differentiation and development and on later myelin production and maintenance.

Kobayashi, H.; Hoffman, E.P.; Matise, T.C. [and others

1994-09-01

24

Medicolegal Corner: When minimally invasive thoracic surgery leads to paraplegia  

PubMed Central

A patient with mild cervical myelopathy due to multilevel ossification of the posterior longitudinal ligament (OPLL) initially underwent a cervical C3-T1 laminectomy with C2-T2 fusion utilizing lateral mass screws. The patient's new postoperative right upper extremity paresis largely resolved within several postoperative months. However, approximately 6 months later, the patient developed increased paraparesis attributed to thoracic OPLL and Ossification of the yellow ligament (OYL) at the T2-T5 and T10-T11 levels. The patient underwent simultaneous minimally invasive (MIS) unilateral MetRx approaches to both regions. Postoperatively, the patient was paraplegic and never recovered function. Multiple mistakes led to permanent paraplegia due to MIS MetRx decompressions for T2-T5 and T10-11 OPLL/OYL in this patient. First, both thoracic procedures should have been performed “open” utilizing a full laminectomy rather than MIS; adequate visualization would have likely averted inadvertent cord injury, and the resultant CSF leak. Second, the surgeon should have used an operating microscope. Third, the operation should have been monitored with somatosensory evoked potentials (SEP), motor evoked potentials (MEP), and EMG (electromyography). Fourth, preoperatively the patient should have received a 1-gram dose of Solumedrol for cord “protection”. Fifth, applying Gelfoam as part of the CSF leak repair is contraindicated (e.g. due to swelling in confined spaces- see insert). Sixth, if the patient had not stopped Excedrin prior to the surgery, the surgery should have been delayed to avoid the increased perioperative risk of bleeding/hematoma. PMID:24843811

Epstein, Nancy E.

2014-01-01

25

Hereditary spastic paraplegia and amyotrophy associated with a novel locus on chromosome 19  

PubMed Central

We identified a family in Mali with two sisters affected by spastic paraplegia. In addition to spasticity and weakness of the lower limbs, the patients had marked atrophy of the distal upper extremities. Homozygosity mapping using single nucleotide polymorphism arrays showed that the sisters shared a region of extended homozygosity at chromosome 19p13.11-q12 that was not shared by controls. These findings indicate a clinically and genetically distinct form of hereditary spastic paraplegia with amyotrophy, designated SPG43. PMID:20039086

Meilleur, K.G.; Traore, M.; Sangare, M.; Britton, A.; Landoure, G.; Coulibaly, S.; Niare, B.; Mochel, F.; La Pean, A.; Rafferty, I.; Watts, C.; Littleton-Kearney, M. T.; Blackstone, C.; Singleton, A.; Fischbeck, K.H.

2010-01-01

26

Striatal dopaminergic functioning in patients with sporadic and hereditary spastic paraplegias with parkinsonism.  

PubMed

Sporadic spastic paraplegia (SSP) and hereditary spastic paraplegia (HSP) belong to a clinical and genetically heterogeneous group of disorders characterized by progressive spasticity and weakness in the lower extremities. The symptoms are associated with pyramidal tract dysfunction and degeneration of the corticospinal tracts. Parkinsonism is uncommon in SSP/HSP patients. However, both disorders are associated with damage to the nigrostriatal dopaminergic system. In the present study, the clinical features of patients with SSP/HSP were investigated, and nigrostriatal dopaminergic binding potential was assessed using dopamine transporter (DAT) single-photon emission computer tomography (SPECT). Nine patients with spastic paraplegia participated in the present study. The subjects underwent DAT SPECT using the agent [2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino]ethanethiolato (3-)-N2,N20,S2,S20]oxo-[IR-(exo-exo)])-[(99)mTc]technetium ([(99)mTc]TRODAT-1). The [(99)mTc]TRODAT-1 SPECT images of five patients appeared normal, whereas the images of four patients revealed reduced striatal ligand uptake. Among the four patients with reduced uptake, two had parkinsonism, and one exhibited periodic limb movements and restless leg syndrome. Our DAT SPECT imaging study shows that reduced DAT density may be observed in patients with parkinsonism. The results of the present study offer an explanation for the spectrum of spastic paraplegia symptoms and the progression of the disorder. PMID:24265532

Kim, Ji Seon; Kim, Jong Min; Kim, Yu Kyeong; Kim, Sang Eun; Yun, Ji Young; Jeon, Beom S

2013-11-01

27

Striatal Dopaminergic Functioning in Patients with Sporadic and Hereditary Spastic Paraplegias with Parkinsonism  

PubMed Central

Sporadic spastic paraplegia (SSP) and hereditary spastic paraplegia (HSP) belong to a clinical and genetically heterogeneous group of disorders characterized by progressive spasticity and weakness in the lower extremities. The symptoms are associated with pyramidal tract dysfunction and degeneration of the corticospinal tracts. Parkinsonism is uncommon in SSP/HSP patients. However, both disorders are associated with damage to the nigrostriatal dopaminergic system. In the present study, the clinical features of patients with SSP/HSP were investigated, and nigrostriatal dopaminergic binding potential was assessed using dopamine transporter (DAT) single-photon emission computer tomography (SPECT). Nine patients with spastic paraplegia participated in the present study. The subjects underwent DAT SPECT using the agent [2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino]ethanethiolato (3-)-N2,N20,S2,S20]oxo-[IR-(exo-exo)])-[99mTc]technetium ([99mTc]TRODAT-1). The [99mTc]TRODAT-1 SPECT images of five patients appeared normal, whereas the images of four patients revealed reduced striatal ligand uptake. Among the four patients with reduced uptake, two had parkinsonism, and one exhibited periodic limb movements and restless leg syndrome. Our DAT SPECT imaging study shows that reduced DAT density may be observed in patients with parkinsonism. The results of the present study offer an explanation for the spectrum of spastic paraplegia symptoms and the progression of the disorder. PMID:24265532

Kim, Ji Seon; Kim, Jong Min; Kim, Yu Kyeong; Kim, Sang Eun; Yun, Ji Young

2013-01-01

28

Cerebrospinal fluid drainage reduces paraplegia after thoracoabdominal aortic aneurysm repair: Results of a randomized clinical trial  

Microsoft Academic Search

Objective: Despite the use of various strategies for the prevention of spinal cord ischemia, paraplegia and paraparesis continue to occur after thoracoabdominal aortic aneurysm (TAAA) repair. Although cerebrospinal fluid drainage (CSFD) is often used as an adjunct for spinal cord protection, its benefit remains unproven. The purpose of this randomized clinical trial was to evaluate the impact of CSFD on

Joseph S. Coselli; Scott A. LeMaire; Cüneyt Köksoy; Zachary C. Schmittling; Patrick E. Curling

2002-01-01

29

Paraplegia in a chiropractic patient secondary to atraumatic dural arteriovenous fistula with perimedullary hypertension: case report  

PubMed Central

Intracranial dural arteriovenous fistulas are abnormal communications between higher-pressure arterial circulation and lower-pressure venous circulation. This abnormal communication can result in important and frequently misdiagnosed neurological abnormalities. A case of rapid onset paraplegia following cervical chiropractic manipulation is reviewed. The patient’s generalized spinal cord edema, lower extremity paraplegia and upper extremity weakness, were initially believed to be a complication of the cervical spinal manipulation that had occurred earlier on the day of admission. Subsequent diagnostic testing determined the patient suffered from impaired circulation of the cervical spinal cord produced by a Type V intracranial arteriovenous fistula and resultant venous hypertension in the pontomesencephalic and anterior spinal veins. The clinical and imaging findings of an intracranial dural arteriovenous fistula with pontomesencephalic venous congestion and paraplegia are reviewed. This case report emphasizes the importance of thorough and serial diagnostic imaging in the presence of sudden onset paraplegia and the potential for error when concluding atypical neurological presentations are the result of therapeutic misadventure. PMID:23830411

2013-01-01

30

SPG11 mutations are common in familial cases of complicated hereditary spastic paraplegia (HSP)  

PubMed Central

Objective Autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC) is a common form of complex HSP. The genetic lesion underlying ARHSP-TCC was localized to chromosome 15q13-q15 and given the designation SPG11. Recently the gene encoding spatacsin (KIAA1840), has been shown to contain mutations that underlie the majority of ARHSP-TCC cases. Methods Here we present a complete analysis of the 40 coding exons of this gene in patients with sporadic (n = 25) or familial (20 probands) complex hereditary spastic paraplegia with and without thinning of the corpus callosum. Results We identified seven mutations, including deletions, insertions and nonsense mutations, which were all predicted to lead to premature truncation of the protein. Conclusion We conclude that mutations on KIAA1840 are frequent in complex ARHSP but an infrequent cause of sporadic complex HSP. PMID:18337587

Paisan-Ruiz, Coro; Dogu, Okan; Yilmaz, Arda; Houlden, Henry; Singleton, Andrew

2009-01-01

31

[Hereditary spastic paraplegia associated with congenital cataracts, mental retardation and peripheral neuropathy].  

PubMed

A 16-year-old male patient was admitted to our hospital with mental retardation and a gradually increasing gait disturbance. He fell easily at age 6, and lost the ability to jump at age 12. At age 13, he lost the ability to run, and developed pes cavus and hammer toes. Spastic paraplegia with mental retardation, congenital cataracts, hyper reflexia, dysarthria, callosal hypogenesis and peripheral neuropathy were evident at age 16. Laboratory examinations did not reveal any underlying disorders. He was diagnosed as having complex spastic paraplegia with cataracts, mental retardation and peripheral neuropathy that might comprise a genetically distinct entity that is unique to Japan, because all prior reports of this combination have been generated only from Japan. PMID:21077357

Hattori, Ayako; Sasaki, Masayuki; Sakuma, Hiroshi; Saito, Yoshiaki; Komaki, Hirofumi; Nakagawa, Eiji; Sugai, Kenji

2010-11-01

32

Erb's paraplegia with primary optic atrophy: Unusual presentation of neurosyphilis: Case report and review of literature  

PubMed Central

Symptomatic neurosyphilis (NS) can have varied syndromic presentations: Meningitis, meningovascular and parenchymatous involvement. Non-tabetic syphilis affecting the spinal cord is rare and only sporadic case reports have been published. The variant of meningomyelitis known as Erb's paraplegia refers to patients of spinal syphilis with very slow progression over many years and predominantly motor signs. Primary optic atrophy occurs twice as frequently in tabes dorsalis as in other types of NS. We describe here a case of a 32-year-old truck driver who presented with Erb's paraplegia with primary optic atrophy. This clinical overlap in NS is extremely rare and to our knowledge is the first case report of its type. PMID:25024583

Sharma, Chandramohan; Nath, Kunal; Kumawat, Banshi Lal; Khandelwal, Dinesh; Jain, Deepak

2014-01-01

33

Cardiovascular responses during arm exercise and orthostatic challenge in individuals with paraplegia  

Microsoft Academic Search

.   In this study the cardiorespiratory responses during arm crank ergometry (ACE) performed at two submaximal intensities (30%\\u000a and 50% of heart rate reserve) and moderate orthostatic challenge were investigated in individuals with paraplegia (PARA).\\u000a The effect of concurrent electrical stimulation (ES)-induced leg muscle contractions on the responses to ACE during orthostatic\\u000a challenge was also investigated. Eight PARA (T5–T12) and

Jacqui Raymond; Glen M. Davis; Jill Clarke; Grace Bryant

2001-01-01

34

Intramedullary Neurenteric Cyst Presenting as Infantile Paraplegia: A Case and Review  

Microsoft Academic Search

The authors report a case of a 3-month-old male child with paraplegia in whom magnetic resonance imaging (MRI) revealed a nonenhancing intramedullary cystic lesion extending from the level of D1 to D7 without any other associated anomaly. Intraoperatively, these findings were confirmed and the spinal cord was found to have splayed circumferentially into a papery thin rim. The patient underwent

Deepak Agrawal; Ashish Suri; A. K. Mahapatra; M. C. Sharma

2002-01-01

35

PLP1 -related inherited dysmyelinating disorders: Pelizaeus-Merzbacher disease and spastic paraplegia type 2  

Microsoft Academic Search

Pelizaeus-Merzbacher disease (PMD) and its allelic disorder, spastic paraplegia type 2 (SPG2), are among the best-characterized dysmyelinating leukodystrophies of the central nervous system (CNS). Both PMD and SPG2 are caused by mutations in the proteolipid protein 1 ( PLP1) gene, which encodes a major component of CNS myelin proteins. Distinct types of mutations, including point mutations and genomic duplications and

Ken Inoue

2005-01-01

36

Mutations in ADAR1, IFIH1, and RNASEH2B Presenting As Spastic Paraplegia.  

PubMed

Background?Hereditary spastic paraplegia is a neurodegenerative phenotype characterized by a progressive loss of corticospinal motor tract function. In a majority of affected individuals the pathogenesis remains undetermined. Methods?We identified a series of patients with a phenotype of nonsyndromic spastic paraplegia in whom no diagnosis had been reached before exome sequencing. We measured the expression of interferon stimulated genes (ISGs) in peripheral blood from these patients. Results?Five patients from four families with previously unexplained spastic paraplegia were identified with mutations in either ADAR1 (one patient), IFIH1 (one patient), or RNASEH2B (three patients from two families). All patients were developmentally normal before the onset of features beginning in the second year of life. All patients remain of normal intellect. Four patients demonstrated normal neuroimaging, while a single patient had features of nonspecific dysmyelination. The patients with ADAR1 and IFIH1-related disease showed a robust interferon signature. The patients with mutations in RNASEH2B demonstrated no (two patients) or a minimal (one patient) upregulation of ISGs compared with controls. Conclusions?Mutations in ADAR1, IFIH1, and RNASEH2B can cause a phenotype of spastic paraplegia with normal neuroimaging, or in association with nonspecific dysmyelination. Although the presence of an interferon signature can be helpful in interpreting the significance of gene variants in this context, patients with pathogenic mutations in RNASEH2B may demonstrate no upregulation of ISGs in peripheral blood. However, it remains possible that type I interferons act as a neurotoxin in the context of all genotypes. PMID:25243380

Crow, Yanick J; Zaki, Maha S; Abdel-Hamid, Mohamed S; Abdel-Salam, Ghada; Boespflug-Tanguy, Odile; Cordeiro, Nuno J V; Gleeson, Joseph G; Gowrinathan, Nirmala Rani; Laugel, Vincent; Renaldo, Florence; Rodriguez, Diana; Livingston, John H; Rice, Gillian I

2014-12-01

37

Anterior Spinal Artery Syndrome: Reversible Paraplegia after Minimally Invasive Spine Surgery  

PubMed Central

Background Context. Percutaneous balloon kyphoplasty is an established minimally invasive technique to treat painful vertebral compression fractures, especially in the context of osteoporosis with a minor complication rate. Purpose. To describe the heparin anticoagulation treatment of paraplegia following balloon kyphoplasty. Study Design. We report the first case of an anterior spinal artery syndrome with a postoperative reversible paraplegia following a minimally invasive spine surgery (balloon kyphoplasty) without cement leakage. Methods. A 75-year-old female patient underwent balloon kyphoplasty for a fresh fracture of the first vertebra. Results. Postoperatively, the patient developed an acute anterior spinal artery syndrome with motor paraplegia of the lower extremities as well as loss of pain and temperature sensation with retained proprioception and vibratory sensation. Complete recovery occurred six hours after bolus therapy with 15.000?IU low-molecular heparin. Conclusion. Spine surgeons should consider vascular complications in patients with incomplete spinal cord syndromes after balloon kyphoplasty, not only after more invasive spine surgery. High-dose low-molecular heparin might help to reperfuse the Adamkiewicz artery. PMID:25210639

Bredow, J.; Oppermann, J.; Keller, K.; Beyer, F.; Boese, C. K.; Zarghooni, K.; Sobottke, R.; Eysel, P.; Siewe, J.

2014-01-01

38

AP5Z1/SPG48 frequency in autosomal recessive and sporadic spastic paraplegia  

PubMed Central

Hereditary spastic paraplegias (HSP) constitute a rare and highly heterogeneous group of neurodegenerative disorders, defined clinically by progressive lower limb spasticity and pyramidal weakness. Autosomal recessive HSP as well as sporadic cases present a significant diagnostic challenge. Mutations in AP5Z1, a gene playing a role in intracellular membrane trafficking, have been recently reported to be associated with spastic paraplegia type 48 (SPG48). Our objective was to determine the relative frequency and clinical relevance of AP5Z1 mutations in a large cohort of 127 HSP patients. We applied a targeted next-generation sequencing approach to analyze all coding exons of the AP5Z1 gene. With the output of high-quality reads and a mean coverage of 51-fold, we demonstrated a robust detection of variants. One 43-year-old female with sporadic complicated paraplegia showed two heterozygous nonsynonymous variants of unknown significance (VUS3; p.[R292W];[(T756I)]). Thus, AP5Z1 gene mutations are rare, at least in Europeans. Due to its low frequency, systematic genetic testing for AP5Z1 mutations is not recommended until larger studies are performed to add further evidence. Our findings demonstrate that amplicon-based deep sequencing is technically feasible and allows a compact molecular characterization of multiple HSP patients with high accuracy. PMID:25333062

Schlipf, Nina A; Schule, Rebecca; Klimpe, Sven; Karle, Kathrin N; Synofzik, Matthis; Wolf, Julia; Riess, Olaf; Schols, Ludger; Bauer, Peter

2014-01-01

39

Anterior spinal artery syndrome: reversible paraplegia after minimally invasive spine surgery.  

PubMed

Background Context. Percutaneous balloon kyphoplasty is an established minimally invasive technique to treat painful vertebral compression fractures, especially in the context of osteoporosis with a minor complication rate. Purpose. To describe the heparin anticoagulation treatment of paraplegia following balloon kyphoplasty. Study Design. We report the first case of an anterior spinal artery syndrome with a postoperative reversible paraplegia following a minimally invasive spine surgery (balloon kyphoplasty) without cement leakage. Methods. A 75-year-old female patient underwent balloon kyphoplasty for a fresh fracture of the first vertebra. Results. Postoperatively, the patient developed an acute anterior spinal artery syndrome with motor paraplegia of the lower extremities as well as loss of pain and temperature sensation with retained proprioception and vibratory sensation. Complete recovery occurred six hours after bolus therapy with 15.000?IU low-molecular heparin. Conclusion. Spine surgeons should consider vascular complications in patients with incomplete spinal cord syndromes after balloon kyphoplasty, not only after more invasive spine surgery. High-dose low-molecular heparin might help to reperfuse the Adamkiewicz artery. PMID:25210639

Bredow, J; Oppermann, J; Keller, K; Beyer, F; Boese, C K; Zarghooni, K; Sobottke, R; Eysel, P; Siewe, J

2014-01-01

40

Heavy reliance on carbohydrate across a wide range of exercise intensities during voluntary arm ergometry in persons with paraplegia  

PubMed Central

Context/objective To describe and compare substrate oxidation and partitioning during voluntary arm ergometry in individuals with paraplegia and non-disabled individuals over a wide range of exercise intensities. Design Cross-sectional study. Setting Clinical research facility. Participants Ten apparently healthy, sedentary men with paraplegia and seven healthy, non-disabled subjects. Interventions Rest and continuous progressive voluntary arm ergometry between 30 and 80% of peak aerobic capacity (VO2peak). Outcome measures Total energy expenditure and whole body rates of fat and carbohydrate oxidation. Results A maximal whole body fat oxidation (WBFO) rate of 0.13 ± 0.07 g/minute was reached at 41 ± 9% VO2peak for subjects with paraplegia, although carbohydrate became the predominant fuel source during exercise exceeding an intensity of 30–40% VO2peak. Both the maximal WBFO rate (0.06 ± 0.04 g/minute) and the intensity at which it occurred (13 ± 3% VO2peak) were significantly lower for the non-disabled subjects than those with paraplegia. Conclusion Sedentary individuals with paraplegia are more capable of oxidizing fat during voluntary arm ergometry than non-disabled individuals perhaps due to local adaptations of upper body skeletal muscle used for daily locomotion. However, carbohydrate is the predominant fuel source oxidized across a wide range of intensities during voluntary arm ergometry in those with paraplegia, while WBFO is limited and maximally achieved at low exercise intensities compared to that achieved by able-bodied individuals during leg ergometry. These findings may partially explain the diminished rates of fat loss imposed by acute bouts of physical activity in those with paraplegia. PMID:23941790

Jacobs, Kevin A.; Burns, Patricia; Kressler, Jochen; Nash, Mark S.

2013-01-01

41

Spastic paraplegia with neurogenic amyotrophy manifesting ballooned axons in sural nerve.  

PubMed

A 21-year-old man had progressive symmetric, distal muscle atrophy and weakness, as well as spasticity of the limbs. Histologic examination of the sural nerve disclosed swollen axons containing membranous tubular profiles, ring tubules, large mitochondria with abnormal cristae, and glycogen like granules. Peripheral sensory nerve fibers also were affected. The pathologic features of the peripheral nerves were similar to those of infantile neuroaxonal dystrophy. Sural nerve biopsy may be useful in the study of pathologic processes in spastic paraplegia. PMID:899737

Shimono, M; Ohta, M; Kuroiwa, Y

1977-07-15

42

Overlapping phenotypes in complex spastic paraplegias SPG11, SPG15, SPG35 and SPG48.  

PubMed

Hereditary spastic paraplegias are a heterogeneous group of neurodegenerative disorders, clinically classified in pure and complex forms. Genetically, more than 70 different forms of spastic paraplegias have been characterized. A subgroup of complicate recessive forms has been distinguished for the presence of thin corpus callosum and white matter lesions at brain imaging. This group includes several genetic entities, but most of the cases are caused by mutations in the KIAA1840 (SPG11) and ZFYVE26 genes (SPG15). We studied a cohort of 61 consecutive patients with complicated spastic paraplegias, presenting at least one of the following features: mental retardation, thin corpus callosum and/or white matter lesions. DNA samples were screened for mutations in the SPG11/KIAA1840, SPG15/ZFYVE26, SPG21/ACP33, SPG35/FA2H, SPG48/AP5Z1 and SPG54/DDHD2 genes by direct sequencing. Sequence variants were found in 30 of 61 cases: 16 patients carried SPG11/KIAA1840 gene variants (26.2%), nine patients carried SPG15/ZFYVE26 variants (14.8%), three patients SPG35/FA2H (5%), and two patients carried SPG48/AP5Z1 gene variants (3%). Mean age at onset was similar in patients with SPG11 and with SPG15 (range 11-36), and the phenotype was mostly indistinguishable. Extrapyramidal signs were observed only in patients with SPG15, and epilepsy in three subjects with SPG11. Motor axonal neuropathy was found in 60% of cases with SPG11 and 70% of cases with SPG15. Subjects with SPG35 had intellectual impairment, spastic paraplegia, thin corpus callosum, white matter hyperintensities, and cerebellar atrophy. Two families had a late-onset presentation, and none had signs of brain iron accumulation. The patients with SPG48 were a 5-year-old child, homozygous for a missense SPG48/AP5Z1 variant, and a 51-year-old female, carrying two different nonsense variants. Both patients had intellectual deficits, thin corpus callosum and white matter lesions. None of the cases in our cohort carried mutations in the SPG21/ACP33 and SPG54/DDH2H genes. Our study confirms that the phenotype of patients with SPG11 and with SPG15 is homogeneous, whereas cases with SPG35 and with SPG48 cases present overlapping features, and a broader clinical spectrum. The large group of non-diagnosed subjects (51%) suggests further genetic heterogeneity. The observation of common clinical features in association with defects in different causative genes, suggest a general vulnerability of the corticospinal tract axons to a wide spectrum of cellular alterations. PMID:24833714

Pensato, Viviana; Castellotti, Barbara; Gellera, Cinzia; Pareyson, Davide; Ciano, Claudia; Nanetti, Lorenzo; Salsano, Ettore; Piscosquito, Giuseppe; Sarto, Elisa; Eoli, Marica; Moroni, Isabella; Soliveri, Paola; Lamperti, Elena; Chiapparini, Luisa; Di Bella, Daniela; Taroni, Franco; Mariotti, Caterina

2014-07-01

43

Subarachnoid Fluid Lactate and Paraplegia after Descending Aorta Aneurysmectomy: Two Compared Case Reports  

PubMed Central

We report a comparison of two cases regarding subjects who underwent thoracoabdominal aorta aneurysmectomy. During the procedure we monitored cerebrospinal fluid lactate concentration. One patient experienced postoperative paraplegia and his cerebrospinal fluid lactate concentration was much higher than that in the other case, whose postoperative outcome was uneventful. Consequently we consider that monitoring the lactate concentration in cerebrospinal fluid during thoracic aorta surgical procedures may be a helpful tool to predict the ischemic spine-cord injury allowing for trying to recover it precociously. PMID:24198975

Malossini, Silvia Eleonora; Pellegrino, Francesco; Cancellieri, Franco

2013-01-01

44

Relation of heart rate recovery to heart rate variability in persons with paraplegia  

Microsoft Academic Search

Purpose  Heart rate recovery (HRR) after treadmill exercise testing is an index of cardiac autonomic activity in non-disabled persons,\\u000a but it is unknown if this is also the case in individuals with spinal cord injury (SCI). We investigated the relationship\\u000a between HRR after maximal arm exercise testing and resting autonomic activity in persons with paraplegia.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  A total of 17 (male n = 9,

Sae Young Jae; Kevin S. Heffernan; Miyoung Lee; Bo Fernhall

2011-01-01

45

Spastic paraplegia, optic atrophy, and neuropathy is linked to chromosome 11q13.  

PubMed

We report an autosomal recessive neurodegenerative disorder in 25 white members from a large inbred Brazilian family, 22 of whom were evaluated clinically. This condition is characterized by (1) subnormal vision secondary to apparently nonprogressive congenital optic atrophy; (2) onset of progressive spastic paraplegia in infancy; (3) onset of progressive motor and sensory axonal neuropathy in late childhood/early adolescence; (4) dysarthria starting in the third decade of life; (5) exacerbated acoustic startle response; and (6) progressive joint contractures and spine deformities. Motor handicap was severe, and all patients were wheelchair bound after 15 years old. We performed a genome-wide screen including 25 affected individuals and 49 of their unaffected relatives. Linkage was detected at 11q13 region with a maximum logarithm of odds score of +14.43, obtained with marker D11S1883. The candidate region, which lies between D11S1908 and D11S1889, encompasses approximately 4.8Mb and has more than 100 genes and expressed sequences. We propose the acronym SPOAN (spastic paraplegia, optic atrophy, and neuropathy) for this complex syndrome. PMID:15852396

Macedo-Souza, Lucia I; Kok, Fernando; Santos, Silvana; Amorim, Simone C; Starling, Alessandra; Nishimura, Agnes; Lezirovitz, Karina; Lino, Angelina M M; Zatz, Mayana

2005-05-01

46

A spastic paraplegia mouse model reveals REEP1-dependent ER shaping.  

PubMed

Axonopathies are a group of clinically diverse disorders characterized by the progressive degeneration of the axons of specific neurons. In hereditary spastic paraplegia (HSP), the axons of cortical motor neurons degenerate and cause a spastic movement disorder. HSP is linked to mutations in several loci known collectively as the spastic paraplegia genes (SPGs). We identified a heterozygous receptor accessory protein 1 (REEP1) exon 2 deletion in a patient suffering from the autosomal dominantly inherited HSP variant SPG31. We generated the corresponding mouse model to study the underlying cellular pathology. Mice with heterozygous deletion of exon 2 in Reep1 displayed a gait disorder closely resembling SPG31 in humans. Homozygous exon 2 deletion resulted in the complete loss of REEP1 and a more severe phenotype with earlier onset. At the molecular level, we demonstrated that REEP1 is a neuron-specific, membrane-binding, and membrane curvature-inducing protein that resides in the ER. We further show that Reep1 expression was prominent in cortical motor neurons. In REEP1-deficient mice, these neurons showed reduced complexity of the peripheral ER upon ultrastructural analysis. Our study connects proper neuronal ER architecture to long-term axon survival. PMID:24051375

Beetz, Christian; Koch, Nicole; Khundadze, Mukhran; Zimmer, Geraldine; Nietzsche, Sandor; Hertel, Nicole; Huebner, Antje-Kathrin; Mumtaz, Rizwan; Schweizer, Michaela; Dirren, Elisabeth; Karle, Kathrin N; Irintchev, Andrey; Alvarez, Victoria; Redies, Christoph; Westermann, Martin; Kurth, Ingo; Deufel, Thomas; Kessels, Michael M; Qualmann, Britta; Hübner, Christian A

2013-10-01

47

Effect of increased load on scapular kinematics during manual wheelchair propulsion in individuals with paraplegia and tetraplegia.  

PubMed

Repetitive loading of the upper extremity musculature during activities like wheelchair propulsion can lead to fatigue of surrounding musculature causing irregular segment kinematics. The goal of this study was to determine the effect of increase in load on the kinematics of the scapula in users with paraplegia and tetraplegia. Data were collected on 18 participants (11 with paraplegia and 7 with tetraplegia) using an electromagnetic motion tracking system (100Hz) and force sensing pushrim (200Hz). The participants propelled under no load and loaded conditions at their customary propulsion velocity. On average a 60N increase in force was elicited with the experimental protocol. Users with tetraplegia showed significant increases (p<.05) in the rate of change of scapular angles in the upward/downward rotation and the retraction/protraction direction under the loaded conditions, whereas users with paraplegia only showed difference in the retraction/protraction rotation direction. Overall both user populations moved towards position of increased downward rotation, anterior tilt and protraction with increase in load hence increasing the risk of impingement. This experiment adds depth to our understanding of dynamic scapular kinematics during wheelchair propulsion under different loading conditions and differences in scapular control between users with paraplegia and tetraplegia. PMID:21782267

Raina, Shashank; McNitt-Gray, Jill L; Mulroy, Sara; Requejo, Philip S

2012-04-01

48

Full Body Gait Analysis May Improve Diagnostic Discrimination Between Hereditary Spastic Paraplegia and Spastic Diplegia: A Preliminary Study  

ERIC Educational Resources Information Center

Hereditary spastic paraplegia (HSP) and spastic diplegia (SD) patients share a strong clinical resemblance. Thus, HSP patients are frequently misdiagnosed with a mild form of SD. Clinical gait analysis (CGA) has been highlighted as a possible tool to support the differential diagnosis of HSP and SD. Previous analysis has focused on the lower-body…

Bonnefoy-Mazure, A.; Turcot, K.; Kaelin, A.; De Coulon, G.; Armand, S.

2013-01-01

49

Spectrum of SPG4 Mutations in a Large Collection of North American Families With Hereditary Spastic Paraplegia  

Microsoft Academic Search

Background: Hereditary spastic paraplegia (HSP) is a neu- rodegenerative disease characterized by progressive spas- ticity and weakness of the lower limbs. The most com- mon form of HSP is caused by mutations in the SPG4 gene, which codes for spastin, an adenosine triphosphatase with various cellular activities (AAA) protein family member. Objective: To investigate a large collection of predomi- nantly

Inge A. Meijer; Collette K. Hand; P. Cossette; Denise A. Figlewicz; Guy A. Rouleau

2002-01-01

50

Primary osteosarcoma of the L2 lamina presenting as “silent” paraplegia: case report and review of the literature  

Microsoft Academic Search

Primary osteosarcomas of the vertebral column are not common, and to our knowledge a total of 78 cases, mostly located in the vertebral body, have been previously reported. We report a primary osteosarcoma of the spine with an extremely rare location — the lamina of the second lumbar vertebra. The patient, a 38-year-old woman, was admitted with paraplegia of a

P. Korovessis; M. Repanti; M. Stamatakis

1995-01-01

51

Mutation Screening of Spastin, Atlastin, and REEP1 in Hereditary Spastic Paraplegia  

PubMed Central

Hereditary spastic paraplegia (HSP) comprises a group of clinically and genetically heterogeneous diseases that affect the upper motor neurons and their axonal projections. Over 40 chromosomal loci have been identified for autosomal dominant, recessive, and X-linked HSP. Mutations in the genes atlastin, spastin and REEP1 are estimated to account for up to 50% of autosomal dominant HSP and currently guide the molecular diagnosis of HSP. Here we report the mutation screening results of 120 HSP patients from North America for spastin, atlastin, and REEP1, with the latter one partially reported previously. We identified mutations in 36.7% of all tested HSP patients and describe 20 novel changes in spastin and atlastin. Our results add to a growing number of HSP disease associated variants and confirm the high prevalence of atlastin, spastin, and REEP1 mutations in the HSP patient population. PMID:20718791

McCorquodale, Donald S.; Ozomaro, Uzoezi; Huang, Jia; Montenegro, Gladys; Kushman, Arielle; Citrigno, Luigi; Price, Justin; Speziani, Fiorella; Pericak-Vance, Margaret A.; Züchner, Stephan

2010-01-01

52

Novel mutation in the ATL1 with autosomal dominant hereditary spastic paraplegia presented as dysautonomia.  

PubMed

SPG3A, which is the second most common type of autosomal dominant hereditary spastic paraplegia (HSP), is caused by mutations in the atlastin GTPase 1 gene, ATL1. We report a case of a patient who presented as dysautonomia and had a novel splicing mutation c.35-3C>T in exon 2 of the ATL1. Orthostatic intolerance, urinary symptoms, hyperreflexia in the biceps and knee jerk, and decreased proprioception in both limbs were observed on neurological examinations. We tested the autonomic function and performed genetic tests for the SPG4 and SPG3A forms of HSP. This case is a genetically confirmed HSP with a novel mutation in SPG3A, and extends the phenotype of SPG3A. PMID:24969372

Shin, Jung-Won; Jung, Keun-Hwa; Lee, Soon-Tae; Moon, Jangsup; Seong, Moon-Woo; Park, Sung Sup; Lee, Sang Kun; Chu, Kon

2014-10-01

53

Rapidly progressive paraplegia due to an extradural lumbar meningocele mimicking a cyst. Case report.  

PubMed

Unlike arachnoid meningoceles, arachnoid cysts frequently cause local pressure effects probably because there is no free communication between the cyst and the subarachnoid space. Following the first detailed description of cystic lesions of spinal nerve roots by Tarlov in 1938, a simplified classification of spinal meningeal cysts was developed in 1988, containing three major categories. The authors report on a lumbar intraspinal extradural meningocele that caused incomplete paraplegia in an otherwise healthy 31-year-old man in whom magnetic resonance imaging revealed stigmata of Scheuermann disease. Intraoperatively, the lesion was classified as a transitional-type lesion, in accordance with Type IA of the Nabors classification, because a communication with the subarachnoid space was observed. After complete removal of the meningocele, the patient's recovery was prompt and complete. PMID:17633492

Fiss, Ingo; Danne, Marco; Hartmann, Christian; Brock, Mario; Stendel, Ruediger

2007-07-01

54

Protrudin regulates endoplasmic reticulum morphology and function associated with the pathogenesis of hereditary spastic paraplegia.  

PubMed

Protrudin is a membrane protein that regulates polarized vesicular trafficking in neurons. The protrudin gene (ZFYVE27) is mutated in a subset of individuals with hereditary spastic paraplegia (HSP), and protrudin is therefore also referred to as spastic paraplegia (SPG) 33. We have now generated mice that express a transgene for dual epitope-tagged protrudin under control of a neuron-specific promoter, and we have subjected highly purified protrudin-containing complexes isolated from the brain of these mice to proteomics analysis to identify proteins that associate with protrudin. Protrudin was found to interact with other HSP-related proteins including myelin proteolipid protein 1 (SPG2), atlastin-1 (SPG3A), REEP1 (SPG31), REEP5 (similar to REEP1), Kif5A (SPG10), Kif5B, Kif5C, and reticulon 1, 3, and 4 (similar to reticulon 2, SPG12). Membrane topology analysis indicated that one of three hydrophobic segments of protrudin forms a hydrophobic hairpin domain similar to those of other SPG proteins. Protrudin was found to localize predominantly to the tubular endoplasmic reticulum (ER), and forced expression of protrudin promoted the formation and stabilization of the tubular ER network. The protrudin(G191V) mutant, which has been identified in a subset of HSP patients, manifested an increased intracellular stability, and cells expressing this mutant showed an increased susceptibility to ER stress. Our results thus suggest that protrudin contributes to the regulation of ER morphology and function, and that its deregulation by mutation is a causative defect in HSP. PMID:24668814

Hashimoto, Yutaka; Shirane, Michiko; Matsuzaki, Fumiko; Saita, Shotaro; Ohnishi, Takafumi; Nakayama, Keiichi I

2014-05-01

55

Lysosomal abnormalities in hereditary spastic paraplegia types SPG15 and SPG11  

PubMed Central

Objective Hereditary spastic paraplegias (HSPs) are among the most genetically diverse inherited neurological disorders, with over 70 disease loci identified (SPG1-71) to date. SPG15 and SPG11 are clinically similar, autosomal recessive disorders characterized by progressive spastic paraplegia along with thin corpus callosum, white matter abnormalities, cognitive impairment, and ophthalmologic abnormalities. Furthermore, both have been linked to early-onset parkinsonism. Methods We describe two new cases of SPG15 and investigate cellular changes in SPG15 and SPG11 patient-derived fibroblasts, seeking to identify shared pathogenic themes. Cells were evaluated for any abnormalities in cell division, DNA repair, endoplasmic reticulum, endosomes, and lysosomes. Results Fibroblasts prepared from patients with SPG15 have selective enlargement of LAMP1-positive structures, and they consistently exhibited abnormal lysosomal storage by electron microscopy. A similar enlargement of LAMP1-positive structures was also observed in cells from multiple SPG11 patients, though prominent abnormal lysosomal storage was not evident. The stabilities of the SPG15 protein spastizin/ZFYVE26 and the SPG11 protein spatacsin were interdependent. Interpretation Emerging studies implicating these two proteins in interactions with the late endosomal/lysosomal adaptor protein complex AP-5 are consistent with shared abnormalities in lysosomes, supporting a converging mechanism for these two disorders. Recent work with Zfyve26?/? mice revealed a similar phenotype to human SPG15, and cells in these mice had endolysosomal abnormalities. SPG15 and SPG11 are particularly notable among HSPs because they can also present with juvenile parkinsonism, and this lysosomal trafficking or storage defect may be relevant for other forms of parkinsonism associated with lysosomal dysfunction. PMID:24999486

Renvoise, Benoit; Chang, Jaerak; Singh, Rajat; Yonekawa, Sayuri; FitzGibbon, Edmond J; Mankodi, Ami; Vanderver, Adeline; Schindler, Alice B; Toro, Camilo; Gahl, William A; Mahuran, Don J; Blackstone, Craig; Pierson, Tyler Mark

2014-01-01

56

Cardiovascular responses to an orthostatic challenge and electrical-stimulation-induced leg muscle contractions in individuals with paraplegia  

Microsoft Academic Search

The purpose of this study was to investigate the cardiovascular and haemodynamic responses that occur during moderate orthostatic\\u000a challenge in people with paraplegia, and the effect of electrical stimulation (ES)-induced leg muscle contractions on their\\u000a responses to orthostatic challenge. Eight males with complete spinal lesions between the 5th and 12th thoracic vertebrae (PARA)\\u000a and eight able-bodied individuals (AB) volunteered for

Jacqui Raymond; Glen M. Davis; Grace Bryant; Jill Clarke

1999-01-01

57

Oxygen uptake and heart rate responses during arm vs combined arm\\/electrically stimulated leg exercise in people with paraplegia  

Microsoft Academic Search

The purpose of this study was to compare the oxygen uptake and heart rate responses during submaximal arm cranking to combined arm cranking+electrical stimulation (ES)-induced leg cycling in individuals with spinal cord injury (SCI). Seven subjects with paraplegia (T4 – T12) performed combined arm and leg cycling exercise for 5 min, followed by arm cranking alone at the same power

Jacqui Raymond; Glen M Davis; Alex Fahey; Mike Climstein; John R Sutton

1997-01-01

58

Comparative Study on the Wrist Positions During Raise Maneuver and Their Effect on Hand Function in Individuals With Paraplegia  

PubMed Central

Objective: To determine the appropriate wrist position in individuals with high-level paraplegia during the RAISE (relief of anatomical ischial skin embarrassment) maneuver. Method: Thirty individuals with high-level paraplegia were randomly selected; 15 individuals performed RAISE maneuver with extended wrist and 15 with neutral wrist. All the subjects who were at least 1 year post spinal cord injury were screened for positive carpal tunnel syndrome symptoms. All the subjects were allowed to participate in a trial of the Jebsen-Taylor Test of Hand Function to familiarize them with the test. Hand function was measured using the Jebsen-Taylor test. Results: During the RAISE maneuver, individuals with paraplegia weight bearing on their hands with wrists in the neutral position showed better hand function (P < .001) when compared to those weight bearing with their wrists in extension. Conclusion: Weight bearing with the wrist in neutral position is advisable for paraplegics to prevent the deterioration in hand function due to carpal tunnel syndrome. PMID:23678284

2013-01-01

59

Grade-III Paraplegia in Spinal Tuberculosis: Follow up of A Case Report and Review of Literature  

PubMed Central

This is a case report of spinal tuberculosis which could not be diagnosed in the early stages. Individuals who work in hospital settings and suffer from psychological stress need to be aware of the various hospital acquired infections and consequences of late diagnoses. A CT scan is indicated to rule out the spinal involvement, at the beginning of a severe backache, which does not respond to painkillers, rest, and if X-ray is normal. It is of immense help and much of the problems like paraplegia and morbidity which are associated with this kind of extra - pulmonary tuberculosis, could be avoided. Once paraplegia sets in, the response to treatment as well as the recovery are slow. The cost of CT Scan or MRI (Magnetic Resonance Imaging), no doubt, is very high, which ranges from Rs.4,500/- to Rs.5,000/- for an average Indian, but which goes a long way in reducing the debilitating conditions, excruciating pain and confinement to bed which occur during the spinal tuberculosis. Prolonged follow-up is essential in cases of Pott’s disease, as it was in the presented case. A strict treatment schedule of 18 months, combined with good nutritional support and bed rest, with spinal braces, is adequate for recovery from immobility and paraplegia caused by an advanced stage of spinal infection. This case therefore, supports an approach of nonoperative treatment over surgery, where the patient had progressive paralysis. PMID:24783114

Hussain, Tahziba

2014-01-01

60

Digital subtraction angiography does not reliably prevent paraplegia associated with lumbar transforaminal epidural steroid injection.  

PubMed

Digital subtraction angiography (DSA) has been touted as a radiologic adjunct to interventional neuraxial procedures where it is imperative to identify vascular compromise during the injection. Transforaminal epidural steroid injections (TFESI) are commonly performed interventions for treating acute and chronic radicular spine pain. We present a case of instantaneous and irreversible paraplegia following lumbar TFESI wherein a local anesthetic test dose, as well as DSA, were used as adjuncts to fluoroscopy. An 80-year-old man with severe lumbar spinal stenosis and chronic L5 radiculopathic pain was evaluated at a university pain management center seeking symptomatic pain relief. Two prior lumbar interlaminar epidural steroid injections (LESI) provided only transient pain relief, and a decision was made to perform right-sided L5-S1 TFESI. A 5-inch, 22-gauge Quincke-type spinal needle with a curved tip was used. Foraminal placement of the needle tip was confirmed with anteroposterior, oblique, and lateral views on fluoroscopy. Aspiration did not reveal any blood or cerebrospinal fluid. Digital subtraction angiography was performed twice to confirm the absence of intravascular contrast medium spread. Subsequently, a 0.5 mL of 1% lidocaine test dose was performed without any changes in neurological status. Two minutes later, a mixture of one mL of 1% lidocaine with 80 mg triamcinolone acetonide was injected. Immediately following the completion of the injection, the patient reported extreme bilateral lower extremity pain. He became diaphoretic, followed by marked weakness in his bilateral lower extremities and numbness up to his lower abdomen. The patient was transferred to the emergency department for evaluation. Magnetic resonance imaging (MRI) of the lumbar and thoracic spine was completed 5 hours postinjection. It showed a small high T2 signal focus in the thoracic spinal cord at the T7-T8 level. The patient was admitted to the critical care unit for neurological observation and treatment with intravenous methylprednisolone. Follow-up MRI revealed a hyper-intense T2 and short-tau inversion recovery signal in the central portion of the spinal cord beginning at the level of the T6 superior endplate and extending caudally to the T9-T10 level with accompanying development of mild spinal cord expansion. The patient was diagnosed with paraplegia from acute spinal cord infarction. At discharge to an acute inpatient rehabilitation program, the patient had persistent bilateral lower extremity paralysis, and incontinence of bowel and bladder functions. In the present patient, DSA performed twice and an anesthetic test dose did not prevent a catastrophic spinal cord infarction and resulting paraplegia. DSA use is clearly not foolproof and may not be sufficient to identify potentially life-or-limb threatening consequences of lumbar TFESI. We believe that this report should open further discussion regarding adding the possibility of these catastrophic events in the informed consent process for lumbar TFESIs, as it has for cervical TFESI. Utilizing blunt needles or larger bevel needles in place of sharp, cutting needles may minimize the chances of this event occurring. Considering eliminating use of particulate steroids for TFESI should be evaluated, although the use of nonparticulate agents remains controversial due to the perception that their respective duration of action is less than that of particulate steroids. PMID:23159970

Chang Chien, George C; Candido, Kenneth D; Knezevic, Nebojsa Nick

2012-01-01

61

Hereditary spastic paraplegia: clinico-pathologic features and emerging molecular mechanisms  

PubMed Central

Hereditary spastic paraplegia (HSP) is a syndrome designation describing inherited disorders in which lower extremity weakness and spasticity are the predominant symptoms. There are more than 50 genetic types of HSP. HSP affects individuals diverse ethnic groups with prevalence estimates ranging from 1.2 to 9.6 per 100,000 [39, 70, 77, 154, 185]. Symptoms may begin at any age. Gait impairment that begins after childhood usually worsens very slowly over many years. Gait impairment that begins in infancy and early childhood may not worsen significantly. Post mortem studies consistently identify degeneration of corticospinal tract axons (maximal in the thoracic spinal cord) and degeneration of fasciculus gracilis fibers (maximal in the cervico-medullary region). HSP syndromes thus appear to involve motor-sensory axon degeneration affecting predominantly (but not exclusively) the distal ends of long central nervous system (CNS) axons. In general, proteins encoded by HSP genes have diverse functions including axon transport (e.g. SPG30/KIF1A, SPG10/KIF5A and possibly SPG4/Spastin); endoplasmic reticulum morphology (e.g. SPG3A/Atlastin, SPG4/Spastin, SPG12/reticulon 2, and SPG31/REEP1, all of which interact); mitochondrial function (e.g. SPG13/chaperonin 60/heat shock protein 60, SPG7/paraplegin; and mitochondrial ATP6; 4) myelin formation (e.g. SPG2/Proteolipid protein and SPG42/Connexin 47); 5) protein folding and ER-stress response (SPG6/NIPA1, SPG8/K1AA0196 (Strumpellin), SGP17/BSCL2 (Seipin) [113-115], “mutilating sensory neuropathy with spastic paraplegia” due to CcT5 mutation and presumably SPG18/ERLIN2); 6) corticospinal tract and other neurodevelopment (e.g. SPG1/L1 cell adhesion molecule and SPG22/thyroid transporter MCT8); 7) fatty acid and phospholipid metabolism (e.g. SPG28/DDHD1, SPG35/FA2H, SPG39/NTE, SPG54/DDHD2, and SPG56/CYP2U1); and 8) endosome membrane trafficking and vesicle formation (e.g. SPG47/AP4B1, SPG48/KIAA0415, SPG50/AP4M1, SPG51/AP4E, SPG52/AP4S1, and VSPG53/VPS37A). The availability of animal models (including bovine, murine, zebrafish, Drosophila, and C. elegans) for many types of HSP permits exploration of disease mechanisms and potential treatments. This review highlights emerging concepts of this large group of clinically similar disorders. For recent review of HSP including historical descriptions, differential diagnosis, and additional references see [78]. PMID:23897027

Fink, John K.

2014-01-01

62

Autologous olfactory ensheathing cell transplantation in human paraplegia: a 3-year clinical trial  

PubMed Central

Olfactory ensheathing cells show promise in preclinical animal models as a cell transplantation therapy for repair of the injured spinal cord. This is a report of a clinical trial of autologous transplantation of olfactory ensheathing cells into the spinal cord in six patients with complete, thoracic paraplegia. We previously reported on the methods of surgery and transplantation and the safety aspects of the trial 1 year after transplantation. Here we address the overall design of the trial and the safety of the procedure, assessed during a period of 3 years following the transplantation surgery. All patients were assessed at entry into the trial and regularly during the period of the trial. Clinical assessments included medical, psychosocial, radiological and neurological, as well as specialized tests of neurological and functional deficits (standard American Spinal Injury Association and Functional Independence Measure assessments). Quantitative test included neurophysiological tests of sensory and motor function below the level of injury. The trial was a Phase I/IIa design whose main aim was to test the feasibility and safety of transplantation of autologous olfactory ensheathing cells into the injured spinal cord in human paraplegia. The design included a control group who did not receive surgery, otherwise closely matched to the transplant recipient group. This group acted as a control for the assessors, who were blind to the treatment status of the patients. The control group also provided the opportunity for preliminary assessment of the efficacy of the transplantation. There were no adverse findings 3 years after autologous transplantation of olfactory ensheathing cells into spinal cords injured at least 2 years prior to transplantation. The magnetic resonance images (MRIs) at 3 years showed no change from preoperative MRIs or intervening MRIs at 1 and 2 years, with no evidence of any tumour of introduced cells and no development of post-traumatic syringomyelia or other adverse radiological findings. There were no significant functional changes in any patients and no neuropathic pain. In one transplant recipient, there was an improvement over 3 segments in light touch and pin prick sensitivity bilaterally, anteriorly and posteriorly. We conclude that transplantation of autologous olfactory ensheathing cells into the injured spinal cord is feasible and is safe up to 3 years of post-implantation, however, this conclusion should be considered preliminary because of the small number of trial patients. PMID:18689435

Feron, F.; Cochrane, J.; Bassingthwaighte, L.; Bayliss, C.; Davies, W.; Fronek, P.; Gray, C.; Kerr, G.; Licina, P.; Nowitzke, A.; Perry, C.; Silburn, P.A.S.; Urquhart, S.; Geraghty, T.

2008-01-01

63

Alteration of Fatty-Acid-Metabolizing Enzymes Affects Mitochondrial Form and Function in Hereditary Spastic Paraplegia  

PubMed Central

Hereditary spastic paraplegia (HSP) is considered one of the most heterogeneous groups of neurological disorders, both clinically and genetically. The disease comprises pure and complex forms that clinically include slowly progressive lower-limb spasticity resulting from degeneration of the corticospinal tract. At least 48 loci accounting for these diseases have been mapped to date, and mutations have been identified in 22 genes, most of which play a role in intracellular trafficking. Here, we identified mutations in two functionally related genes (DDHD1 and CYP2U1) in individuals with autosomal-recessive forms of HSP by using either the classical positional cloning or a combination of whole-genome linkage mapping and next-generation sequencing. Interestingly, three subjects with CYP2U1 mutations presented with a thin corpus callosum, white-matter abnormalities, and/or calcification of the basal ganglia. These genes code for two enzymes involved in fatty-acid metabolism, and we have demonstrated in human cells that the HSP pathophysiology includes alteration of mitochondrial architecture and bioenergetics with increased oxidative stress. Our combined results focus attention on lipid metabolism as a critical HSP pathway with a deleterious impact on mitochondrial bioenergetic function. PMID:23176821

Tesson, Christelle; Nawara, Magdalena; Salih, Mustafa A.M.; Rossignol, Rodrigue; Zaki, Maha S.; Al Balwi, Mohammed; Schule, Rebecca; Mignot, Cyril; Obre, Emilie; Bouhouche, Ahmed; Santorelli, Filippo M.; Durand, Christelle M.; Oteyza, Andres Caballero; El-Hachimi, Khalid H.; Al Drees, Abdulmajeed; Bouslam, Naima; Lamari, Foudil; Elmalik, Salah A.; Kabiraj, Mohammad M.; Seidahmed, Mohammed Z.; Esteves, Typhaine; Gaussen, Marion; Monin, Marie-Lorraine; Gyapay, Gabor; Lechner, Doris; Gonzalez, Michael; Depienne, Christel; Mochel, Fanny; Lavie, Julie; Schols, Ludger; Lacombe, Didier; Yahyaoui, Mohamed; Al Abdulkareem, Ibrahim; Zuchner, Stephan; Yamashita, Atsushi; Benomar, Ali; Goizet, Cyril; Durr, Alexandra; Gleeson, Joseph G.; Darios, Frederic; Brice, Alexis; Stevanin, Giovanni

2012-01-01

64

Autosomal dominant familial spastic paraplegia; Linkage analysis and evidence for linkage to chromosome 2p  

SciTech Connect

Familial spastic paraplegia (FSP) is a degenerative disorder of the motor system characterized by progressive weakness and spasticity of the lower limbs. Little is known about the pathophysiology of this disorder. FSP can be inherited as an autosomal dominant (AD), autosomal recessive, or X-linked trait. We have undertaken linkage analysis for a group of 36 AD FSP families from which we have collected blood samples from 427 individuals, including 148 affected individuals. Typing of polymorphic markers has allowed us to exclude more than 50% of the genome. Recently, linkage for AD FSP to a locus on chromosome 14q was reported. Our AD FSP kindreds were tested for linkage to markers spanning the 20 cM region between D14S69 and D14S66; however, we were not able to establish linkage for any of our families to chromosome 14. Lod scores suggestive of linkage for some AD FSP kindreds have been obtained for markers on chromosome 2p. We have tested seven polymorphic markers spanning the region between D2S405 and D2S177. Our highest aggregate lod score, including all families tested, was obtained at the locus D2S352: 2.4 at 20 cM. Results from HOMOG analysis for linkage heterogeneity will be reported.

Figlewicz, D.A. [Univ. of Rochester, NY (United States); Dube, M.P.; Rouleau, G.A. [McGill Univ., Montreal (Canada)] [and others

1994-09-01

65

Fine mapping and genetic heterogeneity in the pure form of autosomal dominant familial spastic paraplegia.  

PubMed

We evaluated seven families segregating pure, autosomal dominant familial spastic paraplegia (SPG) for linkage to four recently identified SPG loci on chromosomes 2q (1), 8q (2), 12q (3), and 19q (4). These families were previously shown to be unlinked to SPG loci on chromosomes 2p, 14q, and 15q. Two families demonstrated linkage to the new loci. One family (family 3) showed significant evidence for linkage to chromosome 12q, peaking at D12S1691 (maximum lod = 3.22). Haplotype analysis of family 3 did not identify any recombinants among affected individuals in the 12q candidate region. Family 5 yielded a peak lod score of 2.02 at marker D19S868 and excluded linkage to other known SPG loci. Haplotype analysis of family 5 revealed several cross-overs in affected individuals, thereby potentially narrowing the SPG12 candidate region to a 5-cM region between markers D19S868 and D19S220. Three of the families definitively excluded all four loci examined, providing evidence for further genetic heterogeneity of pure, autosomal dominant SPG. In conclusion, these data confirm the presence of SPG10 (chromosome 12), potentially reduce the minimum candidate region for SPG12 (chromosome 19q), and suggest there is at least one additional autosomal dominant SPG locus. PMID:11354831

Ashley-Koch, A; Bonner, E R; Gaskell, P C; West, S G; Tim, R; Wolpert, C M; Jones, R; Farrell, C D; Nance, M; Svenson, I K; Marchuk, D A; Boustany, R M; Vance, J M; Scott, W K; Pericak-Vance, M A

2001-03-01

66

Electrophysiological characterisation of motor and sensory tracts in patients with hereditary spastic paraplegia (HSP)  

PubMed Central

Background Hereditary spastic paraplegias (HSPs) are characterised by lower limb spasticity due to degeneration of the corticospinal tract. We set out for an electrophysiological characterisation of motor and sensory tracts in patients with HSP. Methods We clinically and electrophysiologically examined a cohort of 128 patients with genetically confirmed or clinically probable HSP. Motor evoked potentials (MEPs) to arms and legs, somato-sensory evoked potentials of median and tibial nerves, and nerve conduction studies of tibial, ulnar, sural, and radial nerves were assessed. Results Whereas all patients showed clinical signs of spastic paraparesis, MEPs were normal in 27% of patients and revealed a broad spectrum with axonal or demyelinating features in the others. This heterogeneity can at least in part be explained by different underlying genotypes, hinting for distinct pathomechanisms in HSP subtypes. In the largest subgroup, SPG4, an axonal type of damage was evident. Comprehensive electrophysiological testing disclosed a more widespread affection of long fibre tracts involving peripheral nerves and the sensory system in 40%, respectively. Electrophysiological abnormalities correlated with the severity of clinical symptoms. Conclusions Whereas HSP is primarily considered as an upper motoneuron disorder, our data suggest a more widespread affection of motor and sensory tracts in the central and peripheral nervous system as a common finding in HSP. The distribution patterns of electrophysiological abnormalities were associated with distinct HSP genotypes and could reflect different underlying pathomechanisms. Electrophysiological measures are independent of symptomatic treatment and may therefore serve as a reliable biomarker in upcoming HSP trials. PMID:24107482

2013-01-01

67

Pathogenesis of Autosomal Dominant Hereditary Spastic Paraplegia (SPG6) Revealed by a Rat Model  

PubMed Central

Abstract Hereditary spastic paraplegias (HSPs) are characterized by progressive spasticity and weakness in the lower extremities that result from length-dependent central to peripheral axonal degeneration. Mutations in the non-imprinted Prader-Willi/Angelman syndrome locus 1 (NIPA1) transmembrane protein cause an autosomal dominant form of HSP (SPG6). Here, we report that transgenic (Tg) rats expressing a human NIPA1/SPG6 mutation in neurons (Thy1.2-hNIPA1G106R) show marked early onset behavioral and electrophysiologic abnormalities. Detailed morphologic analyses reveal unique histopathologic findings, including the accumulation of tubulovesicular organelles with endosomal features that start at axonal and dendritic terminals, followed by multifocal vacuolar degeneration in both the CNS and peripheral nerves. In addition, the NIPA1G106R mutation in the spinal cord from older Tg rats results in an increase in bone morphogenetic protein type II receptor expression, suggesting that its degradation is impaired. This Thy1.2-hNIPA1G106R Tg rat model may serve as a valuable tool for understanding endosomal trafficking in the pathogenesis of a subgroup of HSP with an abnormal interaction with bone morphogenetic protein type II receptor, as well as for developing potential therapeutic strategies for diseases with axonal degeneration and similar pathogenetic mechanisms. PMID:24128679

Watanabe, Fumihiro; Arnold, William D.; Hammer, Robert E.; Ghodsizadeh, Odelia; Moti, Harmeet; Schumer, Mackenzie; Hashmi, Ahmed; Hernandez, Anthony; Sneh, Amita; Sahenk, Zarife

2013-01-01

68

Intramuscular viral delivery of paraplegin rescues peripheral axonopathy in a model of hereditary spastic paraplegia  

PubMed Central

Degeneration of peripheral motor axons is a common feature of several debilitating diseases including complicated forms of hereditary spastic paraplegia. One such form is caused by loss of the mitochondrial energy-dependent protease paraplegin. Paraplegin-deficient mice display a progressive degeneration in several axonal tracts, characterized by the accumulation of morphological abnormal mitochondria. We show that adenoassociated virus–mediated (AAV-mediated) intramuscular delivery of paraplegin halted the progression of neuropathological changes and rescued mitochondrial morphology in the peripheral nerves of paraplegin-deficient mice. One single injection before onset of symptoms improved the motor performance of paraplegin-deficient mice for up to 10 months, indicating that the peripheral neuropathy contributes to the clinical phenotype. This study provides a proof of principle that gene transfer may be an effective therapeutic option for patients with paraplegin deficiency and demonstrates that AAV vectors can be successfully employed for retrograde delivery of an intracellular protein to spinal motor neurons, opening new perspectives for several hereditary axonal neuropathies of the peripheral nerves. PMID:16357941

Pirozzi, Marinella; Quattrini, Angelo; Andolfi, Gennaro; Dina, Giorgia; Malaguti, Maria Chiara; Auricchio, Alberto; Rugarli, Elena I.

2006-01-01

69

The hereditary spastic paraplegia-related enzyme DDHD2 is a principal brain triglyceride lipase.  

PubMed

Complex hereditary spastic paraplegia (HSP) is a genetic disorder that causes lower limb spasticity and weakness and intellectual disability. Deleterious mutations in the poorly characterized serine hydrolase DDHD2 are a causative basis for recessive complex HSP. DDHD2 exhibits phospholipase activity in vitro, but its endogenous substrates and biochemical functions remain unknown. Here, we report the development of DDHD2(-/-) mice and a selective, in vivo-active DDHD2 inhibitor and their use in combination with mass spectrometry-based lipidomics to discover that DDHD2 regulates brain triglycerides (triacylglycerols, or TAGs). DDHD2(-/-) mice show age-dependent TAG elevations in the central nervous system, but not in several peripheral tissues. Large lipid droplets accumulated in DDHD2(-/-) brains and were localized primarily to the intracellular compartments of neurons. These metabolic changes were accompanied by impairments in motor and cognitive function. Recombinant DDHD2 displays TAG hydrolase activity, and TAGs accumulated in the brains of wild-type mice treated subchronically with a selective DDHD2 inhibitor. These findings, taken together, indicate that the central nervous system possesses a specialized pathway for metabolizing TAGs, disruption of which leads to massive lipid accumulation in neurons and complex HSP syndrome. PMID:25267624

Inloes, Jordon M; Hsu, Ku-Lung; Dix, Melissa M; Viader, Andreu; Masuda, Kim; Takei, Thais; Wood, Malcolm R; Cravatt, Benjamin F

2014-10-14

70

Revisiting genotype-phenotype overlap in neurogenetics: triplet-repeat expansions mimicking spastic paraplegias.  

PubMed

Hereditary spastic paraplegias (HSPs) constitute a heterogeneous group of neurological disorders, characterized primarily by progressive spasticity and weakness of the lower limbs. HSPs are caused by mutations in multiple genes (at least 48 loci and 28 causative genes). The clinical spectrum of HSPs is wide and important differences have been reported between patients with distinct mutations in the same gene, or even between different family members bearing the same mutation. Many patients with HSP present clinical deficits related to the involvement of neuronal systems other than corticospinal tracts, namely, peripheral nerves, sensory, or cerebellar pathways. These cases may be difficult to differentiate from other neurological diseases (e.g., hereditary ataxias), also genetically and clinically heterogeneous. As an illustration of how overlapping this genotype-phenotype relationship is, and the difficulties that it brings upon the development of neurogenetic algorithms and databases, we review the main clinical and genetic features of HSPs, and summarize reports on cases of triplet-repeat spinocerebellar ataxias that can mimic HSP phenotypes. This complex scenario makes the necessity of high-quality, curated mutation databases even more urgent, in order to develop adequate diagnostic guidelines, correct interpretation of genetic testing, and appropriate genetic counseling. PMID:22753388

Bettencourt, Conceição; Quintáns, Beatriz; Ros, Raquel; Ampuero, Israel; Yáñez, Zuleima; Pascual, Samuel Ignacio; de Yébenes, Justo García; Sobrido, María-Jesús

2012-09-01

71

Mutations in BICD2 cause dominant congenital spinal muscular atrophy and hereditary spastic paraplegia.  

PubMed

Dominant congenital spinal muscular atrophy (DCSMA) is a disorder of developing anterior horn cells and shows lower-limb predominance and clinical overlap with hereditary spastic paraplegia (HSP), a lower-limb-predominant disorder of corticospinal motor neurons. We have identified four mutations in bicaudal D homolog 2 (Drosophila) (BICD2) in six kindreds affected by DCSMA, DCSMA with upper motor neuron features, or HSP. BICD2 encodes BICD2, a key adaptor protein that interacts with the dynein-dynactin motor complex, which facilitates trafficking of cellular cargos that are critical to motor neuron development and maintenance. We demonstrate that mutations resulting in amino acid substitutions in two binding regions of BICD2 increase its binding affinity for the cytoplasmic dynein-dynactin complex, which might result in the perturbation of BICD2-dynein-dynactin-mediated trafficking, and impair neurite outgrowth. These findings provide insight into the mechanism underlying both the static and the slowly progressive clinical features and the motor neuron pathology that characterize BICD2-associated diseases, and underscore the importance of the dynein-dynactin transport pathway in the development and survival of both lower and upper motor neurons. PMID:23664120

Oates, Emily C; Rossor, Alexander M; Hafezparast, Majid; Gonzalez, Michael; Speziani, Fiorella; MacArthur, Daniel G; Lek, Monkol; Cottenie, Ellen; Scoto, Mariacristina; Foley, A Reghan; Hurles, Matthew; Houlden, Henry; Greensmith, Linda; Auer-Grumbach, Michaela; Pieber, Thomas R; Strom, Tim M; Schule, Rebecca; Herrmann, David N; Sowden, Janet E; Acsadi, Gyula; Menezes, Manoj P; Clarke, Nigel F; Züchner, Stephan; Muntoni, Francesco; North, Kathryn N; Reilly, Mary M

2013-06-01

72

Alteration of fatty-acid-metabolizing enzymes affects mitochondrial form and function in hereditary spastic paraplegia.  

PubMed

Hereditary spastic paraplegia (HSP) is considered one of the most heterogeneous groups of neurological disorders, both clinically and genetically. The disease comprises pure and complex forms that clinically include slowly progressive lower-limb spasticity resulting from degeneration of the corticospinal tract. At least 48 loci accounting for these diseases have been mapped to date, and mutations have been identified in 22 genes, most of which play a role in intracellular trafficking. Here, we identified mutations in two functionally related genes (DDHD1 and CYP2U1) in individuals with autosomal-recessive forms of HSP by using either the classical positional cloning or a combination of whole-genome linkage mapping and next-generation sequencing. Interestingly, three subjects with CYP2U1 mutations presented with a thin corpus callosum, white-matter abnormalities, and/or calcification of the basal ganglia. These genes code for two enzymes involved in fatty-acid metabolism, and we have demonstrated in human cells that the HSP pathophysiology includes alteration of mitochondrial architecture and bioenergetics with increased oxidative stress. Our combined results focus attention on lipid metabolism as a critical HSP pathway with a deleterious impact on mitochondrial bioenergetic function. PMID:23176821

Tesson, Christelle; Nawara, Magdalena; Salih, Mustafa A M; Rossignol, Rodrigue; Zaki, Maha S; Al Balwi, Mohammed; Schule, Rebecca; Mignot, Cyril; Obre, Emilie; Bouhouche, Ahmed; Santorelli, Filippo M; Durand, Christelle M; Oteyza, Andrés Caballero; El-Hachimi, Khalid H; Al Drees, Abdulmajeed; Bouslam, Naima; Lamari, Foudil; Elmalik, Salah A; Kabiraj, Mohammad M; Seidahmed, Mohammed Z; Esteves, Typhaine; Gaussen, Marion; Monin, Marie-Lorraine; Gyapay, Gabor; Lechner, Doris; Gonzalez, Michael; Depienne, Christel; Mochel, Fanny; Lavie, Julie; Schols, Ludger; Lacombe, Didier; Yahyaoui, Mohamed; Al Abdulkareem, Ibrahim; Zuchner, Stephan; Yamashita, Atsushi; Benomar, Ali; Goizet, Cyril; Durr, Alexandra; Gleeson, Joseph G; Darios, Frederic; Brice, Alexis; Stevanin, Giovanni

2012-12-01

73

Hereditary spastic paraplegia: LOD-score considerations for confirmation of linkage in a heterogeneous trait  

SciTech Connect

Hereditary spastic paraplegia (HSP) is a degenerative disorder of the motor system, defined by progressive weakness and spasticity of the lower limbs. HSP may be inherited as an autosomal dominant (AD), autosomal recessive, or an X-linked trait. AD HSP is genetically heterogeneous, and three loci have been identified so far: SPG3 maps to chromosome 14q, SPG4 to 2p, and SPG4a to 15q. We have undertaken linkage analysis with 21 uncomplicated AD families to the three AD HSP loci. We report significant linkage for three of our families to the SPG4 locus and exclude several families by multipoint linkage. We used linkage information from several different research teams to evaluate the statistical probability of linkage to the SPG4 locus for uncomplicated AD HSP families and established the critical LOD-score value necessary for confirmation of linkage to the SPG4 locus from Bayesian statistics. In addition, we calculated the empirical P-values for the LOD scores obtained with all families with computer simulation methods. Power to detect significant linkage, as well as type I error probabilities, were evaluated. This combined analytical approach permitted conclusive linkage analyses on small to medium-size families, under the restrictions of genetic heterogeneity. 19 refs., 1 fig., 1 tab.

Dube, M.P.; Kibar, Z.; Rouleau, G.A. [McGill Univ., Quebec (Canada)] [and others

1997-03-01

74

Assessment of the Talk Test and Rating of Perceived Exertion for Exercise Intensity Prescription in Persons With Paraplegia  

PubMed Central

Background: Physical activity recommendations require accurate estimations of exercise intensity. Rating of Perceived Exertion (RPE) and talk test (TT) are 2 commonly recommended techniques to gauge intensity. It is not known whether these are valid to select an exercise intensity that would elicit a training effect for persons with spinal cord injury (SCI). Objective: To define the exercise intensity of each TT stage and RPE exercise intensity category and assess whether persons with paraplegia are able to use the TT to select a “comfortable” exercise workload they could maintain for 15 minutes. Methods: Twelve participants with paraplegia completed 2 arm crank exercise tests on nonconsecutive days within 14 days. Test 1 was an incremental peak effort assessment. Test 2 was a 15-minute simulated exercise session at a participant-selected fixed workload. During each test, participants reported their RPE and performed a TT at 2-minute intervals. Results: The intensity of the first negative TT stage was vigorous (75 ± 15 %VO2R); at low and moderate intensities, perceived effort was greater than measured intensity; at vigorous and maximal intensities, perceived effort matched measured intensity. Individuals successfully used the TT to select an exercise workload they could maintain for 15 minutes. RPE, but not exercise intensity, increased during the 15-minute session. Conclusions: During arm crank exercise when speaking is not comfortable (ie, first negative TT), persons with paraplegia are exercising at vigorous intensity, which is sufficient to elicit training effects. During incremental peak exercise testing, RPE does not appear to accurately index low-moderate exercise intensities. During the simulated exercise session, RPE appeared to index peripheral fatigue. PMID:23459216

Cowan, Rachel E.; Ginnity, Kelly L.; Kressler, Jochen; Nash, Mark S.; Nash, Mark S.

2012-01-01

75

Comparison of 24-hour cardiovascular and autonomic function in paraplegia, tetraplegia, and control groups: Implications for cardiovascular risk  

PubMed Central

Background Fluctuations in 24-hour cardiovascular hemodynamics, specifically heart rate (HR) and blood pressure (BP), are thought to reflect autonomic nervous system (ANS) activity. Persons with spinal cord injury (SCI) represent a model of ANS dysfunction, which may affect 24-hour hemodynamics and predispose these individuals to increased cardiovascular disease risk. Objective To determine 24-hour cardiovascular and ANS function among individuals with tetraplegia (n = 20; TETRA: C4–C8), high paraplegia (n = 10; HP: T2–T5), low paraplegia (n = 9; LP: T7–T12), and non-SCI controls (n = 10). Twenty-four-hour ANS function was assessed by time domain parameters of heart rate variability (HRV); the standard deviation of the 5-minute average R–R intervals (SDANN; milliseconds/ms), and the root-mean square of the standard deviation of the R–R intervals (rMSSD; ms). Subjects wore 24-hour ambulatory monitors to record HR, HRV, and BP. Mixed analysis of variance (ANOVA) revealed significantly lower 24-hour BP in the tetraplegic group; however, BP did not differ between the HP, LP, and control groups. Mixed ANOVA suggested significantly elevated 24-hour HR in the HP and LP groups compared to the TETRA and control groups (P < 0.05); daytime HR was higher in both paraplegic groups compared to the TETRA and control groups (P < 0.01) and nighttime HR was significantly elevated in the LP group compared to the TETRA and control groups (P < 0.01). Twenty-four-hour SDANN was significantly increased in the HP group compared to the LP and TETRA groups (P < 0.05) and rMSSD was significantly lower in the LP compared to the other three groups (P < 0.05). Elevated 24-hour HR in persons with paraplegia, in concert with altered HRV dynamics, may impart significant adverse cardiovascular consequences, which are currently unappreciated. PMID:21903013

Rosado-Rivera, Dwindally; Radulovic, M.; Handrakis, John P.; Cirnigliaro, Christopher M.; Jensen, A. Marley; Kirshblum, Steve; Bauman, William A.; Wecht, Jill Maria

2011-01-01

76

Pharmacologic rescue of axon growth defects in a human iPSC model of hereditary spastic paraplegia SPG3A.  

PubMed

Hereditary spastic paraplegias are a large, diverse group of neurological disorders (SPG1-71) with the unifying feature of prominent lower extremity spasticity, owing to a length-dependent axonopathy of corticospinal motor neurons. The most common early-onset form of pure, autosomal dominant hereditary spastic paraplegia is caused by mutation in the ATL1 gene encoding the atlastin-1 GTPase, which mediates homotypic fusion of ER tubules to form the polygonal ER network. We have identified a p.Pro342Ser mutation in a young girl with pure SPG3A. This residue is in a critical hinge region of atlastin-1 between its GTPase and assembly domains, and it is conserved in all known eukaryotic atlastin orthologs. We produced induced pluripotent stem cells from skin fibroblasts and differentiated these into forebrain neurons to generate a human neuronal model for SPG3A. Axons of these SPG3A neurons showed impaired growth, recapitulating axonal defects in atlastin-1-depleted rat cortical neurons and impaired root hair growth in loss-of-function mutants of the ATL1 ortholog rhd3 in the plant Arabidopsis. Both the microtubule cytoskeleton and tubular ER are important for mitochondrial distribution and function within cells, and SPG3A neurons showed alterations in mitochondrial motility. Even so, it is not clear whether this change is involved in disease pathogenesis. The SPG3A axon growth defects could be rescued with microtubule-binding agents, emphasizing the importance of tubular ER interactions with the microtubule cytoskeleton in hereditary spastic paraplegia pathogenesis. The prominent alterations in axon growth in SPG3A neurons may represent a particularly attractive target for suppression in screens for novel pharmacologic agents. PMID:24908668

Zhu, Peng-Peng; Denton, Kyle R; Pierson, Tyler Mark; Li, Xue-Jun; Blackstone, Craig

2014-11-01

77

Sciatica and Incomplete Paraplegia After Spontaneous Haematoma of the Spinal Cord Due to a Cumarine - Induced Coagulopathy: Case Report  

PubMed Central

Spontaneous spinal haematoma is a rare cause of sciatica. We present a case of a 73 year old patient, who was admitted to our department and suffered from spontaneous sciatica over 24 hours. During the examination, the patient presented undulating symptoms of paraplegia, varying from incomplete loss of power in the left lower limb to complete plegia. The patient presented multiple diseases like biological aortic valve replacement, diabetes, hypertonia in her medical history, etc. Due to an additional absolute arrhythmia she ingested a cumarine medication. The tomographic imaging revealed a spontaneous lumbar and cranial subarachnoidal haematoma. PMID:22629291

Artner, Juraj; Leucht, F; Schulz, C; Cakir, B

2012-01-01

78

Hereditary spastic paraplegia is a novel phenotype for GJA12/GJC2 mutations  

PubMed Central

Recessive mutations in GJA12/GJC2, the gene that encodes the gap junction protein connexin47 (Cx47), cause Pelizaeus-Merzbacher-like disease (PMLD), an early onset dysmyelinating disorder of the CNS, characterized by nystagmus, psychomotor delay, progressive spasticity and cerebellar signs. Here we describe three patients from one family with a novel recessively inherited mutation, 99C>G (predicted to cause an Ile>Met amino acid substitution; I33M) that causes a milder phenotype. All three had a late-onset, slowly progressive, complicated spastic paraplegia, with normal or near-normal psychomotor development, preserved walking capability through adulthood, and no nystagmus. MRI and MR spectroscopy imaging were consistent with a hypomyelinating leukoencephalopathy. The mutant protein forms gap junction plaques at cell borders similar to wild-type (WT) Cx47 in transfected cells, but fails to form functional homotypic channels in scrape-loading and dual whole-cell patch clamp assays. I33M forms overlapping gap junction plaques and functional channels with Cx43, however, I33M/Cx43 channels open only when a large voltage difference is applied to paired cells. These channels probably do not function under physiological conditions, suggesting that Cx47/Cx43 channels between astrocytes and oligodendrocytes are disrupted, similar to the loss-of-function endoplasmic reticulum-retained Cx47 mutants that cause PMLD. Thus, GJA12/GJC2 mutations can result in a milder phenotype than previously appreciated, but whether I33M retains a function of Cx47 not directly related to forming functional gap junction channels is not known. PMID:19056803

Orthmann-Murphy, Jennifer L.; Salsano, Ettore; Abrams, Charles K.; Bizzi, Alberto; Uziel, Graziella; Freidin, Mona M.; Lamantea, Eleonora; Zeviani, Massimo; Scherer, Steven S.

2009-01-01

79

Hereditary spastic paraplegia is a novel phenotype for GJA12/GJC2 mutations.  

PubMed

Recessive mutations in GJA12/GJC2, the gene that encodes the gap junction protein connexin47 (Cx47), cause Pelizaeus-Merzbacher-like disease (PMLD), an early onset dysmyelinating disorder of the CNS, characterized by nystagmus, psychomotor delay, progressive spasticity and cerebellar signs. Here we describe three patients from one family with a novel recessively inherited mutation, 99C>G (predicted to cause an Ile>Met amino acid substitution; I33M) that causes a milder phenotype. All three had a late-onset, slowly progressive, complicated spastic paraplegia, with normal or near-normal psychomotor development, preserved walking capability through adulthood, and no nystagmus. MRI and MR spectroscopy imaging were consistent with a hypomyelinating leukoencephalopathy. The mutant protein forms gap junction plaques at cell borders similar to wild-type (WT) Cx47 in transfected cells, but fails to form functional homotypic channels in scrape-loading and dual whole-cell patch clamp assays. I33M forms overlapping gap junction plaques and functional channels with Cx43, however, I33M/Cx43 channels open only when a large voltage difference is applied to paired cells. These channels probably do not function under physiological conditions, suggesting that Cx47/Cx43 channels between astrocytes and oligodendrocytes are disrupted, similar to the loss-of-function endoplasmic reticulum-retained Cx47 mutants that cause PMLD. Thus, GJA12/GJC2 mutations can result in a milder phenotype than previously appreciated, but whether I33M retains a function of Cx47 not directly related to forming functional gap junction channels is not known. PMID:19056803

Orthmann-Murphy, Jennifer L; Salsano, Ettore; Abrams, Charles K; Bizzi, Alberto; Uziel, Graziella; Freidin, Mona M; Lamantea, Eleonora; Zeviani, Massimo; Scherer, Steven S; Pareyson, Davide

2009-02-01

80

Linkage of the late onset autosomal dominant familial spastic paraplegia (DFSPII) to chromosome 2p markers  

SciTech Connect

Pure familial spastic paraplegias (FSP) is a neurodegenerative disease characterized by spasticity of lower limbs. FSP in inherited as an autosomal dominant (DFSP) or an autosomal recessive (RFSP) trait. DFSP has been classified into early onset (DFSPI) and late onset (DFSPII) based on the mean age of onset in families. A locus for RFSP has been mapped to chromosome 8, while a locus for DFSPI has been mapped to chromosome 14q. Genetic locus heterogeneity was observed in both of these forms. The location of DFSPII locus (or loci) is unknown. We collected DNA samples from 81 individuals including 26 affecteds from three DFSPII families (9998, 840, 581). The mean age of onset of systems was 26.5, 42.5, and 35.2 years, respectively. We first tested 156 DNA markers distributed throughout the human 22 autosomes with family 9998 and positive lod scores were obtained with chromosome 2p markers D2S174 (Z({theta})=2.93 at {theta}=0.00), D2S146 (Z({theta})=1.03 at {theta}=0.00) and D2S177 (Z({theta})=1.04 at {theta}=0.00). Analysis of the 2 additional families confirmed the linkage with a peak lod score of Z({theta})=4.62 at {theta}=0.105 with D2S174. The multipoint linkage analysis using the map D2S175-10cM-D2S174-14cM-D2DS177 suggested that the DFSPII locus most likely maps between D2S174 and D2S177 with Z({theta})=6.11. There was no evidence in our data supporting genetic locus heterogeneity for the DFSPII.

Hentati, A.; Wasserman, B.; Siddique, T. [Northwestern Univ. Medical School, Chicago, IL (United States)] [and others

1994-09-01

81

A patient-derived stem cell model of hereditary spastic paraplegia with SPAST mutations  

PubMed Central

SUMMARY Hereditary spastic paraplegia (HSP) leads to progressive gait disturbances with lower limb muscle weakness and spasticity. Mutations in SPAST are a major cause of adult-onset, autosomal-dominant HSP. Spastin, the protein encoded by SPAST, is a microtubule-severing protein that is enriched in the distal axon of corticospinal motor neurons, which degenerate in HSP patients. Animal and cell models have identified functions of spastin and mutated spastin but these models lack the gene dosage, mutation variability and genetic background that characterize patients with the disease. In this study, this genetic variability is encompassed by comparing neural progenitor cells derived from biopsies of the olfactory mucosa from healthy controls with similar cells from HSP patients with SPAST mutations, in order to identify cell functions altered in HSP. Patient-derived cells were similar to control-derived cells in proliferation and multiple metabolic functions but had major dysregulation of gene expression, with 57% of all mRNA transcripts affected, including many associated with microtubule dynamics. Compared to control cells, patient-derived cells had 50% spastin, 50% acetylated ?-tubulin and 150% stathmin, a microtubule-destabilizing enzyme. Patient-derived cells were smaller than control cells. They had altered intracellular distributions of peroxisomes and mitochondria and they had slower moving peroxisomes. These results suggest that patient-derived cells might compensate for reduced spastin, but their increased stathmin expression reduced stabilized microtubules and altered organelle trafficking. Sub-nanomolar concentrations of the microtubule-binding drugs, paclitaxel and vinblastine, increased acetylated ?-tubulin levels in patient cells to control levels, indicating the utility of this cell model for screening other candidate compounds for drug therapies. PMID:23264559

Abrahamsen, Greger; Fan, Yongjun; Matigian, Nicholas; Wali, Gautam; Bellette, Bernadette; Sutharsan, Ratneswary; Raju, Jyothy; Wood, Stephen A.; Veivers, David; Sue, Carolyn M.; Mackay-Sim, Alan

2013-01-01

82

Hereditary Spastic Paraplegia with a Novel SPAST Mutation Misdiagnosed with Subacute Combined Degeneration.  

PubMed

Autosomal dominant hereditary spastic paraplegia (AD-HSP) is due to mutations in the "spastin" gene (SPAST gene) encoding the AAA protein. The main clinical features of "pure" HSP are progressive lower-limb spasticity with corticospinal tracts and dorsal column degeneration without peripheral neuropathy. Here we report the case of HSP with novel SPAST gene mutation that misdiagnosed with subacute combined degeneration initially. A 58-year-old man with gait disturbance came to our hospital. He was unable to regulate his steps by himself. The impaired gait began 3 years after he had undergone subtotal gastrectomy and chemotherapy for 6 months. Thereafter, he started feeling tingling sensations in the hands and feet and acquired gait difficulties. He denied having a family history of abnormal gait or developmental problem. We diagnosed him with subacute combined degeneration on the evidence of history of gastrectomy, lower normal limit of vitamin B12 (363 pg/ml), apparent absence of vibration sensations and paresthesia in the feet. He was intramuscularly administered cyanocobalamin regularly. However, there was no improvement in his condition. We reconsidered his symptoms and signs, decided to examine the SPAST gene, which is the most common mutation in HSP. The SPAST gene, c.870+1delG, heterozygote, splicing mutation is detected from the gene sample. There was no previous information of this polymorphism or mutation at this locus. We examined his two children, and the same mutation was founded in his son. We report a patient of novel SPAST gene mutation with AD-HSP which is misdiagnosed with SCD. PMID:23833562

Yang, Ji Won; Han, Ji-Young; Seong, Moon-Woo; Sung, Jung-Joon; Park, Sung Sup; Lee, Kwang-Woo

2013-06-01

83

Identical twins with mental retardation, dysarthria, progressive spastic paraplegia, and brachydactyly type E: a new syndrome or variant of Fitzsimmons-Guilbert syndrome?  

PubMed

We report on concordantly affected female identical twins with mental retardation, dysarthria, progressive spastic paraplegia, and brachydactyly type E. The most similar condition reported is the syndrome described by Fitzsimmons and Guilbert in uniovular twins characterized by progressive spastic paraplegia, dysarthria, brachydactyly type E, and cone-shaped epiphyses. During the last 11 years a report of only one other patient with this syndrome has been published; hence, its phenotypic delineation may be only partial. Although our patients might expand the phenotypic spectrum of this syndrome, they may represent a new disorder. PMID:10323731

Lacassie, Y; Arriaza, M I; Duncan, M C; Dijamco, C; McElveen, C; Stahls, P F

1999-05-21

84

Development of a Motor Driven Rowing Machine with Automatic Functional Electrical Stimulation Controller for Individuals with Paraplegia; a Preliminary Study  

PubMed Central

Objective To examine the cardiorespiratory responses of patients with spinal cord injury (SCI) paraplegia using a motor driven rowing machine. Method Ten SCI patients with paraplegia [A (n=6), B (n=1), and C (n=3) by the American Spinal Injury Association impairment scale] were selected. Two rowing techniques were used. The first used a fixed seat with rowing achieved using only upper extremity movement (fixed rowing). The second used an automatically moving seat, facilitating active upper extremity movement and passive lower extremity movement via the motorized seat (motor rowing). Each patient performed two randomly assigned rowing exercise stress tests 1-3 days apart. The work rate (WR), time, respiratory exchange ratio (R), oxygen consumption (VO2), heart rate (HR), metabolic equivalents (METs), and rating of perceived exertion (RPE) were recorded. Results WR, time, VO2, and METs were significantly higher after the motor rowing test than after fixed motor rowing test (p<0.05). HR after motor rowing was significantly lower than fixed rowing (p<0.05). Conclusion Cardiorespiratory responses as VO2, HR and METs can be elicited by the motor rowing for people with paraplegic SCI. PMID:22837974

Jung, Da-Woon; Lee, Bum-Suk; Kim, Min

2012-01-01

85

Comparison of Blood Lactate Elimination in Individuals With Paraplegia and Able-Bodied Individuals During Active Recovery From Exhaustive Exercise  

PubMed Central

Background/Objective: The aim of the present study was to compare blood lactate elimination between individuals with paraplegia (P) and able-bodied (AB) individuals after strenuous arm exercise. Methods: Eight P and 8 AB men (matched for age, height, and weight) participated in this study. Average weekly arm-training volume for P participants (eg, hand bike, wheelchair basketball) and AB participants (eg, swimming, rowing, cross-country skiing) was 4.1 ± 1.6 vs 2.8 ± 0.8 h. A maximal-arm-cranking intensity-graded exercise test to volitional exhaustion was performed by all test participants. Immediately after the exercise test, the participants performed arm cranking for another 30 minutes at a workload of one third of the maximally achieved power output. During this active recovery, mixed-capillary blood samples were taken for lactate analysis. Results: The lactate accumulation constant was significantly higher for P individuals, whereas the lactate elimination constant showed no significant difference between the two groups. Conclusions: Individuals with paraplegia seem to have no disadvantages in lactate elimination after exhaustive arm exercise compared with able-bodied individuals. PMID:18533413

Leicht, Christof; Perret, Claudio

2008-01-01

86

Mutations in DDHD2, Encoding an Intracellular Phospholipase A1, Cause a Recessive Form of Complex Hereditary Spastic Paraplegia  

PubMed Central

We report on four families affected by a clinical presentation of complex hereditary spastic paraplegia (HSP) due to recessive mutations in DDHD2, encoding one of the three mammalian intracellular phospholipases A1 (iPLA1). The core phenotype of this HSP syndrome consists of very early-onset (<2 years) spastic paraplegia, intellectual disability, and a specific pattern of brain abnormalities on cerebral imaging. An essential role for DDHD2 in the human CNS, and perhaps more specifically in synaptic functioning, is supported by a reduced number of active zones at synaptic terminals in Ddhd-knockdown Drosophila models. All identified mutations affect the protein’s DDHD domain, which is vital for its phospholipase activity. In line with the function of DDHD2 in lipid metabolism and its role in the CNS, an abnormal lipid peak indicating accumulation of lipids was detected with cerebral magnetic resonance spectroscopy, which provides an applicable diagnostic biomarker that can distinguish the DDHD2 phenotype from other complex HSP phenotypes. We show that mutations in DDHD2 cause a specific complex HSP subtype (SPG54), thereby linking a member of the PLA1 family to human neurologic disease. PMID:23176823

Schuurs-Hoeijmakers, Janneke H.M.; Geraghty, Michael T.; Kamsteeg, Erik-Jan; Ben-Salem, Salma; de Bot, Susanne T.; Nijhof, Bonnie; van de Vondervoort, Ilse I.G.M.; van der Graaf, Marinette; Nobau, Anna Castells; Otte-Holler, Irene; Vermeer, Sascha; Smith, Amanda C.; Humphreys, Peter; Schwartzentruber, Jeremy; Ali, Bassam R.; Al-Yahyaee, Saeed A.; Tariq, Said; Pramathan, Thachillath; Bayoumi, Riad; Kremer, Hubertus P.H.; van de Warrenburg, Bart P.; van den Akker, Willem M.R.; Gilissen, Christian; Veltman, Joris A.; Janssen, Irene M.; Vulto-van Silfhout, Anneke T.; van der Velde-Visser, Saskia; Lefeber, Dirk J.; Diekstra, Adinda; Erasmus, Corrie E.; Willemsen, Michel A.; Vissers, Lisenka E.L.M.; Lammens, Martin; van Bokhoven, Hans; Brunner, Han G.; Wevers, Ron A.; Schenck, Annette; Al-Gazali, Lihadh; de Vries, Bert B.A.; de Brouwer, Arjan P.M.

2012-01-01

87

Primary osteosarcoma of the L2 lamina presenting as "silent" paraplegia: case report and review of the literature.  

PubMed

Primary osteosarcomas of the vertebral column are not common, and to our knowledge a total of 78 cases, mostly located in the vertebral body, have been previously reported. We report a primary osteosarcoma of the spine with an extremely rare location--the lamina of the second lumbar vertebra. The patient, a 38-year-old woman, was admitted with paraplegia of a short duration without pain. Preoperatively, the patient underwent CT scanning for staging (Enneking IIB) followed by a needle biopsy and local preoperative arterial embolization. An emergency decompressive laminectomy was performed, and stabilization was carried out using methylacrylate. The patient showed a complete neurologic recovery. Combined chemotherapy and local irradiation did not prevent tumor recurrences, which occurred 12 and 19 months after the initial intervention and were associated with recurrent neurologic impairment. The patient died 19 months after the initial presentation, while in paraplegia, from lung metastases. Based on our unique observation, it seems that in primary osteosarcomas located in the posterior elements of the spin, the symptoms are not specific, and the disease may only become manifest when the tumor is no longer resectable. When the tumor is associated with neurologic impairment, spinal canal decompression should be performed even though it does not radically resect the tumor because it significantly improves the quality of the patient's life. PMID:8983662

Korovessis, P; Repanti, M; Stamatakis, M

1995-01-01

88

Non-small cell lung carcinoma in an adolescent manifested by acute paraplegia due to spinal metastases: a case report  

PubMed Central

Introduction Bronchial carcinomas in childhood and adolescence are extremely rare; only individual cases have been reported previously. Case presentation We report on a 16-year-old Caucasian German boy with non-small cell lung carcinoma (squamous cell non-small cell lung carcinoma) stage IV, T4N2M1, without epidermal growth factor receptor overexpression and/or mutation or k-ras mutation. He presented with paraplegia due to spinal metastases of the bronchial carcinoma. No familial predisposition or toxin exposure was identified. Treatment following adult protocols consisted of surgical intervention for spinal metastases, first-line cisplatinum and gemcitabine, irradiation and second-line docetaxel. After a transient response our patient experienced disease progression and died about 10 months later. Conclusion Response and survival in our 16-year-old patient were similar to adult patients with stage IV non-small cell lung carcinoma. PMID:21955922

2011-01-01

89

Paraplegia and squamous cell carcinoma of the bladder in young women: findings from a case-control study.  

PubMed Central

A death certificate-based case-control study was conducted on 207 women aged 25-44 who died of bladder cancer in England and Wales in the period 1971-89 and 411 controls matched on sex, year of death and age at death. An odds ratio of 12.0 (95% CI 1.5-99.7) was found for women with a history of paraplegia. Four of the six paraplegic women were reported to have had squamous cell carcinoma of the bladder compared with only 19 of the 201 non-paraplegic women. These findings suggest that squamous cell carcinomas of the bladder, especially in paraplegics, may be the result of chronic urinary tract infection. PMID:8018530

Dolin, P. J.; Darby, S. C.; Beral, V.

1994-01-01

90

Phenotype and frequency of STUB1 mutations: next-generation screenings in Caucasian ataxia and spastic paraplegia cohorts  

PubMed Central

Background Mutations in the gene STUB1, encoding the protein CHIP (C-terminus of HSC70-interacting protein), have recently been suggested as a cause of recessive ataxia based on the findings in few Chinese families. Here we aimed to investigate the phenotypic and genotypic spectrum of STUB1 mutations, and to assess their frequency in different Caucasian disease cohorts. Methods 300 subjects with degenerative ataxia (n =?167) or spastic paraplegia (n =?133) were screened for STUB1 variants by whole-exome-sequencing (n =?204) or shotgun-fragment-library-sequencing (n =?96). To control for the specificity of STUB1 variants, we screened an additional 1707 exomes from 891 index families with other neurological diseases. Results We identified 3 ataxia patients (3/167 =?1.8%) with 4 novel missense mutations in STUB1, including 3 mutations in its tetratricopeptide-repeat domain. All patients showed evidence of pyramidal tract damage. Cognitive impairment was present only in one and hypogonadism in none of them. Ataxia did not start before age 48 years in one subject. No recessive STUB1 variants were identified in families with other neurological diseases, demonstrating that STUB1 variants are not simply rare polymorphisms ubiquitous in neurodegenerative disease. Conclusions STUB1-disease occurs also in Caucasian ataxia populations (1.8%). Our results expand the genotypic spectrum of STUB1-disease, showing that pathogenic mutations affect also the tetratricopeptide-repeat domain, thus providing clinical evidence for the functional importance of this domain. Moreover, they further delineate the phenotypic core features of STUB1-ataxia. Pyramidal tract damage is a common accompanying feature and can include lower limb spasticity, thus adding STUB1-ataxia to the differential diagnosis of “spastic ataxias”. However, STUB1 is rare in subjects with predominant spastic paraplegia (0/133). In contrast to previous reports, STUB1-ataxia can start even above age 40 years, and neither hypogonadism nor prominent cognitive impairment are obligatory features. PMID:24742043

2014-01-01

91

A Hereditary Spastic Paraplegia Mouse Model Supports a Role of ZFYVE26/SPASTIZIN for the Endolysosomal System  

PubMed Central

Hereditary spastic paraplegias (HSPs) are characterized by progressive weakness and spasticity of the legs because of the degeneration of cortical motoneuron axons. SPG15 is a recessively inherited HSP variant caused by mutations in the ZFYVE26 gene and is additionally characterized by cerebellar ataxia, mental decline, and progressive thinning of the corpus callosum. ZFYVE26 encodes the FYVE domain-containing protein ZFYVE26/SPASTIZIN, which has been suggested to be associated with the newly discovered adaptor protein 5 (AP5) complex. We show that Zfyve26 is broadly expressed in neurons, associates with intracellular vesicles immunopositive for the early endosomal marker EEA1, and co-fractionates with a component of the AP5 complex. As the function of ZFYVE26 in neurons was largely unknown, we disrupted Zfyve26 in mice. Zfyve26 knockout mice do not show developmental defects but develop late-onset spastic paraplegia with cerebellar ataxia confirming that SPG15 is caused by ZFYVE26 deficiency. The morphological analysis reveals axon degeneration and progressive loss of both cortical motoneurons and Purkinje cells in the cerebellum. Importantly, neuron loss is preceded by accumulation of large intraneuronal deposits of membrane-surrounded material, which co-stains with the lysosomal marker Lamp1. A density gradient analysis of brain lysates shows an increase of Lamp1-positive membrane compartments with higher densities in Zfyve26 knockout mice. Increased levels of lysosomal enzymes in brains of aged knockout mice further support an alteration of the lysosomal compartment upon disruption of Zfyve26. We propose that SPG15 is caused by an endolysosomal membrane trafficking defect, which results in endolysosomal dysfunction. This appears to be particularly relevant in neurons with highly specialized neurites such as cortical motoneurons and Purkinje cells. PMID:24367272

Khundadze, Mukhran; Kollmann, Katrin; Koch, Nicole; Biskup, Christoph; Nietzsche, Sandor; Zimmer, Geraldine; Hennings, J. Christopher; Huebner, Antje K.; Symmank, Judit; Jahic, Amir; Ilina, Elena I.; Karle, Kathrin; Schols, Ludger; Kessels, Michael; Braulke, Thomas; Qualmann, Britta; Kurth, Ingo; Beetz, Christian; Hubner, Christian A.

2013-01-01

92

A hereditary spastic paraplegia mouse model supports a role of ZFYVE26/SPASTIZIN for the endolysosomal system.  

PubMed

Hereditary spastic paraplegias (HSPs) are characterized by progressive weakness and spasticity of the legs because of the degeneration of cortical motoneuron axons. SPG15 is a recessively inherited HSP variant caused by mutations in the ZFYVE26 gene and is additionally characterized by cerebellar ataxia, mental decline, and progressive thinning of the corpus callosum. ZFYVE26 encodes the FYVE domain-containing protein ZFYVE26/SPASTIZIN, which has been suggested to be associated with the newly discovered adaptor protein 5 (AP5) complex. We show that Zfyve26 is broadly expressed in neurons, associates with intracellular vesicles immunopositive for the early endosomal marker EEA1, and co-fractionates with a component of the AP5 complex. As the function of ZFYVE26 in neurons was largely unknown, we disrupted Zfyve26 in mice. Zfyve26 knockout mice do not show developmental defects but develop late-onset spastic paraplegia with cerebellar ataxia confirming that SPG15 is caused by ZFYVE26 deficiency. The morphological analysis reveals axon degeneration and progressive loss of both cortical motoneurons and Purkinje cells in the cerebellum. Importantly, neuron loss is preceded by accumulation of large intraneuronal deposits of membrane-surrounded material, which co-stains with the lysosomal marker Lamp1. A density gradient analysis of brain lysates shows an increase of Lamp1-positive membrane compartments with higher densities in Zfyve26 knockout mice. Increased levels of lysosomal enzymes in brains of aged knockout mice further support an alteration of the lysosomal compartment upon disruption of Zfyve26. We propose that SPG15 is caused by an endolysosomal membrane trafficking defect, which results in endolysosomal dysfunction. This appears to be particularly relevant in neurons with highly specialized neurites such as cortical motoneurons and Purkinje cells. PMID:24367272

Khundadze, Mukhran; Kollmann, Katrin; Koch, Nicole; Biskup, Christoph; Nietzsche, Sandor; Zimmer, Geraldine; Hennings, J Christopher; Huebner, Antje K; Symmank, Judit; Jahic, Amir; Ilina, Elena I; Karle, Kathrin; Schöls, Ludger; Kessels, Michael; Braulke, Thomas; Qualmann, Britta; Kurth, Ingo; Beetz, Christian; Hübner, Christian A

2013-01-01

93

Temporary paraplegia resulting from Gorham's disease involving the third lumbar vertebra and proximal femur: a five-year follow-up and review of the literature.  

PubMed

Gorham's disease is a rare musculoskeletal disease of unknown etiology characterized by progressive osteolysis and massive bone destruction. Here, we report an extremely rare case of Gorham's disease involving two far sites in the lumbar spine and trochanteric region, gradually resulting in paraplegia. The patient underwent cord decompression and chemotherapy, and resumed her normal life; she was followed up for nearly five years. PMID:24206415

Esmailiejah, Ali Akbar; Kamalian, Naser; Abbasian, Mohammadreza

2013-11-01

94

Hereditary spastic paraplegia proteins REEP1, spastin, and atlastin-1 coordinate microtubule interactions with the tubular ER network  

PubMed Central

Hereditary spastic paraplegias (HSPs; SPG1–45) are inherited neurological disorders characterized by lower extremity spastic weakness. More than half of HSP cases result from autosomal dominant mutations in atlastin-1 (also known as SPG3A), receptor expression enhancing protein 1 (REEP1; SPG31), or spastin (SPG4). The atlastin-1 GTPase interacts with spastin, a microtubule-severing ATPase, as well as with the DP1/Yop1p and reticulon families of ER-shaping proteins, and SPG3A caused by atlastin-1 mutations has been linked pathogenically to abnormal ER morphology. Here we investigated SPG31 by analyzing the distribution, interactions, and functions of REEP1. We determined that REEP1 is structurally related to the DP1/Yop1p family of ER-shaping proteins and localizes to the ER in cultured rat cerebral cortical neurons, where it colocalizes with spastin and atlastin-1. Upon overexpression in COS7 cells, REEP1 formed protein complexes with atlastin-1 and spastin within the tubular ER, and these interactions required hydrophobic hairpin domains in each of these proteins. REEP proteins were required for ER network formation in vitro, and REEP1 also bound microtubules and promoted ER alignment along the microtubule cytoskeleton in COS7 cells. A SPG31 mutant REEP1 lacking the C-terminal cytoplasmic region did not interact with microtubules and disrupted the ER network. These data indicate that the HSP proteins atlastin-1, spastin, and REEP1 interact within the tubular ER membrane in corticospinal neurons to coordinate ER shaping and microtubule dynamics. Thus, defects in tubular ER shaping and network interactions with the microtubule cytoskeleton seem to be the predominant pathogenic mechanism of HSP. PMID:20200447

Park, Seong H.; Zhu, Peng-Peng; Parker, Rell L.; Blackstone, Craig

2010-01-01

95

Low dose tubulin-binding drugs rescue peroxisome trafficking deficit in patient-derived stem cells in Hereditary Spastic Paraplegia.  

PubMed

Hereditary Spastic Paraplegia (HSP) is a genetically heterogeneous group of disorders, diagnosed by progressive gait disturbances with muscle weakness and spasticity, for which there are no treatments targeted at the underlying pathophysiology. Mutations in spastin are a common cause of HSP. Spastin is a microtubule-severing protein whose mutation in mouse causes defective axonal transport. In human patient-derived olfactory neurosphere-derived (ONS) cells, spastin mutations lead to lower levels of acetylated ?-tubulin, a marker of stabilised microtubules, and to slower speed of peroxisome trafficking. Here we screened multiple concentrations of four tubulin-binding drugs for their ability to rescue levels of acetylated ?-tubulin in patient-derived ONS cells. Drug doses that restored acetylated ?-tubulin to levels in control-derived ONS cells were then selected for their ability to rescue peroxisome trafficking deficits. Automated microscopic screening identified very low doses of the four drugs (0.5?nM taxol, 0.5?nM vinblastine, 2?nM epothilone D, 10?µM noscapine) that rescued acetylated ?-tubulin in patient-derived ONS cells. These same doses rescued peroxisome trafficking deficits, restoring peroxisome speeds to untreated control cell levels. These results demonstrate a novel approach for drug screening based on high throughput automated microscopy for acetylated ?-tubulin followed by functional validation of microtubule-based peroxisome transport. From a clinical perspective, all the drugs tested are used clinically, but at much higher doses. Importantly, epothilone D and noscapine can enter the central nervous system, making them potential candidates for future clinical trials. PMID:24857849

Fan, Yongjun; Wali, Gautam; Sutharsan, Ratneswary; Bellette, Bernadette; Crane, Denis I; Sue, Carolyn M; Mackay-Sim, Alan

2014-01-01

96

Low dose tubulin-binding drugs rescue peroxisome trafficking deficit in patient-derived stem cells in Hereditary Spastic Paraplegia  

PubMed Central

ABSTRACT Hereditary Spastic Paraplegia (HSP) is a genetically heterogeneous group of disorders, diagnosed by progressive gait disturbances with muscle weakness and spasticity, for which there are no treatments targeted at the underlying pathophysiology. Mutations in spastin are a common cause of HSP. Spastin is a microtubule-severing protein whose mutation in mouse causes defective axonal transport. In human patient-derived olfactory neurosphere-derived (ONS) cells, spastin mutations lead to lower levels of acetylated ?-tubulin, a marker of stabilised microtubules, and to slower speed of peroxisome trafficking. Here we screened multiple concentrations of four tubulin-binding drugs for their ability to rescue levels of acetylated ?-tubulin in patient-derived ONS cells. Drug doses that restored acetylated ?-tubulin to levels in control-derived ONS cells were then selected for their ability to rescue peroxisome trafficking deficits. Automated microscopic screening identified very low doses of the four drugs (0.5?nM taxol, 0.5?nM vinblastine, 2?nM epothilone D, 10?µM noscapine) that rescued acetylated ?-tubulin in patient-derived ONS cells. These same doses rescued peroxisome trafficking deficits, restoring peroxisome speeds to untreated control cell levels. These results demonstrate a novel approach for drug screening based on high throughput automated microscopy for acetylated ?-tubulin followed by functional validation of microtubule-based peroxisome transport. From a clinical perspective, all the drugs tested are used clinically, but at much higher doses. Importantly, epothilone D and noscapine can enter the central nervous system, making them potential candidates for future clinical trials. PMID:24857849

Fan, Yongjun; Wali, Gautam; Sutharsan, Ratneswary; Bellette, Bernadette; Crane, Denis I.; Sue, Carolyn M.; Mackay-Sim, Alan

2014-01-01

97

A Genome-Scale DNA Repair RNAi Screen Identifies SPG48 as a Novel Gene Associated with Hereditary Spastic Paraplegia  

PubMed Central

DNA repair is essential to maintain genome integrity, and genes with roles in DNA repair are frequently mutated in a variety of human diseases. Repair via homologous recombination typically restores the original DNA sequence without introducing mutations, and a number of genes that are required for homologous recombination DNA double-strand break repair (HR-DSBR) have been identified. However, a systematic analysis of this important DNA repair pathway in mammalian cells has not been reported. Here, we describe a genome-scale endoribonuclease-prepared short interfering RNA (esiRNA) screen for genes involved in DNA double strand break repair. We report 61 genes that influenced the frequency of HR-DSBR and characterize in detail one of the genes that decreased the frequency of HR-DSBR. We show that the gene KIAA0415 encodes a putative helicase that interacts with SPG11 and SPG15, two proteins mutated in hereditary spastic paraplegia (HSP). We identify mutations in HSP patients, discovering KIAA0415/SPG48 as a novel HSP-associated gene, and show that a KIAA0415/SPG48 mutant cell line is more sensitive to DNA damaging drugs. We present the first genome-scale survey of HR-DSBR in mammalian cells providing a dataset that should accelerate the discovery of novel genes with roles in DNA repair and associated medical conditions. The discovery that proteins forming a novel protein complex are required for efficient HR-DSBR and are mutated in patients suffering from HSP suggests a link between HSP and DNA repair. PMID:20613862

Slabicki, Mikolaj; Theis, Mirko; Krastev, Dragomir B.; Samsonov, Sergey; Mundwiller, Emeline; Junqueira, Magno; Paszkowski-Rogacz, Maciej; Teyra, Joan; Heninger, Anne-Kristin; Poser, Ina; Prieur, Fabienne; Truchetto, Jeremy; Confavreux, Christian; Marelli, Cecilia; Durr, Alexandra; Camdessanche, Jean Philippe; Brice, Alexis; Shevchenko, Andrej; Pisabarro, M. Teresa; Stevanin, Giovanni; Buchholz, Frank

2010-01-01

98

Adaptor protein complex 4 deficiency causes severe autosomal-recessive intellectual disability, progressive spastic paraplegia, shy character, and short stature.  

PubMed

Intellectual disability inherited in an autosomal-recessive fashion represents an important fraction of severe cognitive-dysfunction disorders. Yet, the extreme heterogeneity of these conditions markedly hampers gene identification. Here, we report on eight affected individuals who were from three consanguineous families and presented with severe intellectual disability, absent speech, shy character, stereotypic laughter, muscular hypotonia that progressed to spastic paraplegia, microcephaly, foot deformity, decreased muscle mass of the lower limbs, inability to walk, and growth retardation. Using a combination of autozygosity mapping and either Sanger sequencing of candidate genes or next-generation exome sequencing, we identified one mutation in each of three genes encoding adaptor protein complex 4 (AP4) subunits: a nonsense mutation in AP4S1 (NM_007077.3: c.124C>T, p.Arg42(?)), a frameshift mutation in AP4B1 (NM_006594.2: c.487_488insTAT, p.Glu163_Ser739delinsVal), and a splice mutation in AP4E1 (NM_007347.3: c.542+1_542+4delGTAA, r.421_542del, p.Glu181Glyfs(?)20). Adaptor protein complexes (AP1-4) are ubiquitously expressed, evolutionarily conserved heterotetrameric complexes that mediate different types of vesicle formation and the selection of cargo molecules for inclusion into these vesicles. Interestingly, two mutations affecting AP4M1 and AP4E1 have recently been found to cause cerebral palsy associated with severe intellectual disability. Combined with previous observations, these results support the hypothesis that AP4-complex-mediated trafficking plays a crucial role in brain development and functioning and demonstrate the existence of a clinically recognizable syndrome due to deficiency of the AP4 complex. PMID:21620353

Abou Jamra, Rami; Philippe, Orianne; Raas-Rothschild, Annick; Eck, Sebastian H; Graf, Elisabeth; Buchert, Rebecca; Borck, Guntram; Ekici, Arif; Brockschmidt, Felix F; Nöthen, Markus M; Munnich, Arnold; Strom, Tim M; Reis, Andre; Colleaux, Laurence

2011-06-10

99

Identification of a novel homozygous SPG7 mutation in a Japanese patient with spastic ataxia: making an efficient diagnosis using exome sequencing for autosomal recessive cerebellar ataxia and spastic paraplegia.  

PubMed

Autosomal recessive cerebellar ataxias and autosomal recessive hereditary spastic paraplegias are clinically and genetically heterogeneous disorders with diverse neurological and non-neurological features. We herein describe a Japanese patient with a slowly progressive form of ataxia and spastic paraplegia. Using whole exome sequencing, we identified a novel homozygous frameshift mutation in SPG7, encoding paraplegin, in this patient. This is the first report of an SPG7 mutation in the Japanese population. For disorders previously undetected in a particular population, or unrecognized/atypical phenotypes, exome sequencing may facilitate molecular diagnosis. PMID:23857099

Doi, Hiroshi; Ohba, Chihiro; Tsurusaki, Yoshinori; Miyatake, Satoko; Miyake, Noriko; Saitsu, Hirotomo; Kawamoto, Yuko; Yoshida, Tamaki; Koyano, Shigeru; Suzuki, Yume; Kuroiwa, Yoshiyuki; Tanaka, Fumiaki; Matsumoto, Naomichi

2013-01-01

100

Tetraplegia or paraplegia with brachial diparesis? What is the most appropriate designation for the motor deficit in patients with lower cervical spinal cord injury?  

PubMed

The authors seek to clarify the nomenclature used to describe cervical spinal cord injuries, particularly the use of the terms "tetraplegia", "quadriplegia", "quadriparesis", "tetraparesis", "incomplete quadriplegia" or "incomplete tetraplegia" when applied to patients with lower cervical cord injuries. A review of the origin of the terms and nomenclature used currently to describe the neurological status of patients with SCI in the literature was performed. The terms "tetraplegia", "quadriplegia", "quadriparesis", "tetraparesis", "incomplete quadriplegia" or "incomplete tetraplegia" have been used very often to describe patients with complete lower cervical SCI despite the fact that the clinical scenario is all the same for most of these patients. Most of these patients have total loss of the motor voluntary movements of their lower trunk and inferior limbs, and partial impairment of movement of their superior limbs, preserving many motor functions of the proximal muscles of their arms (superior limbs). A potentially better descriptive term may be "paraplegia with brachial diparesis". In using the most appropriate terminology, the patients with lower cervical SCI currently referred as presenting with "tetraplegia", "quadriplegia", "quadriparesis", "tetraparesis", "incomplete quadriplegia" or "incomplete tetraplegia", might be better described as having "paraplegia with brachial diparesis". PMID:22825074

Figueiredo, Nicandro; Figueiredo, Iara Eberhard; Resnick, Daniel

2013-02-01

101

Infantile-onset ascending hereditary spastic paraplegia with bulbar involvement due to the novel ALS2 mutation c.2761C>T.  

PubMed

Recessive mutations in the alsin gene cause three clinically distinct motor neuron diseases: juvenile amyotrophic lateral sclerosis (ALS2), juvenile primary lateral sclerosis (JPLS) and infantile-onset ascending hereditary spastic paraplegia (IAHSP). A total of 23 different ALS2 mutations have been described for the three disorders so far. Most of these mutations result in a frameshift leading to a premature truncation of the alsin protein. We report the novel ALS2 truncating mutation c.2761C>T; p.R921X detected by homozygosity mapping and sequencing in two infants affected by IAHSP with bulbar involvement. The mutation c.2761C>T resides in the pleckstrin domain, a characteristic segment of guanine nucleotide exchange factors of the Rho GTPase family, which is involved in the overall neuronal development or maintenance. This study highlights the importance of using homozygosity mapping combined with candidate gene analysis to identify the underlying genetic defect as in this Saudi consanguineous family. PMID:24315819

Wakil, Salma M; Ramzan, Khushnooda; Abuthuraya, Rula; Hagos, Samya; Al-Dossari, Haya; Al-Omar, Rana; Murad, Hatem; Chedrawi, Aziza; Al-Hassnan, Zuhair N; Finsterer, Josef; Bohlega, Saeed

2014-02-15

102

Hypokalemic paraplegia in pregnancy.  

PubMed

Hypokalemic myopathy may range from numbness/weakness to complete paralysis. The aetiology may be congenital or acquired. It is characterized by acute muscular weakness with low levels of potassium (<3.5 meq/L). We present a case of 26-year-old multigravida at 36 weeks of gestation with gestational hypertension on treatment, who came with acute onset of pain, numbness and weakness of both legs which worsened following betamethasone injection. She was diagnosed to have Hypokalemic paralysis with potassium levels of 2.1 meq/L. The medical profile remitted promptly on intravenous potassium replacement. Pregnancy was continued till 37 weeks with oral potassium supplements, antihypertensives and regular monitoring of serum potassium levels. The pregnancy was terminated after 37 weeks in view of gestational hypertension. Postpartum period was uneventful, patient was discharged after two weeks when potassium levels and BP returned to normal. PMID:25121034

Kulkarni, Maitri; Tv, Srividya; Gopal, N

2014-06-01

103

Hypokalemic Paraplegia in Pregnancy  

PubMed Central

Hypokalemic myopathy may range from numbness/weakness to complete paralysis. The aetiology may be congenital or acquired. It is characterized by acute muscular weakness with low levels of potassium (<3.5 meq/L). We present a case of 26-year-old multigravida at 36 weeks of gestation with gestational hypertension on treatment, who came with acute onset of pain, numbness and weakness of both legs which worsened following betamethasone injection. She was diagnosed to have Hypokalemic paralysis with potassium levels of 2.1 meq/L. The medical profile remitted promptly on intravenous potassium replacement. Pregnancy was continued till 37 weeks with oral potassium supplements, antihypertensives and regular monitoring of serum potassium levels. The pregnancy was terminated after 37 weeks in view of gestational hypertension. Postpartum period was uneventful, patient was discharged after two weeks when potassium levels and BP returned to normal. PMID:25121034

TV, Srividya; Gopal, N

2014-01-01

104

A new locus ( SPG46 ) maps to 9p21.2-q21.12 in a Tunisian family with a complicated autosomal recessive hereditary spastic paraplegia with mental impairment and thin corpus callosum  

Microsoft Academic Search

Hereditary spastic paraplegia (HSP) with thin corpus callosum (TCC) and mental impairment is a frequent subtype of complicated\\u000a HSP, often inherited as an autosomal recessive (AR) trait. It is clear from molecular genetic analyses that there are several\\u000a underlying causes of this syndrome, with at least six genetic loci identified to date. However, SPG11 and SPG15 are the two major

Amir Boukhris; Imed Feki; Nizar Elleuch; Mohamed Imed Miladi; Anne Boland-Augé; Jérémy Truchetto; Emeline Mundwiller; Nadia Jezequel; Diana Zelenika; Chokri Mhiri; Alexis Brice; Giovanni Stevanin

2010-01-01

105

Spastic Paraplegia Mutation N256S in the Neuronal Microtubule Motor KIF5A Disrupts Axonal Transport in a Drosophila HSP Model  

PubMed Central

Hereditary spastic paraplegias (HSPs) comprise a group of genetically heterogeneous neurodegenerative disorders characterized by spastic weakness of the lower extremities. We have generated a Drosophila model for HSP type 10 (SPG10), caused by mutations in KIF5A. KIF5A encodes the heavy chain of kinesin-1, a neuronal microtubule motor. Our results imply that SPG10 is not caused by haploinsufficiency but by the loss of endogenous kinesin-1 function due to a selective dominant-negative action of mutant KIF5A on kinesin-1 complexes. We have not found any evidence for an additional, more generalized toxicity of mutant Kinesin heavy chain (Khc) or the affected kinesin-1 complexes. Ectopic expression of Drosophila Khc carrying a human SPG10-associated mutation (N256S) is sufficient to disturb axonal transport and to induce motoneuron disease in Drosophila. Neurofilaments, which have been recently implicated in SPG10 disease manifestation, are absent in arthropods. Impairments in the transport of kinesin-1 cargos different from neurofilaments are thus sufficient to cause HSP–like pathological changes such as axonal swellings, altered structure and function of synapses, behavioral deficits, and increased mortality. PMID:23209432

Stanchev, Doychin T.; Schneider, Carola D.; Karle, Kathrin N.; Daub, Katharina J.; Siegert, Vera K.; Flotenmeyer, Matthias; Schwarz, Heinz; Schols, Ludger; Rasse, Tobias M.

2012-01-01

106

A complex form of hereditary spastic paraplegia in three siblings due to somatic mosaicism for a novel SPAST mutation in the mother.  

PubMed

Hereditary spastic paraplegias (HSPs) represent a clinically and genetically heterogeneous group of diseases. Major symptoms comprise progressive bilateral leg stiffness, spasticity at rest and diffuse muscle weakness. Complex forms are characterized by additional symptoms like dementia, cerebellar dysfunction or seizures. Autosomal dominant, autosomal recessive, X-linked recessive and possibly mitochondrial inheritance have been described in familial HSP. The most frequently mutated gene in familial cases of uncomplicated autosomal dominant HSP is SPAST, however de novo mutations in SPAST are rarely found. Here, we report on the clinical and genetic findings in a family with three children afflicted by complex HSP and their unaffected parents. Although autosomal dominant inheritance seemed unlikely in this family, genetic testing revealed a novel SPAST mutation, c.1837G>C (p.Asp613His), in a heterozygous state in all affected individuals and somatic mosaicism of this mutation in the unaffected mother. Our study thus expands the knowledge on SPAST-associated HSP and emphasizes that de novo mutations and somatic mosaicism should be taken into consideration in HSP families presenting with a family history not suggestive for an autosomal dominant inheritance pattern. PMID:25315759

Aulitzky, Anna; Friedrich, Katrin; Gläser, Dieter; Gastl, Regina; Kubisch, Christian; Ludolph, Albert C; Volk, Alexander E

2014-12-15

107

Genetics Home Reference: Spastic paraplegia type 7  

MedlinePLUS

... proteins that form a complex called the m-AAA protease. The m-AAA protease is responsible for assembling ribosomes (cellular structures ... there is a mutation in paraplegin, the m-AAA protease cannot function correctly. Nonfunctional m-AAA proteases ...

108

Acute paraplegia caused by Schistosoma mansoni.  

PubMed

Schistosomiasis affects over 200 million people worldwide. Involvement of the CNS is a rare occurrence. We report 2 young males who presented with rapidly progressing paraparesis associated with urinary incontinence. In both cases, MRI of the spine demonstrated a diffusely enhancing mass at the conus medullaris with extensive spinal cord edema. Laboratory investigations revealed mild peripheral eosinophilia and abnormal, but non-specific, CSF analysis. In one patient, the diagnosis was made based on a rising schistosomal titer with a positive rectal biopsy. In the other patient, spinal cord biopsy revealed a granuloma. Both cases were caused by Schistosoma mansoni and patients were treated with praziquantel and steroid therapy. They both made a remarkable neurological recovery. We emphasize that a high index of suspicion should be raised in the differential diagnosis of transverse myelitis in endemic areas. PMID:24419450

Algahtani, Hussein A; Aldarmahi, Ahmed A; Al-Rabia, Mohammed W; Baeesa, Saleh S

2014-01-01

109

[Hypokalemia-induced paraplegia secondary to acute diarrhea].  

PubMed

Hypokalemia can give a variety of syntomatology but more often courses without it or with inespecific clinical manifestations. In our enviroment the etiology of hypokalemia is wide but one of the most common causes in third world countries are diarrheas. We describe a case of severe hypokalemia due to acute diarrhea which was manifested with severe neurologic symtoms but improves with conventional treatment. PMID:11989102

Ortuño Andériz, F; Cabello Clotet, N; de Diego Gamarra, R; Salaverría Garzón, I; Vázquez Rizaldos, S

2002-02-01

110

Genetics Home Reference: Spastic paraplegia type 3A  

MedlinePLUS

... protein is found in structures known as the endoplasmic reticulum and the Golgi apparatus, which are involved in ... cell components and in the formation of the endoplasmic reticulum and Golgi apparatus, each of which is involved ...

111

The value of sport as a recreation in paraplegia.  

PubMed

On an afternoon in 1944, an able-bodied man attempted to move about in a wheel chair and, using the curved handle of a walking stick as a mallet, to hit a ball and chase after it, at the same time endeavouring to prevent his opponent in a wheel chair from counteracting his movements. The man was Dr. Ludwig Guttmann; the activity was later to become wheel-chair polo and from his simple experiment was born the idea of competitive team sport for paraplegics. Two decades later in Tokyo, paralyzed men and women from twenty-three nations competed in sports demanding of their patiently trained bodies skill, strength, speed and endurance. This was the occasion of the 1964 International Games for the Paralyzed. Paraplegic sport is a success story and the history of its growth of great interest. PMID:25023754

Schneider, G

1966-08-01

112

[Bariatrica paraplegia patient and morbid obesity. New challenge in bariatric surgery].  

PubMed

The loss of mobility due to spinal cord injury is a risk factor for weight gain. Despite the well-documented outcomes of bariatric surgery in outpatients, little information is available about the surgery in paraplegic patients. We present two cases of patients with morbid obesity and spinal cord injury. After several attempts to lose weight conservatively, were assessed by the multidisciplinary team of our hospital and finally intervened by laparoscopic gastric bypass. After surgery have been no post-surgical complications. The patient in case 1, after two years of follow-up, a weight of 84 kg (BMI 25.08 kg/m2). Case 2, after a month of surgery has reduced weight and stopped taking antihypertensive therapy. It 's available to bariatric surgery as an important option to consider if all non-surgical interventions fail is highlighted. PMID:24972486

Gros Herguido, Noelia; Pereira Cunill, José Luis; Barranco Moreno, Antonio; Socas Macias, Maria; Morales-Conde, Salvador; Garcia-Luna, Pedro Pablo

2014-01-01

113

Sacral anterior root stimulators for bladder control in paraplegia: the first 50 cases.  

PubMed Central

The first 50 patients who have received sacral anterior root stimulator implants are presented, with follow-up of from 1 to 9 years. Forty-nine are alive and 43 are regularly using their implants for micturition. Of the 49 living, 39 are "very pleased, without significant reservations", six are pleased on balance but have reservations, and four are dissatisfied. Residual urine volumes are substantially reduced in all patients who are using their implants. Ten of the 12 female patients and the majority of male patients have become continent. The voiding pressure in implant-driven micturition can be regulated by adjusting the stimulus parameters, and is always kept below 90 cm H2O. Of seven patients with ureteric reflux before operation, four have ceased to reflux and the other three are unchanged. Changes in the radiographic appearances of the bladder have been favourable or zero, but there have been two cases of deterioration in the upper urinary tracts. Significant harmful effects have been CSF leaks, urinary infections following post-operative urodynamic study, and accidental damage to roots. Anterior roots nearly always recover from accidental damage, and posterior roots do not. Images PMID:3491180

Brindley, G S; Polkey, C E; Rushton, D N; Cardozo, L

1986-01-01

114

Intra-medullary tuberculoma of the spinal cord presenting with typhoid and paraplegia: a case report  

PubMed Central

Introduction Intra-medullary spinal tuberculoma is a rare form of tuberculosis, with an incidence of only two in 100,000 patients with tuberculosis. We present a case of intra-medullary tuberculoma from Pakistan, which was diagnosed by radiological findings and analysis of cerebrospinal fluid using polymerase chain reaction testing. Case presentation We present the case of a 28-year-old Sindhi male with intra-medullary tuberculoma of the spinal cord at the C3 level. Our patient was treated solely with anti-tubercular drug therapy with no surgical intervention. Conclusions We discuss the possible clinical management of such rare cases, considering both chemotherapeutic and surgical options. Additionally, diagnostic procedures and findings are discussed; we suggest cerebrospinal fluid analysis via polymerase chain reaction and gadolinium-diethylenetriamine pentaacetic acid magnetic resonance imaging as important chemical and radiological tests to be performed in such cases. PMID:23148826

2012-01-01

115

[The importance of a complete diagnostic workup in patients with nontraumatic (partial) paraplegia].  

PubMed

In two women, aged 86 and 56 years, respectively, who suffered from back pain and loss of strength, and in a 55-year-old man who lost sensation and strength in his left leg, spinal-cord compression in connection with vertebral destruction was seen on radiological examination. When spinal-cord compression is the result of a local malignant tumour, the therapy often entails emergency radiotherapy. In the first two patients, histological examination revealed a solitary plasmocytoma and curative high-dose radiotherapy was applied. The third patient also had a lung tumour and received low-dose palliative radiotherapy to the vertebrae, as a metastasis was suspected. Later, however, histopathologic examination of the vertebral lesion revealed osteomyelitis due to Listeria monocytogenes and the lung tumour was diagnosed as a pT2N0M0 broncho-alveolar carcinoma which was surgically removed. When a patient is referred with a nontraumatic spinal-cord injury, it is important to complete the radiological and histological examinations before starting emergency radiotherapy in order to prevent an inadequate or even incorrect treatment. PMID:14723022

Schinagl, D A; Kappelle, A C; van der Maazen, R W; Bussink, J

2003-12-27

116

Spastic paraplegia, dysarthria, brachydactyly, and cone shaped epiphyses: confirmation of the Fitzsimmons syndrome.  

PubMed

A girl with slowly progressive difficulty in walking, dysarthria, growth retardation, brachydactyly, and cone shaped epiphyses is described. This constellation of symptoms was described in 1987 by Fitzsimmons and Guilbert. It probably represents a rare mendelian disorder of unknown cause. PMID:8014978

Hennekam, R C

1994-03-01

117

The pig model of chronic paraplegia: a challenge for experimental studies in spinal cord injury.  

PubMed

The regenerative medicine techniques that are beginning to be applied to the nervous system have led to increased hope in the treatment of diseases that have been considered incurable and that require experimental models on which to test new therapeutic strategies. We present our experience with adult pigs (minipigs) that have undergone a traumatic spinal cord injury (SCI) experimental model, and that have been followed for 1 year. We describe the surgical aspects of our SCI model by acute compression and also describe protocols for daily care and rehabilitation that are necessary to maintain the paraplegic pigs in good health during the months following the injury. Furthermore, we provide in detail the main complications that arise with this experimental model and the treatments used to address these complications. Suitable housing conditions, daily rehabilitation and prevention of complications (i.e., taking the same care applied to patients following SCI) are essential for achieving the absence of mortality and long-term maintenance of the animals. We consider the model that is described here to be feasible and useful for preliminary testing of novel therapeutic strategies aimed at regeneration of the injured spinal cord in paraplegic patients. PMID:22564435

Zurita, Mercedes; Aguayo, Concepción; Bonilla, Celia; Otero, Laura; Rico, Miguel; Rodríguez, Alicia; Vaquero, Jesús

2012-06-01

118

Corticospinal Reorganization after Locomotor Training in a Person with Motor Incomplete Paraplegia  

PubMed Central

Activity-dependent plasticity as a result of reorganization of neural circuits is a fundamental characteristic of the central nervous system that occurs simultaneously in multiple sites. In this study, we established the effects of subthreshold transcranial magnetic stimulation (TMS) over the primary motor cortex region on the tibialis anterior (TA) long-latency flexion reflex. Neurophysiological tests were conducted before and after robotic gait training in one person with a motor incomplete spinal cord injury (SCI) while at rest and during robotic-assisted stepping. The TA flexion reflex was evoked following nonnociceptive sural nerve stimulation and was conditioned by TMS at 0.9?TA motor evoked potential resting threshold at conditioning-test intervals that ranged from 70 to 130?ms. Subthreshold TMS induced a significant facilitation on the TA flexion reflex before training, which was reversed to depression after training with the subject seated at rest. During stepping, corticospinal facilitation of the flexion reflex at early and midstance phases before training was replaced with depression at early and midswing followed by facilitation at late swing after training. These results constitute the first neurophysiologic evidence that locomotor training reorganizes the cortical control of spinal interneuronal circuits that generate patterned motor activity, modifying spinal reflex function, in the chronic lesioned human spinal cord. PMID:23484130

Hajela, Nupur; Mummidisetty, Chaithanya K.; Smith, Andrew C.; Knikou, Maria

2013-01-01

119

Paraplegia by spinal cord compression as the initial manifestation of Hodgkin's disease: a case report.  

PubMed

The 90% of Hodgkin's disease (HD) cases are originated by lymphnodes whereas 10% by extranodal regions as epidural space. Neurologic complications of HD can be classified as directly resulting from the disease or indirectly originated from the disease or from its treatment. Patients very rarely present with spinal cord compression (SCC)  due to epidural HD. Few cases of HD with such presentation have been reported in the literature. Primary spinal extradural HD with no further organ involvement is extremely rare. We report a case of a child with SCC as initial and unique presentation of HD. PMID:25245654

Baroni, Lorenza; Fornaciari, Sara; Predieri, Barbara; Bergonzini, Patrizia; Guerra, Azzurra; Paolucci, Paolo; Iughetti, Lorenzo

2014-01-01

120

Spinal cord perfusion after extensive segmental artery sacrifice: can paraplegia be prevented?  

Microsoft Academic Search

Objective: Understanding the ability of the paraspinal anastomotic network to provide adequate spinal cord perfusion pressure (SCPP) critical for both surgical and endovascular repair of thoracoabdominal aortic aneurysms (TAAA). Methods: To monitor pressure in the collateral circulation, a catheter was inserted into the distal end of the divided first lumbar segmental artery (SA) of 10 juvenile Yorkshire pigs (28.9 3.8

Christian D. Etz; Tobias M. Homann; Konstadinos A. Plestis; Ning Zhang; Maximilian Luehr; Donald J. Weisz; George Kleinman; Randall B. Griepp

2010-01-01

121

Spinal cord perfusion after extensive segmental artery sacrifice: can paraplegia be prevented?  

Microsoft Academic Search

Objective: Understanding the ability of the paraspinal anastomotic network to provide adequate spinal cord perfusion pressure (SCPP) critical for both surgical and endovascular repair of thoracoabdominal aortic aneurysms (TAAA). Methods: To monitor pressure in the collateral circulation, a catheter was inserted into the distal end of the divided first lumbar segmental artery (SA) of 10 juvenile Yorkshire pigs (28.9±3.8kg). SA

Christian D. Etz; Tobias M. Homann; Konstadinos A. Plestis; Ning Zhang; Maximilian Luehr; Donald J. Weisz; George Kleinman; Randall B. Griepp

2007-01-01

122

Endovascular treatment for acute paraplegia after epidural steroid injection in a patient with spinal dural arteriovenous malformation.  

PubMed

Spinal dural arteriovenous fistulas (SDAVFs) are the most common type of spinal arteriovenous malformations. Type 1 spinal arteriovenous malformations are defined by the presence of radiculomeningeal feeders that drain into intradural veins. Patients with these lesions frequently present with chronic myelopathy, which is most often caused by venous hypertension. The authors present the case of a 69-year-old man with acute paraparesis following a lumbar epidural injection, resulting from a previously undiagnosed SDAVF. The patient initially reported right lower-extremity weakness and paresthesias and was referred to an orthopedic practice. His pain and weakness were exacerbated with ambulation. Reevaluation at 4 months was remarkable for groin, mild low-back, and buttock pain. The patient received a right L5-S1 interlaminar epidural steroid injection and became acutely weak. He presented to the emergency department 3 hours after the injection. Once MRI of the lumbar and thoracic spine had been performed, the neurosurgery service was consulted, and it was decided to proceed with emergent spinal angiography with the intent to embolize the fistula. An emergent spinal angiogram was obtained, revealing 2 arterial pedicles emanating from the right T-5 and T-6 radicular arteries. Transarterial embolization was thought to be the most rapid way to potentially obliterate the fistula. The patient exhibited immediate improvement in neurological function, and by 6 hours postprocedure, his neurological function was near normal. He was ambulatory and released to home 3 days after the embolization procedure. PMID:22769730

Oliver, T Adam; Sorensen, Michael; Arthur, Adam S

2012-09-01

123

Vertical ground reaction force-based analysis of powered exoskeleton-assisted walking in persons with motor-complete paraplegia  

PubMed Central

Objective To use vertical ground reaction force (vGRF) to show the magnitude and pattern of mechanical loading in persons with spinal cord injury (SCI) during powered exoskeleton-assisted walking. Research design A cross-sectional study was performed to analyze vGRF during powered exoskeleton-assisted walking (ReWalk™: Argo Medical Technologies, Inc, Marlborough, MA, USA) compared with vGRF of able-bodied gait. Setting Veterans Affairs Medical Center. Participants Six persons with thoracic motor-complete SCI (T1–T11 AIS A/B) and three age-, height-, weight- and gender-matched able-bodied volunteers participated. Interventions SCI participants were trained to ambulate over ground using a ReWalk™. vGRF was recorded using the F-Scan™ system (TekScan, Boston, MA, USA). Outcome measures Peak stance average (PSA) was computed from vGRF and normalized across all participants by percent body weight. Peak vGRF was determined for heel strike, mid-stance, and toe-off. Relative linear impulse and harmonic analysis provided quantitative support for analysis of powered exoskeletal gait. Results Participants with motor-complete SCI, ambulating independently with a ReWalk™, demonstrated mechanical loading magnitudes and patterns similar to able-bodied gait. Harmonic analysis of PSA profile by Fourier transform contrasted frequency of stance phase gait components between able-bodied and powered exoskeleton-assisted walking. Conclusion Powered exoskeleton-assisted walking in persons with motor-complete SCI generated vGRF similar in magnitude and pattern to that of able-bodied walking. This suggests the potential for powered exoskeleton-assisted walking to provide a mechanism for mechanical loading to the lower extremities. vGRF profile can be used to examine both magnitude of loading and gait mechanics of powered exoskeleton-assisted walking among participants of different weight, gait speed, and level of assist. PMID:23820147

Fineberg, Drew B.; Asselin, Pierre; Harel, Noam Y.; Agranova-Breyter, Irina; Kornfeld, Stephen D.; Bauman,, William A.; Spungen, Ann M.

2013-01-01

124

The influence of the reciprocal hip joint link in the Advanced Reciprocating Gait Orthosis on standing performance in paraplegia  

Microsoft Academic Search

The effect of reciprocally linking the hip hinges of a hip-knee-ankle-foot orthosis on standing performance was studied in a comparative trial of the Advanced Reciprocating Gait Orthosis (ARGO) and an ARGO in which the Bowden cable was removed (A_GO). Six male subjects with spinal cord injury (SCI) at T4 to T12 level participated in the study, which was conducted using

G. Baardman; M. J. IJzerman; H. J. Hermens; P. H. Veltink; H. B. K. Boom; G. Zilvold

1997-01-01

125

Development and experimental identification of a biomechanical model of the trunk for functional electrical stimulation control in paraplegia.  

PubMed

Objectives.? Theoretic modeling and experimental studies suggest that functional electrical stimulation (FES) can improve trunk balance in spinal cord injured subjects. This can have a positive impact on daily life, increasing the volume of bimanual workspace, improving sitting posture, and wheelchair propulsion. A closed loop controller for the stimulation is desirable, as it can potentially decrease muscle fatigue and offer better rejection to disturbances. This paper proposes a biomechanical model of the human trunk, and a procedure for its identification, to be used for the future development of FES controllers. The advantage over previous models resides in the simplicity of the solution proposed, which makes it possible to identify the model just before a stimulation session (taking into account the variability of the muscle response to the FES). Materials and Methods.? The structure of the model is based on previous research on FES and muscle physiology. Some details could not be inferred from previous studies, and were determined from experimental data. Experiments with a paraplegic volunteer were conducted in order to measure the moments exerted by the trunk-passive tissues and artificially stimulated muscles. Data for model identification and validation also were collected. Results.? Using the proposed structure and identification procedure, the model could adequately reproduce the moments exerted during the experiments. The study reveals that the stimulated trunk extensors can exert maximal moment when the trunk is in the upright position. In contrast, previous studies show that able-bodied subjects can exert maximal trunk extension when flexed forward. Conclusions.? The proposed model and identification procedure are a successful first step toward the development of a model-based controller for trunk FES. The model also gives information on the trunk in unique conditions, normally not observable in able-bodied subjects (ie, subject only to extensor muscles contraction). PMID:22151147

Vanoncini, Michele; Holderbaum, William; Andrews, Brian

2008-10-01

126

It's About Time Physical Disabilities Came Out in the Open: Part I. Amputation, Monoplegia, Hemiplegia, Triplegia, Quadruplegia, Paraplegia.  

ERIC Educational Resources Information Center

After a definition of the term, mobility impairments, and a discussion of the causes and problems associated with amputation, this document covers, under the major section, Paralysis, six handicapping conditions in terms of how each may affect a student's ability to be successful in both a vocational program and a job. Topics under this section…

Davis, Kay

127

Experimental Analysis of Neurophysiological and Experimential Concomitants of Phantom and Somatic Sensations after Paraplegia, Quadriplegia, or Absence of Limb Due to Amputation or Aplasia.  

National Technical Information Service (NTIS)

The report presents data dealing with phantoms in 521 cases of amputation, 108 cases of amputation in patients additionally suffering a cerebral vascular accident (CVA), 36 cases of terminal aplasia, and gives results of intensive study of the cortical ev...

S. Weinstein, R. J. Vetter

1967-01-01

128

Cold pressor test in tetraplegia and paraplegia suggests an independent role of the thoracic spinal cord in the hemodynamic responses to cold  

Microsoft Academic Search

Background:Cold application to the hand (CAH) is associated in healthy people with increase in heart rate (HR) and blood pressure (BP).Objective:To study hemodynamic responses to CAH in humans following spinal cord injuries of various levels, and examine the effect of spinal cord integrity on the cold pressor response.Design:An experimental controlled study.Setting:The spinal research laboratory, Loewenstein Hospital, Raanana, Israel.Subjects:Thirteen healthy subjects,

A Catz; V Bluvshtein; I Pinhas; S Akselrod; I Gelernter; T Nissel; Y Vered; N Bornstein; A D Korczyn

2008-01-01

129

16 CFR 1207.1 - Scope, purpose, and findings.  

Code of Federal Regulations, 2011 CFR

...associated with swimming pool slides. These risks are (i) quadriplegia and paraplegia resulting from users (primarily adults...example, the revised standard does not address the risk of quadriplegia and paraplegia (except insofar as the standard...

2011-01-01

130

16 CFR 1207.1 - Scope, purpose, and findings.  

...associated with swimming pool slides. These risks are (i) quadriplegia and paraplegia resulting from users (primarily adults...example, the revised standard does not address the risk of quadriplegia and paraplegia (except insofar as the standard...

2014-01-01

131

16 CFR 1207.1 - Scope, purpose, and findings.  

Code of Federal Regulations, 2013 CFR

...associated with swimming pool slides. These risks are (i) quadriplegia and paraplegia resulting from users (primarily adults...example, the revised standard does not address the risk of quadriplegia and paraplegia (except insofar as the standard...

2013-01-01

132

16 CFR 1207.1 - Scope, purpose, and findings.  

Code of Federal Regulations, 2012 CFR

...associated with swimming pool slides. These risks are (i) quadriplegia and paraplegia resulting from users (primarily adults...example, the revised standard does not address the risk of quadriplegia and paraplegia (except insofar as the standard...

2012-01-01

133

ACCESSIBILITY NEEDS IN RESIDENCE "The University of Toronto respects your privacy. The information on this form is collected pursuant to section 2(14) of the University of  

E-print Network

of Hearing Mobility Spina Bifida Chronic Fatigue Syndrome Heart Condition Monoplegia Bowel Hemiplegia (nonprogressive) Arthritis/Rheumatic Syndrome Hemophilia Fibrosis (specify) __________ Paraplegia Blind Deaf Chronic Health Condition

Sokolowski, Marla

134

Spinal cord abscess  

MedlinePLUS

... exam may show signs of: Spinal cord compression Paralysis of the lower body (paraplegia) or of the entire trunk, arms, and legs (quadriplegia) Changes in sensation below the area of involvement ...

135

TICK PARALYSIS IN A WESTERN HARVEST MOUSE (Reithrodontomys megalotis)  

Microsoft Academic Search

An engorging female Ixodes pacificus was observed on a western harvest mouse (Reithrodontomys megalotis) in Humboldt County, California. The mouse demonstrated a flaccid paraplegia, but it appeared to recover fully after the tick was removed.

R. G. BOTZLER; J. ALBRECHT; T. SCHAEFER

1980-01-01

136

Tick paralysis in a western harvest mouse.  

PubMed

An engorging female Ixodes pacificus was observed on a western harvest mouse (Reithrodontomys megalotis) in Humboldt County, California. The mouse demonstrated a flaccid paraplegia, but it appeared to recover fully after the tick was removed. PMID:7431519

Botzler, R G; Albrecht, J; Schaefer, T

1980-04-01

137

Genetics Home Reference: Troyer syndrome  

MedlinePLUS

... ClinicalTrials.gov Research studies PubMed Recent literature OMIM Genetic disorder catalog Conditions > Troyer syndrome On this page: Description ... Troyer syndrome is part of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are ...

138

The effect of ageing in spinal cord injured humans on the blood pressure and heart rate responses during fatiguing isometric exercise  

Microsoft Academic Search

.   Groups of 50 healthy male controls and 50 subjects suffering from paraplegia (aged 20–65 years) were examined as to the inter-relationships\\u000a between age, paraplegia and the strength, endurance, blood pressure and heart rate responses to fatiguing isometric exercise.\\u000a Contractions were maintained in both groups under voluntary effort and through a contraction induced by electrical stimulation\\u000a in the paraplegic group. All contractions were

Jerrold Scott Petrofsky; Michael Laymon

2002-01-01

139

Botulinum Toxin Injections for Pediatric Patients With Hereditary Spastic Paraparesis  

Microsoft Academic Search

Limited information is available on the use of botulinum toxin type A injections for children with hereditary spastic paraplegia. This report includes 12 children with hereditary spastic paraplegia (mean age 4.8 ± 2.5 years) who underwent 1 to 6 sessions of botulinum toxin A injections to the hamstrings, adductors and gastrocnemius muscles. Patients showed both improved muscle tone (mean 1.9

Keren Geva-Dayan; Dafna Domenievitz; Rafat Zahalka; Aviva Fattal-Valevski

2010-01-01

140

Neurological Complications Following Endoluminal Repair of Thoracic Aortic Disease  

SciTech Connect

Open surgery for thoracic aortic disease is associated with significant morbidity and the reported rates for paraplegia and stroke are 3%-19% and 6%-11%, respectively. Spinal cord ischemia and stroke have also been reported following endoluminal repair. This study reviews the incidence of paraplegia and stroke in a series of 186 patients treated with thoracic stent grafts. From July 1997 to September 2006, 186 patients (125 men) underwent endoluminal repair of thoracic aortic pathology. Mean age was 71 years (range, 17-90 years). One hundred twenty-eight patients were treated electively and 58 patients had urgent procedures. Anesthesia was epidural in 131, general in 50, and local in 5 patients. Seven patients developed paraplegia (3.8%; two urgent and five elective). All occurred in-hospital apart from one associated with severe hypotension after a myocardial infarction at 3 weeks. Four of these recovered with cerebrospinal fluid (CSF) drainage. One patient with paraplegia died and two had permanent neurological deficit. The rate of permanent paraplegia and death was 1.6%. There were seven strokes (3.8%; four urgent and three elective). Three patients made a complete recovery, one had permanent expressive dysphasia, and three died. The rate of permanent stroke and death was 2.1%. Endoluminal treatment of thoracic aortic disease is an attractive alternative to open surgery; however, there is still a risk of paraplegia and stroke. Permanent neurological deficits and death occurred in 3.7% of the patients in this series. We conclude that prompt recognition of paraplegia and immediate insertion of a CSF drain can be an effective way of recovering spinal cord function and improving the prognosis.

Morales, J. P.; Taylor, P. R.; Bell, R. E.; Chan, Y. C. [Guy's and St. Thomas' Foundation Hospital NHS Trust, Department of Vascular Surgery (United Kingdom); Sabharwal, T. [Guy's and St. Thomas' Foundation Hospital NHS Trust, Department of Interventional Radiology (United Kingdom); Carrell, T. W. G. [Guy's and St. Thomas' Foundation Hospital NHS Trust, Department of Vascular Surgery (United Kingdom); Reidy, J. F. [Guy's and St. Thomas' Foundation Hospital NHS Trust, Department of Interventional Radiology (United Kingdom)], E-mail: John.Reidy@gstt.nhs.uk

2007-09-15

141

Paraplegic Neurodeficit Management Post Endovascular Graft: A Rare Case of Aortic Dissection  

PubMed Central

Acute aortic dissection is a catastrophic episode that usually presents as a sudden, painful, ripping sensation in the chest or back. It is associated with neurologic sequelae in as many as one-third of patients. We report a case of aortic dissection, presenting as acute paraplegia. A 50-year-old patient presented to us with chief complaints of paraplegia and back pain. On examination, strength was 5/5 in both upper extremities and 0/5 in both lower extremities. Deep tendon reflexes were absent in her legs. CT angiogram of aorta Aortic Dissection Stanford type B / De-Bakey type –III. Patient was treated with endovascular graft for aortic dissection, paraplegia recovered completely. PMID:24298506

Kanse, Vilas Yadavarao; Chongtham, Dhanaraj Singh; Nemichandra, S C; Salam, Kenny Singh

2013-01-01

142

Malignant Rhabdoid Tumor of the Kidney and Spine in an Infant  

PubMed Central

Rhabdoid tumor of the kidney (RTK) is a rare malignancy in infancy. Central nervous system involvement in RTK is already known. However, solitary spinal metastasis in RTK has been hardly reported. The authors report a case of metastatic RTK to spine causing paraplegia in an 8-month-old girl. Since the patient was young, the diagnosis of spine metastasis was delayed until paraplegia was seen after radical nephrectomy. Thorough neurological examination should be performed for early diagnosis of spinal metastasis in young patients with RTK. If there are any abnormal signs in neurologic examination, magnetic resonance images of brain and spine are recommended. PMID:24570822

Park, Sejun; Seo, Jae-Hee; Park, Jun Bum

2014-01-01

143

In Clin Biomech 2006;21 Suppl 1:S45-51 (2005) Shoulder movements during the initial phase of  

E-print Network

of the task. Keywords: shoulder - three dimensional kinematics - wheelchair propulsion - electromagnetic of learning manual wheelchair propulsion in able- bodied subjects Laurence Rouxa , Sylvain Hannetona and Agnès phase of learning wheelchair propulsion by individuals with paraplegia have been partially described

Paris-Sud XI, Université de

144

Acquired motor neuron loss causing severe pelvic limb contractures in a young cat  

Microsoft Academic Search

Presentation This report describes a kitten with paraplegia and extensor rigidity of the pelvic limbs associated with motor neuron loss and chronic denervation of skeletal muscle. Persistent skeletal muscle atrophy and degeneration had resulted in immobile stifle and hock joints and severe pelvic limb rigidity consistent with a neurogenic form of arthrogryposis. Both pelvic limbs were equally affected and the

Cecilia Rohdin; Erika Karlstam; Karin Hultin Jäderlund; G. Diane Shelton

2010-01-01

145

Seppuku: a modern approach to an ancient injury.  

PubMed

A 67 year-old man with paraplegia and depression presented with self-inflicted evisceration and small bowel injury. Damage control surgery was undertaken at emergency laparotomy with definitive anastomosis performed at second-look laparotomy following 24 hours resuscitation in ICU. He had an uncomplicated post-operative course and was discharged to an inpatient psychiatric unit. PMID:24218749

Richardson, A J; Tevlin, R; Larkin, J O; Beddy, D

2013-01-01

146

Spartin Regulates Synaptic Growth and Neuronal Survival by Inhibiting  

E-print Network

receptor endocytosis and trafficking include Drosophila homologs of human proteins associated on Human Development, Vanderbilt University, Nashville, TN 37232, USA 4Department of Oral Anatomy.12.015 SUMMARY Troyer syndrome is a hereditary spastic paraplegia caused by human spartin (SPG20) gene mutations

Broadie, Kendal S.

147

Navigating a Robotic Wheelchair in a Railway Station during Rush Hour  

Microsoft Academic Search

In this paper we describe the hardware design, the control and navigation system, and our preliminary experiments with the robotic wheelchair MAid (Mobility Aid for Elderly and Disabled People). MAid's general task is to transport people with severely impaired motion skills such as, for example, paraplegia, multiple sclerosis, poliomyelitis, or muscular dystrophy. Following the advice of disabled people and physicians

Erwin Prassler; Jens Scholz; Paolo Fiorini

1999-01-01

148

Low Magnitude and High Frequency Mechanical Loading Prevents Decreased Bone Formation Responses  

E-print Network

to osteoporosis or disuse such as in paraplegia or microgravity is a significant health problem. As a treatment for osteoporosis, brief exposure of intact animals or humans to low magnitude and high frequency (LMHF) mechanical osteoporosis or disuse-induced bone loss. J. Cell. Biochem. 106: 306­ 316, 2009. � 2009 Wiley-Liss, Inc. KEY

149

Neurologic Complications in Percutaneous Nephrolithotomy  

PubMed Central

Purpose Percutaneous nephrolithotomy (PCNL) has been the preferred procedure for the removal of large renal stones in Iran since 1990. Recently, we encountered a series of devastating neurologic complications during PCNL, including paraplegia and hemiplegia. There are several reports of neurologic complications following PCNL owing to paradoxical air emboli, but there are no reports of paraplegia following PCNL. Materials and Methods We retrospectively reviewed the medical records of patients who had undergone PCNL in 13 different endourologic centers and retrieved data related to neurologic complications after PCNL, including coma, paraplegia, hemiplegia, and quadriplegia. Results The total number of PCNL procedures in these 13 centers was 30,666. Among these procedures, 11 cases were complicated by neurologic events, and four of these cases experienced paraplegia. All events happened with the patient in the prone position with the use of general anesthesia and in the presence of air injection. There were no reports of neurologic complications in PCNL procedures performed with the patient under general anesthesia and in the prone position and with contrast injection. Conclusions It can be assumed that using room air to opacify the collecting system played a major role in the occurrence of these complications. Likewise, the prone position and general anesthesia may predispose to these events in the presence of air injection. PMID:23526482

Basiri, Abbas; Soltani, Mohammad Hossein; Kamranmanesh, Mohammadreza; Tabibi, Ali; Mohsen Ziaee, Seyed Amir; Nouralizadeh, Akbar; Sharifiaghdas, Farzaneh; Poorzamani, Mahtab; Gharaei, Babak; Ozhand, Ardalan; Lashay, Alireza; Ahanian, Ali; Aminsharifi, Alireza; Sichani, Mehrdad Mohammadi; Asl-Zare, Mohammad; Ali Beigi, Faramarz Mohammad; Najjaran, Vahid; Abedinzadeh, Mehdi

2013-01-01

150

Posttraumatic Stress Disorder in Veterans with Spinal Cord Injury: Trauma-related Risk Factors  

Microsoft Academic Search

Trauma-related risk factors for posttraumatic stress disorder (PTSD) were examined in a sample of 125 veterans with spinal cord injury. Category of injury was found to be the most consistent predictor of PTSD diagnosis and symptom severity with paraplegia predicting more PTSD symptoms than quadriplegia. The occurrence of a head injury at the time of the trauma was found to

Cynthia L. Radnitz; Louis Hsu; Jeffrey Willard; Lysandra Perez-Strumolo; Joanne Festa; Lynn B. Lillian; Stacey Walczak; Dennis D. Tirch; Ilana S. Schlein; Martin Binks; Charles P. Broderick

1998-01-01

151

Primary rhabdomyosarcoma of the central nervous system  

Microsoft Academic Search

A case of primary rhabdomyosarcoma in the brain stem is described in an 8 year old girl. The clinical data showed a right side hemiplegia then a total paralysis of the left sixth cranial nerve and a paraplegia which became lethal in 3 months. The necrospy revealed a tumoral nodule in the left medulla oblongata and pons with diffuse subarachnoidal

Basile Pasquier; Pierre Couderc; Dominique Pasquier; Pann Meng Hong; Jacques Pellat

1975-01-01

152

SCIM – spinal cord independence measure: a new disability scale for patients with spinal cord lesions  

Microsoft Academic Search

The Spinal Cord Independence Measure (SCIM) is a new disability scale developed specifically for patients with spinal cord lesions in order to make the functional assessments of patients with paraplegia or tetraplegia more sensitive to changes. The SCIM includes the following areas of function: self-care (subscore 0 – 20), respiration and sphincter management (0 – 40) and mobility (0 –

A Catz; M Itzkovich; E Agranov; H Ring; A Tamir

1997-01-01

153

Presenilin Mutations: Variations in the Behavioral Phenotype with an Emphasis on the Frontotemporal Dementia Phenotype  

Microsoft Academic Search

The vast majority of families with presenilin (PSEN) mutations have the clinical phenotype of Alzheimer's disease. However, there are reports of patients who carry PSEN mutations and have Alzheimer's disease with a variety of other clinical phenotypes including spastic paraplegia, seizures, myoclonus, parkinsonism, epilepsy and amyloid angiopathy. Remarkably, three of the studied families have frontotemporal dementia (FTD). The mutations associated

Neill R Graff-Radford

154

Canine Thoracolumbar Intervertebral Disk Disease: Diagnosis, Prognosis  

Microsoft Academic Search

Thoracolumbar intervertebral disk disease (IVDD) is a common, important cause of paraspinal hyperesthesia, pelvic limb ataxia, paraparesis, paraplegia, and urinary and fecal in- continence in dogs. A companion article reviewed pathophysiology, epidemiology, physical ex- amination, and emergency medical therapy. This article addresses the diagnosis, prognosis, and treatment of dogs with thoracolumbar IVDD.

John F. Griffin; Jonathan M. Levine; Sharon C. Kerwin; Robert C. Cole

155

Canine thoracolumbar invertebral disk disease: diagnosis, prognosis, and treatment.  

PubMed

Thoracolumbar intervertebral disk disease (IVDD) is a common, important cause of paraspinal hyperesthesia, pelvic limb ataxia, paraparesis, paraplegia, and urinary and fecal incontinence in dogs. A companion article reviewed pathophysiology, epidemiology, physical examination, and emergency medical therapy. This article addresses the diagnosis, prognosis, and treatment of dogs with thoracolumbar IVDD. PMID:19412898

Griffin, John F; Levine, Jonathan; Kerwin, Sharon; Cole, Robert

2009-03-01

156

Opportuni)es for Change The Role of Medical Professionals in  

E-print Network

to prevent / end work disability? · When is the best =me to try it? Chris flu" ­ Chronic illness: renal, cardiac & lung disease, arthri=s, bipolar disorder, cancer, HIV ­ Fixed loss: blindness, amputa=on, paraplegia, mental retarda=on, malforma

157

A generic input device for the multiple master multiple slave system  

Microsoft Academic Search

The growing demand for input devices designed for the severely handicapped led to development of modular features for the open architecture multiple master multiple slave (M3S) system. With its central safety monitor, M3S allows individuals suffering from cerebral palsy, paraplegia, or multiple sclerosis, and other physically debilitating illnesses greater autonomy by allowing them to access a wide range of input

Chiun-fan Chen; Yi-chu Chang; Heng-Yin Chen; Jin-shin Lai; Fok-ching Chong

2004-01-01

158

M3S system prototype - a comprehensive system with straightforward implementation  

Microsoft Academic Search

There is a growing demand for powered wheelchairs to provide mobility for people with upper-limb impairments, i.e., individuals suffering from cerebral palsy, paraplegia, or multiple sclerosis, and others who may depend on a human-friendly wheelchair to conduct their daily activities. The design of the multiple master multiple slave (\\

Chiun-fan Chen; Yi-chu Chang; Jer-junn Luh; Fok-ching Chong

2004-01-01

159

Abstract--We introduce the innovative technologies, based on the concept of "sensory substitution", we are developing in  

E-print Network

in older and/or disabled adults. This paper describes the architecture and the functioning principle to prevent fall in older and/or disabled adults. The tongue-placed electrotactile output device ("Tongue injuries (persons with paraplegia, or tetraplegia); and (2) balance control improvement to prevent fall

Payan, Yohan

160

[Spinal cord compression caused by spinal aneurysmal bone cyst (author's transl)].  

PubMed

Spinal aneurysmal bone cyst is sufficiently rare for the authors to report this case with rapid evolution and development of paraplegia. Total removal was achieved, and clinical recovery remained complete six months after operation. The pathogenic, clinical, radiological, histological and therapeutic aspects are briefly reviewed and discussed. PMID:1225017

Steimlé, R; Pageaut, G; Jacquet, G; Gehin, P; Sexe, C B

1975-01-01

161

Comparison of Heart Rate Response to Tennis Activity between Persons with and without Spinal Cord Injuries: Implications for a Training Threshold  

ERIC Educational Resources Information Center

The purpose of this study was to evaluate the ability of individuals with spinal cord injury (SCI) to reach a training threshold during on-court sport activity. Monitors collected heart rate (HR) data every 5 s for 11 wheelchair tennis players (WCT) with low paraplegia and 11 able-bodied controls matched on experience and skill level (ABT).…

Barfield, J. P.; Malone, Laurie A.; Coleman, Tristica A.

2009-01-01

162

Cerebrospinal fluid may mediate CNS ischemic injury  

PubMed Central

Background The central nervous system (CNS) is extremely vulnerable to ischemic injury. The details underlying this susceptibility are not completely understood. Since the CNS is surrounded by cerebrospinal fluid (CSF) that contains a low concentration of plasma protein, we examined the effect of changing the CSF in the evolution of CNS injury during ischemic insult. Methods Lumbar spinal cord ischemia was induced in rabbits by cross-clamping the descending abdominal aorta for 1 h, 2 h or 3 h followed by 7 d of reperfusion. Prior to ischemia, rabbits were subjected to the following procedures; 1) CSF depletion, 2) CSF replenishment at 0 mmHg intracranial pressure (ICP), and 3) replacement of CSF with 8% albumin- or 1% gelatin-modified artificial CSF, respectively. Motor function of the hind limbs and histopathological changes of the spinal cord were scored. Post-ischemic microcirculation of the spinal cord was visualized by fluorescein isothiocyanate (FITC) albumin. Results The severity of histopathological damage paralleled the neurological deficit scores. Paraplegia and associated histopathological changes were accompanied by a clear post-ischemic deficit in blood perfusion. Spinal cord ischemia for 1 h resulted in permanent paraplegia in the control group. Depletion of the CSF significantly prevented paraplegia. CSF replenishment with the ICP reduced to 0 mmHg, did not prevent paraplegia. Replacement of CSF with albumin- or gelatin-modified artificial CSF prevented paraplegia in rabbits even when the ICP was maintained at 10–15 mmHg. Conclusion We conclude that the presence of normal CSF may contribute to the vulnerability of the spinal cord to ischemic injury. Depletion of the CSF or replacement of the CSF with an albumin- or gelatin-modified artificial CSF can be neuroprotective. PMID:16174300

Wang, Yanming F; Gwathmey, Judith K; Zhang, Guorong; Soriano, Sulpicio G; He, Shunli; Wang, Yanguang

2005-01-01

163

Simultaneous occurrence of brain tumor and myeloradiculopathy in schistosomiasis mansoni: case report.  

PubMed

Simultaneous occurrence of brain tumor and myeloradiculopathy in cases of Manson's schistosomiasis have only rarely been described. We report the case of a 38-year-old man who developed seizures during a trip to Puerto Rico and in whom a brain tumor was diagnosed by magnetic resonance imaging: brain biopsy revealed the diagnosis of schistosomiasis. He was transferred to a hospital in the United States and, during hospitalization, he developed sudden paraplegia. The diagnosis of myeloradiculopathy was confirmed at that time. He was administered praziquantel and steroids. The brain tumor disappeared, but the patient was left with paraplegia and fecal and urinary dysfunction. He has now been followed up in Brazil for one year, and his clinical state, imaging examinations and laboratory tests are presented here. PMID:19684986

Lambertucci, José Roberto; Souza-Pereira, Silvio Roberto; Carvalho, Tânia Antunes

2009-01-01

164

Relationship between duration of spinal cord ischemia and postoperative neurologic deficits in animals.  

PubMed

Stagnara wake-up tests, blood flow measures, somatosensory evoked potentials (SEPs), and neurogenic-motor evoked potentials (NMEPs) were elicited from 20 hogs before and after spinal cord overdistraction at L3-L4. Overdistraction was maintained from 5 to 30 minutes after loss of NMEPs. Results suggest that the longer the duration of overdistraction the greater the likelihood of paraplegia. Blood flow measures indicated that reduced perfusion was greatest at the distraction site but extended proximally and distally. Finally, NMEPs were more sensitive to onset of overdistraction and a more valid indicator of paraplegia than SEPs. NMEPs should provide the surgeon with more time for initiation of intervention techniques than SEPs. Because NMEPs and SEPs provide information regarding different spinal cord tracts, the authors continue to use both methods for monitoring the functional integrity of the human spinal cord during corrective spine surgery. PMID:2259969

Owen, J H; Naito, M; Bridwell, K H; Oakley, D M

1990-09-01

165

Mutations in the mitochondrial protease gene AFG3L2 cause dominant hereditary ataxia SCA28  

Microsoft Academic Search

Autosomal dominant spinocerebellar ataxias (SCAs) are genetically heterogeneous neurological disorders characterized by cerebellar dysfunction mostly due to Purkinje cell degeneration. Here we show that AFG3L2 mutations cause SCA type 28. Along with paraplegin, which causes recessive spastic paraplegia, AFG3L2 is a component of the conserved m-AAA metalloprotease complex involved in the maintenance of the mitochondrial proteome. We identified heterozygous missense

Daniela Di Bella; Federico Lazzaro; Alfredo Brusco; Massimo Plumari; Giorgio Battaglia; Annalisa Pastore; Adele Finardi; Claudia Cagnoli; Filippo Tempia; Marina Frontali; Liana Veneziano; Tiziana Sacco; Enrica Boda; Alessandro Brussino; Florian Bonn; Barbara Castellotti; Silvia Baratta; Caterina Mariotti; Cinzia Gellera; Valentina Fracasso; Stefania Magri; Thomas Langer; Paolo Plevani; Stefano Di Donato; Marco Muzi-Falconi; Franco Taroni

2010-01-01

166

Granulocytic sarcoma in a nonleukemic patient: place of radiotherapy and systemic therapies.  

PubMed

Granulocytic sarcoma is a rare extramedullary tumour, which most often occurs in the course of an acute or chronic leukaemia or myeloproliferative disorders. Rarely it is found before peripheral blood or bone marrow evidence of leukemia is present. We report an unusual case of acute paraplegia at first presentation of a spinal epidural granulocytic sarcoma without any haematological disorder. Therapeutic strategies are discussed in the light of the literature. PMID:21629817

Chargari, C; Jacob, J; Bauduceau, O; Ferrand, F R; De Revel, T; Védrine, L

2011-01-01

167

Granulocytic Sarcoma in a Nonleukemic Patient: Place of Radiotherapy and Systemic Therapies  

PubMed Central

Granulocytic sarcoma is a rare extramedullary tumour, which most often occurs in the course of an acute or chronic leukaemia or myeloproliferative disorders. Rarely it is found before peripheral blood or bone marrow evidence of leukemia is present. We report an unusual case of acute paraplegia at first presentation of a spinal epidural granulocytic sarcoma without any haematological disorder. Therapeutic strategies are discussed in the light of the literature. PMID:21629817

Chargari, C.; Jacob, J.; Bauduceau, O.; Ferrand, F. R.; De Revel, T.; Védrine, L.

2011-01-01

168

Sympathetic nervous system activity and cardiovascular homeostasis during head-up tilt in patients with spinal cord injuries  

Microsoft Academic Search

The relationship between sympathetic nervous system activity and cardiovascular responses to head-up tilt in patients with spinal cord injuries and in able-bodied subjects was studied. Twenty-seven adults, nine in each of the three groups (tetraplegia, paraplegia, and able-bodied subjects) were tilted 70°, head up, for 12 minutes after 20 minutes supine rest. Differences between steady-state measurements of mean arterial pressure,

Sibrand Houtman; Berend Oeseburg; Richard L. Hughson; Maria T. E. Hopman

2000-01-01

169

[Spinal cord protection in surgery of the thoracic, descending, and thoraco-abdominal aorta. Comparison of methods].  

PubMed

The authors compare the strategus needed for the elimination of paraplegia and for protection of abdominal organs after replacement of descending thoracic or thoraco-abdominal aorta. They analyse single technique considering the advantages and the controindications; furthermore they compare these properties and those of possible variants in the light of the presentation; type of disease and general conditions of the patient. These considerations are in agreement with later literature as well as the attitude of the surgeon. PMID:9082233

Zanetti, P P; Sorisio, V; Rosa, G; Cavanenghi, D; Amerio, G M; Zappa, A; Stillo, R; Dutto, C; Castenetto, E; Cardellino, S; Franco, M

1996-09-01

170

MAid: A Robotic Wheelchair Operating in Public Environments  

Microsoft Academic Search

\\u000a In this paper we describe the hardware design, the control and navigation system, and our preliminary experiments with the\\u000a robotic wheelchair MAid (Mobility Aid for Elderly and Disabled People). MAid’s general task is to transport people with severely\\u000a impaired motion skills such as, for example, paraplegia, multiple sclerosis, poliomyelitis, or muscular dystrophy. Following\\u000a the advice of disabled people and physicians

Erwin Prassler; Jens Scholz; Matthias Strobel; Paolo Fiorini

1998-01-01

171

Canine thoracolumbar invertebral disk disease: pathophysiology, neurologic examination, and emergency medical therapy.  

PubMed

Thoracolumbar intervertebral disk disease (IVDD) is a common, important cause of paraspinal hyperesthesia, pelvic limb ataxia, paraparesis, paraplegia, and urinary and fecal incontinence in dogs. Research offers insights into the pathophysiology, diagnosis, prognosis, and treatment of this disorder. The comparative efficacy of many familiar therapies remains unknown and controversial. This article reviews the pathophysiology and epidemiology of this condition and the examination and emergency medical therapy of dogs with suspected thoracolumbar IVDD. PMID:19412899

Griffin, John F; Levine, Jonathan; Kerwin, Sharon

2009-03-01

172

Body composition modifications in people with chronic spinal cord injury after supervised physical activity  

PubMed Central

Background Quantification of body composition variables is important for planning of better activities in relation to individuals with spinal cord injury (SCI). Objectives (1) To evaluate changes in body composition in patients with SCI after a supervised physical activity process; (2) To correlate total body fat with time since injury. Design Pre-post intervention. Setting Sarah Rehabilitation Hospital Network, Brazil. Participants Fifty-three men with SCI aged 18–52 years with duration of injury >3 years. Interventions The subjects were divided into three groups: tetraplegia (TT) (C5–C8), high paraplegia (HP) (T1–T6), and low paraplegia (LP) (T7–L2). Body composition was estimated in the first and last weeks of hospitalization. Outcome measures Body weight (kg), skinfolds sum (mm), absolute (kg), and relative (%) fat and lean body mass. Results Body weight increased in TT and decreased in HP (0.8 kg, 95%CI 0.1–1.5; and ?1.0 kg, 95%CI ?2.0 to 0.0, respectively; P < 0.05). Skinfolds sum decreased only in HP (?13.1 mm, 95%CI ?20.7 to ?5.5; P < 0.05). Absolute and relative body fat decreased significantly in the paraplegia groups. Lean body mass (LBM) percentage increased significantly in the paraplegia groups. Absolute LBM increased in TT and LP (0.8 kg, 95%CI 0.3–1.3; and 1.3 kg, 95%CI 0.8 to 1.8, respectively; P < 0.05). There was no correlation between time since injury and skinfolds sum for the three groups (P < 0.05). Conclusion TT, HP, and LP demonstrated favorable changes in body composition after 29 days of supervised physical activity. However, these changes were different in direction and magnitude. PMID:22330114

Neto, Frederico Ribeiro; Lopes, Guilherme Henrique

2011-01-01

173

Cardiovascular Control During Exercise Insights From Spinal Cord-Injured Humans  

Microsoft Academic Search

Background—We studied the role of the central nervous system, neural feedback from contracting skeletal muscles, and sympathetic activity to the heart in the control of heart rate and blood pressure during 2 levels of dynamic exercise. Methods and Results—Spinal cord-injured individuals (SCI) with (paraplegia, n4) or without (tetraplegia, n6) sympathetic innervation to the heart performed electrically induced exercise. Responses were

Flemming Dela; Thomas Mohr; Christina M. R. Jensen; Hanne L. Haahr; Niels H. Secher; Fin Biering-Sørensen; Michael Kjær

2010-01-01

174

Human-induced pluripotent stem cells pave the road for a better understanding of motor neuron disease.  

PubMed

While motor neuron diseases are currently incurable, induced pluripotent stem cell research has uncovered some disease-relevant phenotypes. We will discuss strategies to model different aspects of motor neuron disease and the specific neurons involved in the disease. We will then describe recent progress to investigate common forms of motor neuron disease: amyotrophic lateral sclerosis, hereditary spastic paraplegia and spinal muscular atrophy. PMID:24821704

Winner, Beate; Marchetto, Maria C; Winkler, Jürgen; Gage, Fred H

2014-09-15

175

Demineralization and pathological physiology of the skeleton in paraplegic rats  

Microsoft Academic Search

Summary  The mechanism of bone loss after a spinal cord section with paraplegia is still largely unknown. The purpose of this study\\u000a was to investigate in paraplegic rats the rate and distribution of bone loss, changes in bone calcium metabolism, and bone\\u000a blood flow. Female Sprague-Dawley rats aged 100–120 days were rendered paraplegic by sectioning the spinal cord at the 11th

M. Verhas; Y. Martinello; M. Mone; A. Heilporn; P. Bergmann; A. Tricot; A. Schoutens

1980-01-01

176

Acute hind limb paralysis secondary to an extradural spinal cord Cryptococcus gattii lesion in a dog  

PubMed Central

A 2-year-old, spayed female, German short-haired pointer was presented with a 1-day history of non-ambulatory paraplegia with absent deep pain perception. A computed tomography scan revealed an irregular eighth thoracic vertebral body and an extradural compressive lesion. Decompression was performed and abnormal tissues were submitted for analysis. Findings were consistent with a Cryptococcus gattii infection. PMID:24155428

Kurach, Lindsey; Wojnarowicz, Chris; Wilkinson, Tom; Sereda, Colin

2013-01-01

177

[Mediastinal localization of a growing teratoma syndrome: a case report].  

PubMed

The development of testicular germ cell tumors may be marked by a rare phenomenon: the growing teratoma syndrome. It consists of residual masses, usually retroperitoneal and, more rarely, thoracic, that appear during or after chemotherapy, although the tumor markers are normalized. We report a case of posterior mediastinal localization. This mediastinal localization is very rare, and because of the proximity to intercostal arteries, induces a risk of postoperative paraplegia. PMID:24646785

Ngabou, U D; Dusaud, M; Boddaert, G; Grand, B; Houlgatte, A; Pons, F

2014-08-01

178

Os odontoideum with bipartite atlas and segmental instability: a case report  

Microsoft Academic Search

We report on the case of a 15-year-old adolescent who presented with a transient paraplegia and hyposensibility of the upper\\u000a extremities after sustaining a minor hyperflexion trauma to the cervical spine. Neuroimaging studies revealed atlantoaxial\\u000a dislocation and ventral compression of the rostral spinal cord with increased cord signal at C1\\/C2 levels caused by an os\\u000a odontoideum, as well as anterior

Michael Osti; Helmut Philipp; Berthold Meusburger; Karl-Peter Benedetto

2006-01-01

179

Effects of compression stockings on sympathetic activity and heart rate variability in individuals with spinal cord injury  

PubMed Central

Objective To investigate whether wearing graduated compression stockings (GCS) could affect the sympatho-adrenergic and heart rate variability (HRV) responses at rest and after a strenuous wheelchair exercise in individuals with spinal cord injury (SCI). Design Crossover trial. Setting Department of Physical Medicine and Rehabilitation, Saint Etienne, France. Participants Nine men with SCI (five with low paraplegia: LP, four with high paraplegia: HP). Interventions Two maximal wheelchair exercise tests: with and without GCS (21 mmHg). Main outcome measures HRV measurements: high frequency (HF), low frequency (LF), and LF/HF ratio. Norepinephrine (NOR) and epinephrine (EPI), at rest and post-exercise. Secondary measures were: blood pressure, heart rate, maximal power output, oxygen uptake, stroke volume, cardiac output, at rest, during and after exercise. Results When wearing GCS: LFnuwavelet-post significantly increased and HFnuwavelet-post significantly decreased (P < 0.05) in SCI subjects, leading to an enhance ratio of LFwavelet/HFwavelet and a significantly increased in NORrest (P < 0.05). Conclusions GCS induces an enhanced sympathetic activity in individuals with paraplegia, regardless of the level of the injury. Enhanced post-exercise sympathetic activity with GCS may help prevent orthostatic hypotension or post-exercise hypotension. PMID:22333734

Rimaud, Diana; Calmels, Paul; Pichot, Vincent; Bethoux, Francois; Roche, Frederic

2012-01-01

180

Alsin Related Disorders: Literature Review and Case Study with Novel Mutations  

PubMed Central

Mutations in the ALS2 gene cause three distinct disorders: infantile ascending hereditary spastic paraplegia, juvenile primary lateral sclerosis, and autosomal recessive juvenile amyotrophic lateral sclerosis. We present a review of the literature and the case of a 16-year-old boy who is, to the best of our knowledge, the first Portuguese case with infantile ascending hereditary spastic paraplegia. Clinical investigations included sequencing analysis of the ALS2 gene, which revealed a heterozygous mutation in exon 5 (c.1425_1428del p.G477Afs*19) and a heterozygous and previously unreported variant in exon 3 (c.145G>A p.G49R). We also examined 42 reported cases on the clinical characteristics and neurophysiological and imaging studies of patients with known ALS2 gene mutations sourced from PubMed. This showed that an overlap of phenotypic manifestations can exist in patients with infantile ascending hereditary spastic paraplegia, juvenile primary lateral sclerosis, and juvenile amyotrophic lateral sclerosis.

Flor-de-Lima, Filipa; Sampaio, Mafalda; Nahavandi, Nahid; Fernandes, Susana; Leao, Miguel

2014-01-01

181

Influence of neurological level on immune function following spinal cord injury: a review.  

PubMed

Due to the high incidence of lifelong infections in persons with spinal cord injury (SCI), the authors examined level of injury-related immune characteristics in a cohort of subjects with chronic SCI. Since the sympathetic nervous system and the endocrine system are known to be modulators of immune function, one possible explanation for heightened incidence of infections includes dysregulation of sympathetic outflow tracts in individuals with tetraplegia or high paraplegia. Natural killer cell cytotoxicity (NKCC) and bactericidal function of circulating neutrophils were assayed in a group of 10 individuals with chronic complete cervical SCI, a group of 8 individuals with paraplegia with injuries below the main sympathetic outflow (T-10 and below) and a group of 18 age- and sex-matched controls. In addition, a psychiatric assessment of depression was performed as well as assays of pituitary and adrenal functions. Analyses revealed no significant differences in immune function between all subjects with SCI combined and their matched controls. Further analyses stratifying based on presence or absence of sympathetic dysregulation revealed significantly impaired phagocytic ability and a trend toward reduced NKCC in the group with tetraplegia compared with their controls. Hormonal assays showed that dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DS) were higher in individuals with tetraplegia than controls, but no such differences were observed in individuals with paraplegia compared with their controls. The results of this study suggest that individuals sustaining complete cervical SCI experience alterations in immune function, while those with lesions at or below T-10 do not. These findings of level of injury related immune alteration could not be explained by mood differences. This paper is a review of previously published work and the authors' current thinking regarding increased acquisition of infections in this population. PMID:10914353

Campagnolo, D I; Bartlett, J A; Keller, S E

2000-01-01

182

Completely Intracorporeal Robotic-Assisted Laparoscopic Ileovesicostomy  

PubMed Central

We present a report of a completely intracorporeal robotic-assisted laparoscopic ileovesicostomy with long term follow-up. The patient was a 55-year-old man with paraplegia secondary to tropical spastic paresis resulting neurogenic bladder dysfunction. The procedure was performed using a da Vinci Surgical system (Intuitive Surgical, Sunnyvale, CA) and took 330 minutes with an estimated blood loss of 100?mL. The patient recovered without perioperative complications. He continues to have low pressure drainage without urethral incontinence over two years postoperatively. PMID:24600527

Dolat, MaryEllen T.; Wade, Greg; Grob, B. Mayer; Hampton, Lance J.; Klausner, Adam P.

2014-01-01

183

A novel mutation in VCP causes Charcot-Marie-Tooth Type 2 disease.  

PubMed

Mutations in VCP have been reported to account for a spectrum of phenotypes that include inclusion body myopathy with Paget's disease of the bone and frontotemporal dementia, hereditary spastic paraplegia, and 1-2% of familial amyotrophic lateral sclerosis. We identified a novel VCP mutation (p.Glu185Lys) segregating in an autosomal dominant Charcot-Marie-Tooth disease type 2 family. Functional studies showed that the Glu185Lys variant impaired autophagic function leading to the accumulation of immature autophagosomes. VCP mutations should thus be considered for genetically undefined Charcot-Marie-Tooth disease type 2. PMID:25125609

Gonzalez, Michael A; Feely, Shawna M; Speziani, Fiorella; Strickland, Alleene V; Danzi, Matt; Bacon, Chelsea; Lee, Youjin; Chou, Tsui-Fen; Blanton, Susan H; Weihl, Conrad C; Zuchner, Stephan; Shy, Michael E

2014-11-01

184

Molecular Genetic Analysis of the PLP1 Gene in 38 Families with PLP1 -related disorders: Identification and Functional Characterization of 11 Novel PLP1 Mutations  

Microsoft Academic Search

Background  The breadth of the clinical spectrum underlying Pelizaeus-Merzbacher disease and spastic paraplegia type 2 is due to the extensive\\u000a allelic heterogeneity in the X-linked PLP1 gene encoding myelin proteolipid protein (PLP). PLP1 mutations range from gene duplications of variable size found in 60-70% of patients to intragenic lesions present in 15-20%\\u000a of patients.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Forty-eight male patients from 38 unrelated families

Serena Grossi; Stefano Regis; Roberta Biancheri; Matthew Mort; Susanna Lualdi; Enrico Bertini; Graziella Uziel; Odile Boespflug-Tanguy; Alessandro Simonati; Fabio Corsolini; Ercan Demir; Valentina Marchiani; Antonio Percesepe; Franco Stanzial; Andrea Rossi; Catherine Vaurs-Barrière; David N Cooper; Mirella Filocamo

2011-01-01

185

Lower motor neuron paralysis with extensive cord atrophy in parainfectious acute transverse myelitis.  

PubMed

We describe a young patient of acute transverse myelitis (ATM) who developed true lower motor neuron (LMN) type flaccid paraplegia as a result of anterior horn cell damage in the region of cord inflammation that extended from conus upwards up to the D4 transverse level. We infer that flaccidity in acute phase of ATM is not always due to spinal shock and may represent true LMN paralysis particularly if the long segment myelits is severe and extending up to last spinal segment. PMID:25221410

Pradhan, Sunil; Kumar, Ajit

2014-07-01

186

Neurologic complications associated with influenza vaccination: two adult cases.  

PubMed

We describe two adult cases of neurologic complications occurring after influenza vaccination. The first case was a 62-year-old man who experienced convulsions 5 days after vaccination, and the second case was a 70-year-old man who exhibited paraplegia 7 days after vaccination. Diagnoses of acute disseminated encephalomyelitis and transverse myelitis with acute motor axonal neuropathy were made, respectively, and steroid pulse therapy and intravenous gamma globulin therapy alleviated the patients' symptoms. Although the efficacy and cost benefit of influenza vaccination have been widely accepted, such neurologic complications might occur in the elderly or even in adults. PMID:12636241

Nakamura, Naoko; Nokura, Kazuya; Zettsu, Takaaki; Koga, Hiroshi; Tachi, Masayuki; Terada, Masaki; Katoh, Hideshi; Itoh, Yuri; Osawa, Hiroyuki; Ozeki, Toshihiko; Yamamoto, Hiroko

2003-02-01

187

Unusual presentations of abdominal aortic aneurysms.  

PubMed

A review of the records of 100 consecutive patients undergoing surgical repair of abdominal aortic aneurysms disclosed two individuals who presented in a fashion sufficiently rare as to warrant detailed discussion. The first had concomitant rupture and thrombosis manifested by lower extremity paraplegia and anesthesia, and the second had documented DIC in conjunction with a stable aneurysm. The latter completely resolved with heparin and subsequent surgical repair. Each of these presentations has had documentation in the surgical literature in less than five instances, and both case histories are given, followed by a review of the literature and theories as to the underlying pathophysiology. PMID:7217187

Keagy, B A; Pharr, W F; Bowes, D E

1981-01-01

188

From new genetics to everyday knowledge: Ideas about how genetic diseases are transmitted in two large Brazilian families  

NASA Astrophysics Data System (ADS)

This study focuses on everyday or lay understandings of inheritance. In the northeastern Brazil, 100 individuals were interviewed in order to describe how they explain the origin of genetic disorders affecting their relatives for several generations. There were involved 60 individuals from a large consanguineous family with many members affected with a neurodegenerative disorder, SPOAN syndrome (spastic paraplegia, optic atrophy and neuropathy), and 40 individuals of another family living with neurofibromatosis type 1 (NF1). The results indicate that families here studied have built narratives to explain the origin of genetic diseases, saying that an ancestor infected with syphilis gave rise to disorders and birthmarks transmitted to descendents.

Santos, Silvana; Bizzo, Nelio

2005-07-01

189

SPG11 Presenting with Tremor  

PubMed Central

Background Hereditary spastic paraplegias (HSPs) are a clinically and genetically heterogeneous group of neurological diseases, which typically present with progressive lower extremity weakness and spasticity causing progressive walking difficulties. Complicating neurological or extraneurological features may be present. Case Report We describe a 19-year-old male who was referred because of an action tremor of the hands; he later developed walking difficulties. Callosal atrophy was present on his cerebral magnetic resonance imaging scan, prompting genetic testing for SPG11, which revealed homozygous mutations. Discussion The clinical features, differential diagnosis and management of SPG11, the most common form of autosomal recessive complicated HSP with a thin corpus callosum are discussed. PMID:23439843

Schneider, Susanne A.; Mummery, Catherine J.; Mehrabian, Mohadeseh; Houlden, Henry; Bain, Peter G.

2012-01-01

190

Circumscribed myositis ossificans of the masseter muscle: report of a case  

PubMed Central

Summary Myositis Ossificans (MO) is an unusual pathological entity still largely unknown, characterized by dystrophic calcification leading to heterotopic ossification of intramuscular connective tissue. The masticatory muscles are exceptionally involved. Four distinct types of myositis ossificans have been described: MO Progressiva, which is a genetic disorder involving several muscular groups; MO Circumscripta, limited to a single muscle and generally due to calcification of an intramuscular haematoma following severe trauma and progressive ossification; MO Pseudo-malignant limited to soft tissue and not associated to any trauma; MO associated to paraplegia. A case of circumscribed myositis ossificans of the masseter muscle in a 62 years-old woma is reportedn. PMID:24629814

PIOMBINO, P.; ORABONA, G. DELL'AVERSANA; ABBATE, V.; FINI, G.; LIBERATORE, G.M.; MICI, E.; BELLI, E.

2013-01-01

191

Circumscribed myositis ossificans of the masseter muscle: report of a case.  

PubMed

Myositis Ossificans (MO) is an unusual pathological entity still largely unknown, characterized by dystrophic calcification leading to heterotopic ossification of intramuscular connective tissue. The masticatory muscles are exceptionally involved. Four distinct types of myositis ossificans have been described: MO Progressiva, which is a genetic disorder involving several muscular groups; MO Circumscripta, limited to a single muscle and generally due to calcification of an intramuscular haematoma following severe trauma and progressive ossification; MO Pseudo-malignant limited to soft tissue and not associated to any trauma; MO associated to paraplegia. A case of circumscribed myositis ossificans of the masseter muscle in a 62 years-old woman is reported. PMID:24629814

Piombino, P; Dell'Aversana Orabona, G; Abbate, V; Fini, G; Liberatore, G M; Mici, E; Belli, E

2013-01-01

192

Longitudinal myelitis in systemic lupus erythematosus: a paediatric case.  

PubMed

Acute transverse myelitis (ATM) is a very rare manifestation of the central nervous system in systemic lupus erythematosus (SLE), especially in case of involvement of continuous segments (longitudinal myelitis). We describe a 12-year-old female with lupus correlated with transverse myelitis with a longitudinal involvement of the spinal cord (D2 to D10) at the onset of the disease. Despite the administration of an early aggressive therapy, the outcome proved to be unfavourable. After 2 years of follow-up, the child still complains of paraplegia, sphincter incontinency and ipo-paresthesias of both legs. PMID:21792641

Campana, Andrea; Buonuomo, Paola Sabrina; Insalaco, Antonella; Bracaglia, Claudia; Di Capua, Matteo; Cortis, Elisabetta; Ugazio, Alberto G

2012-08-01

193

Gait ataxia as a presenting symptom of malignant epidural spinal cord compression.  

PubMed Central

A 68 year old man with prostatic carcinoma developed spinal cord compression. The sole presenting feature was painless gait ataxia indistinguishable from cerebellar ataxia. He was investigated for cerebellar disease but the correct diagnosis was made when he subsequently presented with paraplegia and classical signs of spinal cord compression. Surgical decompression failed to produce neurological recovery. We discuss the importance of recognizing this unusual presentation of spinal cord compression, its possible mechanism and evidence that it may be under-reported. Images Figure 1 Figure 2 PMID:3774706

Karp, S. J.; Ho, R. T.

1986-01-01

194

[Slowly progressive dysarthria in primary lateral sclerosis].  

PubMed

Slowly progressive dysarthria over many years may be the only sign of primary lateral sclerosis (PLS). Clinically it presents as pseudobulbar palsy which can be differentiated from amyotrophic lateral sclerosis (ALS) by the longer disease duration (> or =4 years), central pathological magnetic-evoked potentials to the tongue and lack of denervation in EMG. In contrast, hereditary spastic paraplegia (HSP) is characterized by a primary spasticity of the lower limbs, mostly later onset, the fact that other family members are affected and in isolated cases by positive genetic testing for mutations. PMID:20532474

Urban, P P; Wellach, I; Pohlmann, C

2010-08-01

195

Tuberculosis of spine: neurological deficit.  

PubMed

The most dreaded neurological complications in TB spine occur in active stage of disease by mechanical compression, instability and inflammation changes, while in healed disease, these occur due to intrinsic changes in spinal cord secondary to internal salient in long standing kyphotic deformity. A judicious combination of conservative therapy and operative decompression when needed should form a comprehensive integrated course of treatment for TB spine with neurological complications. The patients showing relatively preserved cord with evidence of edema/myelitis with predominantly fluid collection in extradural space on MRI resolve on non-operative treatment, while the patients with extradural compression of mixed or granulomatous nature showing entrapment of spinal cord should be undertaken for early surgical decompression. The disease focus should be debrided with removal of pus caseous tissue and sequestra. The viable bone should only be removed to decompress the spinal cord and resultant gap should be bridged by bone graft. The preserved volume of spinal cord with edema/myelitis and wet lesion on MRI usually would show good neural recovery. The spinal cord showing myelomalacia with reduced cord volume and dry lesion likely to show a poor neural recovery. The internal kyphectomy is indicated for paraplegia with healed disease. These cases are bad risk for surgery and neural recovery. The best form of treatment of late onset paraplegia is the prevention of development of severe kyphosis in initial active stage of disease. PMID:22565802

Jain, Anil K; Kumar, Jaswant

2013-06-01

196

Perioperative implications of retrograde flow in both the subclavian arteries in an adult undergoing surgical repair of coarctation of aorta.  

PubMed

During surgical repair of coarctation of aorta (CoA), management of spinal cord ischemia and prevention of paraplegia is an important issue. The risk factors for paraplegia include level and duration of aortic-clamping, clamping of left subclavian artery (SCA), intraoperative temperature, variability of collateral circulation to the spinal cord, cerebrospinal fluid pressure, upper body arterial pressure, and aortic pressure beyond the aortic clamp. A short clamp time (<30 min), and distal aortic pressure>60 mmHg, minimizes the risks of spinal cord injury. In an adult patient during surgical repair of CoA, the arterial pressure in the femoral artery remained around 45 mmHg and repair took 83 min of aortic-clamping. Neurological assessment on regaining consciousness showed no deficit of lower limbs. Aortic root angiogram had shown retrograde filling of both SCAs. A unique situation in which clamping of SCAs would increase flow to the spinal cord as their clamping would stop stealing of blood and aortic-clamping proximal to CoA will further increase collateral flow; because of these reasons, the patient tolerated prolonged aortic-clamping despite low distal aortic pressure without neurological deficit. However, aortic-clamping increased left ventricular after-load and the patient developed worsening of mitral regurgitation and pulmonary hypertension during aortic clamping. PMID:21123195

Neema, Praveen Kumar; Manikandan, Sethuraman; Bodhey, Narendra; Gupta, Arun Kumar

2011-02-01

197

A Spinal Arteriovenous Fistula in a 3-Year Old Boy  

PubMed Central

We present a case of a 3-year-old boy with neurodegeneration. Family history reveals Rendu-Osler-Weber disease. Magnetic resonance imaging (MRI) of the spinal cord and spinal angiography showed a spinal arteriovenous fistula with venous aneurysm, causing compression of the lumbar spinal cord. Embolisation of the fistula was executed, resulting in clinical improvement. A week after discharge he was readmitted with neurologic regression. A second MRI scan revealed an intraspinal epidural haematoma and increase in size of the aneurysm with several new arterial feeders leading to it. Coiling of the aneurysm and fistulas was performed. Postoperative, the spinal oedema increased despite corticoids, causing more extensive paraplegia of the lower limbs and a deterioration of his mental state. A laminectomy was performed and the aneurysm was surgically removed. Subsequently, the boy recovered gradually. A new MRI scan after two months showed less oedema and a split, partly affected spinal chord. This case shows the importance of excluding possible arteriovenous malformations in a child presenting with progressive neurodegeneration. In particular when there is a family history for Rendu-Osler-Weber disease, scans should be performed instantly to rule out this possibility. The case also highlights the possibility of good recovery of paraplegia in paediatric Rendu-Osler-Weber patients. PMID:24707424

Crijnen, Thomas E. M.; Voormolen, Maurits H. J.; Robert, Dominique; Jorens, Philippe G.; Ramet, Jose

2014-01-01

198

[Surgery of the descending thoracic and thoraco-abdominal arteries. Report of 105 cases].  

PubMed

The Authors show their casistic of about 105 cases of thoracic descending and thoraco-abdominal aorta pathologies between 1.1.1993 and 30.12.1995. After a short introduction about the improvements in anesthesia and reanimation of these pathologies as well as the good reliability of diagnostic and currently available instruments, mortality and mobility parameters are taken into account, the last one referring to paraplegia and ARF. The casistic is evaluated splitting the cases into 2 groups, urgent surgery and election surgery, and differentiating the aneurysm type from the dissection type. Besides, the mortality and mobility are reported for any pathology, with a discussion of the parameters which drove the choice of the most suitable methodology to be adopted (ECC femoro-subclavian shunt, simple clamping). The results achieved show a mortality of 40% in urgency, between 5 and 15% in election, with a rate of paraplegia around 8-10% and a ARF between 5 and 15%. These data match the literature statistics and support the quality of the adopted methodologies. PMID:9303858

Zanetti, P P; Rosa, G; Sorisio, V; Cavanenghi, D; Amerio, G M; Stillo, R; Zappa, A; Cardellino, S; Franco, M; Muncinelli, M

1997-07-01

199

Validity of Computer Adaptive Tests of Daily Routines for Youth with Spinal Cord Injury  

PubMed Central

Objective: To evaluate the accuracy of computer adaptive tests (CATs) of daily routines for child- and parent-reported outcomes following pediatric spinal cord injury (SCI) and to evaluate the validity of the scales. Methods: One hundred ninety-six daily routine items were administered to 381 youths and 322 parents. Pearson correlations, intraclass correlation coefficients (ICC), and 95% confidence intervals (CI) were calculated to evaluate the accuracy of simulated 5-item, 10-item, and 15-item CATs against the full-item banks and to evaluate concurrent validity. Independent samples t tests and analysis of variance were used to evaluate the ability of the daily routine scales to discriminate between children with tetraplegia and paraplegia and among 5 motor groups. Results: ICC and 95% CI demonstrated that simulated 5-, 10-, and 15-item CATs accurately represented the full-item banks for both child- and parent-report scales. The daily routine scales demonstrated discriminative validity, except between 2 motor groups of children with paraplegia. Concurrent validity of the daily routine scales was demonstrated through significant relationships with the FIM scores. Conclusion: Child- and parent-reported outcomes of daily routines can be obtained using CATs with the same relative precision of a full-item bank. Five-item, 10-item, and 15-item CATs have discriminative and concurrent validity. PMID:23671380

Haley, Stephen M.

2013-01-01

200

Adult Hip Flexion Contracture due to Neurological Disease: A New Treatment Protocol--Surgical Treatment of Neurological Hip Flexion Contracture  

PubMed Central

Congenital, traumatic, or extrinsic causes can lead people to paraplegia; some of these are potentially; reversible and others are not. Paraplegia can couse hip flexion contracture and, consequently, pressure sores, scoliosis, and hyperlordosis; lumbar and groin pain are strictly correlated. Scientific literature contains many studies about children hip flexion related to neurological diseases, mainly caused by cerebral palsy; only few papers focus on this complication in adults. In this study we report our experience on surgical treatment of adult hip flexion contracture due to neurological diseases; we have tried to outline an algorithm to choose the best treatment avoiding useless or too aggressive therapies. We present 5 cases of adult hips flexion due to neurological conditions treated following our algorithm. At 1-year-follow-up all patients had a good clinical outcome in terms of hip range of motion, pain and recovery of walking if possible. In conclusion we think that this algorithm could be a good guideline to treat these complex cases even if we need to treat more patients to confirm this theory. We believe also that postoperation physiotherapy it is useful in hip motility preservation, improvement of muscular function, and walking ability recovery when possible. PMID:24707293

Nicodemo, Alberto; Arrigoni, Chiara; Bersano, Andrea; Masse, Alessandro

2014-01-01

201

Late-onset spastic ataxia phenotype in a patient with a homozygous DDHD2 mutation.  

PubMed

Autosomal recessive cerebellar ataxias and autosomal recessive hereditary spastic paraplegias (ARHSPs) are clinically and genetically heterogeneous neurological disorders. Herein we describe Japanese siblings with a midlife-onset, slowly progressive type of cerebellar ataxia and spastic paraplegia, without intellectual disability. Using whole exome sequencing, we identified a homozygous missense mutation in DDHD2, whose mutations were recently identified as the cause of early-onset ARHSP with intellectual disability. Brain MRI of the patient showed a thin corpus callosum. Cerebral proton magnetic resonance spectroscopy revealed an abnormal lipid peak in the basal ganglia, which has been reported as the hallmark of DDHD2-related ARHSP (SPG 54). The mutation caused a marked reduction of phospholipase A1 activity, supporting that this mutation is the cause of SPG54. Our cases indicate that the possibility of SPG54 should also be considered when patients show a combination of adult-onset spastic ataxia and a thin corpus callosum. Magnetic resonance spectroscopy may be helpful in the differential diagnosis of patients with spastic ataxia phenotype. PMID:25417924

Doi, Hiroshi; Ushiyama, Masao; Baba, Takashi; Tani, Katsuko; Shiina, Masaaki; Ogata, Kazuhiro; Miyatake, Satoko; Fukuda-Yuzawa, Yoko; Tsuji, Shoji; Nakashima, Mitsuko; Tsurusaki, Yoshinori; Miyake, Noriko; Saitsu, Hirotomo; Ikeda, Shu-Ichi; Tanaka, Fumiaki; Matsumoto, Naomichi; Yoshida, Kunihiro

2014-01-01

202

Polymerase chain reaction and Southern blot-based analysis of the C9orf72 hexanucleotide repeat in different motor neuron diseases.  

PubMed

The GGGGCC-hexanucleotide repeat expansion in C9orf72 is the most common genetic cause of familial amyotrophic lateral sclerosis and frontotemporal dementia. This study determined the frequency of C9orf72 repeat expansions in different motor neuron diseases (amyotrophic lateral sclerosis (ALS), motor neuron diseases affecting primarily the first or the second motor neuron and hereditary spastic paraplegia). Whereas most studies on C9orf72 repeat expansions published so far rely on a polymerase chain reaction-based screening, we applied both polymerase chain reaction-based techniques and Southern blotting. Furthermore, we determined the sensitivity and specificity of Southern blotting of the C9orf72 hexanucleotide repeat in DNA derived from lymphoblastoid cell lines. C9orf72 repeat expansions were found in 27.1% out of 166 familial ALS patients, only once in 68 sporadic ALS patients, and not in 61 hereditary spastic paraplegia patients or 52 patients with motor neuron diseases affecting clinically primarily either the first or the second motor neuron. We found hints for a correlation between C9orf72 repeat length and the age of onset. Somatic instability of the C9orf72 repeat was observed in lymphoblastoid cell lines compared with DNA derived from whole blood from the same patient and therefore caution is warranted for repeat length determination in immortalized cell lines. PMID:24378086

Hübers, Annemarie; Marroquin, Nicolai; Schmoll, Birgit; Vielhaber, Stefan; Just, Marlies; Mayer, Benjamin; Högel, Josef; Dorst, Johannes; Mertens, Thomas; Just, Walter; Aulitzky, Anna; Wais, Verena; Ludolph, Albert C; Kubisch, Christian; Weishaupt, Jochen H; Volk, Alexander E

2014-05-01

203

The Troyer syndrome (SPG20) protein spartin interacts with Eps15  

SciTech Connect

The hereditary spastic paraplegias comprise a group of inherited neurological disorders in which the primary manifestation is spastic weakness of the lower extremities. Troyer syndrome is an autosomal recessive form of spastic paraplegia caused by a frameshift mutation in the spartin (SPG20) gene. Currently, neither the localization nor the functions of the spartin protein are known. In this study, we generated anti-spartin antibodies and found that spartin is both cytosolic and membrane-associated. Using a yeast two-hybrid approach, we screened an adult human brain library for binding partners of spartin. We identified Eps15, a protein known to be involved in endocytosis and the control of cell proliferation. This interaction was confirmed by fusion protein 'pull-down' experiments as well as a cellular redistribution assay. Our results suggest that spartin might be involved in endocytosis, vesicle trafficking, or mitogenic activity, and that impairment in one of these processes may underlie the long axonopathy in patients with Troyer syndrome.

Bakowska, Joanna C. [Cellular Neurology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 35, Room 2C-913, 9000 Rockville Pike, Bethesda, MD 20892-3704 (United States); Jenkins, Russell [Cellular Neurology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 35, Room 2C-913, 9000 Rockville Pike, Bethesda, MD 20892-3704 (United States); Pendleton, James [Cellular Neurology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 35, Room 2C-913, 9000 Rockville Pike, Bethesda, MD 20892-3704 (United States); Blackstone, Craig [Cellular Neurology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 35, Room 2C-913, 9000 Rockville Pike, Bethesda, MD 20892-3704 (United States)]. E-mail: blackstc@ninds.nih.gov

2005-09-09

204

Spartin Regulates Synaptic Growth and Neuronal Survival by Inhibiting BMP-Mediated Microtubule Stabilization  

PubMed Central

SUMMARY Troyer syndrome is a hereditary spastic paraplegia caused by human spartin (SPG20) gene mutations. We have generated a Drosophila disease model showing that Spartin functions presynaptically with endocytic adaptor Eps15 to regulate synaptic growth and function. Spartin inhibits bone morphogenetic protein (BMP) signaling by promoting endocytic degradation of BMP receptor wishful thinking (Wit). Drosophila fragile X mental retardation protein (dFMRP) and Futsch/MAP1B are downstream effectors of Spartin and BMP signaling in regulating microtubule stability and synaptic growth. Loss of Spartin or elevation of BMP signaling induces age-dependent progressive defects resembling hereditary spastic paraplegias, including motor dysfunction and brain neurodegeneration. Null spartin phenotypes are prevented by administration of the microtubule-destabilizing drug vinblastine. Together, these results demonstrate that Spartin regulates both synaptic development and neuronal survival by controlling microtubule stability via the BMP-dFMRP-Futsch pathway, suggesting that impaired regulation of microtubule stability is a core pathogenic component in Troyer syndrome. PMID:23439121

Nahm, Minyeop; Lee, Min-Jung; Parkinson, William; Lee, Mihye; Kim, Haeran; Kim, Yoon-Jung; Kim, Sungdae; Cho, Yi Sul; Min, Byung-Moo; Bae, Yong Chul; Broadie, Kendal; Lee, Seungbok

2013-01-01

205

[Non-tuberculous spondylodiscitis. Multicenter study of 19 cases].  

PubMed

19 patients diagnosed as non-tuberculous infectious spondylodiscitis (NTIS) have been studied retrospectively over the last 10 years in three general hospitals. The etiology of 13 cases was confirmed (there were nine cases of Staphylococcus aureus, two of Brucella, one of Pseudomonas aeruginosa and another of Salmonella typhi), and the diagnosis of the remaining cases was based on clinical and radiological data as well as on the evolution with antibiotic treatment. The age of the majority of these patients ranged between 40 and 60 years (p less than 0.05), showing a clear predominance of males (p less than 0.05). The most frequently appearing symptom at the beginning of the disease was local pain which was observed in nine patients; the rest presented mixed symptoms which led to misdiagnosis at admission; an exploratory laparotomy was carried out in one patient. The interval from the symptoms' onset to diagnosis ranged between two and sixteen weeks, with an average of 6.8 weeks. The VSG had values between 22 and 148 mm during the first hour, with an average of 83.3 mm. Seven patients underwent surgery, six of them presenting paraparesis-paraplegia, while another presented cervical spondylodiscitis. One patient passed away, two persisted with paraparesis-paraplegia as an irreversible sequela and one with persistent local pain. PMID:2535664

Gómez Rodríguez, N; Martínez Vázquez, C; Sopeña, B; Portela, J; Carbajo, M; Guerra, V; Arasa, X; Barrio Gómez, E

1989-04-01

206

Transthoracic approach for Pott's disease.  

PubMed

Spinal tuberculosis with paraplegia, although decreasing in incidence, remains a problem in certain sections of the United States and in most underdeveloped nations. Evacuations of the tuberculous abscess, debridement of necrotic bone, and fusion of the anterior spine are maneuvers performed increasingly by thoracic surgeons. Twenty-two patients with Pott's disease and symptoms of back pain, gibbous deformity, and neurological deficit underwent thoracotomy. Nine were paraplegic prior to operation. Postoperatively, spinal fusion occurred in all cases. All paraplegic patients can walk now, and 17 of the 22 treated operatively have been completely rehabilitated and are in school or working. The average hospital stay was 2.4 months. There was 1 operative death. Medical treatment for Pott's disease consisted of bed rest and chemotherapy and resulted in progressive neurological deficit in 2 patients with an average hospital stay of 2.2 years. We believe operative treatment offers two distinct advantages: excellent reversal of even long-standing paraplegia and markedly shortened hospital stay. PMID:776109

Richardson, J D; Campbell, D L; Grover, F L; Arom, K V; Wilkins, K; Wissinger, J P; Trinkle, J K

1976-06-01

207

[A case of spastic paraparesis with mental deterioration and markedly thin corpus callosum--callosal dysfunction demonstrated by magnetic stimulation].  

PubMed

We have studied function of the corpus callosum in a patient with spastic paraparesis with mental deterioration and markedly thin corpus callosum using magnetic stimulation methods. In a 21-year-old woman with slowly progressive gait disturbance, neurological examination showed mental deterioration, euphoria, spastic paraparesis, bilateral Babinski's sign, and hyperesthesia caudal to the eighth thoracic level. No abnormalities were observed in electroencephalograms. Magnetic resonance imaging (MRI) studies of the brain showed cerebral cortical atrophy, markedly thin corpus callosum, and dilated cavum septum pellucidum and cavum Vergae, but spinal cord MRIs showed no abnormalities. The lysosomal enzyme activities, whose reduction was known to cause leukodystrophy, were all normal. Very long chain fatty acid was not increased in her blood, which is against adrenoleukodystrophy. She had no anti-HTLV-1 virus antibody. Based on these clinical features and the results of biochemical analyses, we diagnosed this patient as having spastic paraplegia associated with hypoplasia of the corpus callosum (Nojima and Iwabuchi). We performed three studies on the central motor pathways in this patient. The latencies of responses recorded from upper or lower limb muscles were all within the normal range, despite that the thresholds were slightly increased. This suggests that axonal degeneration occurs in the central motor pathways, which is consistent with the autopsy findings of a patient with hereditary spastic paraplegia associated with hypoplasia of the corpus callosum. Connection between the bilateral motor cortices was investigated by magnetic stimulation of both motor cortices. The suppression of the motor cortex evoked by stimulation of the contralateral motor cortex through the corpus callosum was absent in this patient. Intracortical inhibition within the motor cortex was demonstrated to be normal by a paired-magnetic stimulation technique. Based on the results of these results of these two experiments, we conclude that the function of the corpus callosum was disturbed in the present patient. This report first shows the functional abnormality of the extremely thin corpus callosum in a patient with hereditary spastic paraplegia associated with hypoplasia of the corpus callosum. PMID:9805987

Katayama, T; Sakamoto, N; Kuroda, K; Yahara, O; Ugawa, Y

1998-05-01

208

Substandard urological care of elderly patients with spinal cord injury: an unrecognized epidemic?  

PubMed Central

Background We report the anecdotal observation of substandard urological care of elderly paraplegic patients in the community suffering from long-term sequelae of spinal cord injuries. This article is designed to increase awareness of a problem that is likely underreported and may represent the ‘tip of the iceberg’ related to substandard care provided to the vulnerable population of elderly patients with chronic neurological impairment. Findings A registered Nurse changed the urethral catheter of an 80-year-old-male with paraplegia; patient developed profuse urethral bleeding and septicaemia. Ultrasound revealed balloon of Foley catheter located in membranous urethra. Flexible cystoscopy was performed and a catheter was inserted over a guide wire. Urethral bleeding recurred 12 days later. This patient was discharged after protracted stay in spinal unit. A nurse changed urethral catheter in an 82-year-old male with paraplegia. The catheter did not drain urine; patient developed pain in lower abdomen. The balloon of Foley catheter was visible behind the urethral meatus, which indicated that the balloon had been inflated in penile urethra. The catheter was removed and a 16 French Foley catheter was inserted per urethra. About 1300 ml of urine was drained. A 91-year-old lady with paraplegia underwent routine ultrasound examination of urinary tract by a Consultant Radiologist, who reported a 4 cm × 3 cm soft tissue mass in the urinary bladder. Cystoscopy was performed without anaesthesia in lithotomy position. Cystoscopy revealed normal bladder mucosa; no stones; no tumour. Following cystoscopy, the right knee became swollen and there was deformity of lower third of right thigh. X-ray revealed fracture of lower third of right femur. Femoral fracture was treated by immobilisation in full plaster cast. Follow-up ultrasound examination of urinary tract, performed by a senior Radiologist, revealed normal outline of urinary bladder with no tumour or calculus. Conclusion The adverse outcomes can be averted if elderly spinal cord injury patients are treated by senior, experienced health professionals, who are familiar with changes in body systems due to old age, compounded further by spinal cord injury. PMID:24447309

2014-01-01

209

[Long-term follow-up in patients with spinal cord injury - prevention and comprehensive care].  

PubMed

Patients with spinal cord injuries suffer not only from sensory and motor deficits, but from failure of the autonomic nerve system which in consequence involves many organs and metabolic pathways. These deficits lead to a different approach to these patients and their medical, psychological and social problems. Three examples will illustrate the different approaches to typical medical problems of these patients. Regularly ambulatory long term follow up visits in specialized centres in close collaboration with general practitioners help to diminish complications and rehospitalisations. Facing the now ageing population with a spinal cord injury we need evidence based guidelines in follow up and preventive strategies for these patients. We updated these recommendations recently. The brochure is available on the webside oft he swiss society of paraplegia www.ssop.ch. PMID:24425548

Spreyermann, Regula; Michel, Franz

2014-01-15

210

[Absconding of a patient from an acute psychiatric ward. Whom do the courts hold liable?].  

PubMed

An involuntarily admitted patient absconds from a mental health hospital, which works on the open-door-system. Two days after leaving, he falls from a balcony on the fifth floor of a residential building and injures himself severely (paraplegia). The court case concerning damages and responsibility for paying the costs of the medical treatment eventually reaches the Kammergericht, the highest court of the state of Berlin. The main question in each trial was whether the hospital had violated its duty and was responsible for the accident and the resulting severe injuries. Relying on the hospital's documentation, the courts noted that closing the door of a ward is actually only one of the various possibilities of preventing absconding. The Kammergericht accepted the arguments of the hospital that prevention of absconding can also be achieved by intensive personal care and that security measures should not disturb the therapeutic alliance with the patient. PMID:20183774

Fähndrich, Erdmann; Munk, Ingrid

2010-03-01

211

[Neurologic complications of surgery of the spine in children].  

PubMed

Neurological deficiency can occur during or after spinal surgery. The most severe complications are seen after instrumental correction for scoliosis or kyphosis. Regression of paraplegia, paraparesia and Brown-Sequard syndrome is never a certainty and usually incomplete. Preoperative manoeuvres and evoked potentials do not provide absolute security and metal instrumentation should always be used prudently. The main risk factors are vertebral malformation, major kyphosis, preoperative signs of neurological deficit, excessive correction and double anterior and posterior access. Finally, the canal is poorly vascularized from T4 to T8 or T9 which can raise further problems. Cordal deficiency during or following almost always requires removal of the metal implant, and exploration of the canal possibly with MRI. Injury include direct contusion of the spinal cord, devascularization and compressive haematomas. The frequency of neurological complications is currently about 1% and only extreme prudence and knowledge of causes can reduce this rate. PMID:8665810

Carlioz, H; Ouaknine, M

212

Spinal cord ischemia after aortic surgery.  

PubMed

This article discusses the etiology of spinal cord ischemia (SCI) mechanisms that may lead to paraplegia during open and endovascular repair from an anatomical and physiological perspective as well as the role of various protective measures used in prevention of this dreadful complication of aortic surgery. There are many adjuncts that must be considered to reduce the risk of spinal cord injury, such as revascularisation of intercostal arteries, maintenance of high mean blood pressure, spinal cord drainage and a few new promising models like NIRS and MISACE which usefulness is yet to be determined. These measures and techniques as well as possible etiology mechanisms of SCI are discussed, highlighting the evidence available for each method, the practical ways in which they may be used, giving some new theories and explanations. PMID:25017787

Davidovic, L; Ilic, N

2014-12-01

213

Epidemiologic Change of Patients With Spinal Cord Injury  

PubMed Central

Objective To evaluate the epidemiologic change of patients with spinal cord injury who were admitted to a Rehabilitation Hospital, Yonsei University College of Medicine, during 1987-1996 and 2004-2008. Methods Medical records of 629 patients with spinal cord injury admitted to the Rehabilitation Hospital, Yonsei University College of Medicine, from 2004 to 2008 were collected and reviewed retrospectively. Results The male-to-female ratio decreased to 2.86:1, the mean age at injury increased, nontraumatic etiology increased, traffic accident remained to be the most common in traumatic spinal cord injury, and falling increased significantly. Tumor was the most common etiology in nontraumatic spinal cord injury, tetraplegia and incomplete injuries occurred more than paraplegia and complete injuries, indwelling catheter was the most common voiding method, and the duration of hospitalization decreased. Conclusion Many trends changed in epidemiology of spinal cord injury. PMID:23525183

Shin, Ji Cheol; Yu, Su Jin; Yang, Hea Eun; Yoon, Seo Yeon

2013-01-01

214

Acupuncture for back pain, knee pain and insomnia in transverse myelitis - a case report.  

PubMed

This case report describes the use of acupuncture for back pain, knee pain and insomnia in a 49 year old woman with a recent diagnosis of transverse myelitis with paraplegia, sensory disturbance, and bladder and bowel dysfunction. She was receiving intensive in-patient multi-disciplinary rehabilitation but was struggling to participate fully due to pain and poor sleep quality. She received a course of acupuncture in addition to standard care and reported substantial benefits including reduction in pain, improved sleep and mood, and reduction in daytime fatigue. Effective symptom control allowed this patient to participate more fully in her rehabilitation programme. Reduction of knee pain and sleep disturbance was maintained until discharge, 15 weeks after the last acupuncture treatment. This case report suggests that acupuncture may be an option to consider for other patients with pain or sleep disturbance that is interfering with their rehabilitation programme. PMID:18818565

Vaghela, Sonia A; Donnellan, Clare P

2008-09-01

215

Steroid-induced Spinal Epidural Lipomatosis after Suprasella Tumor Resection  

PubMed Central

Spinal epidural lipomatosis (SEL) is an abnormal localized accumulation of fat tissues in the epidural space. It is strongly related with steroid administration. The symptoms of SEL are various and range from back pain to paraplegia. In severe cases, decompressive laminectomy is the choice of treatment. A 32-year-old woman who had been under long-term steroid administration after suprasellar tumor resection was admitted for both leg radiating pain and weakness. She was diagnosed with SEL and had a decompressive laminectomy. During the operation, we found the nerve roots were compressed by epidural fat tissues and engorged vessels. After the operation, her radiating pain was relieved and motor weakness was improved. PMID:24757466

Kim, Si On; Park, Keuk Kyu; Kwon, Young Jun; Shin, Hyun Chul

2013-01-01

216

Acute Spontaneous Spinal Subdural Hematoma with Vague Symptoms  

PubMed Central

Spinal subdural hematoma is a rarely reported disease and spontaneous spinal subdural hematomas (SSDH) without underlying pathological changes are even rarer. The patients usually show typical symtoms such as back pain, quadriplegia, paraplegia or sensory change. But rarely, patients may show atypical symptoms such as hemiparesis and misdiagnosed to cerebrovascular accident. We recently experienced a case of SSDH, where the patient initially showed vague symptoms, such as the sudden onset of headache which we initially misdiagnosed as subarachnoid hemorrhage. In this case, the headache of patient improved but the neck pain persisted until hospital day 5. Therefre, we conducted the MRI of cervical spine and finally confirmed SSDH. The patient was managed conservatively and improved without recurrence. In this case report, we discuss the clinical features of SSDH with emphasis on the importance of an early diagnosis. PMID:25368774

Chung, Jaehwan; Hwang, Soo-Hyun; Han, Jong-Woo

2014-01-01

217

[The thoracic aorta aneurism stenting].  

PubMed

27 patients with thoracic aortic aneurism with dissection type III were operated on and stented. The mean age was 56±11,17 years. Men were 24, women 3. 1 patient developed intraoperative stent-graft leakage type IV, and 1 - type II. Both cases needed no additional manipulations. Minimal invasiveness of the procedure and pain absence allowed early activisation of patients. 2 patients had postoperative paraplegia, which was successfully treated by spinal drainage. There were no lethal cases. The long-term follow-up showed no leakage on CT scans; 11 patients demonstrated complete closure of false canal of the stented segment. The overall survival rate was 92.6% after 60 months of follow-up. Unfavorable results were registered in 29.6%. PMID:23503388

Abugov, S A; Belov, Iu V; Puretski?, M V; Strutsenko, M V; Saakian, Iu M; Poliakov, R S; Khovrin, V V; Charchian, E R

2013-01-01

218

Recovery from and Clearance of Rabies Virus in a Domestic Ferret  

PubMed Central

Here we document the case of a domestic ferret (Mustela putorius) that survived experimental inoculation with rabies virus of skunk origin. The ferret showed initial clinical signs of rabies (hindlimb paralysis) on day 81 after inoculation. The animal survived with paraplegia but otherwise was in an adequate nutritional state until the end of the observation period (PI day 181). At necropsy, no gross lesions were observed. Microscopic lesions were found in sections of cerebrum and spinal cord. In both tissues, the lesions were similar but were more severe with loss of neuronal parenchyma in the spinal cord. The lesions consisted of locally extensive areas with proliferation of astrocytes and moderate numbers of glial cells. Severely affected areas also contained clearly defined vacuoles in the neuropil. Multifocal areas of involvement showed mononuclear cuffing of blood vessels. In a few areas, the cuffing extended to the meninges. Rabies virus antigen was not detected by immunohistochemistry of tissue sections. PMID:21439220

Hamir, Amir N; Niezgoda, Michael; Rupprecht, Charles E

2011-01-01

219

Spinal cord injury in an inner city hospital.  

PubMed

During the first six years of existence of the rehabilitation unit in a black inner city major municipal hospital, 53 patients with spinal cord injury were admitted. A retrospective study of these patients sought answers to questions concerning etiology, patient characteristics, services provided and method of delivery, and advantages and disadvantages of rehabilitation in a community hospital. Findings revealed differences in causation of spinal cord injury between women and men and between patients with paraplegia and quadriplegia. tthe male paraplegic patients were the youngest; their life style led to spinal cord injury. Social factors such as inadequate housing, lack of transportation, and insufficient financial resources were deterrents to rehabilitation. An approach that emphasized consideration of all the psychosocial factors was developed. Evaluation and treatment were extended into the community. Lack of peer groups and multiphasic programs were the major disadvantages. PMID:623516

Macauley, C A; Weiss, L

1978-02-01

220

Spinal Epidural Hematoma After Thrombolysis for Deep Vein Thrombosis with Subsequent Pulmonary Thromboembolism: A Case Report  

SciTech Connect

A 38-year-old male was initially admitted for left leg swelling. He was diagnosed as having deep vein thrombosis (DVT) in the left leg and a pulmonary thromboembolism by contrast-enhanced chest computed tomography (CT) with delayed lower extremity CT. The DVT was treated by thrombolysis and a venous stent. Four hours later, he complained of severe back pain and a sensation of separation of his body and lower extremities; he experienced paraplegia early in the morning of the following day. Magnetic resonance imaging showed a spinal epidural hematoma between T11 and L2, which decompressed following surgery. We, therefore, report a case of a spinal epidural hematoma after thrombolysis in a case of DVT with a pulmonary thromboembolism.

Han, Young-Min, E-mail: ymhan@chonbuk.ac.kr; Kwak, Ho-Sung; Jin, Gong-Young; Chung, Gyung-Ho [Chonbuk National University Medical School, Departments of Radiology (Korea, Republic of); Song, Kyung-Jin [Chonbuk National University Medical School, Departments of Orthopedic Surgery (Korea, Republic of)

2006-06-15

221

Adaptor protein complexes and intracellular transport  

PubMed Central

The AP (adaptor protein) complexes are heterotetrameric protein complexes that mediate intracellular membrane trafficking along endocytic and secretory transport pathways. There are five different AP complexes: AP-1, AP-2 and AP-3 are clathrin-associated complexes; whereas AP-4 and AP-5 are not. These five AP complexes localize to different intracellular compartments and mediate membrane trafficking in distinct pathways. They recognize and concentrate cargo proteins into vesicular carriers that mediate transport from a donor membrane to a target organellar membrane. AP complexes play important roles in maintaining the normal physiological function of eukaryotic cells. Dysfunction of AP complexes has been implicated in a variety of inherited disorders, including: MEDNIK (mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis and keratodermia) syndrome, Fried syndrome, HPS (Hermansky–Pudlak syndrome) and HSP (hereditary spastic paraplegia). PMID:24975939

Park, Sang Yoon; Guo, Xiaoli

2014-01-01

222

Spinal ischemia following abdominal aortic surgery.  

PubMed Central

Serious spinal cord ischemia may follow infrarenal abdominal aortic surgery. Five cases are summarized and added to the 23 previously published cases in order to identify this syndrome, emphasize its importance, and draw attention to the possibility of spontaneous recovery which may occur. The multifactorial complex which comprises each patient's clinical picture clouds a precise and specific cause for paraplegia in these cases. However, neither hypotension, steal phenomena nor emboli are necessary for completion of the syndrome. The relevant spinal cord arterial anatomy indicates that the common anomalies which occur favor development of spinal cord ischemia in the arteriosclerotic population which requires aortic surgery. No means of prevention is possible at this time. Images Fig. 1. Fig. 2. PMID:1130846

Ferguson, L R; Bergan, J J; Conn, J; Yao, J S

1975-01-01

223

Spinal Cord Stroke: Acute Imaging and Intervention  

PubMed Central

Spinal cord infarction is an uncommon disease and as such is often a diagnostic challenge for clinicians. It can vary in its onset, severity, outcome, and recovery from patient to patient. Treatment options for this relatively rare condition also remain elusive. Current consensus recommendations are antiplatelet therapy and the symptomatic management of associated complications such as paraplegia and thromboembolic disease. There are multiple studies in surgical literature of a variety of interventions and adjuncts used for reducing the risk of ischemic spinal cord neurological injury, seen most often in the setting of thoracoabdominal aortic repair operations. We report two cases of acute non-surgical-related spinal cord infarcts, where early diagnosis was made and aggressive, early treatments instituted. With often devastating outcomes, we highlight the need for early detection and that interventions, commonly used in preventing neurological injury after high-risk aneurysm repairs, may be beneficial in treating and reducing the severity of disability in acute spinal cord stroke. PMID:22937358

Lynch, Karen; Oster, Joel; Apetauerova, Diana; Hreib, Kinan

2012-01-01

224

The Role of Stent-Grafts in the Management of Aortic Trauma  

SciTech Connect

Stent graft has resulted in major advances in the treatment of trauma patients with blunt traumatic aortic injury (TAI) and has become the preferred method of treatment at many trauma centers. In this review, we provide an overview of the place of stent grafts for the management of this disease. As a whole, TEVAR repair of TAIs offers a survival advantage and reduction in major morbidity, including paraplegia, compared with open surgery. However, endovascular procedures in trauma require a sophisticated multidisciplinary and experienced team approach. More research and development of TAI-specific endograft devices is needed and large, multicenter studies will help to clarify the role of TEVAR compared with open repair of TAI.

Rousseau, Herve, E-mail: rousseau.h@chu-toulouse.fr; Elaassar, Omar [Rangueil Hospital, Department of Radiology (France); Marcheix, Bertrand; Cron, Christophe [Rangueil Hospital, Department of Cardio-Vascular Surgery (France); Chabbert, Valerie; Combelles, Sophie [Rangueil Hospital, Department of Radiology (France); Dambrin, Camille; Leobon, Bertrand [Rangueil Hospital, Department of Cardio-Vascular Surgery (France); Moreno, Ramiro; Otal, Philippe; Auriol, Julien [Rangueil Hospital, Department of Radiology (France)

2012-02-15

225

[Complications of treatment of neuroblastoma].  

PubMed

This article is based on two patients whose tumorous growths were successfully treated and who were cured of tumours and whose treatment had severe consequences. In one female patient, surgical removal of the tumour from the thoracic cavity resulted in haemorrhage into the spinal canal, leading to an irreversible transverse lesion of the cord with paraplegia. In the second patient, irradation with x-rays resulted in extremely severe radiation damage ultimately causing the death of the patient. Within the framework of this discussion, these problems are illuminated in detail. The emphasis is on severe damage in patients in whom the tumour itself has been cured in the course of the requisite therapeutic procedure. The author draws special attention to a stage-correlated treatment of neuroblastoma. PMID:7180204

Hopfgartner, L

1982-11-01

226

Surgical management of thoracic malignancy in childhood: eight years' experience in Leeds.  

PubMed

During the period 1978 to 1986, 13 children aged 2-15 years underwent surgical resection of malignant thoracic tumours. Five children with neuroblastomas presented with chest pain and infections, pleural effusions, dysphagia, lymphadenopathy and paraplegia. Chemo- and radiotherapy were given preoperatively to previously diagnosed cases and postoperatively to all survivors. At operation, complete tumour clearance was possible in only two cases. Two children remain alive with no sign of recurrence at 6 and 7 1/2 years. Eight children with pulmonary metastases had undergone resection of the primary tumour and systemic chemotherapy. All were asymptomatic and were detected by chest radiographs. Wedge resection or lobectomy was performed. Two required contralateral resections at 4 months. Two children remain alive with no evidence of recurrence at 2 and 6 1/2 years. We conclude that aggressive surgical resection of childhood thoracic malignancy is worthwhile, but cooperation with a paediatric oncology team is essential. PMID:3408150

Lodge, J P; Hamilton, J R; Walker, D R; Bailey, C C

1988-03-01

227

Effects of spinal cord lesioning on somatosensory and neurogenic-motor evoked potentials.  

PubMed

Somatosensory (SEPs) and neurogenic-motor evoked potentials (NMEPs) were elicited from 16 hogs and two humans before, during, and after spinal cordotomy, dorsal, or ventral root rhizotomy. Results indicated that SEPs appear to be insensitive to the effects of motor tract lesioning in hogs and humans. In every case of motor paraplegia, SEPs remained unchanged in the presence of abnormal ischiatic/sciatic NMEPs. These results suggest that SEPs are not adequately sensitive to the functional status of the motor system in hogs and humans. Ischiatic/sciatic NMEPs remained unchanged after sensory tract lesioning, suggesting that these NMEPs are insensitive to the functional status of the sensory system. These results suggest that SEPs and NMEPs should be used in combination when monitoring spinal cord function during surgeries that place that structure at risk. PMID:2772714

Owen, J H; Jenny, A B; Naito, M; Weber, K; Bridwell, K H; McGhee, R

1989-07-01

228

Late Prevertebral and Spinal Abscess following Chemoradiation for Laryngeal Squamous Cell Carcinoma  

PubMed Central

Objective. Advanced primary supraglottic tumors (i.e., T3 or T4) have traditionally been treated surgically and postoperative radiotherapy. In the last 2 decades, some patients were treated with chemoradiation avoiding surgery. Case Report. We describe a 55-year old female who presented with respiratory distress and paraplegia seven years after treatment for a T3N0M0 supraglottic squamous cell carcinoma. CT scan showed prevertebral and intraspinal air descending from C4 to D3 vertebras. Epidural and prevertebral abscesses were confirmed by neck exploration. Necrosis was observed in the retropharyngeal, prevertebral, and vertebral tissues. Conclusion. Prevertebral and spinal abscess may result from chemotherapy and radiotherapy to the head and neck. Physicians caring for head and neck cancer patients treated with chemotherapy and radiation should be aware of this rare severe complication. PMID:24716067

Hindy, Jawad; Shelef, Ilan; Slovik, Yuval; Joshua, Ben-Zion

2014-01-01

229

Lumbosacral plexus injury following vaginal delivery with epidural analgesia -A case report-  

PubMed Central

A 26 year old, healthy, 41 week primiparous woman received a patient-controlled epidural analgesia (PCEA) and experienced paraplegia 11 hours later after a vaginal delivery. This was thought to be the result of complications from PCEA but there was no specific abnormality on magnetic resonance imaging (MRI) of the lumbosacral spine. On an electromyography (EMG) study performed 15 days following delivery, signs of tibial neuropathy were present and peripheral nerve injury during vaginal delivery was suspected. Motor weakness and hypoesthesia of both lower extremities improved rapidly, but a decrease in the desire to urinate or defecate, followed by urinary incontinence and constipation persisted, We suspected the sacral plexus had been severely damaged during vaginal delivery. Seven months later, the patient's conditions improved but had not fully recovered. PMID:23459069

Park, Seil; Park, Sung Wook

2013-01-01

230

Motor Weakness after Caudal Epidural Injection Using the Air-acceptance Test  

PubMed Central

Air injected into the epidural space may spread along the nerves of the paravertebral space. Depending on the location of the air, neurologic complications such as multiradicular syndrome, lumbar root compression, and even paraplegia may occur. However, cases of motor weakness caused by air bubbles after caudal epidural injection are rare. A 44-year-old female patient received a caudal epidural injection after an air-acceptance test. Four hours later, she complained of motor weakness in the right lower extremity and numbness of the S1 dermatome. Magnetic resonance imaging showed no anomalies other than an air bubble measuring 13 mm in length and 0.337 ml in volume positioned near the right S1 root. Her symptoms completely regressed within 48 hours. PMID:23862003

Lee, Mi Hyeon; Han, Cheol Sig; Lee, Sang Hoon; Lee, Jeong Hyun; Choi, Eun Mi; Choi, Young Ryong

2013-01-01

231

[Double-barreled wet colostomy: analysis of a urinary diversion].  

PubMed

We analyse our experience in performing the wet colostomy, also called urocolostomy and present seven cases treated at our hospital in which this was used. We present: a) three women, one underwent an urocolostomy as a result of a myelomeningocele with urinary and fecal incontinence, another because of a pelvic malignancy, and the third after developing a post radiotherapy cysto-proctitis; b) four men, one underwent this surgical procedure as a result of a traumatic paraplegia with multiple urinary fistulae and neurogenic bladder, the other three were secondary to pelvic malignancies (two bladder and one sigmoid malignacies). The outcome was fine in all cases with no pyelonephritis or metabolic imbalances; in all cases it represented a good option for these patients. PMID:14587236

Blanco Díez, A; Fernández Rosado, E; Alvarez Castelo, L; Sánchez Rodríguez-Losada, J; Chantada Abal, V; Novás Castro, S; Barbagelata López, A; Serrano Barrientos, J; González Martín, M

2003-09-01

232

Pr\\'{e}sentation d'une m\\'{e}thodologie d'\\'{e}valuation de la faisabilit\\'{e} de la substitution sensorielle par \\'{e}lectrostimulation linguale pour la pr\\'{e}vention des escarres chez le bl\\'{e}ss\\'{e} m\\'{e}dullaire parapl\\'{e}gique  

E-print Network

Pressure ulcers are recognized as a major health issue in individuals with spinal cord injuries and new approaches to prevent this pathology are necessary. An innovative health strategy is being developed through the use of computer and sensory substitution via the tongue in order to compensate for the sensory loss in the buttock area for individuals with paraplegia. This sensory compensation will enable individuals with spinal cord injuries to be aware of a localized excess of pressure at the skin/seat interface and, consequently, will enable them to prevent the formation of pressure ulcers by relieving the cutaneous area of suffering. This work reports an initial evaluation of this approach and the feasibility of creating an adapted behavior, with a change in pressure as a response to electro-stimulated information on the tongue.

Moreau-Gaudry, A; Chenu, O; Demongeot, J; Payan, Y; Moreau-Gaudry, Alexandre; Prince, Anne; Chenu, Olivier; Demongeot, Jacques; Payan, Yohan

2006-01-01

233

Genetics of familial and sporadic amyotrophic lateral sclerosis.  

PubMed

Diseases affecting motor neurons, such as amyotrophic lateral sclerosis (Lou Gerhig's disease), hereditary spastic paraplegia and spinal bulbar muscular atrophy (Kennedy's disease) are a heterogeneous group of chronic progressive diseases and are among the most puzzling yet untreatable illnesses. Over the last decade, identification of mutations in genes predisposing to these disorders has provided the means to better understand their pathogenesis. The discovery 13 years ago of SOD1 mutations linked to ALS, which account for less than 2% of total cases, had a major impact in the field. However, despite intensive research effort, the pathways leading to the specific motor neurons degeneration in the presence of SOD1 mutations have not been fully identified. This review provides an overview of the genetics of both familial and sporadic forms of ALS. PMID:16503123

Gros-Louis, Francois; Gaspar, Claudia; Rouleau, Guy A

2006-01-01

234

Emerging themes of ER organization in the development and maintenance of axons  

PubMed Central

The endoplasmic reticulum (ER) is a continuous membrane system comprising the nuclear envelope, polyribosome-studded peripheral sheets, and a polygonal network of smooth tubules extending throughout the cell. Though protein biosynthesis, transport, and quality control in the ER have been extensively studied, mechanisms underlying the heterogeneous architecture of the ER have been clarified more recently. These insights have increased interest in ER morphology changes associated with the development of neuronal axons and dendrites as well as their integration with pre- and postsynaptic signaling pathways. A number of proteins involved in shaping and distributing the ER network are mutated in neurological disorders, particularly the hereditary spastic paraplegias, emphasizing the importance of proper ER morphology for the establishment and maintenance of highly-polarized neurons. PMID:20678923

Renvoise, Benoit; Blackstone, Craig

2010-01-01

235

Management of Acute Aortic Syndrome and Chronic Aortic Dissection  

SciTech Connect

Acute aortic syndrome (AAS) describes several life-threatening aortic pathologies. These include intramural hematoma, penetrating aortic ulcer, and acute aortic dissection (AAD). Advances in both imaging and endovascular treatment have led to an increase in diagnosis and improved management of these often catastrophic pathologies. Patients, who were previously consigned to medical management or high-risk open surgical repair, can now be offered minimally invasive solutions with reduced morbidity and mortality. Information from the International Registry of Acute Aortic Dissection (IRAD) database demonstrates how in selected patients with complicated AAD the 30-day mortality from open surgery is 17% and endovascular stenting is 6%. Despite these improvements in perioperative deaths, the risks of stroke and paraplegia remain with endovascular treatment (combined outcome risk 4%). The pathophysiology of each aspect of AAS is described. The best imaging techniques and the evolving role of endovascular techniques in the definitive management of AAS are discussed incorporating strategies to reduce perioperative morbidity.

Nordon, Ian M., E-mail: inordon@sgul.ac.uk; Hinchliffe, Robert J.; Loftus, Ian M.; Morgan, Robert A.; Thompson, Matt M. [St George's Hospital, St. George's Vascular Institute, St. James' Wing (United Kingdom)

2011-10-15

236

The Endoplasmic Reticulum-based Acetyltransferases, ATase1 and ATase2, Associate with the Oligosaccharyltransferase to Acetylate Correctly Folded Polypeptides.  

PubMed

The endoplasmic reticulum (ER) has two membrane-bound acetyltransferases responsible for the endoluminal N(?)-lysine acetylation of ER-transiting and -resident proteins. Mutations that impair the ER-based acetylation machinery are associated with developmental defects and a familial form of spastic paraplegia. Deficient ER acetylation in the mouse leads to defects of the immune and nervous system. Here, we report that both ATase1 and ATase2 form homo- and heterodimers and associate with members of the oligosaccharyltransferase (OST) complex. In contrast to the OST, the ATases only modify correctly folded polypetides. Collectively, our studies suggest that one of the functions of the ATases is to work in concert with the OST and "select" correctly folded from unfolded/misfolded transiting polypeptides. PMID:25301944

Ding, Yun; Dellisanti, Cosma D; Ko, Mi Hee; Czajkowski, Cynthia; Puglielli, Luigi

2014-11-14

237

An aggressive vertebral hemangioma in pregnancy: a case report  

PubMed Central

Introduction Pregnancy-related compressive myelopathy secondary to vertebral hemangioma is a rare occurrence and its treatment antepartum is rare. Case presentation A 19-year-old North African woman in her 38th week of pregnancy presented with paraplegia that progressed within 2 days after a rapidly progressive weakness of her lower limbs. Magnetic resonance imaging studies showed compression of her spinal cord in front of the fourth thoracic vertebra for suspected tuberculous spondylitis. A Caesarean section was done followed by corpectomy with a bone graft because we intraoperatively discovered a vertebral hemangioma. Pathology showed an aggressive hemangioma. Conclusion At any term of pregnancy, extensive neurological involvement which is rapidly progressive due to compression should be considered for immediate decompression. PMID:24943121

2014-01-01

238

Open fenestration for complicated acute aortic B dissection  

PubMed Central

Acute type B aortic dissection (ABAD) is a serious cardiovascular emergency in which morbidity and mortality are often related to the presence of complications at clinical presentation. Visceral, renal, and limb ischemia occur in up to 30% of patients with ABAD and are associated with higher in-hospital mortality. The aim of the open fenestration is to resolve the malperfusion by creating a single aortic lumen at the suprarenal or infrarenal level. This surgical procedure is less invasive than total aortic replacement, thus not requiring extracorporeal support and allowing preservation of the intercostal arteries, which results in decreased risk of paraplegia. Surgical aortic fenestration represents an effective and durable option for treating ischemic complications of ABAD, particularly for patients with no aortic dilatation. In the current endovascular era, this open technique serves as an alternative option in case of contraindications or failure of endovascular management of complicated ABAD. PMID:25133107

Segreti, Sara; Grassi, Viviana; Lomazzi, Chiara; Cova, Marta; Piffaretti, Gabriele; Rampoldi, Vincenzo

2014-01-01

239

Artificial Tongue-Placed Tactile Biofeedback for perceptual supplementation: application to human disability and biomedical engineering  

E-print Network

The present paper aims at introducing the innovative technologies, based on the concept of "sensory substitution" or "perceptual supplementation", we are developing in the fields of human disability and biomedical engineering. Precisely, our goal is to design, develop and validate practical assistive biomedical and/technical devices and/or rehabilitating procedures for persons with disabilities, using artificial tongue-placed tactile biofeedback systems. Proposed applications are dealing with: (1) pressure sores prevention in case of spinal cord injuries (persons with paraplegia, or tetraplegia); (2) ankle proprioceptive acuity improvement for driving assistance in older and/or disabled adults; and (3) balance control improvement to prevent fall in older and/or disabled adults. This paper presents results of three feasibility studies performed on young healthy adults.

Vuillerme, Nicolas; Moreau-Gaudry, Alexandre; Demongeot, Jacques; Payan, Yohan

2007-01-01

240

Pressure sensor-based tongue-placed electrotactile biofeedback for balance improvement - Biomedical application to prevent pressure sores formation and falls  

E-print Network

We introduce the innovative technologies, based on the concept of "sensory substitution", we are developing in the fields of biomedical engineering and human disability. Precisely, our goal is to design, develop and validate practical assistive biomedical and/or technical devices and/or rehabilitating procedures for persons with disabilities, using artificial tongue-placed tactile biofeedback systems. Proposed applications are dealing with: (1) pressure sores prevention in case of spinal cord injuries (persons with paraplegia, or tetraplegia); and (2) balance control improvement to prevent fall in older and/or disabled adults. This paper describes the architecture and the functioning principle of these biofeedback systems and presents preliminary results of two feasibility studies performed on young healthy adults.

Vuillerme, Nicolas; Pinsault, Nicolas; Moreau-Gaudry, Alexandre; Fleury, Anthony; Demongeot, Jacques; Payan, Yohan

2007-01-01

241

Epidural hematoma associated with spinal fracture in diffuse idiopathic skeletal hyperostosis.  

PubMed

The authors describe the clinical findings, radiographic appearance and surgical treatment of a spinal epidural hematoma (SEH) associated with spinal fracture in diffuse idiopathic skeletal hyperostosis (DISH). An 81-year-old male patient injured after falling from a 2.5 m tree presented with severe back pain. On plain radiographs and CT images, DISH with anterolateral osteophytes and fused thoracolumbar vertebrae was found along with a T12 fracture. Patient was initially treated with bed rest followed by placement into a body cast. Three weeks later, he presented with incomplete paraplegia of his lower limbs. CT images did not reveal any fracture displacement, but MRI images showed an epidural hematoma compressing the dura mater. The patient was successfully treated by posterior fixation surgery using pedicle screws and rod with vertebroplasty. We aimed to report a unique case of a SEH complicating a spinal fracture in DISH. PMID:24535802

Tauchi, Ryoji; Imagama, Shiro; Satake, Kotaro; Iwase, Toshiki; Ishiguro, Naoki

2014-01-01

242

Physical and social condition of rehabilitated spinal cord injury patients in Japan: a long-term review.  

PubMed

In 1983, 28 Rohsai Hospitals in Japan cooperated to study 926 spinal cord injury (SCI) patients to reveal the problems of their rehabilitation. Fifty per cent complained of poor physical condition and were anxious about their health. In addition to complications rising from the SCI, the morbidities of heart disease, diabetes mellitus, liver disease, hypertension and CVA were higher than the Japanese average. It was noted that 1) 44% of tetraplegic patients were confined to living in their home. 2) Ageing exerted a serious influence upon daily life. 3) Crutch gait for patients with paraplegia was not practical. It was also shown that utilisation of automobiles played an important role in extending social activities. For SCI patients, especially those with tetraplegia, it was very difficult to find employment. The rate of employment was only 30% in all and 46% of these were self-employed. PMID:3047634

Nakajima, A; Honda, S

1988-06-01

243

Delayed Visceral and Spinal Cord Malperfusion after Axillo-Bifemoral Bypass for Complicated Acute Type B Aortic Dissection  

PubMed Central

We describe a successfully treated case of acute type B aortic dissection complicated with lower extremity, visceral, and spinal cord malperfusion. To restore perfusion to both lower extremities, we performed an emergency right axillo-bifemoral bypass. Furthermore, we performed total arch replacement, including primary entry closure, because of delayed visceral organ ischemia. Unexpectedly, delayed paraplegia occurred after hospital discharge; however, the patient recovered without any neurologic sequelae after early introduction of hyperbaric oxygen therapy. Because another episode of organ malperfusion in the long term cannot be anticipated, and even though the previous organ malperfusion episode was treated successfully, close observation is mandatory for detecting clinical manifestations in combination with the availability of imaging modalities. PMID:25298840

Tomioka, Hideyuki; Katahira, Seiichiro; Hoshino, Takeshi; Hanzawa, Kazuhiko

2014-01-01

244

Adaptor protein complexes and intracellular transport.  

PubMed

The AP (adaptor protein) complexes are heterotetrameric protein complexes that mediate intracellular membrane trafficking along endocytic and secretory transport pathways. There are five different AP complexes: AP-1, AP-2 and AP-3 are clathrin-associated complexes; whereas AP-4 and AP-5 are not. These five AP complexes localize to different intracellular compartments and mediate membrane trafficking in distinct pathways. They recognize and concentrate cargo proteins into vesicular carriers that mediate transport from a donor membrane to a target organellar membrane. AP complexes play important roles in maintaining the normal physiological function of eukaryotic cells. Dysfunction of AP complexes has been implicated in a variety of inherited disorders, including: MEDNIK (mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis and keratodermia) syndrome, Fried syndrome, HPS (Hermansky-Pudlak syndrome) and HSP (hereditary spastic paraplegia). PMID:24975939

Park, Sang Yoon; Guo, Xiaoli

2014-01-01

245

Cerebellar vermis hypoplasia in a patient with Bardet-Biedl syndrome.  

PubMed

Laurence-Moon-Bardet-Biedl syndome is an autosomal recessive condition characterized by retinal dystrophy, obesity, mental retardation, distal limb anomaly, hypogonadism, and renal dysfunction. The symptoms vary among families and even among affected siblings. Certain clinical signs have been used to identify subgroups of patients with this complex condition. Laurence-Moon syndrome as a distinct entity is rare and features paraplegia in the absence of polydactyly or obesity. Bardet-Biedl syndrome is characterized by distal limb anomaly, obesity, and renal involvement, but neurologic symptoms are very unusual. We report a patient exhibiting characteristic features of Bardet-Biedl syndrome in addition to cerebellar vermis hypoplasia and mega cisterna magna. PMID:12150587

Baskin, Esra; Kayiran, Sinan Mahir; Oto, Sibel; Alehan, Füsun; Agildere, A Muhtesem; Saatçi, Umit

2002-05-01

246

Physical activity, quality of life, and functional autonomy of adults with spinal cord injuries.  

PubMed

This study aimed to perform a systematic review of studies that address the influence of physical activity on the quality of life and functional independence of adult individuals with spinal cord injury. The review was performed using data obtained from the MEDLINE, CINAHL, SciELO, LILACS, SPORTDiscus, Web of Science, Academic Search Premier, and PEDro databases using the following keywords: quality of life; functional independence; autonomy; independence; physical activity; activities of daily living; physical exercise; tetraplegia; paraplegia; spinal cord injury; physical disabilities; and wheelchair. Eleven studies met the inclusion criteria. Although there was a lack of consensus among the selected studies, the majority of them presented a strong correlation between physical activity and variables of quality of life and/or functional independence. Thus, physical activity appears to have an important influence on social relationships, functional independence, psychological factors, and physical aspects, which can enhance quality of life and independence in the performance of daily activities. PMID:24197622

Kawanishi, Camilla Yuri; Greguol, Márcia

2013-10-01

247

Results of open thoracoabdominal aortic aneurysm repair  

PubMed Central

Background Open surgical repair of thoracoabdominal aortic aneurysms (TAAAs) enables the effective replacement of the diseased aortic segment and reliably prevents aneurysm rupture. However, these operations also carry substantial risk of perioperative morbidity and mortality, principally caused by the associated ischemic insult involving the spinal cord, kidneys, and other abdominal viscera. Here, we describe the early outcomes of a contemporary series of open TAAA repairs. Methods We reviewed the outcomes of 823 open TAAA repairs performed between January 2005 and May 2012. Of these, 209 (25.4%) were Crawford extent I repairs, 264 (32.1%) were extent II, 157 (19.1%) were extent III, and 193 (23.5%) were extent IV. Aortic dissection was present in 350 (42.5%) cases, and aneurysm rupture was present in 37 (4.5%). Adjuncts used during the procedures included cerebrospinal fluid drainage in 639 (77.6%) cases, left heart bypass in 430 (52.2%), and cold renal perfusion in 674 (81.9%). Results The composite endpoint, adverse outcome—defined as operative death, renal failure that necessitated dialysis at discharge, stroke, or permanent paraplegia or paraparesis—occurred after 131 (15.9%) procedures. There were 69 (8.4%) operative deaths. Permanent paraplegia or paraparesis occurred after 42 (5.1%) cases, stroke occurred after 27 (3.3%), and renal failure necessitating permanent dialysis occurred after 45 (5.5%). Conclusions Although open surgical repair of the thoracoabdominal aorta can be life-saving to patients at risk for fatal aneurysm rupture, these operations remain challenging and are associated with substantial risk of early death and major complications. Additional improvements are needed to further reduce the risks associated with TAAA repair, particularly as increasing numbers of patients with advanced age and multiple or severe comorbidities present for treatment. PMID:23977510

Price, Matt D.; Green, Susan Y.; Zarda, Samantha; Coselli, Joseph S.

2012-01-01

248

Physiological Responses to Exergaming After Spinal Cord Injury  

PubMed Central

Purpose: To investigate whether exergaming satisfies guideline-based intensity standards for exercise conditioning (40%/50% oxygen uptake reserve [VO2R] or heart rate reserve (HRR), or 64%/70% of peak heart rate [HRpeak]) in persons with paraplegia. Methods: Nine men and women (18-65 years old) with chronic paraplegia (T1-L1, AIS A-C) underwent intensity-graded arm cycle exercise (AE) to evaluate VO2peak and HRpeak. On 2 randomized nonconsecutive days, participants underwent graded exercise using a custom arm cycle ergometer that controls the video display of a Nintendo Gamecube (GameCycle; Three Rivers Holdings LLC, Mesa, AZ) or 15 minutes of incrementally wrist-weighted tennis gameplay against a televised opponent (XaviX Tennis System; SSD Co Ltd, Kusatsu, Japan). Results: GameCycle exergaming (GCE) resistance settings ?0.88 Nm evoked on average ?50% VO2R. During XaviX Tennis System exergaming (XTSE) with wrist weights ?2 lbs, average VO2 reached a plateau of ~40% VO2R. Measurements of HR were highly variable and reached average values ?50% HRR during GCE at resistance settings ?0.88 Nm. During XTSE, average HR did not reach threshold levels based on HRR for any wrist weight (20%-35% HRR). Conclusions: On average, intensity responses to GCE at resistance setting ?0.88 Nm were sufficient to elicit exercise intensities needed to promote cardiorespiratory fitness in individuals with SCI. The ability of XTSE to elicit cardiorespiratory fitness benefits is most likely limited to individuals with very low fitness levels and may become subminimal with time if used as a conditioning stimulus. PMID:23459619

Burns, Patricia; Kressler, Jochen; Nash, Mark S.

2012-01-01

249

Pott's Spine: Diagnostic Imaging Modalities and Technology Advancements.  

PubMed

Spinal tuberculosis (TB) or Pott's spine is the commonest extrapulmonary manifestation of TB. It spreads through hematogenous route. Clinically, it presents with constitutional symptoms, back pain, tenderness, paraplegia or paraparesis, and kyphotic or scoliotic deformities. Pott's spine accounts for 2% of all cases of TB, 15% of extrapulmonary, and 50% of skeletal TB. The paradiscal, central, anterior subligamentous, and neural arch are the common vertebral lesions. Thoracic vertebrae are commonly affected followed by lumbar and cervical vertebrae. Plain radiographs are usually the initial investigation in spinal TB. For a radiolucent lesion to be apparent on a plain radiograph there should be 30% of bone mineral loss. Computed tomographic scanning provides much better bony detail of irregular lytic lesions, sclerosis, disc collapse, and disruption of bone circumference than plain radiograph. Magnetic resonance imaging (MRI) is the best diagnostic modality for Pott's spine and is more sensitive than other modalities. MRI frequently demonstrates disc collapse/destruction, cold abscess, vertebral wedging/collapse, marrow edema, and spinal deformities. Ultrasound and computed tomographic guided needle aspiration or biopsy is the technique for early histopathological diagnosis. Recently, the coexistence of human immunodeficiency virus infections and TB has been increased globally. In recent years, diffusion-weighted MRI (DW-MRI) and apparent diffusion coefficient values in combination with MRI are used to some extent in the diagnosis of spinal TB. We have reviewed related literature through internet. The terms searched on Google scholar and PubMed are TB, extrapulmonary TB, skeletal TB, spinal TB, Pott's spine, Pott's paraplegia, MRI, and computed tomography (CT). PMID:24020048

Ansari, Sajid; Amanullah, Md Farid; Ahmad, Kaleem; Rauniyar, Raj Kumar

2013-07-01

250

Pott's Spine: Diagnostic Imaging Modalities and Technology Advancements  

PubMed Central

Spinal tuberculosis (TB) or Pott's spine is the commonest extrapulmonary manifestation of TB. It spreads through hematogenous route. Clinically, it presents with constitutional symptoms, back pain, tenderness, paraplegia or paraparesis, and kyphotic or scoliotic deformities. Pott's spine accounts for 2% of all cases of TB, 15% of extrapulmonary, and 50% of skeletal TB. The paradiscal, central, anterior subligamentous, and neural arch are the common vertebral lesions. Thoracic vertebrae are commonly affected followed by lumbar and cervical vertebrae. Plain radiographs are usually the initial investigation in spinal TB. For a radiolucent lesion to be apparent on a plain radiograph there should be 30% of bone mineral loss. Computed tomographic scanning provides much better bony detail of irregular lytic lesions, sclerosis, disc collapse, and disruption of bone circumference than plain radiograph. Magnetic resonance imaging (MRI) is the best diagnostic modality for Pott's spine and is more sensitive than other modalities. MRI frequently demonstrates disc collapse/destruction, cold abscess, vertebral wedging/collapse, marrow edema, and spinal deformities. Ultrasound and computed tomographic guided needle aspiration or biopsy is the technique for early histopathological diagnosis. Recently, the coexistence of human immunodeficiency virus infections and TB has been increased globally. In recent years, diffusion-weighted MRI (DW-MRI) and apparent diffusion coefficient values in combination with MRI are used to some extent in the diagnosis of spinal TB. We have reviewed related literature through internet. The terms searched on Google scholar and PubMed are TB, extrapulmonary TB, skeletal TB, spinal TB, Pott's spine, Pott's paraplegia, MRI, and computed tomography (CT). PMID:24020048

Ansari, Sajid; Amanullah, Md. Farid; Ahmad, Kaleem; Rauniyar, Raj Kumar

2013-01-01

251

Genetic Analysis of Inherited Leukodystrophies  

PubMed Central

Importance The leukodystrophies comprise a clinically and genetically heterogeneous group of progressive hereditary neurological disorders mainly affecting the myelin in the central nervous system. Their onset is variable from childhood to adulthood and presentation can be with a variety of clinical features that include mainly for adult-onset cases cognitive decline, seizures, parkinsonism, muscle weakness, neuropathy, spastic paraplegia, personality/behavioral problems, and dystonia. Recently, Rademakers and colleagues identified mutations in the CSF1R gene as the cause of hereditary diffuse leukoencephalopathy with spheroids (HDLS), offering the possibility for an in-life diagnosis. The detection of mutations in this gene in cases diagnosed with different clinical entities further demonstrated the difficulties in the clinical diagnosis of HDLS. Objective To better understand the genetic role of mutations in this gene, we sequenced a large cohort of adult-onset leukodystrophy cases. Design Whole-exome sequencing and follow up-screening by Sanger sequencing. Setting Collaborative study between the Institute of Neurology, University College London and the Inserm, Paris, France. Participants A total of 114 probands, mostly European patients, with a diagnosis of adult-onset leukodystrophy or atypical cases that could fit within a picture of leukodystrophy. These included 3 extended families within the spectrum of leukodystrophy phenotype. Interventions Whole-exome sequencing in a family and Sanger sequencing of CSF1R. Main Outcomes and Measures Mutations in CSF1R. Results We identified 12 probands with mutations in CSF1R. The clinical diagnoses given to these patients included dementia with spastic paraplegia, corticobasal degeneration syndrome, and stroke disorders. Our study shows that CSF1R mutations are responsible for a significant proportion of clinically and pathologically proven HDLS. Conclusions and Relevance These results give an indication of the frequency of CSF1R mutations in a European leukodystrophy series and expand the phenotypic spectrum of disorders that should be screened for this gene. PMID:23649896

Bras, Jose; Rohrer, Jonathan D.; Taipa, Ricardo; Lashley, Tammaryn; Dupuits, Celine; Gurunlian, Nicole; Mochel, Fanny; Warren, Jason D.; Hannequin, Didier; Sedel, Frederic; Depienne, Christel; Camuzat, Agnes; Golfier, Veronique; Du Boisgueheneuc, Foucaud; Schottlaender, Lucia; Fox, Nick C.; Beck, Jonathan; Mead, Simon; Rossor, Martin N.; Hardy, John; Revesz, Tamas; Brice, Alexis; Houlden, Henry

2014-01-01

252

Treating cerebral palsy with aculaser therapy  

NASA Astrophysics Data System (ADS)

A single, open and non comparative study was conducted at Anwar Shah Trust for C.P. & Paralysis in collaboration with the Departments of Neurology and Neurosurgery, Children Hospital Lahore, Pakistan to evaluate the effects of ACULASER THERAPY in childern suffering from Cerebral Palsy (C.P.) and associated Neurological Disorders like epilepsy, cortical blindness, spasticity, hemiplegia, paraplegia, diplegia, quadriplegia, monoplegia, sensory-neural deafness and speech disorders. In all 250 childern were treated and the data was gathered during a period of 3 years from December 2003 till December 2006. These children were further classified according to the type of C.P. (spastic, athetoid, mixed) they suffered from and associated Neurological Disorders. This article shows results in C.P. childern who were treated with ACULASER THERAPY for minimum 6 weeks and more or had minimum of 15 treatment sessions and more. This article also shows that those childern who were given a break in the treatment for 1 month to 1 year did not show any reversal of the signs and symptoms. Analysis of the data showed that out of 171 children with Spasticity and Stiffness 147 showed marked improvement showing 87% success rate, out of 126 children with Epileptic fits, there was a significant reduction in the intensity, frequency and duration of Epileptic fits in 91 children showing 72% success rate, out of 48 children with Cortical Blindness 30 children showed improvement accounting for 63% efficacy rate, out of 105 children with Hearing Difficulties, 63 showed marked improvement accounting for 60% improvement rate, out of 190 children with Speech Disorders 122 showed improvement reflecting 64% improvement rate, out of 96 children with Hemiplegia 71 showed improvement in movement, tone and power accounting for 74% improvement rate, out of 76 children with Quadriplegia 52 showed improvement in gross and fine motor functions showing 69% success rate and out of 58 children with Paraplegia of lower limbs 44 showed improvement in weight bearing, standing and movement accounting for 76% improvement rate.

Anwar, Shahzad; Nazir Khan, Malik M.; Nadeem Khan, Malik M.; Qazi, Faiza M.; Awan, Abid H.; Dar, Irfan

2008-03-01

253

Aculaser therapy for the treatment of cerebral palsy  

NASA Astrophysics Data System (ADS)

A single, open and non comparative study was conducted at Anwar Shah Trust for C.P. & Paralysis in collaboration with the Departments of Neurology and Neurosurgery, Children Hospital Lahore, Pakistan to evaluate the effects of ACULASER THERAPY in childern suffering from Cerebral Palsy (C.P.) and associated Neurological Disorders like epilepsy, cortical blindness, spasticity, hemiplegia, paraplegia, diplegia, quadriplegia, monoplegia, sensoryneural deafness and speech disorders. In all 500 children were treated and the data was gathered during a period of 4 years from December 2006 till December 2010. These children were further classified according to the type of C.P. (spastic, athetoid, mixed) they suffered from and associated Neurological Disorders. This article shows results in C.P. childern who were treated with ACULASER THERAPY for a minimum of 08 weeks and more or had minimum of 15 treatment sessions and more. This article also shows that those childern who were given a break in the treatment for 1 month to 1 year did not show any reversal of the signs and symptoms. Analysis of the data showed that out of 342 children with Spasticity and Stiffness 294 showed marked improvement showing 87% success rate, out of 252 children with Epileptic fits, there was a significant reduction in the intensity, frequency and duration of Epileptic fits in 182 children showing 72% success rate, out of 96 children with Cortical Blindness 60 children showed improvement accounting for 63% efficacy rate, out of 210 children with Hearing Difficulties, 126 showed marked improvement accounting for 60% improvement rate, out of 380 children with Speech Disorders 244 showed improvement reflecting 64 % improvement rate, out of 192 children with Hemiplegia 142 showed improvement in movement, tone and power accounting for 74% improvement rate, out of 152 children with Quadriplegia 104 showed improvement in gross and fine motor functions showing 69% success rate and out of 116 children with Paraplegia of lower limbs 88 showed improvement in weight bearing, standing and movement accounting for 76% improvement rate.

Anwar, Shahzad; Nazir Khan, Malik M.; Nadeem Khan, Malik M.; Qazi, Faiza M.; Awan, Abid H.; Ammad, Haseeb U.

2012-03-01

254

Elephant trunk technique for hybrid aortic arch repair.  

PubMed

The original elephant trunk technique was developed by Borst in 1983 for the treatment of aortic arch aneurysms. This technique reduced operative risks, but was associated with cumulative mortality rates of 6.9 % for the first stage and 7.5 % for the second stage. Patients also waited a long time between two major surgical procedures. Only 50.4 % of patients underwent the second-stage surgery, and there was a significant interval mortality rate of 10.7 %. With the advent of stent-graft techniques, two different hybrid elephant trunk techniques were developed. One technique is first-stage elephant trunk graft placement followed by second-stage endovascular completion. The conventional elephant trunk graft provides a good landing zone for the stent-graft, and endovascular completion is a useful alternative to conventional second-stage surgery. This method has few major complications, and a postoperative paraplegia rate of 1.1 %. The other technique is the frozen elephant trunk technique. This technique eliminates the need for subsequent endovascular completion, and is particularly useful for the treatment of acute type A dissection because it can achieve a secure seal. However, it is associated with a higher rate of spinal cord ischemia than other methods such as the original elephant trunk technique. The left subclavian artery (LSA) is often lost when performing a hybrid elephant trunk procedure. Revascularization of the LSA should be performed to prevent arm ischemia and neurological complications such as paraplegia or stroke, although the level of evidence for this recommendation is low. PMID:23943042

Miyamoto, Yuji

2014-03-01

255

Aerobic and anaerobic arm-cranking power outputs of males with lower limb impairments: relationship with sport participation intensity, age, impairment and functional classification.  

PubMed

Fifty individuals with lower limb impairments including spinal cord injury, polio and amputations underwent aerobic and anaerobic arm-cranking tests in a standardized laboratory setting. Based on linear regression models applied with age as dependent variable aerobic performance variable including HRmax (R = 0.395, P = 0.004), and POaer (R = 0.31, P = 0.021) were subjected to ANCOVA adjusting for age in order to determine the significance of participation intensity (competitive vs leisure) and type of physical impairment. Anaerobic performance variables were not influenced by age and thereby subjected to 1-Way ANOVA with the same independent variables. Participation intensity and type of impairment significantly discriminated (P < 0.001) between athletes in all power variables. Linear regression models have shown moderate but significant (P < 0.001) relationship with functional ability (bases on International Wheelchair Basketball Federation classification system). In anaerobic mean power (MP) classification accounted for 42% of the variance, while in anaerobic peak power (PP) and aerobic Power (POaer) for 38% and 30% respectively. By means of a post hoc Tukey analysis significant differences were observed between athletes with a high level paraplegia (class 1) and those with one leg affected by polio or amputations (classes 4, 4.5). Athletes with low level paraplegia and two legs affected by polio (classes 2-3.5) had values in-between. Based on the descriptive evaluation, a three group scheme was conceptualized and resubjected to ANOVA. Significant intergroup differences were thus obtained only for PP. Descriptive PP data for each group were transformed into a five category table in order to provide reference values for fitness-estimation in males with lower limb impairments of various etiologies. PMID:9554023

Hutzler, Y; Ochana, S; Bolotin, R; Kalina, E

1998-03-01

256

Effect of a Cooling Vest on Core Temperature in Athletes With and Without Spinal Cord Injury  

PubMed Central

Background: It is well accepted that persons with spinal cord injury (SCI) have impaired ability to regulate core temperature due to impaired vasomotor and sudomotor activity below their level of injury. Impaired heat dissipation puts SCI athletes at great risk of exercise-induced hyperthermia (EIH) (>37.8°C). There is minimal evidence for efficacy of any specific cooling method in SCI athletes in a thermoneutral sport-specific setting. Objective: To evaluate the extent of EIH in persons with and without SCI and subsequently examine the effect of a cooling vest to attenuate rise in core body temperature (Tc). Methods: SCI (n = 17) and able-bodied (AB; n = 19) athletes participated in a 60-minute intermittent sprinting exercise in a thermoneutral (21.1°C-23.9°C) environment. Participants were separated according to their level of injury: tetraplegia defined as above T1 (TP; n = 6), high paraplegia defined as T5 through T1 (HP; n = 5), low paraplegia defined as T6 and below (LP; n = 6), and AB (n = 19). Tc was recorded at 15-minute intervals using an ingestible thermometer pill. This protocol was completed with a cooling vest (V) and without a cooling vest (NV). Results: All SCI and most AB athletes experienced EIH. After 60 minutes, Tc of TP athletes was significantly increased compared to HP (P = .03) and AB athletes (P = .007). There was no significant effect of the vest on Tc over time for any group. Conclusions: TP athletes have the highest risk of exercise-induced hyperthermia. The cooling vest does not significantly attenuate rise in Tc in SCI or AB athletes. PMID:24574824

Trbovich, Michelle

2014-01-01

257

Application of rapid artificial cardiac pacing in thoracic endovascular aortic repair in aged patients  

PubMed Central

Objective To compare the safety, efficacy, and impact on stent graft positioning between rapid artificial cardiac pacing (RACP), induced hypotension and sodium nitroprusside (SNP) induced hypotension during thoracic endovascular aortic repair (TEVAR) for Stanford B aortic dissection. Methods One hundred and sixty-eight patients, who were diagnosed with Stanford B aortic dissection and who underwent selective TEVAR in Guangdong General Hospital and the People’s Hospital of Baoan District, Shenzhen, People’s Republic of China, were enrolled in this study. Patients were randomly divided into a RACP group (n=77) and a SNP group (n=91). During localization and deployment of the stent graft, hypotension was induced by RACP or intravenous SNP, according to randomization. Hemodynamics, landing precision (deviation from planned placement site), duration of procedure, renal function, neurocognitive function, and incidence of endoleaks and paraplegia/hemiplegia were compared. Except for methods of inducing hypotension, TEVAR was performed according to the same protocol in each group. Results RACP was successfully performed in all patients assigned to the RACP group. Compared with the SNP group, blood pressure was significantly lower (43±5 versus 81±6 mmHg, P=0.003) and the restoration time of blood pressure and the operation duration were significantly shorter (7±2 versus 451±87 seconds, P<0.001; 87±15 versus 106±18 minutes, P<0.001, respectively) in the RACP group. Stent graft localization/deployment was more precise in the RACP group (2±1 versus 5±2 mm, P<0.001). Compared to baseline, there was no significant change after TEVAR in either group in regard to renal function, neurocognitive function, and incidence of endoleaks and paraplegia/hemiplegia. Conclusion RACP can be safely applied to patients undergoing TEVAR for Stanford B dissection. RACP can shorten the operation duration and facilitate precise graft localization/deployment. PMID:24403824

Chen, Jun; Huang, Wenhui; Luo, Songyuan; Yang, Dahao; Xu, Zhengrong; Luo, Jianfang

2014-01-01

258

One-year follow-up of Chinese people with spinal cord injury: A preliminary study  

PubMed Central

Background A tertiary spinal cord injury (SCI) center was established in the northern region of Hong Kong, China and a multidisciplinary SCI rehabilitation program was developed to reintegrate patients into the community. Objective To investigate functional outcomes for Chinese people with SCI across a 1-year period. Design Longitudinal prospective design. Methods Thirty community-dwelling participants with traumatic SCI were recruited. Functional status was measured using functional independence measure (FIM) on admission, upon discharge, 1-month, 3-month, 6-month, and 1-year post-discharge. Information on use of assistive devices and life role were also obtained. Results Twenty-three (76.67%) participants were men. Seventeen participants (10 with tetraplegia and 7 with paraplegia) were classified ASIA A, B, or C; 13 (7 with tetraplegia and 6 with paraplegia) were classified as ASIA D. Significant differences in FIM motor scores were only found between the tetraplegia group and three other diagnostic groups using Bonferroni post-hoc tests of repeated measure ANOVA (analysis of variance) (P < 0.05). Longitudinally, contrast tests of repeated measure ANOVA showed significant differences during the hospitalization period for all diagnostic groups. People in the ASIA D group showed significant functional improvement even after 1-year post-discharge (P < 0.05). At 1-year post-discharge, only two participants were engaged in either remunerative employment or academic pursuit. Conclusion Despite functional status improvement, few people with traumatic SCI were re-engaged in productive life role 1 year after discharge. Studies with longer follow-up would be beneficial. PMID:23433330

Chan, Sam Chi Chung; Chan, Alice Po Shan

2013-01-01

259

The Alu-rich genomic architecture of SPAST predisposes to diverse and functionally distinct disease-associated CNV alleles.  

PubMed

Intragenic copy-number variants (CNVs) contribute to the allelic spectrum of both Mendelian and complex disorders. Although pathogenic deletions and duplications in SPAST (mutations in which cause autosomal-dominant spastic paraplegia 4 [SPG4]) have been described, their origins and molecular consequences remain obscure. We mapped breakpoint junctions of 54 SPAST CNVs at nucleotide resolution. Diverse combinations of exons are deleted or duplicated, highlighting the importance of particular exons for spastin function. Of the 54 CNVs, 38 (70%) appear to be mediated by an Alu-based mechanism, suggesting that the Alu-rich genomic architecture of SPAST renders this locus susceptible to various genome rearrangements. Analysis of breakpoint Alus further informs a model of Alu-mediated CNV formation characterized by small CNV size and potential involvement of mechanisms other than homologous recombination. Twelve deletions (22%) overlap part of SPAST and a portion of a nearby, directly oriented gene, predicting novel chimeric genes in these subjects' genomes. cDNA from a subject with a SPAST final exon deletion contained multiple SPAST:SLC30A6 fusion transcripts, indicating that SPAST CNVs can have transcriptional effects beyond the gene itself. SLC30A6 has been implicated in Alzheimer disease, so these fusion gene data could explain a report of spastic paraplegia and dementia cosegregating in a family with deletion of the final exon of SPAST. Our findings provide evidence that the Alu genomic architecture of SPAST predisposes to diverse CNV alleles with distinct transcriptional--and possibly phenotypic--consequences. Moreover, we provide further mechanistic insights into Alu-mediated copy-number change that are extendable to other loci. PMID:25065914

Boone, Philip M; Yuan, Bo; Campbell, Ian M; Scull, Jennifer C; Withers, Marjorie A; Baggett, Brett C; Beck, Christine R; Shaw, Christine J; Stankiewicz, Pawel; Moretti, Paolo; Goodwin, Wendy E; Hein, Nichole; Fink, John K; Seong, Moon-Woo; Seo, Soo Hyun; Park, Sung Sup; Karbassi, Izabela D; Batish, Sat Dev; Ordóñez-Ugalde, Andrés; Quintáns, Beatriz; Sobrido, María-Jesús; Stemmler, Susanne; Lupski, James R

2014-08-01

260

Analysis of industrial tasks as a tool for the inclusion of people with disabilities in the work market.  

PubMed

This article describes the application of a model for analyzing industrial tasks that was developed to identify jobs that could potentially be filled by people with disabilities (DP) and to serve as a guideline for a company hiring policy. In Brazil, Law No. 8213/91 makes it obligatory to hire DP based on quotas that are established according to the number of employees in a public and private company. Using a set of methods and techniques based on ergonomic work analysis and on occupational therapy, we sought to build a model to indicate the skills required to perform industrial tasks. The model was applied at 19 workstations at a Brazilian aircraft manufacturer in 2002. The task supervisor and the operator performing the task were interviewed, the work activity was filmed, a kinesiological analysis was done, the task was observed and a checklist was applied to help recognize and systematize the skills involved in performing the job task. The last step consisted of correlating the skills required to perform the task to the potential skills of the various types of disability. It was found that 100% of the jobs could be filled by workers with low-level paraplegia, 89% by workers with general paraplegia, 0% with low-level tetraplegia, 47% with auditory impairment, 42% with hemiplegia, 68% with upper limb amputees wearing adequate prostheses, and 89% handicapped wheelchair users. The company hired 14 DP based on the results of this model. The model proved adequate for analyzing industrial tasks with a view to the inclusion of DP, and it can be applied to other sectors of industrial production. PMID:18452126

Simonelli, Angela Paula; Camarotto, João Alberto

2008-01-01

261

Long-term outcomes in thoracoabdominal aortic aneurysm repair for chronic type B dissection  

PubMed Central

Introduction Open repair for chronic aortic dissection remains a challenging surgical option. Different centers report diverse experiences and outcomes pertaining to thoracoabdominal aortic aneurysm repair (TAAAR) for chronic type B dissection. We highlight our center’s experience and results on a background of published literature and current evidence. Methods We reviewed 214 open TAAAR performed between October 1998 and February 2014. Of these, chronic type B dissection was present in 62 (29.0%) patients. We reviewed these patients in terms of demographics, operative characteristics and outcomes. Thirteen (21.0%) patients had surgery on the descending thoracic aorta [Category A =2 (3.2%), B =0 (0%), C =11 (17.7%)] and 49 (79.0%) in the thoracoabdominal thoracic aorta [Crawford extent I =5 (8.1%), extent II =39 (62.9%), extent III =4 (6.5%), extent IV =1 (1.6%)]. Left heart bypass was used in 12 (19.4%) patients. Results The composite in-hospital endpoint, adverse outcome—defined as operative death, renal failure necessitating dialysis at discharge, stroke, or permanent paraplegia or paraparesis—occurred after 28 (45.2%) procedures. There were 14 (22.6%) operative deaths. In-hospital mortality was seven (16.3%) out of 43 elective patients, and increased to seven (36.8%) of the 19 non-elective ones. Permanent paraplegia or paraparesis occurred after two (3.2%) cases, stroke occurred after seven (11.3%) and renal failure requiring dialysis occurred after 16 (25.8%). Mean follow-up time was 3.2 years and actuarial 5-year mortality was 27.4% [nine (14.5%) elective and eight (12.9%) non-elective patients]. Conclusions TAAAR in chronic type B dissection carries a substantial risk of early adverse outcomes. The results could be well alleviated with cases directed towards specialized regional and supra-regional centers. Although the endovascular approaches offer relatively low mortality and morbidity, there is a lack of long-term data and guidelines on their use. There is a need for a multidisciplinary international registry on the management of thoracoabdominal aortic aneurysms and dissection. This would provide a degree of guidance on relevant clinical and surgical judgments and outcomes. PMID:25133101

Bashir, Mohamad; Shaw, Matthew; Fok, Matthew; Harrington, Deborah; Field, Mark; Kuduvalli, Manoj

2014-01-01

262

Experimental and clinical assessment of the adequacy of partial bypass in maintenance of spinal cord blood flow during operations on the thoracic aorta.  

PubMed

We studied both experimentally and clinically the efficacy of partial bypass techniques in maintaining spinal cord blood flow and physiological function during surgical procedures on the thoracoabdominal aorta. We attempted to define the level of distal aortic pressure required to safely ensure normal neurological function in the absence of critical intercostal occlusion. Six dogs underwent left thoracotomy with baseline measurements of spinal cord blood flow and spinal cord impulse conduction (somatosensory evoked potentials). Following exclusion of the entire descending thoracic aorta from the left subclavian artery to the T-13 level, partial left atrium-femoral artery bypass was instituted, and baseline levels of proximal and distal aortic pressure were maintained during a 30-minute stabilization period. Mean distal aortic pressure then was progressively altered at 30-minute intervals to 100, 70, and 40 mm Hg. Measurements of spinal cord blood flow and somatosensory evoked potential were repeated at the end of each interval for comparison with baseline. No significant changes in spinal cord blood flow or somatosensory evoked potential were observed in any animal with a distal aortic pressure greater than or equal to 70 mm Hg. With a pressure of 40 mm Hg, normal flow and somatosensory evoked potentials were maintained in 5 of the 6 dogs. Loss of somatosensory evoked potential, with simultaneous loss of spinal cord blood flow at the T-6 level, occurred in 1 dog. Restoration of distal aortic pressure to 70 mm Hg in all animals resulted in immediate return of somatosensory evoked potential. Loss of somatosensory evoked potential routinely occurred in animals with a distal aortic pressure less than 40 mm Hg. Clinically, 9 patients have undergone operation for lesions of the thoracoabdominal aorta using shunt or bypass techniques. Normal somatosensory evoked potentials were preserved in 7 patients with maintenance of adequate distal aortic pressure (greater than or equal to 60 mm Hg) without evidence of postoperative neurological deficit. Two patients showed hypotensive somatosensory evoked potential loss (distal aortic pressure less than 40 mm Hg). Prolonged distal hypotension (85 minutes of aortic cross-clamping) in the latter resulted in paraplegia. We conclude that maintenance of a distal aortic pressure greater than 60 to 70 mm Hg will uniformly preserve spinal cord blood flow in the absence of critical intercostal exclusion. Should distal aortic pressure be inadequate, early reversible changes in the somatosensory evoked potential will alert the surgeon. Failure to institute measures to reverse these changes may result in paraplegia. PMID:6625737

Laschinger, J C; Cunningham, J N; Nathan, I M; Knopp, E A; Cooper, M M; Spencer, F C

1983-10-01

263

Treatment of patients with aortic dissection presenting with peripheral vascular complications.  

PubMed Central

The incidence of peripheral vascular complications in 272 patients with aortic dissection during a 25-year span was determined, as was outcome after a uniform, aggressive surgical approach directed at repair of the thoracic aorta. One hundred twenty-eight patients (47%) presented with acute type A dissection, 70 (26%) with chronic type A, 40 (15%) with acute type B, and 34 (12%) with chronic type B dissections. Eighty-five patients (31%) sustained one or more peripheral vascular complications: Seven (3%) had a stroke, nine (3%) had paraplegia, 66 (24%) sustained loss of a peripheral pulse, 22 (8%) had impaired renal perfusion, and 14 patients (5%) had compromised visceral perfusion. Following repair of the thoracic aorta, local peripheral vascular procedures were unnecessary in 92% of patients who presented with absence of a peripheral pulse. The operative mortality rate for all patients was 25% +/- 3% (68 of 272 patients). For the subsets of individuals with paraplegia, loss of renal perfusion, and compromised visceral perfusion, the operative mortality rates (+/- 70% confidence limits) were high: 44% +/- 17% (4 of 9 patients), 50% +/- 11% (11 of 22 patients), and 43% +/- 14% (6 of 14 patients), respectively. The mortality rates were lower for patients presenting with stroke (14% +/- 14% [1 of 7 patients]) or loss of peripheral pulse (27% +/- 6% [18 of 66 patients]). Multivariate analysis revealed that impaired renal perfusion was the only peripheral vascular complication that was a significant independent predictor of increased operative mortality risk (p = 0.024); earlier surgical referral (replacement of the appropriate section of the thoracic aorta) or more expeditious diagnosis followed by surgical renal artery revascularization after a thoracic procedure may represent the only way to improve outcome in this high-risk patient subset. Early, aggressive thoracic aortic repair (followed by aortic fenestration and/or abdominal exploration with or without direct visceral or renal vascular reconstruction when necessary) can save some patients with compromised visceral perfusion; however, once visceral infarction develops the prognosis is also poor. Increased awareness of these devastating complications of aortic dissection and the availability of better diagnostic tools today may improve the survival rate for these patients in the future. The initial surgical procedure should include repair of the thoracic aorta in most patients. PMID:2256762

Fann, J I; Sarris, G E; Mitchell, R S; Shumway, N E; Stinson, E B; Oyer, P E; Miller, D C

1990-01-01

264

Brain-computer interface controlled robotic gait orthosis  

PubMed Central

Background Excessive reliance on wheelchairs in individuals with tetraplegia or paraplegia due to spinal cord injury (SCI) leads to many medical co-morbidities, such as cardiovascular disease, metabolic derangements, osteoporosis, and pressure ulcers. Treatment of these conditions contributes to the majority of SCI health care costs. Restoring able-body-like ambulation in this patient population can potentially reduce the incidence of these medical co-morbidities, in addition to increasing independence and quality of life. However, no biomedical solution exists that can reverse this loss of neurological function, and hence novel methods are needed. Brain-computer interface (BCI) controlled lower extremity prostheses may constitute one such novel approach. Methods One able-bodied subject and one subject with paraplegia due to SCI underwent electroencephalogram (EEG) recordings while engaged in alternating epochs of idling and walking kinesthetic motor imagery (KMI). These data were analyzed to generate an EEG prediction model for online BCI operation. A commercial robotic gait orthosis (RoGO) system (suspended over a treadmill) was interfaced with the BCI computer to allow for computerized control. The subjects were then tasked to perform five, 5-min-long online sessions where they ambulated using the BCI-RoGO system as prompted by computerized cues. The performance of this system was assessed with cross-correlation analysis, and omission and false alarm rates. Results The offline accuracy of the EEG prediction model averaged 86.30% across both subjects (chance: 50%). The cross-correlation between instructional cues and the BCI-RoGO walking epochs averaged across all subjects and all sessions was 0.812±0.048 (p-value <10?4). Also, there were on average 0.8 false alarms per session and no omissions. Conclusion These results provide preliminary evidence that restoring brain-controlled ambulation after SCI is feasible. Future work will test the function of this system in a population of subjects with SCI. If successful, this may justify the future development of BCI-controlled lower extremity prostheses for free overground walking for those with complete motor SCI. Finally, this system can also be applied to incomplete motor SCI, where it could lead to improved neurological outcomes beyond those of standard physiotherapy. PMID:24321081

2013-01-01

265

Current management and outcome of chronic type B aortic dissection: results with open and endovascular repair since the advent of thoracic endografting  

PubMed Central

Background Thoracic endovascular aortic repair (TEVAR) has become the preferred treatment for chronic type B aortic dissection (CTBAD) at our institution. However, it remains incapable of treating all patients with CTBAD. The present study aims to review our contemporary results with open and endovascular CTBAD repairs since the advent of thoracic endografting. Methods The records of all patients undergoing index repair of CTBAD (chronic DeBakey type IIIA, IIIB and repaired type I) at our institution between June 2005 and December 2013, were retrospectively reviewed. Results A total of 107 patients underwent CTBAD repair, of whom 70% (n=75) underwent endovascular-based procedures [44 TEVAR, 27 hybrid arch and four hybrid thoracoabdominal aortic aneurysm (TAAA) repair] and 30% (n=32) underwent open procedures (nine open descending and 23 open TAAA). Connective tissue disease (CTD), prior aortic surgery and DeBakey dissection type were strongly associated with the choice of operation. The rates of stroke, paraplegia and operative mortality following endovascular-based repairs were 0%, 0% and 4% (n=3), respectively. Adverse neurologic events were higher following open repair, and rates of stroke, paraplegia, and operative mortality were 16% (n=5), 9% (n=3), and 6% (n=2), respectively. However, 1- and 5-year survival rates were similar for endovascular-based repairs (86% and 65%, respectively), and open repairs (88% and 79%, respectively). Over a median follow-up interval of 34 months, the rate of descending aortic reintervention was 24% (n=18) following endovascular-based repairs and 0% following open repairs (P=0.001). Forty-four percent (n=8) of descending aortic reinterventions were required to treat stent graft complications (five endoleak, two stent graft collapse and one stent graft-induced new entry tear) and the remainder were required to treat metachronous pathology (n=2) or progressive aneurysmal disease related to persistent distal fenestrations (n=8). Conclusions Endovascular repair of CTBAD was associated with excellent procedural and survival outcomes, but at the expense of further reinterventions. Open repair remains relevant for patients who are not candidates for endovascular repair and was associated with higher procedural morbidity but similar overall survival and fewer reinterventions. PMID:24967165

Andersen, Nicholas D.; Keenan, Jeffrey E.; Ganapathi, Asvin M.; Gaca, Jeffrey G.; McCann, Richard L.

2014-01-01

266

A potential protective effect of ?-tocopherol on vascular complication in spinal cord reperfusion injury in rats  

PubMed Central

Background Paraplegia remains a potential complication of spinal cord ischemic reperfusion injury (IRI) in which oxidative stress induced cyclooxygenase activities may contribute to ischemic neuronal damage. Prolonged administration of vitamin E (?-TOL), as a potent biological antioxidant, may have a protective role in this oxidative inflammatory ischemic cascade to reduce the incidence of paraplegia. The present study was designed to evaluate the preventive value of ?-TOL in IRI of spinal cord. Methods For this study, 50 male Sprague-Dawley rats were used and divided into five experimental groups (n = 10): Control group (C); ?-TOL control group (CE) which received intramuscular (i.m.) ?-TOL injections (600 mg/kg); Sham operated group (S), IRI rats were subjected to laparotomy and clamping of the aorta just above the bifurcation for 45 min, then the clamp was released for 48 hrs for reperfusion; and IRIE rats group, received 600 mg/kg of ?-TOL i.m. twice weekly for 6 weeks, followed by induction of IRI similar to the IRI group. At the end of the experimental protocol; motor, sensory and placing/stepping reflex evaluation was done. Plasma nitrite/nitrate (NOx) was measured. Then animals' spinal cord lumbar segments were harvested and homogenized for measurement of the levels of prostaglandin E2 (PGE2), malondialdehyde (MDA) and advanced oxidation products (AOPP), while superoxide dismutase (SOD) and catalase (CAT) activity were evaluated. Results Induction of IRI in rats resulted in significant increases in plasma levels of nitrite/nitrate (p < 0.001) and spinal cord homogenate levels of PGE2, MDA, advanced oxidation protein products AOPP and SOD with significant reduction (p < 0.001) in CAT homogenate levels. Significant impairment of motor, sensory functions and placing/stepping reflex was observed with IRI induction in the spinal cord (p < 0.001). ?-TOL administration in IRIE group significantly improved all the previously measured parameters compared with IRI group. Conclusions ?-TOL administration significantly prevents the damage caused by spinal cord IRI in rats with subsequent recovery of both motor and sensory functions. Alpha-tocopherol improves the oxidative stress level with subsequent reduction of the incidence of neurological deficits due to spinal cord IRI conditions. PMID:20609232

2010-01-01

267

Venous diversion trapping and growth of blood-borne cancer cells en route to the lungs.  

PubMed Central

A proportion of W-256 tumour cells injected intravenously into a tail vein of the rat are diverted into venous plexuses en route to the lungs; here tumour cells remain trapped, proliferate and form invasive solid tumours in the pelvis and hindquarters, which cause paraplegia, metastases and death. Also, cells trapped in veins produce tumour nodules distributed along the length of the tail; this effect in markedly enhanced by temporarily arresting the outflow of blood from the tail for a few seconds only immediately after cells are injected. Continous monitoring of the radioactive signal over the lungs after W-256 cells labelled with 125IUDR were injected showed that massaging the tail or intravenously injecting isotonic saline into the tail dislodged cells trapped in veins. In heparinized rats, tail trapping was markedly reduced, although not entirely abolished, and venous trapping in vertebral and pravertebral regions was decreased. The anatomical distribution of growth of the trapped cells in rats closely resembled metastases involving dissemination via the "vertebral venous system" produced by certain cancers in man. Labelled tumour cells trapped in the lungs of untreated mature rats commenced dying rapidly in situ wiht 1-2 h after injection; the majority had disappeared within 24 h, and less than 1% of the injected tumour cells survived to form lung colonies. Experimental evidence is presented which indicates that the lungs play a vital role in rapidly eliminating a high proportion of blood-borne cancer cells in the adult individual. Images Fig. 1 Fig. 2 Fig. 3 PMID:1156508

Van Den Brenk, H. A.; Burch, W. M.; Kelly, H.; Orton, C.

1975-01-01

268

Development of AMPA receptor and GABA B receptor-sensitive spinal hyper-reflexia after spinal air embolism in rat: a systematic neurological, electrophysiological and qualitative histopathological study  

PubMed Central

Decompression sickness results from formation of bubbles in the arterial and venous system, resulting in spinal disseminated neurodegenerative changes and may clinically be presented by motor dysfunction, spinal segmental stretch hyper-reflexia (i.e., spasticity) and muscle rigidity. In our current study, we describe a rat model of spinal air embolism characterized by the development of similar spinal disseminated neurodegenerative changes and functional deficit. In addition, the anti-spastic potency of systemic AMPA receptor antagonist (NGX424) or GABA B receptor agonist (baclofen) treatment was studied. To induce spinal air embolism, animals received an intra-aortic injection of air (50–200 ?l/kg). After embolism, the development of spasticity was measured using computer-controlled ankle rotation. Animals receiving 150 or 200 ?l of intra-aortic air injections displayed motor dysfunction with developed spastic (50–60% of animals) or flaccid (25–35% of animals) paraplegia at 5–7 days. MRI and spinal histopathological analysis showed disseminated spinal cord infarcts in the lower thoracic to sacral spinal segments. Treatment with NGX424 or baclofen provided a potent anti-spasticity effect (i.e., stretch hyper-reflexia inhibition). This model appears to provide a valuable experimental tool to study the pathophysiology of air embolism-induced spinal injury and permits the assessment of new treatment efficacy targeted to modulate neurological symptoms resulting from spinal air embolism. PMID:22721766

Kakinohana, Osamu; Scadeng, Miriam; Corleto, Jose A.; Sevc, Juraj; Lukacova, Nadezda; Marsala, Martin

2012-01-01

269

Mid-Term Results After Endovascular Stent-Grafting of Descending Aortic Aneurysms in High-Risk Patients  

SciTech Connect

Purpose. To analyze our experience with endovascular stent-grafting of descending aortic aneurysms in high-risk patients. Methods. Nineteen patients underwent endovascular stent-graft repair of descending aortic aneurysms using the Talent Stent Graft System (Medtronic). All patients were considered high-risk for open surgical repair due to their age, requirement for emergency surgery, and comorbidities. Computed tomography and/or MR tomography were performed at 3, 6 and 12 months postoperatively and thereafter every 12 months. Results. Secondary technical success was 100%. Thirty-day mortality was 5%. Incidence of postoperative stroke and paraplegia were 5% each. One patient required a second stent-graft due to a type I endoleak during the same hospital stay (primary technical success 95%). All patients have been followed for a median of 20 months. No migration, wire fractures or endoleak appeared during follow-up. Conclusion. Endovascular stent-grafting had a low 30-day mortality and morbidity in high-risk patients. One patient developed an aortoesophageal fistula 40 days after stent implantation. Stent-graft repair is a valuable supplement to surgical therapy in high-risk patients.

Brandt, Michael, E-mail: mbrandt@kielheart.uni-kiel.de; Walluscheck, Knut P. [University Hospital Schleswig-Holstein, Department of Cardiovascular Surgery (Germany); Jahnke, Thomas [University Hospital Schleswig-Holstein, Department of Diagnostic Radiology (Germany); Attmann, Tim [University Hospital Schleswig-Holstein, Department of Cardiovascular Surgery (Germany); Heller, Martin [University Hospital Schleswig-Holstein, Department of Diagnostic Radiology (Germany); Cremer, Jochen [University Hospital Schleswig-Holstein, Department of Cardiovascular Surgery (Germany); Mueller-Huelsbeck, Stefan [University Hospital Schleswig-Holstein, Department of Diagnostic Radiology (Germany)

2006-10-15

270

Design of Optimal Treatments for Neuromusculoskeletal Disorders using Patient-Specific Multibody Dynamic Models  

PubMed Central

Disorders of the human neuromusculoskeletal system such as osteoarthritis, stroke, cerebral palsy, and paraplegia significantly affect mobility and result in a decreased quality of life. Surgical and rehabilitation treatment planning for these disorders is based primarily on static anatomic measurements and dynamic functional measurements filtered through clinical experience. While this subjective treatment planning approach works well in many cases, it does not predict accurate functional outcome in many others. This paper presents a vision for how patient-specific multibody dynamic models can serve as the foundation for an objective treatment planning approach that identifies optimal treatments and treatment parameters on an individual patient basis. First, a computational paradigm is presented for constructing patient-specific multibody dynamic models. This paradigm involves a combination of patient-specific skeletal models, muscle-tendon models, neural control models, and articular contact models, with the complexity of the complete model being dictated by the requirements of the clinical problem being addressed. Next, three clinical applications are presented to illustrate how such models could be used in the treatment design process. One application involves the design of patient-specific gait modification strategies for knee osteoarthritis rehabilitation, a second involves the selection of optimal patient-specific surgical parameters for a particular knee osteoarthritis surgery, and the third involves the design of patient-specific muscle stimulation patterns for stroke rehabilitation. The paper concludes by discussing important challenges that need to be overcome to turn this vision into reality. PMID:21785529

Fregly, Benjamin J.

2011-01-01

271

Somatosensory evoked potentials in Hallervorden-Spatz-neuroaxonal-dystrophy complex with dorsal column involvement.  

PubMed

Two patients with a marked hypointensity of the globus pallidus on magnetic resonance imaging (MRI), which is known to be diagnostic for Hallervorden-Spatz disease (HSD), are presented. Patient 1 fell ill at about 10 years of age with visual disturbance, spastic paraplegia and mild ataxia, while patient 2 was affected during the second year of life with clinical features compatible with infantile neuroaxonal dystrophy (INAD). The two patients had certain clinical features in common; upper and lower motor neuron involvement, visual disturbance secondary to optic nerve atrophy, and dorsal column dysfunction, the evidence of which was seen from abnormal somatosensory evoked potentials (SEPs) obtained after posterior tibial nerve stimulation. In both patients, electron microscopic examination of the biopsied skin or sural nerve showed dystrophic axons, spheroids, and involvement of the peripheral nerve was indicated. Sharing of these clinical, pathological and MRI characteristics by the two patients supports the view of Seitelberger, who regarded HSD and INAD as constituents of a single disease entity, therefore the two patients were described as belonging to a disease spectrum of "Hallervorden-Spatz-neuroaxonal-dystrophy complex (HS-ND)." Sensory impairment has been a rare clinical feature in "HS-ND" complex, although its existence is not inconceivable considering the usual affection of the dorsal column/lemniscal pathway with spheroids. SEP was considered very useful in disclosing this often unmanifested sensory disturbance in "HS-ND" complex. PMID:2335040

Mutoh, K; Okuno, T; Ito, M; Mikawa, H

1990-04-01

272

Phosphoinositides Differentially Regulate Protrudin Localization through the FYVE Domain*  

PubMed Central

Protrudin is a FYVE (Fab 1, YOTB, Vac 1, and EEA1) domain-containing protein involved in transport of neuronal cargoes and implicated in the onset of hereditary spastic paraplegia. Our image-based screening of the lipid binding domain library revealed novel plasma membrane localization of the FYVE domain of protrudin unlike canonical FYVE domains that are localized to early endosomes. The membrane binding study by surface plasmon resonance analysis showed that this FYVE domain preferentially binds phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2), and phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) unlike canonical FYVE domains that specifically bind phosphatidylinositol 3-phosphate (PtdIns(3)P). Furthermore, we found that these phosphoinositides (PtdInsP) differentially regulate shuttling of protrudin between endosomes and plasma membrane via its FYVE domain. Protrudin mutants with reduced PtdInsP-binding affinity failed to promote neurite outgrowth in primary cultured hippocampal neurons. These results suggest that novel PtdInsP selectivity of the protrudin-FYVE domain is critical for its cellular localization and its role in neurite outgrowth. PMID:23043110

Gil, Jung-Eun; Kim, Eui; Kim, Il-Shin; Ku, Bonsu; Park, Wei Sun; Oh, Byung-Ha; Ryu, Sung Ho; Cho, Wonhwa; Heo, Won Do

2012-01-01

273

Clinical mitochondrial genetics  

PubMed Central

The last decade has been an age of enlightenment as far as mitochondrial pathology is concerned. Well established nuclear genetic diseases, such as Friedreich's ataxia,12 Wilson disease,3 and autosomal recessive hereditary spastic paraplegia,4 have been shown to have a mitochondrial basis, and we are just starting to unravel the complex nuclear genetic disorders which directly cause mitochondrial dysfunction (table 1). However, in addition to the 3 billion base pair nuclear genome, each human cell typically contains thousands of copies of a small, 16.5 kb circular molecule of double stranded DNA (fig 1). Mitochondrial DNA (mtDNA) accounts for only 1% of the total cellular nucleic acid content. It encodes for 13 polypeptides which are essential for aerobic metabolism and defects of the mitochondrial genome are an important cause of human disease.9293 Since the characterisation of the first pathogenic mtDNA defects in 1988,513 over 50 point mutations and well over 100 rearrangements of the mitochondrial genome have been associated with human disease9495 (http://www.gen.emory.edu/mitomap.html). These disorders form the focus of this article.???Keywords: mitochondrial DNA; mitochondrial disease; heteroplasmy; genetic counselling PMID:10874629

Chinnery, P.; Howell, N.; Andrews, R.; Turnbull, D.

1999-01-01

274

Adult polyglucosan body disease in a patient originally diagnosed with Fabry's disease.  

PubMed

Adult polyglucosan body disease is a rare autosomal recessive disease, caused by glycogen branching enzyme gene mutations, characterised by urinary dysfunction, spastic paraplegia with vibration sense loss, peripheral neuropathy, and cognitive impairment. Fabry's disease is an X-linked lysosomal storage disorder caused by ?-galactosidase A gene mutations; neurological manifestations include cerebrovascular accidents, small-fibre neuropathy and autonomic dysfunction. Here, we report the case of a 44-year-old Sicilian male with stroke-like episodes, hypohidrosis and mild proteinuria, which led to the diagnosis of Fabry's disease after a hemizygous mutation (p.Ala143Thr) in ?-galactosidase A gene was detected. Subsequently, he developed progressive walking difficulties and dementia, which were considered atypical for Fabry's disease. Therefore, we performed additional investigations that eventually led to the diagnosis of adult polyglucosan body disease caused by two novel missense mutations (p.Asp413His and p.Gly534Val) in the glycogen branching enzyme gene. Recently, the pathogenic role of the p.Ala143Thr mutation in causing Fabry's disease has been questioned. This case underlines the importance of performing further investigations when facing with atypical features even in the presence of a genetic diagnosis of a rare disease. PMID:24380807

Sagnelli, A; Savoiardo, M; Marchesi, C; Morandi, L; Mora, M; Morbin, M; Farina, L; Mazzeo, A; Toscano, A; Pagliarani, S; Lucchiari, S; Comi, G P; Salsano, E; Pareyson, D

2014-03-01

275

A new mutation in GJC2 associated with subclinical leukodystrophy.  

PubMed

Recessive mutations in GJC2, the gene-encoding connexin 47 (Cx47), cause Pelizaeus-Merzbacher-like disease type 1, a severe dysmyelinating disorder. One recessive mutation (p.Ile33Met) has been associated with a much milder phenotype--hereditary spastic paraplegia type 44. Here, we present evidence that a novel Arg98Leu mutation causes an even milder phenotype--a subclinical leukodystrophy. The Arg98Leu mutant forms gap junction plaques in HeLa cells comparable to wild-type Cx47, but electrical coupling was 20-fold lower in cell pairs expressing Arg98Leu than for cell pairs expressing wild-type Cx47. On the other hand, coupling between Cx47Arg98Leu and Cx43WT expressing cells did not show such reductions. Single channel conductance and normalized steady-state junctional conductance-junctional voltage (G j-V j) relations differed only slightly from those for wild-type Cx47. Our data suggest that the minimal phenotype in this patient results from a reduced efficiency of opening of Cx47 channels between oligodendrocyte and oligodendrocyte with preserved coupling between oligodendrocyte and astrocyte, and support a partial loss of function model for the mild Cx47 associated disease phenotypes. PMID:25059390

Abrams, Charles K; Scherer, Steven S; Flores-Obando, Rafael; Freidin, Mona M; Wong, Sarah; Lamantea, Eleonora; Farina, Laura; Scaioli, Vidmer; Pareyson, Davide; Salsano, Ettore

2014-10-01

276

The Fifth Adaptor Protein Complex  

PubMed Central

Adaptor protein (AP) complexes sort cargo into vesicles for transport from one membrane compartment of the cell to another. Four distinct AP complexes have been identified, which are present in most eukaryotes. We report the existence of a fifth AP complex, AP-5. Tagged AP-5 localises to a late endosomal compartment in HeLa cells. AP-5 does not associate with clathrin and is insensitive to brefeldin A. Knocking down AP-5 subunits interferes with the trafficking of the cation-independent mannose 6-phosphate receptor and causes the cell to form swollen endosomal structures with emanating tubules. AP-5 subunits can be found in all five eukaryotic supergroups, but they have been co-ordinately lost in many organisms. Concatenated phylogenetic analysis provides robust resolution, for the first time, into the evolutionary order of emergence of the adaptor subunit families, showing AP-3 as the basal complex, followed by AP-5, AP-4, and AP-1 and AP-2. Thus, AP-5 is an evolutionarily ancient complex, which is involved in endosomal sorting, and which has links with hereditary spastic paraplegia. PMID:22022230

Hirst, Jennifer; D. Barlow, Lael; Francisco, Gabriel Casey; Sahlender, Daniela A.; Seaman, Matthew N. J.; Dacks, Joel B.; Robinson, Margaret S.

2011-01-01

277

[Fractionated conformal stereotactic irradiation of recurrent sacral tumour. Case report and first description of the method in Hungary].  

PubMed

Non-invasive procedures completing traditional surgical treatment play an increasing role in the management of central nervous system malignancies. Conformal stereotactic irradiation (radiosurgery) has become a routine method in intracranial malignancies. However, application of this modality in tumours of the spinal cord and spinal column is much more difficult to perform. It is because extracranial organs can be only inaccurately fixed, and radio-sensitivity of the spinal cord and risks of radionecrosis with ensuing paraplegia are high. A recurrent sacrum chordoma treated by means of this modality - first reported in Hungary - has been chosen for case presentation as the criteria for radiotherapy such as high dose to target volume, minimal dose to neighbouring structures highly sensitive to radiation are best met in these tumours by means of conformal stereotactic radiotherapy. On the basis of further 13 extracranial cases treated with this method one can conclude that high precision stereotactic conformal radiotherapy offers up-grade to traditional radiotherapy despite the fact that it is a time-consuming procedure. The oncological efficiency, the reduced risks of side effects and the improved quality of life due to this treatment modality compensate duly for the increased labour input. PMID:24353993

Horváth, Zsolt; Szávai, József; Bellyei, Szabolcs; Farkas, Róbert; Mangel, László; Kovács, Péter; Sebestyén, Zsolt; Kasó, Gábor; Gömöri, Éva; Horváth, Gábor; Ésik, Olga; Dóczi, Tamás

2013-12-01

278

Metabolic rate and cardiorespiratory response during hybrid cycling versus handcycling at equal subjective exercise intensity levels in people with spinal cord injury.  

PubMed

Objective To compare the metabolic rate and cardiorespiratory response during hybrid cycling versus handcycling at equal subjective exercise intensity levels in people with spinal cord injury (SCI). Design Cross-sectional study. Setting Amsterdam Rehabilitation Research Centre | Reade, Amsterdam, The Netherlands. Methods On separate days, nine individuals with a motor complete paraplegia or tetraplegia (eight men, age 40 ± 13 years, time since injury 12 ± 10 years) performed 5-minute bouts of hybrid cycling (day 1) and handcycling (day 2) at moderate (level 3 on a 10-point rating of perceived exertion (RPE) scale) and vigorous (RPE level 6) subjective exercise intensity, while respiratory gas exchange was measured by open-circuit spirometry and heart rate was monitored using radiotelemetry. Outcome measures Metabolic rate (calculated with the Weir equation) and cardiorespiratory response (heart rate, oxygen pulse, and ventilation). Results Overall, the metabolic rate during hybrid cycling was 3.4 kJ (16%) higher (P = 0.006) than during handcycling. Furthermore, compared with handcycling, the overall heart rate and ventilation during hybrid cycling was 11 bpm (11%) and 5.3 l/minute (18%) higher (P = 0.004 and 0.024), respectively, while the oxygen pulse was the same (P = 0.26). Conclusion Hybrid cycling induces a higher metabolic rate and cardiorespiratory response at equal RPE levels than handcycling, suggesting that hybrid cycling is more suitable for fighting obesity and increasing cardiorespiratory fitness in individuals with SCI. PMID:24621028

Bakkum, Arjan J T; de Groot, Sonja; Onderwater, Mark Q; de Jong, Jelle; Janssen, Thomas W J

2014-11-01

279

Radiotherapy of Bone Metastasis in Breast Cancer Patients - Current Approaches  

PubMed Central

Bone metastases (BM) represent the most frequent indication for palliative radiotherapy in patients with breast cancer. BM increase the risk of skeletal-related events defined as pathological fractures, spinal cord compression, and, most frequently, bone pain. The therapeutic goals of palliative radiotherapy for BM are pain relief, recalcification, and stabilization, reducing spinal cord compression and minimizing the risk of paraplegia. In advanced tumor stages radiotherapy may also be used to alleviate symptoms of generalized bone metastasis. This requires an individual approach including factors, such as life expectancy and tumor progression at different sites. Side effects of radiation therapy of the middle and lower spine may include nausea and emesis requiring adequate antiemetic prophylaxis. Irradiation of large bone marrow areas may cause myelotoxicity making monitoring of blood cell counts mandatory. Radiotherapy is an effective tool in palliation treatment of BM and is part of an interdisciplinary approach. Preferred technique, targeting, and different dose schedules are described in the guidelines of the German Society for Radiooncology (DEGRO) which are also integrated in 2012 recommendations of the Working Group Gynecologic Oncology (AGO). PMID:22740796

Feyer, Petra C.; Steingraeber, Maria

2012-01-01

280

A New Health Strategy to Prevent Pressure Ulcer Formation in Paraplegics using Computer and Sensory Substitution via the Tongue  

E-print Network

Pressure ulcers are recognized as a major health issue in individuals with spinal cord injuries and new approaches to prevent this pathology are necessary. An innovative health strategy is being developed through the use of computer and sensory substitution via the tongue in order to compensate for the sensory loss in the buttock area for individuals with paraplegia. This sensory compensation will enable individuals with spinal cord injuries to be aware of a localized excess of pressure at the skin/seat interface and, consequently, will enable them to prevent the formation of pressure ulcers by relieving the cutaneous area of suffering. This work reports an initial evaluation of this approach and the feasibility of creating an adapted behavior, with a change in pressure as a response to electro-stimulated information on the tongue. Obtained during a clinical study in 10 healthy seated subjects, the first results are encouraging, with 92% success in 100 performed tests. These results, which have to be complete...

Moreau-Gaudry, A; Demongeot, J; Payan, Y; Moreau-Gaudry, Alexandre; Prince, Anne; Demongeot, Jacques; Payan, Yohan

2006-01-01

281

Effect of locomotor training on motor recovery and walking ability in patients with incomplete spinal cord injury: a case series.  

PubMed

[Purpose] The aim of this study was to describe the effect of locomotor training on a treadmill for three individuals who have an incomplete spinal cord injury (SCI). [Subjects and Methods] Three indivduals (2 males, 1 female) with incomplete paraplegia participated in this prospective case series. All subjects participated in locomotor training for a maximum of 20 minutes on a motorized treadmill without elevation at a comfortable walking speed three days a week for four weeks as an adjunct to a conventional physiotherapy program. The lower extremity strength and walking capabilities were used as the outcome measures of this study. Lower extremity strength was measured by lower extremity motor score (LEMS). Walking capability was assessed using the Walking Index for Spinal Cord Injury (WISCI II). [Results] An increase in lower extremity motor score and walking capabilities at the end of training program was found. [Conclusion] Gait training on a treadmill can enhance motor recovery and walking capabilities in subjects with incomplete SCI. Further research is needed to generalize these findings and to identify which patients might benefit from locomotor training. PMID:25013303

Anwer, Shahnawaz; Equebal, Ameed; Palekar, Tushar J; Nezamuddin, M; Neyaz, Osama; Alghadir, Ahmad

2014-06-01

282

The clinical maze of mitochondrial neurology  

PubMed Central

Mitochondrial diseases involve the respiratory chain, which is under the dual control of nuclear and mitochondrial DNA (mtDNA). The complexity of mitochondrial genetics provides one explanation for the clinical heterogeneity of mitochondrial diseases, but our understanding of disease pathogenesis remains limited. Classification of Mendelian mitochondrial encephalomyopathies has been laborious, but whole-exome sequencing studies have revealed unexpected molecular aetiologies for both typical and atypical mitochondrial disease phenotypes. Mendelian mitochondrial defects can affect five components of mitochondrial biology: subunits of respiratory chain complexes (direct hits); mitochondrial assembly proteins; mtDNA translation; phospholipid composition of the inner mitochondrial membrane; or mitochondrial dynamics. A sixth category—defects of mtDNA maintenance—combines features of Mendelian and mitochondrial genetics. Genetic defects in mitochondrial dynamics are especially important in neurology as they cause optic atrophy, hereditary spastic paraplegia, and Charcot–Marie–Tooth disease. Therapy is inadequate and mostly palliative, but promising new avenues are being identified. Here, we review current knowledge on the genetics and pathogenesis of the six categories of mitochondrial disorders outlined above, focusing on their salient clinical manifestations and highlighting novel clinical entities. An outline of diagnostic clues for the various forms of mitochondrial disease, as well as potential therapeutic strategies, is also discussed. PMID:23835535

DiMauro, Salvatore; Schon, Eric A.; Carelli, Valerio; Hirano, Michio

2014-01-01

283

Squamous Cell Carcinoma (Marjolin's Ulcer) Arising in a Sacral Decubitus Ulcer Resulting in Humoral Hypercalcemia of Malignancy.  

PubMed

Long-standing burns, fissures, and ulcers that undergo malignant transformation into a variety of malignancies, including squamous cell carcinoma, is commonly referred to as a Marjolin's ulcer. It is well recognized that squamous cell carcinomas of the lung and esophagus can cause humoral hypercalcemia of malignancy secondary to paraneoplastic secretion of parathyroid hormone-related peptide. However, it is extremely rare for a squamous cell carcinoma developing in a sacral decubitus ulcer to cause humoral hypercalcemia of malignancy. We describe the first case of a patient found to have elevated serum levels of parathyroid hormone related peptide related to his Marjolin's ulcer. A 45-year-old African American man with T6 paraplegia and a sacral decubitus ulcer present for 20 years was admitted for hypercalcemia of unclear etiology. He was subsequently found to have elevated parathyroid hormone related peptide and an excisional biopsy from the ulcer showed invasive squamous cell carcinoma suggestive of humoral hypercalcemia of malignancy. The patient ultimately succumbed to sepsis while receiving chemotherapy for his metastatic squamous cell carcinoma. Humoral hypercalcemia of malignancy is a rare and likely underrecognized complication that can occur in a Marjolin's ulcer. PMID:25197285

O'Malley, John T; Schoppe, Candace; Husain, Sameera; Grossman, Marc E

2014-01-01

284

Endovascular Surgery for Traumatic Thoracic Aortic Injury: Our Experience with Five Cases, Two of Whom were Young Patients  

PubMed Central

Objectives: We present our experience of endovascular surgery for traumatic aortic injury and the results of our procedures. Materials and Methods: From January 2009 to December 2013, we performed endovascular repairs of traumatic thoracic aortic injury on 5 male patients 16–75 years old (mean, 50.8), two of whom were young. Three of the patients had multiple organ injuries. The mean interval time to the operation is 22.0 hours (range, 10–36). All patients underwent endovascular repair with heparinization. The isthmus regions were seen in three cases and all of them were needed left subclavian artery (LSA) coverage. In the two young patients, the deployed stent graft was 22 mm (22.2% oversizing for diameter of aorta) and 26 mm (36.8% oversizing), respectively. Results: The procedures were successful in all patients, with no early mortality, paraplegia or stroke. During 3–63 months (mean, 30.8) follow-up period, no one experienced stent graft-related complications. One patient with LSA coverage experienced arm ischemia but the symptom improved with time. Conclusion: Endovascular surgery for traumatic thoracic aortic injury can be performed safely with low mortality or morbidity even in young small aorta. Accumulation of clinical experience and evaluation of long-term outcomes are necessary.

Matsumoto, Takashi; Matsuyama, Sho; Fukumura, Fumio; Ando, Hiromi; Tanaka, Jiro; Uchida, Takayuki

2014-01-01

285

Anatomical distribution of HTLV-I proviral sequence in an autopsy case of HTLV-I associated myelopathy: a polymerase chain reaction study.  

PubMed

HTLV-I associated myelopathy (HAM) is a slowly progressive paraplegia of the lower extremities observed among HTLV-I carriers. An autopsy of a typical HAM case in which perivascular lymphocytic infiltration was not limited to the central nervous system was examined. Spinal dorsal roots, salivary gland, lungs, liver and kidney showed non-specific, but unusual sporadic perivascular lymphocytic infiltration, which resembled the findings in the spinal cord. To investigate the anatomical distribution of HTLV-I provirus, the HTLV-I proviral sequences, tax and pol, were amplified from the formalin-fixed paraffin-embedded tissues of the autopsy case using polymerase chain reaction (PCR). By PCR, strong HTLV-I provirus signals were detected in the spinal cord, peripheral nerve, muscle, lungs and liver. Weak signals were detected in the medulla oblongata, optic nerve and lymph node, while the other organs, including the cerebrum, were negative. The data from this study show the specific distribution of HTLV-I provirus in the distinct organs of a HAM patient. PMID:8025646

Sueyoshi, K; Goto, M; Johnosono, M; Sato, E; Shibata, D

1994-01-01

286

Musculoskeletal Deterioration and Hemicorporectomy After Spinal Cord Injury  

PubMed Central

Background and Purpose The long-term management following an hemicorporectomy (HCP) is not well documented in the scientific literature. The purpose of this case report is to describe the 25-year history of a man with a spinal cord injury who experienced severe musculoskeletal deterioration and hemicorporectomy. Case Description The client sustained T10 complete paraplegia at age 18 years, developed severe decubitus ulcers, and required an HCP as a lifesaving measure 13 years later. The authors describe the chronology of several rehabilitation and prosthetic strategies and speculate on factors that may have contributed to their successes and failures. Outcomes The client survived 12 years after the HCP and returned to independent mobility, self-care, and schooling despite complications with continued skin breakdown. Over the 12 years following discharge from the hospital after the spinal cord injury, he spent 749 days in the hospital. During the 12 years he lived after discharge from the hospital following the HCP, he was hospitalized 190 days. Discussion The authors discuss factors contributing to the client’s musculoskeletal deterioration including chronic wounds, postural deviations, and incomplete adherence to pressure-relief recommendations and raise considerations for physical therapists who treat patients after HCP. PMID:12620090

Dudley-Javoroski, Shauna

2014-01-01

287

Characterization of maspardin, responsible for human Mast syndrome, in an insect species and analysis of its evolution in metazoans  

NASA Astrophysics Data System (ADS)

Mast syndrome is a complicated form of human hereditary spastic paraplegias, caused by a mutation in the gene acid cluster protein 33, which encodes a protein designated as "maspardin." Maspardin presents similarity to the ?/?-hydrolase superfamily, but might lack enzymatic activity and rather be involved in protein-protein interactions. Association with the vesicles of the endosomal network also suggested that maspardin may be involved in the sorting and/or trafficking of molecules in the endosomal pathway, a crucial process for maintenance of neuron health. Despite a high conservation in living organisms, studies of maspardin in other animal species than mammals were lacking. In the cotton armyworm Spodoptera littoralis, an insect pest model, analysis of an expressed sequence tag collection from antenna, the olfactory organ, has allowed identifying a maspardin homolog ( SlMasp). We have investigated SlMasp tissue distribution and temporal expression by PCR and in situ hybridization techniques. Noteworthy, we found that maspardin was highly expressed in antennae and associated with the structures specialized in odorant detection. We have, in addition, identified maspardin sequences in numerous "nonmammalian" species and described here their phylogenetic analysis in the context of metazoan diversity. We observed a strong conservation of maspardin in metazoans, with surprisingly two independent losses of this gene in two relatively distant ecdysozoan taxa that include major model organisms, i.e., dipterans and nematodes.

Chertemps, Thomas; Montagné, Nicolas; Bozzolan, Françoise; Maria, Annick; Durand, Nicolas; Maïbèche-Coisne, Martine

2012-07-01

288

Endovascular Management of Thoracic Aortic Aneurysms  

SciTech Connect

The overall survival of patients with thoracic aortic aneurysm (TAA) has improved significantly in the past few years. Endovascular treatment, proposed as an alternative to surgery, has been considered a therapeutic innovation because of its low degree of invasiveness, which allows the treatment of even high-surgical risk patients with limited complications and mortality. A major limitation is the lack of adequate evidence regarding long-term benefit and durability because follow-up has been limited to just a few years even in the largest series. The combination of endovascular exclusion with visceral branch revascularization for the treatment of thoraco-abdominal aortic aneurysms involving the visceral aorta has also been attempted. As an alternative, endografts with branches represent a technological evolution that allows treatment of complex anatomy. Even if only small numbers of patients and short follow-up are available, this technical approach, which has with limited mortality (<10%) and paraplegia rates, to expand endovascular treatment to TAA seems feasible. With improved capability to recognize proper anatomy and select clinical candidates, the choice of endovascular stent-graft placement may offer a strategy to optimize management and improve prognosis.

Fattori, Rossella, E-mail: rossella.fattori@unibo.it; Russo, Vincenzo; Lovato, Luigi; Buttazzi, Katia; Rinaldi, Giovanni [University Hospital S. Orsola, Cardiovascular Radiology Unit, Cardio-Thoracic-Vascular Department (Italy)

2011-12-15

289

Hydronephrosis and renal failure following inadequate management of neuropathic bladder in a patient with spinal cord injury: Case report of a preventable complication  

PubMed Central

Background Condom catheters are indicated in spinal cord injury patients in whom intravesical pressures during storage and voiding are safe. Unmonitored use of penile sheath drainage can lead to serious complications. Case report A 32-year old, male person, sustained complete paraplegia at T-11 level in 1985. He had been using condom catheter. Eleven years after sustaining spinal injury, intravenous urography showed no radio-opaque calculus, normal appearances of kidneys, ureters and bladder. Blood urea and Creatinine were within reference range. A year later, urodynamics revealed detrusor pressure of 100?cm water when detrusor contraction was initiated by suprapubic tapping. This patient was advised intermittent catheterisation and take anti-cholinergic drug orally; but, he wished to continue penile sheath drainage. Nine years later, this patient developed bilateral hydronephrosis and renal failure. Indwelling urethral catheter drainage was established. Five months later, ultrasound examination of urinary tract revealed normal kidneys with no evidence of hydronephrosis. Conclusion Spinal cord injury patients with high intravesical pressure should not have penile sheath drainage as these patients are at risk for developing hydronephrosis and renal failure. Intermittent catheterisation along with antimuscarinic drug should be the preferred option for managing neuropathic bladder. PMID:23014062

2012-01-01

290

Neuromuscular scoliosis.  

PubMed

The purpose of this focused review is to provide an overview of neuromuscular scoliosis from the perspective of the rehabilitation physician. Scoliosis is a common consequence of neuromuscular diseases, including central nervous system disorders such as cerebral palsy and spinal cord injury; motor neuron disorders, for example, spinal muscular atrophy; muscle fiber disorders, for example, Duchenne muscular dystrophy; multifactorial disorders, for example, spina bifida; and many other neuropathic and myopathic conditions. Unlike adolescent idiopathic scoliosis, which is the most common form of spinal deformity, neuromuscular scoliosis is more severe and more progressive, and is associated with more morbidity. Factors that contribute to this spinal deformity include asymmetric paraplegia, imbalance of mechanical forces, intraspinal and congenital anomalies of the spine, altered sensory feedback, and abnormal posture via central pathways. Spinal deformity combined with limitations due to an underlying neuromuscular condition lead to significant physiologic impairments that affect limb movement, cardiopulmonary function, gait, standing, sitting, balance, trunk stability, bimanual activities, activities of daily living, and pain, as well as concerns with self-image and social interactions. Evaluation and management of this population requires understanding of disease progression, pulmonary status, functional limitations, indications for conservative and surgical interventions, and social considerations. PMID:24247014

Allam, Anand M; Schwabe, Aloysia L

2013-11-01

291

Periodically Relieving Ischial Sitting Load to Decrease the Risk of Pressure Ulcers  

PubMed Central

Objective To investigate the relieving effect on interface pressure of an alternate sitting protocol involving a sitting posture that reduces ischial support. Design Repeated measures in 2 protocols on 3 groups of subjects. Setting Laboratory. Participants Twenty able-bodied persons, 20 persons with paraplegia, and 20 persons with tetraplegia. Interventions Two 1-hour protocols were used: alternate and normal plus pushup. In the alternate protocol, sitting posture was alternated every 10 minutes between normal (sitting upright with ischial support) and with partially removed ischial support (WO-BPS) postures; in the normal plus pushup protocol, sitting was in normal posture with pushups (lifting the subject off the seat) performed every 20 minutes. Main Outcome Measure Interface pressure on seat and backrest. Results In WO-BPS posture, the concentrated interface pressure observed around the ischia in normal posture was significantly repositioned to the thighs. By cyclically repositioning the interface pressure, the alternate protocol was superior to the normal plus pushup protocol in terms of a significantly lower average interface pressure over the buttocks. Conclusions A sitting protocol periodically reducing the ischial support helps lower the sitting load on the buttocks, especially the area close to ischial tuberosities. PMID:17601466

Makhsous, Mohsen; Rowles, Diane M.; Rymer, William Z.; Bankard, James; Nam, Ellis K.; Chen, David; Lin, Fang

2010-01-01

292

Septic shock with tension fecothorax as a delayed presentation of a gunshot diaphragmatic rupture  

PubMed Central

Diaphragmatic rupture (DR) after thoracoabdominal trauma has a reported rate of 0.8% to 5% and up to 30% of diaphragmatic hernias are accompanied with delayed diagnosis. The DR occurs after high-energy blunt or penetrating (stab or gunshot wounds) trauma. The purpose of this article is to analyze the DR, its clinical presentation, complications and possible causes of the delay in diagnosis, whilst recording a rare interesting case. A 44-year old moribund male with a fifteen years history of paraplegia, came to the emergency department with a clinical presentation of extremely severe respiratory distress. Chest X-ray showed the colon present in the left hemithorax. The onset of symptoms was 48 hours before, resulting in hemodynamic instability and severe sepsis condition. Emergency left thoracotomy and laparotomy were carried out. A rupture of the left hemidiaphragm was found as well as intrathoracic presence of colon, incarcerated and perforated, feces and omentum, also incarcerated and necrotic. There were dense adhesions between the ectopic viscera and the thoracic structures. The necrotic parts of the colon and the omentum were mobilized, and then resected. The viable parts of the colon were laboriously reintroduced into the intraperitoneal cavity. We conclude that early diagnosis is crucial to the morbidity and mortality after DR. The course and the kinetic energy of bullets determine the extent of the wound and the size of the DR. The diagnosis of rupture of the diaphragm after penetrating trauma is sometimes difficult and delay can lead to life threatening complications. PMID:24255791

Papachristos, Ioannis C.; Daliakopoulos, Stavros I.; Chatzoulis, Kostas; Lampridis, Savvas; Svarnas, Grigorios; Katsiadramis, Ioannis

2013-01-01

293

Sensory ataxia as a prominent clinical presentation in three families with mutations in CYP7B1.  

PubMed

Pathogenic mutations in CYP7B1 account for SPG5, an autosomal recessive hereditary spastic paraplegia characterized by a complex phenotype including visual problems and cerebellar dysfunction. Sensory ataxia is not usually regarded as a typical clinical feature of SPG5. The purpose of this study was to describe six patients showing features of sensory ataxia as the prominent and/or initial symptoms of SPG5. Six patients from three distinct pedigrees (three women, three men; age 49.5 ± 18.2 years), all presenting gait unsteadiness and frequent falls since childhood, underwent clinical and molecular investigations. All showed marked sensory ataxic gait with positive Romberg's sign, as well as severely impaired position and vibration sense. Comparatively minor signs of pyramidal involvement were also detected. In four of the patients, brain MRI showed white matter hyperintensities on T2-weighted images. An already reported homozygous c.889A>G (p.T297A) mutation in SPG5/CYP7B1 was found in five patients from two families, whereas the remaining case harbored the novel c.250_251delC/p.L84Ffs*6 and c.266A>C/p.Y89S variants. Marked and enduring sensory ataxia can be a pivotal sign in SPG5, and expands the phenotypic spectrum associated with mutations in CYP7B1. PMID:24519355

Di Fabio, Roberto; Marcotulli, Christian; Tessa, Alessandra; Leonardi, Luca; Storti, Eugenia; Pierelli, Francesco; Santorelli, Filippo M; Casali, Carlo

2014-04-01

294

Evolving experience with thoracoabdominal aortic aneurysm repair at a single institution.  

PubMed

Fifty-seven patients underwent repair of atherosclerotic thoracoabdominal aortic aneurysms between 1978 and 1990. Five patients had urgent surgery for rupture. The 30-day operative mortality rate for the entire group was 18% (10 patients). Before July 1987, 19 patients (group 1) were operated on by use of a technique previously described. In these earlier patients the peritoneum was routinely entered, the diaphragm was divided radially, and no heparin was given. Among patients in group 1 there was a 30-day operative mortality rate of 42% (8 patients), and morbidity included myocardial infarction 4 (21%), respiratory failure 9 (47%), renal failure 12 (63%), bleeding requiring reoperation 4 (21%), and intestinal ischemia 3 (16%). Since July 1987 a standardized approach to all elective thoracoabdominal aortic aneurysms has been used in 38 patients (group 2). This method uses a left thoracoabdominal incision, circumferential division of the hemidiaphragm, retronephric totally extraperitoneal aortic exposure, single lung anesthesia, full heparinization, the graft inclusion technique, and liberal use of visceral endarterectomy. Patients in group 2 sustained a 30-day operative mortality rate of 5% (2 patients) and morbidity included myocardial infarction 2 (5%), respiratory failure 10 (26%), renal failure 11 (29%), bleeding requiring reoperation 1 (3%), paraplegia 6 (16%), and paraparesis 4 (11%). Modern surgery for repair of thoracoabdominal aortic aneurysm results in acceptably low operative mortality rates. Spinal cord ischemia remains an unresolved source of morbidity. PMID:2038102

Golden, M A; Donaldson, M C; Whittemore, A D; Mannick, J A

1991-06-01

295

Acute aortic occlusion presenting with lower limb paralysis.  

PubMed

In a two year period eight patients have presented with acute aortic occlusion and a poor outcome in seven. Initial failure to diagnose aortic occlusion, with a mean delay from presentation to diagnosis of 24 hours, was mainly responsible. All patients had varying degrees of paralysis on presentation which misled clinicians although other findings of acute ischaemia (pain, absent pulses, colour change and anaesthesia) were always present. Two patients were initially referred to a neurologist, another to a neurosurgeon, and the fourth to an orthopaedic surgeon. Even after diagnosis had been established, the need for urgent revascularization was not always recognized, the mean time from diagnosis to revascularization being 13 hours. Unnecessary aortography contributed to this delay in four patients. In two patients operative treatment was not undertaken while six were treated operatively by: aortic bifurcation graft (3), aortic thromboendarterectomy and femoropopliteal bypass (1), open aortic embolectomy (1) and bilateral femoral embolectomy (1). The causes of aortic occlusion were thrombosis of an atherosclerotic aorta (5), thrombosis of an aneurysm (2) and embolism (1). In the latter patient, the heparin induced thrombocytopenia syndrome (HITS) was primarily responsible. The outcomes in the eight patients were death (5), paraplegia (1), amputation (1), and uncomplicated recovery (1). The single patient who made an uncomplicated recovery had the shortest delay from presentation to revascularization of only 2 1/4 hours. Acute aortic occlusion rivals aortic rupture as a vascular emergency and demands immediate operative intervention. PMID:1939328

Meagher, A P; Lord, R S; Graham, A R; Hill, D A

1991-01-01

296

Fractured neck of femur below long spinopelvic fixation for Charcot spine: a case report  

PubMed Central

Introduction We present a case of a patient with a previously undescribed complication: intertrochanteric femoral neck insufficiency fracture after long-segment instrumented spinopelvic fusion to the ilium for Charcot spine. Case presentation A 42-year-old Caucasian man with post-traumatic complete T6 paraplegia presented to our institution after developing Charcot spinal arthropathy at L3 and L4 and symptoms of autonomic dysreflexia 21 years after his original spinal cord injury. Multiple anterior and posterior surgeries were required to eventually achieve stabilization of his thoracolumbar spine to his pelvis and resolution of symptoms. The most distal fixation point was two iliac wing screws bilaterally. At 10 weeks after the final spinal surgery and after posterior spinal bony consolidation had occurred, he sustained an intertrochanteric femoral neck fracture, distal to the iliac fixation, whilst bending forward in his wheelchair. His proximal femoral fracture was internally fixed with an intramedullary device. Conclusions Spinal Charcot’s arthropathy is a rare condition that may occur in patients with post-traumatic spinal cord injury. Although associated with high risk of complications, circumferential instrumented fusion in Charcot spine can restore spinal stability. Insufficiency fractures of the proximal femur are possible complications of long spinopelvic fusions. PMID:24378187

2013-01-01

297

Isotopic scintigraphy combined with computed tomography: A useful method for investigating inefficiency of intrathecal baclofen.  

PubMed

Background: Intrathecal baclofen infusion is an established method for the treatment of generalized and disabling spasticity. The most frequent technical problems are due to catheter /pump disconnections, but diagnosis of dysfunction may be difficult. Case report: We report here the case of a 53-year-old woman with spastic paraplegia treated with intrathecal baclofen. Spasticity remained uncontrolled despite a gradual increase in baclofen dosage. On plain radiographs the distal end of the catheter was found to be pointing downwards with the catheter tip at level L5 and no apparent disconnection or failure. Indium111 diethylenetriamine penta-acetic acid (DTPA) scintigraphy combined with computed tomography revealed that the activity of the radioisotope was highest next to the first sacral vertebra and that there was no leakage. Radioisotope activity above the lumbar level was very low. The catheter tip was therefore repositioned to level T7. One month later, spasticity was well controlled and a second scintigraphy confirmed high activity of intrathecal radioisotope up to the basal cisterns. Discussion: The combination of Indium111 DTPA scinti-graphy with computed tomography allows anatomical and functional investigation of intrathecal drug administration. In this case report this approach showed that the inefficiency of intrathecal baclofen was due to the caudal orientation of the catheter. PMID:24715222

Frémondière, Flavie; Saoût, Virginie; Lacœuille, Franck; Ferrapie, Anne-Laure; Menei, Philippe; Couturier, Olivier; Richard, Isabelle; Dinomais, Mickaël

2014-06-25

298

Non-Parkinson movement disorders  

PubMed Central

Summary Solutions to the major riddles in movement disorders are appearing at a breathtaking pace: 1) loss-of-function mutations in PRRT2, which encodes a cell surface protein expressed in neurons, have been found in many patients with paroxysmal kinesigenic dyskinesias; 2) mutations in CIZ1, which encodes a protein involved in cell-cycle control at the G1-S checkpoint, have been identified in a small percentage of patients with cervical dystonia; and 3) finally, after many years of genetics and identification of more than 25 disease-associated genes, cellular studies related to the pathobiology of hereditary spastic paraplegia are converging on defects in modeling the endoplasmic reticulum and membrane trafficking. On the treatment front, the distinctive syndromes of faciobrachial dystonic seizures with anti-LRI1 antibodies and anti-N-methyl-d-aspartic acid encephalitis with orobuccolingual dyskinesias are becoming increasingly recognized by clinicians as imminently treatable conditions. Also on the treatment front, the first phase I trial of MRI-guided high-intensity focused ultrasound for essential tremor has been completed and intraoperative MRI is currently being used to place electrodes in the brains of patients with medically intractable dystonia. Definitive etiologies and efficacious treatments for non–Parkinson disease movement disorders are no longer wishful thinking. PMID:23634381

2013-01-01

299

Deficient Import of Acetyl-CoA into the ER Lumen Causes Neurodegeneration and Propensity to Infections, Inflammation, and Cancer  

PubMed Central

The import of acetyl-CoA into the ER lumen by AT-1/SLC33A1 is essential for the N?-lysine acetylation of ER-resident and ER-transiting proteins. A point-mutation (S113R) in AT-1 has been associated with a familial form of spastic paraplegia. Here, we report that AT-1S113R is unable to form homodimers in the ER membrane and is devoid of acetyl-CoA transport activity. The reduced influx of acetyl-CoA into the ER lumen results in reduced acetylation of ER proteins and an aberrant form of autophagy. Mice homozygous for the mutation display early developmental arrest. In contrast, heterozygous animals develop to full term, but display neurodegeneration and propensity to infections, inflammation, and cancer. The immune and cancer phenotypes are contingent on the presence of pathogens in the colony, whereas the nervous system phenotype is not. In conclusion, our results reveal a previously unknown aspect of acetyl-CoA metabolism that affects the immune and nervous systems and the risk for malignancies. PMID:24828632

Peng, Yajing; Li, Mi; Clarkson, Ben D.; Pehar, Mariana; Lao, Patrick J.; Hillmer, Ansel T.; Barnhart, Todd E.; Christian, Bradley T.; Mitchell, Heather A.; Bendlin, Barbara B.; Sandor, Matyas

2014-01-01

300

Single-stage repair of adult aortic coarctation and concomitant cardiovascular pathologies: a new alternative surgical approach  

PubMed Central

Background Coarctation of the aorta in the adulthood is sometimes associated with additional cardiovascular pathologies that require intervention. Ideal approach in such patients is uncertain. Anatomic left-sided short aortic bypass from the arcus aorta to descending aorta via median sternotomy allows simultaneuos repair of both complex aortic coarctation and concomitant cardiac operation. Materials Four adult patients were underwent Anatomic left-sided short aortic bypass operation for complex aortic coarctation through median sternotomy using deep hypothermic circulatory arrest. Concomitant cardiac operations were Bentall procedure for annuloaortic ectasia in one patient, coronary artery bypass grafting for three vessel disease in two patient, and patch closure of ventricular septal defect in one patient. Results All patients survived the operation and were alive with patent bypass at a mean follow-up of 36 months. No graft-related complications occurred, and there were no instances of stroke or paraplegia. Conclusion We conclude that single-stage repair of adult aortic coarctation with concomitant cardiovascular lesions can be performed safely using this newest technique. PMID:16803624

Yilmaz, Mert; Polat, Bulent; Saba, Davit

2006-01-01

301

Uncoupling of neuroinflammation from axonal degeneration in mice lacking the myelin protein tetraspanin-2.  

PubMed

Deficiency of the major constituent of central nervous system (CNS) myelin, proteolipid protein (PLP), causes axonal pathology in spastic paraplegia type-2 patients and in Plp1(null) -mice but is compatible with almost normal myelination. These observations led us to speculate that PLP's role in myelination may be partly compensated for by other tetraspan proteins. Here, we demonstrate that the abundance of the structurally related tetraspanin-2 (TSPAN2) is highly increased in CNS myelin of Plp1(null) -mice. Unexpectedly, Tspan2(null) -mutant mice generated by homologous recombination in embryonic stem cells displayed low-grade activation of astrocytes and microglia in white matter tracts while they were fully myelinated and showed no signs of axonal degeneration. To determine overlapping functions of TSPAN2 and PLP, Tspan2(null) *Plp1(null) double-mutant mice were generated. Strikingly, the activation of astrocytes and microglia was strongly enhanced in Tspan2(null) *Plp1(null) double-mutants compared with either single-mutant, but the levels of dysmyelination and axonal degeneration were not increased. In this model, glial activation is thus unlikely to be caused by axonal pathology, and vice versa does not potentiate axonal degeneration. Our results support the concept that multiple myelin proteins have distinct roles in the long-term preservation of a healthy CNS, rather than in myelination per se. PMID:24038504

de Monasterio-Schrader, Patricia; Patzig, Julia; Möbius, Wiebke; Barrette, Benoit; Wagner, Tadzio L; Kusch, Kathrin; Edgar, Julia M; Brophy, Peter J; Werner, Hauke B

2013-11-01

302

Pott's Disease in a 2-Year-Old Child Treated by Decompression and Anterior-Posterior Instrumented Fusion  

PubMed Central

Introduction. Paraplegia and kyphotic deformity are two major disease-related problems of spinal tuberculosis, especially in the early age disease. In this study a 2-year-old boy who underwent surgical decompression, correction, and 360° instrumented fusion via simultaneous anterior-posterior technique for Pott's disease was reported. Case Report. A 2-year-and-9-month-old boy presented with severe back pain and paraparesis of one-month duration. Thoracic magnetic resonance imaging demonstrated destruction with a large paraspinal abscess involving T5-T6-T7 levels, compressing the spinal cord. The paraspinal abscess drained and three-level corpectomy was performed at T5-6-7 with transthoracic approach. Anterior instrumentation and fusion was performed with structural 1 autogenous fibula and rib graft using screw-rod system. In prone position pedicle screws were inserted at T4 and T8 levels and rods were placed. Six months after surgery, there was no weakness or paraparesis and no correction loss at the end of follow-up period. Discussion. In cases of vertebral osteomyelitis with severe anterior column destruction in the very early child ages the use of anterior structural grafts and instrumentation in combination with posterior instrumentation is safe and effective in maintenance of the correction achieved and allows efficient stabilization and early mobilization. PMID:24744934

Erdem, Mehmet Nuri; Sever, Cem; Korkmaz, Mehmet Fatih; Karaca, Sinan; Kirac, Ferit; Tezer, Mehmet

2014-01-01

303

Pott's Disease in a 2-Year-Old Child Treated by Decompression and Anterior-Posterior Instrumented Fusion.  

PubMed

Introduction. Paraplegia and kyphotic deformity are two major disease-related problems of spinal tuberculosis, especially in the early age disease. In this study a 2-year-old boy who underwent surgical decompression, correction, and 360° instrumented fusion via simultaneous anterior-posterior technique for Pott's disease was reported. Case Report. A 2-year-and-9-month-old boy presented with severe back pain and paraparesis of one-month duration. Thoracic magnetic resonance imaging demonstrated destruction with a large paraspinal abscess involving T5-T6-T7 levels, compressing the spinal cord. The paraspinal abscess drained and three-level corpectomy was performed at T5-6-7 with transthoracic approach. Anterior instrumentation and fusion was performed with structural 1 autogenous fibula and rib graft using screw-rod system. In prone position pedicle screws were inserted at T4 and T8 levels and rods were placed. Six months after surgery, there was no weakness or paraparesis and no correction loss at the end of follow-up period. Discussion. In cases of vertebral osteomyelitis with severe anterior column destruction in the very early child ages the use of anterior structural grafts and instrumentation in combination with posterior instrumentation is safe and effective in maintenance of the correction achieved and allows efficient stabilization and early mobilization. PMID:24744934

Erdem, Mehmet Nuri; Sever, Cem; Korkmaz, Mehmet Fatih; Karaca, Sinan; Kirac, Ferit; Tezer, Mehmet

2014-01-01

304

Genetics and Pathophysiology of Neurodegeneration with Brain Iron Accumulation (NBIA)  

PubMed Central

Our understanding of the syndromes of Neurodegeneration with Brain Iron Accumulation (NBIA) continues to grow considerably. In addition to the core syndromes of pantothenate kinase-associated neurodegeneration (PKAN, NBIA1) and PLA2G6-associated neurodegeneration (PLAN, NBIA2), several other genetic causes have been identified (including FA2H, C19orf12, ATP13A2, CP and FTL). In parallel, the clinical and pathological spectrum has broadened and new age-dependent presentations are being described. There is also growing recognition of overlap between the different NBIA disorders and other diseases including spastic paraplegias, leukodystrophies and neuronal ceroid lipofuscinosis which makes a diagnosis solely based on clinical findings challenging. Autopsy examination of genetically-confirmed cases demonstrates Lewy bodies, neurofibrillary tangles, and other hallmarks of apparently distinct neurodegenerative disorders such as Parkinson’s disease (PD) and Alzheimer’s disease. Until we disentangle the various NBIA genes and their related pathways and move towards pathogenesis-targeted therapies, the treatment remains symptomatic. Our aim here is to provide an overview of historical developments of research into iron metabolism and its relevance in neurodegenerative disorders. We then focus on clinical features and investigational findings in NBIA and summarize therapeutic results reviewing reports of iron chelation therapy and deep brain stimulation. We also discuss genetic and molecular underpinnings of the NBIA syndromes. PMID:23814539

Schneider, Susanne A; Dusek, Petr; Hardy, John; Westenberger, Ana; Jankovic, Joseph; Bhatia, Kailash P

2013-01-01

305

Sliding and Lower Limb Mechanics during Sit-Stand-Sit Transitions with a Standing Wheelchair  

PubMed Central

Purpose. This study aimed to investigate the shear displacement between the body and backrest/seat, range of motion (ROM), and force acting on the lower limb joints during sit-stand-sit transitions by operating an electric-powered standing wheelchair. Methods and Materials. The amounts of sliding along the backrest and the seat plane, ROM of lower limb joints, and force acting on the knee/foot were measured in twenty-four people with paraplegia. Results. Without an antishear mechanism, the shear displacement was approximately 9 cm between the user's body and the backrest/seat surfaces. During standing up, the user's back slid down and the thigh was displaced rearward, but they moved in opposite directions when wheelchair sat back down. A minimum of 60 degrees of ROM at the hip and knee was needed during sit-stand-sit transitions. The maximal resultant forces acting on the knee restraints could reach 23.5% of body weight. Conclusion. Sliding between the body and backrest/seat occurred while transitioning from sitting to standing and vice versa. A certain amount of ROM at lower limb joints and force acting on the knee was necessitated during sit-stand-sit transitions. Careful consideration needs to be given to who the user of the electric powered standing wheelchair is. PMID:25105120

Fang, Wei-Chien; Chang, Jyh-Jong; Kuo, Chang-Chih

2014-01-01

306

Retrograde labeling, transduction, and genetic targeting allow cellular analysis of corticospinal motor neurons: implications in health and disease.  

PubMed

Corticospinal motor neurons (CSMN) have a unique ability to receive, integrate, translate, and transmit the cerebral cortex's input toward spinal cord targets and therefore act as a "spokesperson" for the initiation and modulation of voluntary movements that require cortical input. CSMN degeneration has an immense impact on motor neuron circuitry and is one of the underlying causes of numerous neurodegenerative diseases, such as primary lateral sclerosis (PLS), hereditary spastic paraplegia (HSP), and amyotrophic lateral sclerosis (ALS). In addition, CSMN death results in long-term paralysis in spinal cord injury patients. Detailed cellular analyses are crucial to gain a better understanding of the pathologies underlying CSMN degeneration. However, visualizing and identifying these vulnerable neuron populations in the complex and heterogeneous environment of the cerebral cortex have proved challenging. Here, we will review recent developments and current applications of novel strategies that reveal the cellular and molecular basis of CSMN health and vulnerability. Such studies hold promise for building long-term effective treatment solutions in the near future. PMID:24723858

Jara, Javier H; Genç, Bar??; Klessner, Jodi L; Ozdinler, P Hande

2014-01-01

307

Fibromyalgia and arachnoiditis presented as an acute spinal disorder  

PubMed Central

Background: Adhesive arachnoiditis is a chronic, insidious condition that causes debilitating intractable pain and a range of other neurological problems. Its pathophysiology is not well understood. This manuscript discusses its presentations, which can mimic an acute spinal disorder, its hypothetical pathophysiology, treatment, and its relationship with fibromyalgia. Case Description: The authors present a case of a 47-year-old female who presented with clinical features mimicking an acute spinal disorder but later found to have an adhesive arachnoiditis. She was admitted following a trauma with complaints of back pain and paraplegia. On examination, there was marked tenderness over thoracolumbar spine with lower limbs upper motor neuron weakness. An urgent magnetic resonance imaging (MRI) of the spine revealed multiple lesions at her thoracic and lumbar spinal canals, which did not compress the spinal cord. Therefore, conservative management was initiated. Despite on regular therapies, her back and body pain worsened and little improvement in her limbs power was noted. Laminectomy was pursued and found to have spinal cord arachnoiditis. Subsequently, she was operated by other team members for multiple pelvic masses, which later proved to be benign. After gathering all the clinical information obtained at surgery and after taking detailed history inclusive of cognitive functions, diagnosis of an adhesive arachnoiditis syndrome was made. Currently, she is managed by neuropsychologist and pain specialist. Conclusion: This case report highlights the importance of knowing an adhesive arachnoiditis syndrome – a rarely discussed pathology by the neurosurgeon, which discloses a significant relationship between immune and nervous systems.

Idris, Zamzuri; Ghazali, Faizul H.; Abdullah, Jafri M.

2014-01-01

308

Feasibility of robotic-assisted locomotor training in children with central gait impairment.  

PubMed

Intensive, task-specific training enabled by a driven gait orthosis (DGO) may be a cost-effective means of improving walking performance in children. A paediatric DGO has recently been developed. This study was the first paediatric trial aimed to determine the feasibility of robotic-assisted treadmill training in children with central gait impairment (n=26; 11 females, 15 males; mean age 10 y 1 mo [SD 4 y]; range 5 y 2 mo-19 y 5 mo). Diagnoses of the study group included cerebral palsy (n=19; Gross Motor Function Classification System Levels I-IV), traumatic brain injury (n=1), Guillain-Barré syndrome (n=2), incomplete paraplegia (n=2), and haemorrhagic shock (n=1), and encephalopathy (n=1). Sixteen children were in-patients and 10 were outpatients. Twenty-four of the 26 patients completed the training which consisted of a mean of 19 sessions (SD 2.2; range 13-21) in the in-patient group and 12 sessions (SD 1.0; range 10-13) in the outpatient group. Gait speed and 6-Minute Walking Test increased significantly (p<0.01). Functional Ambulation Categories and Standing dimension (in-patient group p<0.01; outpatient group p<0.05) of the Gross Motor Function Measure improved significantly. DGO training was successfully integrated into the rehabilitation programme and findings suggest an improvement of locomotor performance. PMID:18039236

Meyer-Heim, A; Borggraefe, I; Ammann-Reiffer, C; Berweck, St; Sennhauser, F H; Colombo, G; Knecht, B; Heinen, F

2007-12-01

309

[The features of cardio-respiratory system and autonomic regulation in parasportsmen with spinal injury].  

PubMed

A comprehensive study of the functional state of basketball athletes in wheelchairs with spinal cord injuries in the T6-T10 and paraplegia (n = 9, mean age 26.6 +/- 1.7 years) was held. As a control, we used disability groups with a similar injury, leading an active life (n = 13, mean age 44.5 +/- 2.6 years), athletes ( = 14, mean age 24.6 +/- 1.3 years) and healthy physically active men (n = 15, the average age of 24.9 +/- 0.6 years). In the athletes in wheelchairs it was revealed an increase in the length of the body in a sitting position, the increase in tidal volume and increasing in the effectiveness of the functional respiratory tests. These changes in the state of the musculoskeletal system and autonomic systems to ensure physical activity classified as adaptive and due to sports training. In the state of the cardiovascular system and its autonomic regulation parasportsmen showed a reduction in trauma-induced increase in diastolic blood pressure and increase in the magnitude of arterial baroreflex sensitivity, decreased due to spinal injury. These data indicate availability of compensatory processes aimed at optimizing the cardiovascular system through the mechanisms of baroreflex regulation. PMID:23101369

Ternovo?, K S; Romanchuk, A P; Sorokin, M Iu; Pankova, N B

2012-01-01

310

Cardiorespiratory fitness and muscular strength of wheelchair users.  

PubMed Central

The classification of lower-limb disabilities is commonly based on the site of the spinal cord lesion or the amount of functional muscle. Another important variable in assessing wheelchair users is their ability to carry out the activities of daily living. The cardiorespiratory fitness of those with lower-limb disabilities is usually assessed with arm-ergometry and wheelchair tests, each of which has some advantages. Muscle strength and endurance are also important aspects of the disabled person's ability to function. Fitness is often poor in the disabled, and normal wheelchair use does not seem to prove an adequate training stimulus. Exercise with an arm ergometer and with pulleys and participation in vigorous wheelchair sports can improve physical condition. Participation in exercise programs should be based on the results of a fitness assessment and on the level of the spinal cord lesion in those with paraplegia. Progression in such programs should be gradual to ensure that the exerciser does not become discouraged and drop out of classes before fitness is increased. Data on wheelchair athletes suggest that, with persistence, many individuals in wheelchairs can adjust relatively well to their disabilities. Images FIG. 1 FIG. 2 PMID:6459841

Davis, G. M.; Kofsky, P. R.; Kelsey, J. C.; Shephard, R. J.

1981-01-01

311

Squamous Cell Carcinoma (Marjolin's Ulcer) Arising in a Sacral Decubitus Ulcer Resulting in Humoral Hypercalcemia of Malignancy  

PubMed Central

Long-standing burns, fissures, and ulcers that undergo malignant transformation into a variety of malignancies, including squamous cell carcinoma, is commonly referred to as a Marjolin's ulcer. It is well recognized that squamous cell carcinomas of the lung and esophagus can cause humoral hypercalcemia of malignancy secondary to paraneoplastic secretion of parathyroid hormone-related peptide. However, it is extremely rare for a squamous cell carcinoma developing in a sacral decubitus ulcer to cause humoral hypercalcemia of malignancy. We describe the first case of a patient found to have elevated serum levels of parathyroid hormone related peptide related to his Marjolin's ulcer. A 45-year-old African American man with T6 paraplegia and a sacral decubitus ulcer present for 20 years was admitted for hypercalcemia of unclear etiology. He was subsequently found to have elevated parathyroid hormone related peptide and an excisional biopsy from the ulcer showed invasive squamous cell carcinoma suggestive of humoral hypercalcemia of malignancy. The patient ultimately succumbed to sepsis while receiving chemotherapy for his metastatic squamous cell carcinoma. Humoral hypercalcemia of malignancy is a rare and likely underrecognized complication that can occur in a Marjolin's ulcer.

O'Malley, John T.; Schoppe, Candace; Husain, Sameera; Grossman, Marc E.

2014-01-01

312

Effects of disodium dichloromethylene diphosphonate on hypercalcemia produced by bone metastases.  

PubMed Central

The aim of this study was to determine the ability of disodium dichloromethylene diphosphonate (Cl2MDP) to reduce the hypercalcemia secondary to skeletal metastases and induced by stimulation of bone resorption by malignant cells. Five patients with hypercalcemia due to bone metastases of breast or renal cancer were treated orally for 4 wk with 3,200 mg of Cl2MDP and 4 wk with a placebo in a double blind, crossover study. During the Cl2MDP period of administration four patients experienced a rapid and significant decrease in serum calcium and urinary calcium excretion together with an increase in alkaline phosphatase. In the remaining patient who developed a sudden paraplegia at the onset of the therapy followed by a marked increase in serum calcium levels and urinary calcium excretion, Cl2MDP was able to reverse this worsening of hypercalcemia or to reduce serum and urinary calcium to normal values. For all patients, urinary hydroxyproline excretion was unchanged during the Cl2MDP period when compared with the prestudy or placebo periods. From these results, and because of the rapid relapse of hypercalcemia during the placebo period or after withdrawal of the treatment, we can conclude that Cl2MDP is capable of reducing excessive mobilization of calcium resulting from bone metastases. PMID:6444955

Chapuy, M C; Meunier, P J; Alexandre, C M; Vignon, E P

1980-01-01

313

Fishing for causes and cures of motor neuron disorders.  

PubMed

Motor neuron disorders (MNDs) are a clinically heterogeneous group of neurological diseases characterized by progressive degeneration of motor neurons, and share some common pathological pathways. Despite remarkable advances in our understanding of these diseases, no curative treatment for MNDs exists. To better understand the pathogenesis of MNDs and to help develop new treatments, the establishment of animal models that can be studied efficiently and thoroughly is paramount. The zebrafish (Danio rerio) is increasingly becoming a valuable model for studying human diseases and in screening for potential therapeutics. In this Review, we highlight recent progress in using zebrafish to study the pathology of the most common MNDs: spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS) and hereditary spastic paraplegia (HSP). These studies indicate the power of zebrafish as a model to study the consequences of disease-related genes, because zebrafish homologues of human genes have conserved functions with respect to the aetiology of MNDs. Zebrafish also complement other animal models for the study of pathological mechanisms of MNDs and are particularly advantageous for the screening of compounds with therapeutic potential. We present an overview of their potential usefulness in MND drug discovery, which is just beginning and holds much promise for future therapeutic development. PMID:24973750

Patten, Shunmoogum A; Armstrong, Gary A B; Lissouba, Alexandra; Kabashi, Edor; Parker, J Alex; Drapeau, Pierre

2014-07-01

314

Traumatic Aortic Injury: Single-center Comparison of Open versus Endovascular Repair  

PubMed Central

Background Conventional open repair is a suboptimal therapy for blunt traumatic aortic injury (BTAI) due to the high postoperative mortality and morbidity rates. Recent advances in the thoracic endovascular repair technique may improve outcomes so that it becomes an attractive therapeutic option. Materials and Methods From August 2003 to March 2012, 21 patients (mean age, 45.81 years) with BTAI were admitted to our institution. Of these, 18 cases (open repair in 11 patients and endovascular repair in 7 patients) were retrospectively reviewed and the early perioperative results of the two groups were compared. Results Although not statistically significant, there was a trend toward the reduction of mortality in the endovascular repair group (18.2% vs. 0%). There were no cases of paraplegia or endoleak. Statistically significant reductions in heparin dosage, blood loss, and transfusion amounts during the operations and in procedure duration were observed. Conclusion Compared with open repair, endovascular repair can be performed with favorable mortality and morbidity rates. However, relatively younger patients who have acute aortic arch angulation and a small aortic diameter may be a therapeutic challenge. Improvements in graft design, delivery sheaths, and graft durability are the cornerstone of successful endovascular repair. PMID:23275921

Cho, Jun Woo; Lee, Sub; Jang, Jae Seok

2012-01-01

315

Spinal tuberculosis: A review  

PubMed Central

Spinal tuberculosis is a destructive form of tuberculosis. It accounts for approximately half of all cases of musculoskeletal tuberculosis. Spinal tuberculosis is more common in children and young adults. The incidence of spinal tuberculosis is increasing in developed nations. Genetic susceptibility to spinal tuberculosis has recently been demonstrated. Characteristically, there is destruction of the intervertebral disk space and the adjacent vertebral bodies, collapse of the spinal elements, and anterior wedging leading to kyphosis and gibbus formation. The thoracic region of vertebral column is most frequently affected. Formation of a ‘cold’ abscess around the lesion is another characteristic feature. The incidence of multi-level noncontiguous vertebral tuberculosis occurs more frequently than previously recognized. Common clinical manifestations include constitutional symptoms, back pain, spinal tenderness, paraplegia, and spinal deformities. For the diagnosis of spinal tuberculosis magnetic resonance imaging is more sensitive imaging technique than x-ray and more specific than computed tomography. Magnetic resonance imaging frequently demonstrates involvement of the vertebral bodies on either side of the disk, disk destruction, cold abscess, vertebral collapse, and presence of vertebral column deformities. Neuroimaging-guided needle biopsy from the affected site in the center of the vertebral body is the gold standard technique for early histopathological diagnosis. Antituberculous treatment remains the cornerstone of treatment. Surgery may be required in selected cases, e.g. large abscess formation, severe kyphosis, an evolving neurological deficit, or lack of response to medical treatment. With early diagnosis and early treatment, prognosis is generally good. PMID:22118251

Garg, Ravindra Kumar; Somvanshi, Dilip Singh

2011-01-01

316

A Monoclonal Antibody Against Human MUDENG Protein  

PubMed Central

MUDENG (mu-2-related death-inducing gene, MuD) encodes a predicted ?54-kDa protein in humans, considered to be involved in trafficking proteins from endosomes toward other membranous compartments as well as in inducing cell death. Here we report on the generation of a mouse monoclonal antibody (MAb) against the middle domain of human (h) MuD. This IgG sub 1 MAb, named M3H9, recognizes residues 244–326 in the middle domain of the MuD protein. Thus, the MuD proteins expressed in an astroglioma cell line and primary astrocytes can be detected by the M3H9 MAb. We showed that M3H9 MAb can be useful in enzyme-linked immunosorbent assay (ELISA) and immunoblot experiments. In addition, M3H9 MAb can detect the expression of the MuD protein in formalin-fixed, paraffin-embedded mouse ovary and uterus tissues. These results indicate that the MuD MAb M3H9 could be useful as a new biomarker of hereditary spastic paraplegia and other related diseases. PMID:23909422

Wagley, Yadav; Choi, Jun-Ha; Wickramanayake, Dimuthu Dhammika; Choi, Geun-Yeol; Kim, Chang-Kyu; Kim, Tae-Hyoung

2013-01-01

317

Spastin-Interacting Protein NA14/SSNA1 Functions in Cytokinesis and Axon Development.  

PubMed

Hereditary spastic paraplegias (HSPs) are a genetically diverse group of inherited neurological disorders (SPG1-72) with the cardinal feature of prominent lower-extremity spasticity due to a length-dependent axonopathy of corticospinal motor neurons. The most frequent form of autosomal dominant HSP results from mutations of the SPG4 gene product spastin. This is an ATPase associated with diverse cellular activities (AAA) protein that binds to and severs microtubules. While spastin participates in crucial cellular processes such as cytokinesis, endosomal tubulation, and axon development, its role in HSP pathogenesis remains unclear. Spastin interacts in cells with the NA14 protein, a major target for auto-antibodies in Sjögren's syndrome (nuclear autoantigen 1; SSNA1). Our analysis of endogenous spastin and NA14 proteins in HeLa cells and rat cortical neurons in primary culture revealed a clear distribution of both proteins to centrosomes, with NA14 localizing specifically to centrioles. Stable NA14 knockdown in cell lines dramatically affected cell division, in particular cytokinesis. Furthermore, overexpression of NA14 in neurons significantly increased axon outgrowth and branching, while also enhancing neuronal differentiation. We postulate that NA14 may act as an adaptor protein regulating spastin localization to centrosomes, temporally and spatially regulating the microtubule-severing activity of spastin that is particularly critical during the cell cycle and neuronal development. PMID:25390646

Goyal, Uma; Renvoisé, Benoît; Chang, Jaerak; Blackstone, Craig

2014-01-01

318

Spinal cord injuries in children and adolescents.  

PubMed

This chapter provides an overview of spinal cord injuries (SCI) in children and adolescents, including epidemiology, medical and musculoskeletal complications, rehabilitation and psychosocial aspects. Males are more commonly affected than females during adolescence; however, as the age at injury decreases, the preponderance of males becomes less marked, and by 3 years of age the number of females with SCIs equals that of males. The neurologic level and degree of completeness varies with age; among children injured prior to 12 years of age approximately two-thirds are paraplegic and approximately two-thirds have complete lesions. Among adolescents, approximately 50% have paraplegia and 55% have complete lesions. Management of pediatric-onset SCI should be family centered and developmentally based, responsive to the dynamic changes that occur during growth and development. Distinctive anatomical and physiological features of children and adolescents, along with growth and development, are responsible for unique manifestations and complications of pediatric SCI. SCI without radiological abnormalities (SCIWORA), birth injuries, lap-belt injuries, upper cervical injuries, and the delayed onset of neurological deficits are relatively unique to pediatric SCI. Children who sustain their SCI before puberty experience a higher incidence of musculoskeletal complications, such as scoliosis and hip dislocation. PMID:23098710

Vogel, Lawrence C; Betz, Randall R; Mulcahey, M J

2012-01-01

319

Model for in vivo analysis of immune response to Herpes Simplex virus, type 1 infections  

SciTech Connect

A murine model was developed which allowed study of autologous humoral and cellular immune responses (CCMI) to a Herpes Simplex Virus, type 1 (HSV-1) infection. Lethal irradiation was used to render BAlb/c mice non-responsive to T-dependent and T-independent antigens. The immune system of the irradiated animals was reconstituted with either HSV-1 primed or non-immune syngeneic spleen cells and the mice were infected with HSV-1 in the rear footpad. Whereas unirradiated mice showed no symptoms of infection, X-irradiated animals followed a clinical course of lesions, monoplegia, paraplegia and death by day 9. Irradiated animals reconstituted with HSV-1 primed spleen cells recovered from the HSV-1 infection following a transient appearance of lesions. HSV-1 infected, immunodeficient animals reconstituted with unprimed spleen cells survived for 12 days post infection. Removal of T cells from the reconstituting cell population prevented both the recovery mediated by the primed cells and the partial protection mediated by the unprimed cells, however, removal of B cells had no effect on the course of infection. The role of autologous anti-HSV-1 antibody in protection from an HSV-1 infection was assessed HSV-1 primed mice treated with cyclophosphamide to abolish their cell mediated immunity.

Alexander, T.S.

1987-01-01

320

The role of spartin and its novel ubiquitin binding region in DALIS occurrence  

PubMed Central

Troyer syndrome is an autosomal recessive hereditary spastic paraplegia (HSP) caused by frameshift mutations in the SPG20 gene that results in a lack of expression of the truncated protein. Spartin is a multifunctional protein, yet only two conserved domains—a microtubule-interacting and trafficking domain and a plant-related senescence domain involved in cytokinesis and mitochondrial physiology, respectively—have been defined. We have shown that overexpressed spartin binds to the Ile44 hydrophobic pocket of ubiquitin, suggesting spartin might contain a ubiquitin-binding domain. In the present study, we demonstrate that spartin contributes to the formation of dendritic aggresome-like induced structures (DALIS) through a unique ubiquitin-binding region (UBR). Using short hairpin RNA, we knocked down spartin in RAW264.7 cells and found that DALIS frequency decreased; conversely, overexpression of spartin increased the percentage of cells containing DALIS. Using nuclear magnetic resonance spectroscopy, we characterized spartin's UBR and defined the UBR's amino acids that are key for ubiquitin binding. We also found that spartin, via the UBR, binds Lys-63–linked ubiquitin chains but does not bind Lys-48–linked ubiquitin chains. Finally, we demonstrate that spartin's role in DALIS formation depends on key residues within its UBR. PMID:24523286

Karlsson, Amelia B.; Washington, Jacqueline; Dimitrova, Valentina; Hooper, Christopher; Shekhtman, Alexander; Bakowska, Joanna C.

2014-01-01

321

Posteriorly migrated thoracic disc herniation: a case report  

PubMed Central

Introduction Posterior epidural migration of thoracic disc herniation is extremely rare but may occur in the same manner as in the lumbar spine. Case presentation A 53-year-old Japanese man experienced sudden onset of incomplete paraplegia after lifting a heavy object. Magnetic resonance imaging revealed a posterior epidural mass compressing the spinal cord at the T9-T10 level. The patient underwent emergency surgery consisting of laminectomy at T9-T10 with right medial facetectomy, removal of the mass lesion, and posterior instrumented fusion. Histological examination of the mass lesion yielded findings consistent with sequestered disc material. His symptoms resolved, and he was able to resume walking without a cane 4 weeks after surgery. Conclusions Pre-operative diagnosis of posterior epidural migration of herniated thoracic disc based on magnetic resonance imaging alone may be overlooked, given the rarity of this pathology. However, this entity should be considered among the differential diagnoses for an enhancing posterior thoracic extradural mass. PMID:23402642

2013-01-01

322

The clinical maze of mitochondrial neurology.  

PubMed

Mitochondrial diseases involve the respiratory chain, which is under the dual control of nuclear and mitochondrial DNA (mtDNA). The complexity of mitochondrial genetics provides one explanation for the clinical heterogeneity of mitochondrial diseases, but our understanding of disease pathogenesis remains limited. Classification of Mendelian mitochondrial encephalomyopathies has been laborious, but whole-exome sequencing studies have revealed unexpected molecular aetiologies for both typical and atypical mitochondrial disease phenotypes. Mendelian mitochondrial defects can affect five components of mitochondrial biology: subunits of respiratory chain complexes (direct hits); mitochondrial assembly proteins; mtDNA translation; phospholipid composition of the inner mitochondrial membrane; or mitochondrial dynamics. A sixth category-defects of mtDNA maintenance-combines features of Mendelian and mitochondrial genetics. Genetic defects in mitochondrial dynamics are especially important in neurology as they cause optic atrophy, hereditary spastic paraplegia, and Charcot-Marie-Tooth disease. Therapy is inadequate and mostly palliative, but promising new avenues are being identified. Here, we review current knowledge on the genetics and pathogenesis of the six categories of mitochondrial disorders outlined above, focusing on their salient clinical manifestations and highlighting novel clinical entities. An outline of diagnostic clues for the various forms of mitochondrial disease, as well as potential therapeutic strategies, is also discussed. PMID:23835535

DiMauro, Salvatore; Schon, Eric A; Carelli, Valerio; Hirano, Michio

2013-08-01

323

Pr\\'evention des escarres chez les parapl\\'egiques : une nouvelle approche par \\'electrostimulation linguale  

E-print Network

Pressure ulcers are recognized as a major health issue in individuals with spinal cord injuries and new approaches to prevent this pathology are necessary. An innovative health strategy is being developed through the use of computer and sensory substitution via the tongue in order to compensate for the sensory loss in the buttock area for individuals with paraplegia. This sensory compensation will enable individuals with spinal cord injuries to be aware of a localized excess of pressure at the skin/seat interface and, consequently, will enable them to prevent the formation of pressure ulcers by relieving the cutaneous area of suffering. This work reports an initial evaluation of this approach and the feasibility of creating an adapted behavior, with a change in pressure as a response to electro-stimulated information on the tongue. Obtained during a clinical study in 10 healthy seated subjects, the first results are encouraging, with 92% success in 100 performed tests. These results, which have to be complete...

Moreau-Gaudry, Alexandre; Demongeot, Jacques; Payan, Yohan

2006-01-01

324

Case report: extra pulmonary tuberculosis in sickle cell disease.  

PubMed

In apparently healthy individuals, tuberculosis (TB) affects mainly the lungs however, worsening immune status tend to predispose to an increased tendency for extra-pulmonary tuberculosis (EPTB). We report the case of a 22 year old known sickle cell anaemia (HBS) female student with three-month history of bilateral hip pain, weight loss and swelling of the left hip with multiple discharging sinuses, paraplegia and recurrent fever. There was no preceding history of trauma. Full Blood Count (FBC) revealed leukocytosis with neutrophilia, monocytosis, thrombocytosis and Packed Cell Volume (PCV) of 23%. Erythrocyte sedimentation rate (ESR) was 120mm/Hr (Western Green) and retroviral screening was negative. Bacteriologic culture of the discharging sinuses grew Escherichia coli and Staphylococcus aureus, both sensitive to sparfloxacin. Smear microscopy for acid-fast-bacilli (AFB) was negative. Chest X-Ray was reported normal but X-Ray of the pelvis showed loss of L4/L5 disc space and appearances suggestive of avascular necrosis of the femoral heads. Clinical and haematological profile of the patient started to improve by the second month on therapeutic trial of anti-TB regimen. She had nine-month course of therapy and later discharged to physiotherapy clinic. Management of EPTB requires a high index of clinical suspicion and well-equipped laboratory to support the diagnosis. Therefore, this case report highlights the need to upgrade TB-diagnostic facilities in this environment. PMID:17312749

Kehinde, A O; Olaniyi, J A; Fakunle, E E

2006-09-01

325

A firearm bullet lodged into the thoracic spinal canal without vertebral bone destruction: a case report  

PubMed Central

Introduction Firearm injuries account for 13% to 17% of all spinal cord injuries, and are generally caused during warfare or assault with intent to kill. Spinal cord injuries caused by firearms are usually observed in patients aged 15 to 34 years old, and are especially common among men. Case presentation We report the case of a 28-year-old Iraqi man who was referred to our radiology department with lower limb paraplegia secondary to a gunshot wound. We performed 64-slice computerized tomography with two-dimensional and three-dimensional reconstruction of the thoracolumbar spine. On the two-dimensional and three-dimensional reconstructed axial images of the thoracolumbar spine, an intra-canalicular bullet nucleus was found at the mid-spinal cord at the T8 level, with no evidence of vertebral bone destruction. Conclusions To the best of our knowledge, there is only one previous report in the literature describing a case of a bullet nucleus lodged into the inferior epidural spinal canal without destruction of the vertebral bone. With the rise of violence worldwide the incidence of gunshot injuries continues to increase, and, thus, it is essential for radiologists to have a clear understanding of gunshot injuries and the findings on radiographic images. PMID:21733154

2011-01-01

326

Membrane-shaping disorders: a common pathway in axon degeneration.  

PubMed

Neurons with long projections are particularly liable to damage, which is reflected by a large group of hereditary neurodegenerative disorders that primarily affect these neurons. In the group of hereditary spastic paraplegias motor axons of the central nervous system degenerate, while distal pure motor neuropathies, Charcot-Marie-Tooth disorders and the group of hereditary sensory and autonomic neuropathies are characterized by degeneration of peripheral nerve fibres. Because the underlying pathologies share many parallels, the disorders are also referred to as axonopathies. A large number of genes has been associated with axonopathies and one of the emerging subgroups encodes membrane-shaping proteins with a central reticulon homology domain. Association of these proteins with lipid bilayers induces positive membrane curvature and influences the architecture of cellular organelles. Membrane-shaping proteins closely cooperate and directly interact with each other, but their structural features and localization to distinct subdomains of organelles suggests mutually exclusive roles. In some individuals a mutation in a shaping protein can result in upper motor neuron dysfunction, whereas in other patients it can lead to a degeneration of peripheral neurons. This suggests that membrane-shaping disorders might be considered as a continuous disease-spectrum of the axon. PMID:25281866

Hübner, Christian A; Kurth, Ingo

2014-12-01

327

Grave's Disease with Severe Hepatic Dysfunction: A Diagnostic and Therapeutic Challenge  

PubMed Central

Hepatic dysfunction in a patient with thyrotoxicosis may result from hyperthyroidism per se, as a side effect of antithyroid drugs, and causes unrelated to hyperthyroidism which sometimes causes diagnostic and therapeutic difficulties. A young female patient was admitted to our hospital with symptoms of thyrotoxicosis, diffuse goiter and ophthalmopathy along with cholestatic pattern of jaundice, and proximal muscle weakness. She was treated with propylthiouracil with gradual recovery. She was continuing her antithyroid medication with regular follow-up. The patient was readmitted a few months later with worsening thyrotoxicosis, proximal muscle weakness, fever, and a hepatocellular pattern of jaundice with sepsis. Propylthiouracil was stopped and lithium along with steroid coverage was given to control her thyrotoxicosis which was later changed to methimazole. Broad spectrum antibiotic therapy was also started but without any response. During her hospital stay, the patient also developed a flaccid paraplegia resembling Guillain-Barre syndrome. IV steroid was started for the neuropathy but meanwhile the patient succumbed to her illness. So in centers where facility for radioiodine therapy is not readily available, some definite well-tested protocols should be formulated to address such common but complicated clinical situations. PMID:25317178

Sarma, Dipti; Kaimal Saikia, Uma; Choudhury, Bipul Kumar

2014-01-01

328

Development and Treatments of Inflammatory Cells and Cytokines in Spinal Cord Ischemia-Reperfusion Injury  

PubMed Central

During aortic surgery, interruption of spinal cord blood flow might cause spinal cord ischemia-reperfusion injury (IRI). The incidence of spinal cord IRI after aortic surgery is up to 28%, and patients with spinal cord IRI might suffer from postoperative paraplegia or paraparesis. Spinal cord IRI includes two phases. The immediate spinal cord injury is related to acute ischemia. And the delayed spinal cord injury involves both ischemic cellular death and reperfusion injury. Inflammation is a subsequent event of spinal cord ischemia and possibly a major contributor to spinal cord IRI. However, the development of inflammatory mediators is incompletely demonstrated. And treatments available for inflammation in spinal cord IRI are insufficient. Improved understanding about spinal cord IRI and the development of inflammatory cells and cytokines in this process will provide novel therapeutic strategies for spinal cord IRI. Inflammatory cytokines (e.g., TNF-? and IL-1) may play an important role in spinal cord IRI. For treatment of several intractable autoimmune diseases (e.g., rheumatoid arthritis), where inflammatory cytokines are involved in disease progression, anti-inflammatory cytokine antagonist is now available. Hence, there is great potential of anti-inflammatory cytokine antagonist for therapeutic use of spinal cord IRI. We here review the mediators and several possibilities of treatment in spinal cord IRI. PMID:23956505

Zhu, Ping; Li, Jia-xin; Fujino, Masayuki; Zhuang, Jian; Li, Xiao-Kang

2013-01-01

329

An unusually long survival of a patient with glioblastoma of spinal cord: a case report.  

PubMed

Primary glioblastoma of spinal cord are rare and are associated with poor survival especially in adults. We report a case of glioblastoma of thoracic spinal cord (D3 to D6) in an adult treated with partial resection surgery and radiation therapy with a survival of six years with good quality of life. The patient had paraplegia at presentation but improved after surgery and radiation therapy to grade 4 in both lower limbs. After 5 years, he developed new lesion in a different location of the spine (L1, L2 & L5) along with multiple lesions over entire spine and was treated with radiation therapy and a year later developed a new lesion intracranially in the posterior fossa involving cerebellopontine angle region infiltrating brainstem. He was treated with palliative radiotherapy and is on chemotherapy with Temozolomide and is still alive with ability to do activities of daily living at the time of this report. Radiation therapy provided prolonged local control with effective palliation of symptoms and good quality of life in this patient enabling to do activities of daily living. PMID:24959488

Varghese, Sunitha Susan; Sebastian, Patricia; Joseph, Vivek; Chacko, Geeta; Backianathan, Selvamani

2014-04-01

330

W R Gowers 1895: two unpublished post-graduate lectures.  

PubMed

On 10 May 1893, William Gowers began a series of weekly clinical demonstrations at the National Hospital for the Relief and Cure of the Paralysed and Epileptic at Queen Square, London. The contents of some of these demonstrations were published as 'Post-graduate Clinical Lectures' in the Clinical Journal, and in other learned periodicals. Some were also later included in his book Clinical Lectures on Diseases of the Nervous System. Recently, the manuscripts of what appear to be verbatim transcripts of two further but unpublished demonstrations from Gowers' course in 1895 came to light, one containing alterations made in Gowers' handwriting. The first concerned a case of disseminated sclerosis and its differentiation from hysterical paraplegia, the second transverse myelitis and its consequences for bladder function. Why these lectures were never published remains uncertain, but their relatively unedited contents reveal something of the neurological knowledge, diagnostic reasoning, clinical examination and teaching methods employed by one of the great pioneers of clinical neurology. PMID:22396392

Lees, Andrew J; Woodward, R M P; Scott, Ann E M; Eadie, Mervyn J

2012-10-01

331

Spastin-Interacting Protein NA14/SSNA1 Functions in Cytokinesis and Axon Development  

PubMed Central

Hereditary spastic paraplegias (HSPs) are a genetically diverse group of inherited neurological disorders (SPG1-72) with the cardinal feature of prominent lower-extremity spasticity due to a length-dependent axonopathy of corticospinal motor neurons. The most frequent form of autosomal dominant HSP results from mutations of the SPG4 gene product spastin. This is an ATPase associated with diverse cellular activities (AAA) protein that binds to and severs microtubules. While spastin participates in crucial cellular processes such as cytokinesis, endosomal tubulation, and axon development, its role in HSP pathogenesis remains unclear. Spastin interacts in cells with the NA14 protein, a major target for auto-antibodies in Sjögren's syndrome (nuclear autoantigen 1; SSNA1). Our analysis of endogenous spastin and NA14 proteins in HeLa cells and rat cortical neurons in primary culture revealed a clear distribution of both proteins to centrosomes, with NA14 localizing specifically to centrioles. Stable NA14 knockdown in cell lines dramatically affected cell division, in particular cytokinesis. Furthermore, overexpression of NA14 in neurons significantly increased axon outgrowth and branching, while also enhancing neuronal differentiation. We postulate that NA14 may act as an adaptor protein regulating spastin localization to centrosomes, temporally and spatially regulating the microtubule-severing activity of spastin that is particularly critical during the cell cycle and neuronal development. PMID:25390646

Chang, Jaerak; Blackstone, Craig

2014-01-01

332

Detailed Shoulder MRI Findings in Manual Wheelchair Users with Shoulder Pain  

PubMed Central

Shoulder pain and pathology are common in manual wheelchair (MWC) users with paraplegia, and the biomechanical mechanism of injury is largely unknown. Establishing patterns of MRI characteristics in MWC users would help advance understanding of the mechanical etiology of rotator cuff disease, thus improving the logic for prescribed interventions. The purpose of this study was to report detailed shoulder MRI findings in a sample of 10?MWC users with anterolateral shoulder pain. The imaging assessments were performed using our standardized MRI Assessment of the Shoulder (MAS) guide. The tendon most commonly torn was the supraspinatus at the insertion site in the anterior portion in either the intrasubstance or articular region. Additionally, widespread tendinopathy, CA ligament thickening, subacromial bursitis, labral tears, and AC joint degenerative arthrosis and edema were common. Further reporting of detailed shoulder imaging findings is needed to confirm patterns of tears in MWC users regarding probable tendon tear zone, region, and portion. This investigation was a small sample observational study and did not yield data that can define patterns of pathology. However, synthesis of detailed findings from multiple studies could define patterns of pathological MRI findings allowing for associations of imaging findings to risk factors including specific activities. PMID:25180192

Morrow, Melissa M. B.; Van Straaten, Meegan G.; Murthy, Naveen S.; Braman, Jonathan P.; Zanella, Elia; Zhao, Kristin D.

2014-01-01

333

Novel mutational mechanism in man: Expansion of trinucleotide repeats  

SciTech Connect

An analysis of a novel, recently discovered class of mutations in man - an expansion, i.e., an increase of the copy number of intragenic unstable trinucleotide repeats - is presented. The expansion of trinucleotide X chromosome syndrome (two separate variants of the disease - FRAXA and FRAXE), myotonic dystrophy, spinal and bulbar Kennedy`s amyotrophy, Huntington`s chorea, type 1 spinocerebellar ataxia, and dentatorubral-pallidolyusian atrophy. The discovery of triplet expansion allows a satisfactory explanation on the molecular level of a series of unusual clinical genetic phenomena, such as anticipation, the {open_quotes}paternal transmission{close_quotes} effect, the {open_quotes}Sherman paradox,{close_quotes} and others. The common properties and the distinctions of unstable trinucleotide mutations in the nosologic forms mentioned above are analyzed comprehensively. These features include the mechanism by which these mutations cause disease, the time of their appearance in ontogenesis, and various clinical genetic correlations. The evolutionary origin of this class of mutations and, in particular, the role of alleles with an {open_quotes}intermediate{close_quotes} triplet number, which are the persistent reservoir of mutations arising de novo in a population, are also discussed. The possible implication of unstable trinucleotide repeats for a series of other hereditary diseases, such as type 2, spinocerebellar ataxia, Machado-Joseph disease, hereditary spastic paraplegia, essential tremor, schizophrenia, and others, is also suggested. 108 refs., 1 tab.

Ilarioshkin, S.N.; Ivanova-Smolenskaya, I.A.; Markova, E.D. [Research Institute of Neurology, Moscow (Russian Federation)

1995-11-01

334

Spinal cord compression by B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma in a patient seropositive for human immunodeficiency virus: a case report  

PubMed Central

Introduction Although non-Hodgkin’s lymphoma is one of the most common and frequently fatal of the acquired immune deficiency syndrome-defining illnesses, survival has improved significantly since the introduction of antiretroviral therapy. Patients with spinal cord compression resulting from non-Hodgkin’s lymphoma present with clinically acute or rapidly progressive neurologic deficits. The purpose of this case report is to present a case of a patient seropositive for human immunodeficiency virus with spinal cord compression due to B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma. Case presentation A 40-year-old Asian man, who was seropositive for human immunodeficiency virus, presented with progressive neurological deficits. Magnetic resonance images of his thoracic spine showed an epidural mass from T2 to T4, resulting in severe cord compression. Emergent surgical decompression and biopsy were performed, followed by palliative radiation therapy. The pathologic findings showed that the specimen was compatible with B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma. Palliative radiation therapy was performed; however, leptomeningeal seeding and pulmonary embolism led to his death. Conclusions When a patient infected with human immunodeficiency virus presents with a rapidly progressive spinal tumor accompanying paraplegia, non-Hodgkin’s lymphoma should be considered, and surgical decompression should be weighed with respect to the patient’s general condition and the subtype/prognosis of the lymphoma. PMID:25274079

2014-01-01

335

Myelo-meningocele: A multi-disciplinary problem  

PubMed Central

Background: Myelo-meningoceles are part of congenital afflictions of the spinal column. They arise from the failure of the neural tube to fuse properly during early embryonic growth. The causes and sequalae are multiple and, therefore, require multiple disciplines, to handle them. This study assessed the role of inter-disciplinary approach in the management of myelo-meningoceles. Materials and Methods: From 1975 to 2007, the author repaired 20 midline lumbar and lumbo-sacral myelo-meningoceles; 5 in Jamaica and 15 in Nigeria. There were 11 males and 9 females. Their ages, at operation, ranged from 1 to 168 days. All had urine and faecal incontinence and severe paraparesis to paraplegia. Skeletal deformities were present in 16 cases. The operations were carried out under routine general anaesthesia and in prone position. All cases were followed-up for up to 60 months, apart from one who died 4 days at home after discharge. Results: There were no deaths within the period of hospitalisation, usually about 14 days. Those followed-up have not made much improvement, though they were able to sit up without support and move around by shifting on their buttocks on the floor. Conclusion: We must continue to help these patients, but under the umbrella of specialised rehabilitation centres with the different specialists working together to make these patients attain a meaningful life and be useful to themselves and the society. PMID:24970975

Nnamdi, Ibe Michael Onwuzuruike

2014-01-01

336

Thoracic vertebral body fracture after total hip replacement in diffuse idiopathic skeletal hyperostosis.  

PubMed

This article describes the critical clinical sequelae of a patient with diffuse idiopathic skeletal hyperostosis who sustained an acute iatrogenic thoracic vertebral body fracture with subsequent spinal cord injury after a total hip replacement, with a final lethal course.A 57-year-old woman was referred to the authors' institution after undergoing a total hip replacement in the supine position for secondary osteoarthritis. Postoperatively, the patient had symptoms of an incomplete paraplegia. Computed tomography scan and magnetic resonance imaging revealed diffuse idiopathic skeletal hyperostosis and an acute unstable fracture of T11 with spinal contusion. A posterior spinal fusion of T10-L1 with laminectomy of T11 was performed immediately on admission. Postoperatively, no improvement of the neurological deficit was observed. After developing multiorgan failure while in intensive care, the patient died 2 months after the total hip replacement.The morphological and functional symptoms of diffuse idiopathic skeletal hyperostosis with the typical ossification of the longitudinal ligaments and the associated loss of bending forces of the spine were detected postoperatively. This severe case demonstrates that the surgeon must be alert to possible complications due to intraoperative maneuvers in patients with stiffened spinal disorders undergoing total hip replacement. PMID:22691644

Königshausen, Matthias; Dudda, Marcel; Merle, Christian; Schildhauer, Thomas Armin; Fehmer, Tobias

2012-06-01

337

Adolf von Strümpell: a key yet neglected protagonist of neurology.  

PubMed

German internist and neurologist Adolf von Strümpell (1853-1925) was a leading figure in German neurosciences around 1900 and helped to establish neurology as a discipline in its own right. He made contributions that were crucial to the development of the subject and in many cases his were the first descriptions of complex diseases such as Bechterew disease (ankylosing spondylitis), primary lateral sclerosis, hereditary spastic paraplegia, and syphilis. His Textbook of Special Pathology and Therapy of Internal Diseases, published in English as Text-book of Medicine for Students and Practitioners, and in particular the subvolume on neurological diseases, were the guiding manuals for the training in neurology for decades. However, despite his pioneering achievements, his name has almost become unknown within medical terminology. This article, therefore, wishes to revive an awareness not only of the most important stages in Strümpell's life in Erlangen, Leipzig, Breslau (Wroc?aw), and Vienna, but also of his scientific achievements, focusing primarily on his neurological studies. To this end, the article reviews his most important publications on the subject and seeks to evaluate their and hence Strümpell's impact on the understanding of certain illnesses. PMID:22527226

Engmann, Birk; Wagner, Armin; Steinberg, Holger

2012-10-01

338

Total vertebrectomy for stabilisation of chronic spinal lumbar luxation in a paraplegic dog without nociception.  

PubMed

An adult male crossbred dog was referred with a history of a road traffic accident that took place 1 month earlier. Neurological examination revealed paraplegia with absent nociception in the pelvic limbs. On epaxial palpation, significant curvature of the anatomical axis of the spine between the third and fourth lumbar vertebrae was observed, with the presence of a bone end almost piercing the dog's skin. Survey radiographs of the lumbar spine revealed severe dislocation between L3 and L4 vertebrae. During surgery, the spinal cord was not visible between the dislocated segments. Because of difficulties in reducing the lumbar luxation during surgery, vertebrectomy and vertebral shortening were performed. After alignment between vertebrae L3 and L5, eight cortical orthopaedic screws and bone cement were used for fixation. After 30 days, the dog started to use a wheelchair and was considered by its owner to have a good quality of life with no evidence of pain. To the authors' knowledge, this is the first case of severe luxation treated by total vertebrectomy and spine shortening in a dog. This surgery can be considered as an option in the management of severe spine luxation when the spinal cord is physically transected. PMID:24962201

Tertuliano Marinho, P V; Zani, C C; De Biasi, F; Bahr Arias, M V

2014-10-01

339

Unique Function of Kinesin Kif5A in Localization of Mitochondria in Axons.  

PubMed

Mutations in Kinesin proteins (Kifs) are linked to various neurological diseases, but the specific and redundant functions of the vertebrate Kifs are incompletely understood. For example, Kif5A, but not other Kinesin-1 heavy-chain family members, is implicated in Charcot-Marie-Tooth disease (CMT) and Hereditary Spastic Paraplegia (HSP), but the mechanism of its involvement in the progressive axonal degeneration characteristic of these diseases is not well understood. We report that zebrafish kif5Aa mutants exhibit hyperexcitability, peripheral polyneuropathy, and axonal degeneration reminiscent of CMT and HSP. Strikingly, although kif5 genes are thought to act largely redundantly in other contexts, and zebrafish peripheral neurons express five kif5 genes, kif5Aa mutant peripheral sensory axons lack mitochondria and degenerate. We show that this Kif5Aa-specific function is cell autonomous and is mediated by its C-terminal tail, as only Kif5Aa and chimeric motors containing the Kif5Aa C-tail can rescue deficits. Finally, concurrent loss of the kinesin-3, kif1b, or its adaptor kbp, exacerbates axonal degeneration via a nonmitochondrial cargo common to Kif5Aa. Our results shed light on Kinesin complexity and reveal determinants of specific Kif5A functions in mitochondrial transport, adaptor binding, and axonal maintenance. PMID:25355224

Campbell, Philip D; Shen, Kimberle; Sapio, Matthew R; Glenn, Thomas D; Talbot, William S; Marlow, Florence L

2014-10-29

340

Potential beneficial effects of granulocyte colony-stimulating factor therapy for spastic paraparesis in a patient with kyphoscoliosis: a case report.  

PubMed

Congenital kyphosis and kyphoscoliosis are much less common than congenital scoliosis and more serious because these curves can progress rapidly and can lead to spinal cord compression and paraplegia. A 15-year-old boy presented with congenital kyphoscoliosis along with spastic paraparesis (American Spinal Injury Association Impairment Scale grade C). We examined the safety and effectiveness of a low dose of analog granulocyte colony-stimulating factor (G-CSF) in this patient. G-CSF 5 µg/kg was given subcutaneously, daily for 5 days per month for 3 months. Laboratory tests, including blood, biochemical tests, and CD34+ cells (marker hematopoietic progenitor cells) were performed, in addition to clinical examination. Clinical examination revealed an increase of muscle strength in the upper limbs and decrease spasticity in the lower limbs between baseline and day 90 and day 180. We found no serious adverse event, drug-related platelet reduction, or splenomegaly. Leukocyte levels remained below 21,000/µL. CD34+ increased significantly at day 5 of G-CSF administration. Low-dose G-CSF was safe and well tolerated by the patient. A significant increase in muscle strength in this patient with spastic paraparesis after 3 months of treatment may indicate beneficial effects of G-CSF factor in this disorder. These results are inspiring and warrant further studies. PMID:24752769

Sienkiewicz, Dorota; Ku?ak, Wojciech; Okurowska-Zawada, Bo?ena; Wojtkowski, Janusz; Paszko-Patej, Gra?yna; Dmitruk, El?bieta; Kalinowska, Anna; Okulczyk, Kamila

2014-10-01

341

Retrograde labeling, transduction, and genetic targeting allow cellular analysis of corticospinal motor neurons: implications in health and disease  

PubMed Central

Corticospinal motor neurons (CSMN) have a unique ability to receive, integrate, translate, and transmit the cerebral cortex's input toward spinal cord targets and therefore act as a “spokesperson” for the initiation and modulation of voluntary movements that require cortical input. CSMN degeneration has an immense impact on motor neuron circuitry and is one of the underlying causes of numerous neurodegenerative diseases, such as primary lateral sclerosis (PLS), hereditary spastic paraplegia (HSP), and amyotrophic lateral sclerosis (ALS). In addition, CSMN death results in long-term paralysis in spinal cord injury patients. Detailed cellular analyses are crucial to gain a better understanding of the pathologies underlying CSMN degeneration. However, visualizing and identifying these vulnerable neuron populations in the complex and heterogeneous environment of the cerebral cortex have proved challenging. Here, we will review recent developments and current applications of novel strategies that reveal the cellular and molecular basis of CSMN health and vulnerability. Such studies hold promise for building long-term effective treatment solutions in the near future. PMID:24723858

Jara, Javier H.; Genc, Bar?s; Klessner, Jodi L.; Ozdinler, P. Hande

2014-01-01

342

Three Routes to Suppression of the Neurodegenerative Phenotypes Caused by Kinesin Heavy Chain Mutations  

PubMed Central

Kinesin-1 is a motor protein that moves stepwise along microtubules by employing dimerized kinesin heavy chain (Khc) subunits that alternate cycles of microtubule binding, conformational change, and ATP hydrolysis. Mutations in the Drosophila Khc gene are known to cause distal paralysis and lethality preceded by the occurrence of dystrophic axon terminals, reduced axonal transport, organelle-filled axonal swellings, and impaired action potential propagation. Mutations in the equivalent human gene, Kif5A, result in similar problems that cause hereditary spastic paraplegia (HSP) and Charcot–Marie–Tooth type 2 (CMT2) distal neuropathies. By comparing the phenotypes and the complementation behaviors of a large set of Khc missense alleles, including one that is identical to a human Kif5A HSP allele, we identified three routes to suppression of Khc phenotypes: nutrient restriction, genetic background manipulation, and a remarkable intramolecular complementation between mutations known or likely to cause reciprocal changes in the rate of microtubule-stimulated ADP release by kinesin-1. Our results reveal the value of large-scale complementation analysis for gaining insight into protein structure–function relationships in vivo and point to possible paths for suppressing symptoms of HSP and related distal neuropathies. PMID:22714410

Djagaeva, Inna; Rose, Debra J.; Lim, Angeline; Venter, Chris E.; Brendza, Katherine M.; Moua, Pangkong; Saxton, William M.

2012-01-01

343

Connexin 43 (GJA1) Mutations Cause the Pleiotropic Phenotype of Oculodentodigital Dysplasia  

PubMed Central

Gap junctions are assemblies of intercellular channels that regulate a variety of physiologic and developmental processes through the exchange of small ions and signaling molecules. These channels consist of connexin family proteins that allow for diversity of channel composition and conductance properties. The human connexin 43 gene, or GJA1, is located at human chromosome 6q22-q23 within the candidate region for the oculodentodigital dysplasia locus. This autosomal dominant syndrome presents with craniofacial (ocular, nasal, and dental) and limb dysmorphisms, spastic paraplegia, and neurodegeneration. Syndactyly type III and conductive deafness can occur in some cases, and cardiac abnormalities are observed in rare instances. We found mutations in the GJA1 gene in all 17 families with oculodentodigital dysplasia that we screened. Sixteen different missense mutations and one codon duplication were detected. These mutations may cause misassembly of channels or alter channel conduction properties. Expression patterns and phenotypic features of gja1 animal mutants, reported elsewhere, are compatible with the pleiotropic clinical presentation of oculodentodigital dysplasia. PMID:12457340

Paznekas, William A.; Boyadjiev, Simeon A.; Shapiro, Robert E.; Daniels, Otto; Wollnik, Bernd; Keegan, Catherine E.; Innis, Jeffrey W.; Dinulos, Mary Beth; Christian, Cathy; Hannibal, Mark C.; Jabs, Ethylin Wang

2003-01-01

344

Molecular mechanisms of gap junction mutations in myelinating cells.  

PubMed

There is an emerging group of neurological disorders that result from genetic mutations affecting gap junction proteins in myelinating cells. The X-linked form of Charcot Marie Tooth disease (CMT1X) is caused by numerous mutations in the GJB1 gene encoding the gap junction protein connexin32 (Cx32), which is expressed in both Schwann cells in the PNS and oligodendrocytes in the CNS. Patients with CMT1X present mainly with a progressive peripheral neuropathy, showing mixed axonal and demyelinating features. In many cases there is also clinical or subclinical involvement of the CNS with acute or chronic phenotypes of encephalopathy. Furthermore, mutations in the GJA12/GJC2 gene encoding the gap junction protein Cx47, which is expressed in oligodendrocytes, have been identified in families with progressive leukodystrophy, known as Pelizaeus-Merzbacher-like disease, as well as in patients with hereditary spastic paraplegia. Recent studies have provided insights into the pattern of gap junction protein expression and function in CNS and PNS myelinating cells. Furthermore, in vitro and in vivo disease models have clarified some of the molecular and cellular mechanisms underlying these disorders. Here we provide an overview of the clinical, genetic, and neurobiological aspects of gap junction disorders affecting the nervous system. PMID:20607661

Sargiannidou, Irene; Markoullis, Kyriaki; Kleopa, Kleopas A

2010-09-01

345

Emergency Diagnosis of Giant Cell Tumour (GCT) of Spine by Image Guided Fine Needle Aspiration Cytology (FNAC)  

PubMed Central

Giant cell tumour (GCT) of spine is an extremely rare neoplasm accounting 0.5% to 1.5% of all cases. The patient usually presents with weakness of lower limbs. We describe a case of 25-year-old male who presented with sudden onset of paraplegia. On plain radiograph there was an osteolytic lesion in T9 vertebra. Computed tomography (CT) scan revealed expansile lytic lesion in T9 vertebral body with involvement of posterior elements on right side with associated soft tissue mass in the extradural location extending into the spinal cord. Further Magnetic Resonance Imaging (MRI) scan (T1 contrast) showed the enhancing extradural mass involving spinal cord from D 8-10 levels. A provisional radiological diagnosis of GCT was made. A CT guided FNAC of the mass was performed which revealed typical cytological features of Giant cell tumour. Role of image guided Fine Needle Aspiration Cytology (FNAC) of vertebral mass and its role in emergency situations with clear emphasis on differential diagnosis is highlighted. PMID:25177571

Chaudhry, Manish; Singh, Amitoj

2014-01-01

346

Proton magnetic resonance spectroscopy and cognition in patients with spastin mutations.  

PubMed

The hereditary spastic paraplegias (HSP) are heterogeneous neurodegenerative disorders characterized by progressive spasticity and weakness in the lower limbs. Axonal loss in the long corticospinal tracts has been shown. Supraspinal symptoms and findings in the most common dominant HSP type, SPG4, support the theory that the disease also causes cerebral neuronal damage in specific parts of the brain. To investigate whether SPG4-HSP is associated with neuronal biochemical changes detectable on MR spectroscopy (MRS), single-voxel proton MRS of the brain was performed in eight subjects from four families with genetically confirmed SPG4-type HSP and eight healthy age-matched controls. Volumes of interest (VOI) were located in the frontal white matter and motor cortex. N-acetyl-aspartate-to-creatine ratio (NAA/Cr), N-acetyl-aspartate-to-choline (NAA/Cho), cholin to creatin (Cho/Cr) and myo-inositol-to-creatine (Ins/Cr) ratios were calculated for both locations. Neuropsychological tests were performed to support the neuroradiological findings. The Cho/Cr ratio in motor cortex (MC) of SPG4-HSP subjects was significantly lower than in controls. This reduction of the Cho/Cr ratio in SPG4 subjects was significantly associated with age-related verbal learning- and memory (CVLT) reduction. Our findings support involvement of motor cortex in SPG4-HSP. Proton MRS could be a useful tool for detecting metabolite abnormalities in areas of brain that appear normal on MRI. Cho/Cr ratio may be a marker of neurodegenerative process in SPG4-HSP. PMID:19084842

Erichsen, A K; Server, A; Landrø, N I; Sandvik, L; Tallaksen, C M E

2009-02-15

347

Spartin activates atrophin-1-interacting protein 4 (AIP4) E3 ubiquitin ligase and promotes ubiquitination of adipophilin on lipid droplets  

PubMed Central

Background Spartin protein is involved in degradation of epidermal growth factor receptor and turnover of lipid droplets and a lack of expression of this protein is responsible for hereditary spastic paraplegia type 20 (SPG20). Spartin is a multifunctional protein that associates with many cellular organelles, including lipid droplets. Recent studies showed that spartin interacts with E3 ubiquitin ligases that belong to the neural precursor cell-expressed developmentally downregulated gene (Nedd4) family, including atrophin-1-interacting protein 4 (AIP4/ITCH). However, the biological importance of the spartin-AIP4 interaction remains unknown. Results In this study, we show that spartin is not a substrate for AIP4 activity and that spartin's binding to AIP4 significantly increases self-ubiquitination of this E3 ligase, indicating that spartin disrupts the AIP4 autoinhibitory intramolecular interaction. Correspondingly, spartin has a seven times higher binding affinity to the WW region of AIP4 than the binding of the WW region has to the catalytic homologues of the E6-associated protein C-terminus (HECT) domain, as measured by enzyme-linked immunosorbent assay. We also show that spartin recruits AIP4 to lipid droplets and promotes ubiquitination of lipid droplet-associated protein, adipophilin, which regulates turnover of lipid droplets. Conclusions Our findings demonstrate that spartin acts as an adaptor protein that activates and recruits AIP4 E3 ubiquitin ligase to lipid droplets and by this means regulates the level of ubiquitination of adipophilin and potentially other lipid-associated proteins. We propose that this is one of the mechanisms by which spartin regulates lipid droplet turnover and might contribute to the pathology of SPG20. PMID:20504295

2010-01-01

348

Neuronal phospholipid deacylation is essential for axonal and synaptic integrity.  

PubMed

Recessively-inherited deficiency in the catalytic activity of calcium-independent phospholipase A2-beta (iPLA2?) and neuropathy target esterase (NTE) causes infantile neuroaxonal dystrophy and hereditary spastic paraplegia, respectively. Thus, these two related phospholipases have non-redundant functions that are essential for structural integrity of synapses and axons. Both enzymes are expressed in essentially all neurons and also have independent roles in glia. iPLA2? liberates sn-2 fatty acid and lysophospholipids from diacyl-phospholipids. Ca(2+)-calmodulin tonically-inhibits iPLA2?, but this can be alleviated by oleoyl-CoA. Together with fatty acyl-CoA-mediated conversion of lysophospholipid to diacyl-phospholipid this may regulate sn-2 fatty acyl composition of phospholipids. In the nervous system, iPLA2? is especially important for the turnover of polyunsaturated fatty acid-associated phospholipid at synapses. More information is required on the interplay between iPLA2? and iPLA2-gamma in deacylation of neuronal mitochondrial phospholipids. NTE reduces levels of phosphatidylcholine (PtdCho) by degrading it to glycerophosphocholine and two free fatty acids. The substrate for NTE may be nascent PtdCho complexed with a phospholipid-binding protein. Protein kinase A-mediated phosphorylation enhances PtdCho synthesis and may allow PtdCho accumulation by coordinate inhibition of NTE activity. NTE operates primarily at the endoplasmic reticulum in neuronal soma but is also present in axons. NTE-mediated PtdCho homeostasis facilitates membrane trafficking and this appears most critical for the integrity of axon terminals in the spinal cord and hippocampus. For maintenance of peripheral nerve axons, iPLA2? activity may be able to compensate for NTE-deficiency but not vice-versa. Whether agonists acting at neuronal receptors modulate the activity of either enzyme remains to be determined. This article is part of a Special Issue entitled Phospholipids and Phospholipid Metabolism. PMID:22903185

Glynn, Paul

2013-03-01

349

Neuropathy Target Esterase Is Required for Adult Vertebrate Axon Maintenance  

PubMed Central

The enzyme neuropathy target esterase (NTE) is present in neurons and deacylates the major membrane phospholipid, phosphatidylcholine (PtdCho). Mutation of the NTE gene or poisoning by neuropathic organophosphates—chemical inhibitors of NTE—causes distal degeneration of long spinal axons in humans. However, analogous neuropathological changes have not been reported in nestin-cre:NTEfl/fl mice with NTE-deficient neural tissue. Furthermore, altered PtdCho homeostasis has not been detected in NTE-deficient vertebrates. Here, we describe distal degeneration of the longest spinal axons in ?3-week-old nestin-cre:NTEfl/fl mice and in adult C57BL/6J mice after acute dosing with a neuropathic organophosphate: in both groups early degenerative lesions were followed by swellings comprising accumulated axoplasmic material. In mice dosed acutely with organophosphate, maximal numbers of lesions, in the longest spinal sensory axon tract, were attained within days and were preceded by a transient rise in neural PtdCho. In nestin-cre:NTEfl/fl mice, sustained elevation of PtdCho over many months was accompanied by progressive degeneration and massive swelling of axons in sensory and motor spinal tracts and by increasing hindlimb dysfunction. Axonal lesion distribution closely resembled that in hereditary spastic paraplegia (HSP). The importance of defective membrane trafficking in HSP and the association of NTE with the endoplasmic reticulum—the starting point for the constitutive secretory pathway and transport of neuronal materials into axons—prompted investigation for a role of NTE in secretion. Cultured NTE-deficient neurons displayed modestly impaired secretion, consistent with neuronal viability and damage in vivo initially restricted to distal parts of the longest axons. PMID:19759306

Read, David J.; Li, Yong; Chao, Moses V.; Cavanagh, John B.

2009-01-01

350

Overview of Psychosocial Health Among Youth with Spinal Cord Injury  

PubMed Central

Background: Psychosocial health can be conceptualized as being mentally, emotionally, and socially well. Little is known about normative psychosocial development among children and adolescents with spinal cord injury (SCI). Objective: To provide a comprehensive overview of psychosocial health of 410 youth with SCI from ages 2 to 18 years. To understand developmental trends, data are presented separately for ages 2-5, 6-12, 13-15, and 16-18 years. Methods: Youth with SCI were recruited from 1 of 3 pediatric specialty hospitals within a single hospital system. Structured surveys assessing community participation, quality of life (QOL), and mental health (including anxiety and depression) were completed by youth with SCI (for ages 6-18) or their primary caregivers (for ages 2-5). Descriptive statistics were used to assess how patients scored on all standardized measures. Results: Of the 410 participants, 56% were male, 64% were Caucasian, 66% had paraplegia, and 55% had complete injuries. On average, the participants were 12 years old (SD 4.87) at interview and 7.26 years old (SD 5.97) at injury. Psychosocial health outcomes were described for each of the 4 age groups: 2-5 years (n = 52), 6-12 (n = 142), 13-15 (n = 82), and 16-18 (n = 134) years. Conclusions: As compared to published norms, this sample of youth with SCI seemed to be experiencing decreased levels of community participation and QOL, but also decreased levels of anxiety and depression. These data provide needed information to clinicians regarding how youth with SCI may typically experience psychosocial health and where their patients fit into that typical experience. PMID:23671383

2013-01-01

351

Regional Lidocaine Infusion Reduces Postischemic Spinal Cord Injury in Rabbits  

PubMed Central

Paraplegia secondary to spinal cord ischemia is a devastating complication in operations on the descending and thoracoabdominal aorta. We hypothesized that the tolerance of the spinal cord to an ischemic insult could be improved by means of regional administration of lidocaine. Thirty-one New Zealand white rabbits were anesthetized and spinal cord ischemia was induced by the placement of clamps both below the left renal vein and above the aortic bifurcation. The animals were divided into 5 groups. Aortic occlusion time was 20 minutes in Group 1 and 30 minutes in all other groups. Groups 1 and 2 functioned as controls. Lidocaine (Group 5) or normal saline solution (Group 3) was infused into the isolated aortic segment after cross-clamping. Group 4 animals received 20% mannitol regionally, before and after reperfusion. Postoperatively, rabbits were classified as either neurologically normal or injured (paralyzed or paretic). Among controls, 20 minutes of aortic occlusion did not produce any neurologic deficit (Group 1: 0/4 injured), while 30 minutes of occlusion resulted in more consistent injury (Group 2: 6/8 injured). Animals that received normal saline (Group 3) or mannitol (Group 4) regionally showed 80% neurologic injury (4/5). Animals treated with the regional lidocaine infusion (Group 5) showed much better neurologic outcomes (7/9 normal: 78%). This superiority of Group 5 over Groups 2, 3, and 4 was significant (P < 0.02). We conclude that regional administration of lidocaine reduced neurologic injury secondary to spinal cord ischemia and reperfusion after aortic occlusion in the rabbit model. PMID:11678249

Apaydin, Anil Z.; Buket, Suat

2001-01-01

352

Disorders of phospholipids, sphingolipids and fatty acids biosynthesis: toward a new category of inherited metabolic diseases.  

PubMed

We wish to delineate a novel, and rapidly expanding, group of inborn errors of metabolism with neurological/muscular presentations: the defects in phospholipids, sphingolipids and long chain fatty acids biosynthesis. At least 14 disorders have been described so far. Clinical presentations are diverse but can be divided into (1) diseases of the central nervous system; (2) peripheral neuropathies; and (3) muscular/cardiac presentations. (1) Leukodystrophy and/or iron deposits in basal ganglia is a common feature of phospholipase A2 deficiency, fatty acid hydroxylase deficiency, and pantothenate kinase-associated neurodegeneration. Infantile epilepsy has been reported in GM3 synthetase deficiency. Spastic quadriplegia with ichthyosis and intellectual disability are the presenting signs of the elongase 4 deficiency and the Sjogren-Larsson syndrome caused by fatty aldehyde dehydrogenase deficiency. Spastic paraplegia and muscle wasting are also seen in patients with mutations in the neuropathy target esterase gene. (2) Peripheral neuropathy is a prominent feature in PHARC syndrome due to ?/?-hydrolase 12 deficiency, and in hereditary sensory autonomic neuropathy type I due to serine palmitoyl-CoA transferase deficiency. (3) Muscular/cardiac presentations include recurrent myoglobinuria in phosphatidate phosphatase 1 (Lipin1) deficiency; cardiomyopathy and multivisceral involvement in Barth syndrome secondary to tafazzin mutations; congenital muscular dystrophy due to choline kinase deficiency, Sengers syndrome due to acylglycerol kinase deficiency and Chanarin Dorfman syndrome due to ?/?- hydrolase 5 deficiency. These synthesis defects of complex lipid molecules stand at the frontier between classical inborn errors of metabolism and other genetic diseases involving the metabolism of structural proteins. PMID:22814679

Lamari, F; Mochel, F; Sedel, F; Saudubray, J M

2013-05-01

353

The safe use of spinal drains in thoracic aortic surgery.  

PubMed

Paraplegia is a devastating complication which may occur following surgery on the thoracic aorta. The use of a cerebrospinal fluid drain (CSFD) has helped reduce the incidence of neurological deficit; however, the management of patients with a CSFD postsurgery requires nurses and doctors to have expertise and awareness of the associated complications. The National Patient Safety Agency (UK) has highlighted a number of cases involving inadvertent spinal injections throughout the UK National Health Service (NHS). To this end we have introduced a protocol or 'care bundle' for safe CSFD care as well as drain management. The protocol was developed by medical and nursing staff at our institution based on clinical experience and literature reviews over a two-year period (2008-2010). Interventions undertaken during the development of the protocol included discussion with the UK National Patient Safety Agency (NPSA). Content of the protocol was reviewed by internal regulatory bodies within the hospital prior to ratification and general dissemination. Clear guidance is given within the policy on the standards expected when caring for the line and managing drainage according to agreed parameters of spinal cord perfusion pressure. The protocol constitutes five documents which guide staff in the care of CSFD, its routine management, documentation and interventions necessary once neurological deficit is detected. Document 1 which is a checklist, communication tool and aide-memoire was developed to ensure effective management, when the patient arrives in intensive care unit (ICU) from theatre. Document 2 ensures that early detection of a neurological deficit is noted and with Document 3 is acted upon immediately to reverse the injury. Document 4 provides information on the safe administration of analgesia via the spinal drain and has reference to the Glasgow Coma Scale. Document 5 is a bespoke observation chart for documenting CSFD pressure and cerebrospinal fluid drainage. In conclusion, the protocol acts as a guide for safe management of the CSFD and directs staff in reacting to detection of neurological deficit. PMID:21795413

Field, Mark; Doolan, Jim; Safar, Maria; Kuduvalli, Manoj; Oo, Aung; Mills, Keith; Kendall, Jonathan; Desmond, Michael

2011-12-01

354

Semiconditional Electrical Stimulation of Pudendal Nerve Afferents Stimulation to Manage Neurogenic Detrusor Overactivity in Patients with Spinal Cord Injury  

PubMed Central

Objective To evaluate the effect of semiconditional electrical stimulation of the pudendal nerve afferents for the neurogenic detrusor overactivity in patients with spinal cord injury. Forty patients (36 males, 4 males) with spinal cord injury who had urinary incontinence and frequency, as well as felt bladder contraction with bladder filling sense or autonomic dysreflexic symptom participated in this study. Method Patients with neurogenic detrusor overactivity were subdivided into complete injury and incomplete injury groups by ASIA classification and subdivided into tetraplegia and paraplegia groups by neurologic level of injury. Bladder function, such as bladder volumes infused to the bladder until the first occurrence of neurogenic detrusor overactivity (Vini) and the last contraction suppressed by electrical stimulation (Vmax) was measured by water cystometry (CMG) and compared with the results of each subgroup. Results Among the 40 subjects, 35 patients showed neurogenic detrusor overactivity in the CMG study. Among these 35 patients, detrusor overactivity was suppressed effectively by pudendal nerve afferent electrical stimulation in 32 patients. The infusion volume until the occurrence of the first reflex contraction (Vini) was 99.4±80.3 ml. The volume of saline infused to the bladder until the last contraction suppressed by semiconditional pudendal nerve stimulation (Vmax) was 274.3±93.2 ml, which was significantly greater than Vini. In patients with good response to the pudendal nerve afferent stimulation, the bladder volume significantly increased by stimulation in all the patients. Conclusion In this study, semiconditional electrical stimulation on the dorsal penile afferent nerve could effectively inhibit neurogenic detrusor overactivity and increase bladder volume in patients with spinal cord injury. PMID:22506182

Lee, Young-Hee; Im, Hyung Tae; Lee, Kye-Wook; Kim, Sung Hoon; Hur, Dong Min

2011-01-01

355

The neuronal chemokine CX3CL1/fractalkine selectively recruits NK cells that modify experimental autoimmune encephalomyelitis within the central nervous system.  

PubMed

Leukocyte trafficking to the central nervous system (CNS), regulated in part by chemokines, determines severity of the demyelinating diseases multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). To examine chemokine receptor CX3CR1 in EAE, we studied CX3CR1(GFP/GFP) mice, in which CX3CR1 targeting by insertion of Green Fluorescent Protein (GFP) allowed tracking of CX3CR1+ cells in CX3CR1(+/GFP) animals and cells destined to express CX3CR1 in CX3CR1(GFP/GFP) knockouts. NK cells were markedly reduced in the inflamed CNS of CX3CR1-deficient mice with EAE, whereas recruitment of T cells, NKT cells and monocyte/macrophages to the CNS during EAE did not require CX3CR1. Impaired recruitment of NK cells in CX3CR1(GFP/GFP) mice was associated with increased EAE-related mortality, nonremitting spastic paraplegia and hemorrhagic inflammatory lesions. The absence of CD1d did not affect the severity of EAE in CX3CR1(GFP/GFP) mice, arguing against a role for NKT cells. Accumulation of NK cells in livers of wild-type (WT) and CX3CR1(GFP/GFP) mice with cytomegalovirus hepatitis was equivalent, indicating that CX3CL1 mediated chemoattraction of NK cells was relatively specific for the CNS. These results are the first to define a chemokine that governs NK cell migration to the CNS, and the findings suggest novel therapeutic manipulation of CX3CR1+ NK cells. PMID:16675847

Huang, DeRen; Shi, Fu-Dong; Jung, Steffen; Pien, Gary C; Wang, Jintang; Salazar-Mather, Thais P; He, Toby T; Weaver, Jennifer T; Ljunggren, Hans-Gustaf; Biron, Christine A; Littman, Dan R; Ransohoff, Richard M

2006-05-01

356

Sensory neuropathy with bone destruction due to a mutation in the membrane-shaping atlastin GTPase 3.  

PubMed

Many neurodegenerative disorders present with sensory loss. In the group of hereditary sensory and autonomic neuropathies loss of nociception is one of the disease hallmarks. To determine underlying factors of sensory neurodegeneration we performed whole-exome sequencing in affected individuals with the disorder. In a family with sensory neuropathy with loss of pain perception and destruction of the pedal skeleton we report a missense mutation in a highly conserved amino acid residue of atlastin GTPase 3 (ATL3), an endoplasmic reticulum-shaping GTPase. The same mutation (p.Tyr192Cys) was identified in a second family with similar clinical outcome by screening a large cohort of 115 patients with hereditary sensory and autonomic neuropathies. Both families show an autosomal dominant pattern of inheritance and the mutation segregates with complete penetrance. ATL3 is a paralogue of ATL1, a membrane curvature-generating molecule that is involved in spastic paraplegia and hereditary sensory neuropathy. ATL3 proteins are enriched in three-way junctions, branch points of the endoplasmic reticulum that connect membranous tubules to a continuous network. Mutant ATL3 p.Tyr192Cys fails to localize to branch points, but instead disrupts the structure of the tubular endoplasmic reticulum, suggesting that the mutation exerts a dominant-negative effect. Identification of ATL3 as novel disease-associated gene exemplifies that long-term sensory neuronal maintenance critically depends on the structural organisation of the endoplasmic reticulum. It emphasizes that alterations in membrane shaping-proteins are one of the major emerging pathways in axonal degeneration and suggests that this group of molecules should be considered in neuroprotective strategies. PMID:24459106

Kornak, Uwe; Mademan, Inès; Schinke, Marte; Voigt, Martin; Krawitz, Peter; Hecht, Jochen; Barvencik, Florian; Schinke, Thorsten; Gießelmann, Sebastian; Beil, F Timo; Pou-Serradell, Adolf; Vílchez, Juan J; Beetz, Christian; Deconinck, Tine; Timmerman, Vincent; Kaether, Christoph; De Jonghe, Peter; Hübner, Christian A; Gal, Andreas; Amling, Michael; Mundlos, Stefan; Baets, Jonathan; Kurth, Ingo

2014-03-01

357

Variant non ketotic hyperglycinemia is caused by mutations in LIAS, BOLA3 and the novel gene GLRX5.  

PubMed

Patients with nonketotic hyperglycinemia and deficient glycine cleavage enzyme activity, but without mutations in AMT, GLDC or GCSH, the genes encoding its constituent proteins, constitute a clinical group which we call 'variant nonketotic hyperglycinemia'. We hypothesize that in some patients the aetiology involves genetic mutations that result in a deficiency of the cofactor lipoate, and sequenced genes involved in lipoate synthesis and iron-sulphur cluster biogenesis. Of 11 individuals identified with variant nonketotic hyperglycinemia, we were able to determine the genetic aetiology in eight patients and delineate the clinical and biochemical phenotypes. Mutations were identified in the genes for lipoate synthase (LIAS), BolA type 3 (BOLA3), and a novel gene glutaredoxin 5 (GLRX5). Patients with GLRX5-associated variant nonketotic hyperglycinemia had normal development with childhood-onset spastic paraplegia, spinal lesion, and optic atrophy. Clinical features of BOLA3-associated variant nonketotic hyperglycinemia include severe neurodegeneration after a period of normal development. Additional features include leukodystrophy, cardiomyopathy and optic atrophy. Patients with lipoate synthase-deficient variant nonketotic hyperglycinemia varied in severity from mild static encephalopathy to Leigh disease and cortical involvement. All patients had high serum and borderline elevated cerebrospinal fluid glycine and cerebrospinal fluid:plasma glycine ratio, and deficient glycine cleavage enzyme activity. They had low pyruvate dehydrogenase enzyme activity but most did not have lactic acidosis. Patients were deficient in lipoylation of mitochondrial proteins. There were minimal and inconsistent changes in cellular iron handling, and respiratory chain activity was unaffected. Identified mutations were phylogenetically conserved, and transfection with native genes corrected the biochemical deficiency proving pathogenicity. Treatments of cells with lipoate and with mitochondrially-targeted lipoate were unsuccessful at correcting the deficiency. The recognition of variant nonketotic hyperglycinemia is important for physicians evaluating patients with abnormalities in glycine as this will affect the genetic causation and genetic counselling, and provide prognostic information on the expected phenotypic course. PMID:24334290

Baker, Peter R; Friederich, Marisa W; Swanson, Michael A; Shaikh, Tamim; Bhattacharya, Kaustuv; Scharer, Gunter H; Aicher, Joseph; Creadon-Swindell, Geralyn; Geiger, Elizabeth; MacLean, Kenneth N; Lee, Wang-Tso; Deshpande, Charu; Freckmann, Mary-Louise; Shih, Ling-Yu; Wasserstein, Melissa; Rasmussen, Malene B; Lund, Allan M; Procopis, Peter; Cameron, Jessie M; Robinson, Brian H; Brown, Garry K; Brown, Ruth M; Compton, Alison G; Dieckmann, Carol L; Collard, Renata; Coughlin, Curtis R; Spector, Elaine; Wempe, Michael F; Van Hove, Johan L K

2014-02-01

358

Whole-exome sequencing identifies homozygous AFG3L2 mutations in a spastic ataxia-neuropathy syndrome linked to mitochondrial m-AAA proteases.  

PubMed

We report an early onset spastic ataxia-neuropathy syndrome in two brothers of a consanguineous family characterized clinically by lower extremity spasticity, peripheral neuropathy, ptosis, oculomotor apraxia, dystonia, cerebellar atrophy, and progressive myoclonic epilepsy. Whole-exome sequencing identified a homozygous missense mutation (c.1847G>A; p.Y616C) in AFG3L2, encoding a subunit of an m-AAA protease. m-AAA proteases reside in the mitochondrial inner membrane and are responsible for removal of damaged or misfolded proteins and proteolytic activation of essential mitochondrial proteins. AFG3L2 forms either a homo-oligomeric isoenzyme or a hetero-oligomeric complex with paraplegin, a homologous protein mutated in hereditary spastic paraplegia type 7 (SPG7). Heterozygous loss-of-function mutations in AFG3L2 cause autosomal-dominant spinocerebellar ataxia type 28 (SCA28), a disorder whose phenotype is strikingly different from that of our patients. As defined in yeast complementation assays, the AFG3L2(Y616C) gene product is a hypomorphic variant that exhibited oligomerization defects in yeast as well as in patient fibroblasts. Specifically, the formation of AFG3L2(Y616C) complexes was impaired, both with itself and to a greater extent with paraplegin. This produced an early-onset clinical syndrome that combines the severe phenotypes of SPG7 and SCA28, in additional to other "mitochondrial" features such as oculomotor apraxia, extrapyramidal dysfunction, and myoclonic epilepsy. These findings expand the phenotype associated with AFG3L2 mutations and suggest that AFG3L2-related disease should be considered in the differential diagnosis of spastic ataxias. PMID:22022284

Pierson, Tyler Mark; Adams, David; Bonn, Florian; Martinelli, Paola; Cherukuri, Praveen F; Teer, Jamie K; Hansen, Nancy F; Cruz, Pedro; Mullikin For The Nisc Comparative Sequencing Program, James C; Blakesley, Robert W; Golas, Gretchen; Kwan, Justin; Sandler, Anthony; Fuentes Fajardo, Karin; Markello, Thomas; Tifft, Cynthia; Blackstone, Craig; Rugarli, Elena I; Langer, Thomas; Gahl, William A; Toro, Camilo

2011-10-01

359

Protective and risk factors in amateur equestrians and description of injury patterns: A retrospective data analysis and a case - control survey  

PubMed Central

Background In Switzerland there are about 150,000 equestrians. Horse related injuries, including head and spinal injuries, are frequently treated at our level I trauma centre. Objectives To analyse injury patterns, protective factors, and risk factors related to horse riding, and to define groups of safer riders and those at greater risk Methods We present a retrospective and a case-control survey at conducted a tertiary trauma centre in Bern, Switzerland. Injured equestrians from July 2000 - June 2006 were retrospectively classified by injury pattern and neurological symptoms. Injured equestrians from July-December 2008 were prospectively collected using a questionnaire with 17 variables. The same questionnaire was applied in non-injured controls. Multiple logistic regression was performed, and combined risk factors were calculated using inference trees. Results Retrospective survey A total of 528 injuries occured in 365 patients. The injury pattern revealed as follows: extremities (32%: upper 17%, lower 15%), head (24%), spine (14%), thorax (9%), face (9%), pelvis (7%) and abdomen (2%). Two injuries were fatal. One case resulted in quadriplegia, one in paraplegia. Case-control survey 61 patients and 102 controls (patients: 72% female, 28% male; controls: 63% female, 37% male) were included. Falls were most frequent (65%), followed by horse kicks (19%) and horse bites (2%). Variables statistically significant for the controls were: Older age (p = 0.015), male gender (p = 0.04) and holding a diploma in horse riding (p = 0.004). Inference trees revealed typical groups less and more likely to suffer injury. Conclusions Experience with riding and having passed a diploma in horse riding seem to be protective factors. Educational levels and injury risk should be graded within an educational level-injury risk index. PMID:21294862

2011-01-01

360

Mice with a deletion of the major central myelin protein exhibit hypersensitivity to noxious thermal stimuli: involvement of central sensitization.  

PubMed

Null mutations in the gene encoding the major myelin protein of the central nervous system, proteolipid protein 1 (PLP1), cause an X-linked form of spastic paraplegia (SPG2) associated with axonal degeneration. While motor symptoms are the best known manifestations of this condition, its somatosensory disturbances have been described but poorly characterized. We carried out a longitudinal study in an animal model of SPG2 - mice carrying a deletion of the Plp1 gene (Plp-null mice). Plp-null mice exhibited severe early-onset thermal hyperalgesia, in the absence of thermal allodynia. We first performed an electrophysiological testing which showed an early decrease in peripheral and spinal conduction velocities in Plp null mice. Such as the abnormal sensitive behaviors, this slowing of nerve conduction was observed before the development of myelin abnormalities at the spinal level, from 3months of age, and without major morphological defects in the sciatic nerve. To understand the link between a decrease in nerve velocity and an increased response to thermal stimuli before the appearance of myelin abnormalities, we focused our attention on the dorsal horn of the spinal cord, the site of integration of somatosensory information. Immunohistochemical studies revealed an early-onset activation of astrocytes and microglia that worsened with age, associated later in age with perturbation of the expression of the sensory neuropeptides calcitonin-gene-related peptide and galanin. Taken together, these results represent complementary data supporting the hypothesis that Plp-null mice suffer from ganglionopathy associated with late onset central demyelination but with few peripheral nerve alterations, induced by the glial-cell-mediated sensitization of the spinal cord. The mechanism suggested here could underlie pain experiments in other leukodystrophies as well as in other non-genetic demyelinating diseases such as multiple sclerosis. PMID:24423646

Petit, Bérengère; Giraudet, Fabrice; Béchon, Céline; Bardin, Laurent; Avan, Paul; Boespflug-Tanguy, Odile; Bégou, Mélina

2014-05-01

361

The kinesin-3, unc-104 regulates dendrite morphogenesis and synaptic development in Drosophila.  

PubMed

Kinesin-based transport is important for synaptogenesis, neuroplasticity, and maintaining synaptic function. In an anatomical screen of neurodevelopmental mutants, we identified the exchange of a conserved residue (R561H) in the forkhead-associated domain of the kinesin-3 family member Unc-104/KIF1A as the genetic cause for defects in synaptic terminal- and dendrite morphogenesis. Previous structure-based analysis suggested that the corresponding residue in KIF1A might be involved in stabilizing the activated state of kinesin-3 dimers. Herein we provide the first in vivo evidence for the functional importance of R561. The R561H allele (unc-104(bris)) is not embryonic lethal, which allowed us to investigate consequences of disturbed Unc-104 function on postembryonic synapse development and larval behavior. We demonstrate that Unc-104 regulates the reliable apposition of active zones and postsynaptic densities, possibly by controlling site-specific delivery of its cargo. Next, we identified a role for Unc-104 in restraining neuromuscular junction growth and coordinating dendrite branch morphogenesis, suggesting that Unc-104 is also involved in dendritic transport. Mutations in KIF1A/unc-104 have been associated with hereditary spastic paraplegia and hereditary sensory and autonomic neuropathy type 2. However, we did not observe synapse retraction or dystonic posterior paralysis. Overall, our study demonstrates the specificity of defects caused by selective impairments of distinct molecular motors and highlights the critical importance of Unc-104 for the maturation of neuronal structures during embryonic development, larval synaptic terminal outgrowth, and dendrite morphogenesis. PMID:23770702

Kern, Jeannine V; Zhang, Yao V; Kramer, Stella; Brenman, Jay E; Rasse, Tobias M

2013-09-01

362

Effect of sports activity on bone mineral density in wheelchair athletes.  

PubMed

The present study carried out a measurement of body composition and a nutrition survey, targeting 28 male wheelchair athletes and comparing them with 25 male physically able healthy athletes as the controls. The DXA method was used to measure bone mineral density (BMD), percentage of body fat (% body fat), and lean body mass (LBM). Possible factors affecting the BMD of the wheelchair athletes with spinal injuries were analyzed including age, body part, type of sport, area of injury, length of injury, and the length of time it took before restarting sports activity after injury. BMD in the arms, body trunk, legs, and entire body was measured. There were no significant differences in the BMD of the wheelchair athletes by age group (from 20 to 29, from 30 to 39, and 40 years and older), by sports (basketball, track and field, and tennis), and by area of injury (high and low paraplegia). BMD in the legs (r = -0.549, P < 0.01), body trunk (r = -0.414, P < 0.05), and entire body (r = -0.452, P < 0.05) of the wheelchair athletes was negatively correlated with the period since injury; however, no such a relationship was observed in the arms. In addition, the multiple regression analysis for BMD of each body region showed that the earlier the wheelchair athletes restarted sports after injury, the higher values the BMD of legs (r = -0.467, P < 0.05), body trunk (r = -0.469, P < 0.05), and entire body (r = -0.488, P < 0.05), independent of age and sports. The leg BMD of the wheelchair athletes was lower than that of the physically able athletes, with a BMD 76.5% of the controls. The present study suggests that restarting sports activity in a timely manner after treatment and rehabilitation for the injury is useful in preventing loss of BMD in wheelchair athletes and ultimately improving their quality of life. PMID:18095071

Miyahara, Kimiko; Wang, Da-Hong; Mori, Keiko; Takahashi, Kayo; Miyatake, Nobuyuki; Wang, Bing-Ling; Takigawa, Tomoko; Takaki, Jiro; Ogino, Keiki

2008-01-01

363

Effect of spinal cord injury upon prostate: adenocarcinoma of prostate in a spinal cord injury patient - a case report  

PubMed Central

Introduction Following spinal cord injury, prostate undergoes atrophy probably due to interruption of neuro-hormonal pathways. The incidence of carcinoma of prostate is lower in patients with spinal cord injury above T-10 than in those with lesion below T-10. Case presentation A Caucasian male sustained T-4 paraplegia in 1991 at the age of 59-years. He had long-term indwelling urethral catheter. In May 1995, routine blood test showed prostate-specific antigen to be 17.7 mg/ml. Prostate biopsy revealed moderately differentiated primary adenocarcinoma of prostate; Gleason score was 3+3. Bone scans showed no evidence of metastatic bone disease. Bilateral orchidectomy was performed in September 1995. MRI of pelvis revealed no evidence of spread beyond prostatic capsule. There was no pelvic lymphadenopathy. In October 1996, this patient got chest infection and recovered fully after taking amoxicillin. In February 2001, he developed pneumonia and was prescribed cefuroxime intravenously. In March 2001, cystoscopy and electrohydraulic lithotripsy of vesical calculi were carried out. In August 2001, this patient was admitted to spinal unit for management of pressure sores. He expired on 28 June 2002 in local hospital. Cause of death was recorded as acute ventricular failure, congestive heart failure, chronic respiratory failure and spinal cord injury. Conclusion Although prostate gland undergoes atrophy in men who sustained spinal cord injury in early age, physicians should be vigilant and look for prostatic diseases particularly in men, who have sustained spinal cord injury during later period of life. Patients with cervical and upper dorsal lesions are at risk of developing potentially life-threatening chest complications after major surgical procedures including radical prostatectomy. Therefore, it may be advisable to consider chemoprevention of prostate cancer with Finasteride, especially in men, who sustained cervical and upper dorsal spinal cord injury during later part of their life. PMID:20062548

2009-01-01

364

Bronchial hyperresponsiveness testing in athletes of the Swiss Paralympic team  

PubMed Central

Background The aim of this study was to assess airway hyperresponsiveness to eucapnic voluntary hyperventilation and dry powder mannitol challenge in athletes aiming to participate at the Paralympic Games 2008 in Beijing, especially in athletes with spinal cord injury. Methods Forty-four athletes with a disability (27 with paraplegia (group 1), 3 with tetraplegia (group 2) and 14 with other disabilities such as blindness or single limb amputations (group 3) performed spirometry, skin prick testing, measurement of exhaled nitric oxide, eucapnic voluntary hyperventilation challenge test (EVH) and mannitol challenge test (MCT). A fall in FEV1 of ?10% in either challenge test was deemed positive for exercise-induced bronchoconstriction. Results Fourteen (32%) athletes were atopic and 7 (16%) had a history of physician-diagnosed asthma. Absolute lung function values were significantly lower in patients of group 1 and 2 compared to group 3. Nine (20%) athletes were positive to EVH (8 paraplegics, 1 tetraplegic), and 8 (18%) athletes were positive to MCT (7 paraplegics, 1 tetraplegic). Fourteen (22.7%) subjects were positive to at least one challenge; only three athletes were positive to both tests. None of the athletes in group 3 had a positive test. Both challenge tests showed a significant association with physician-diagnosed asthma status (p?=?0.0001). The positive and negative predictive value to diagnose physician-diagnosed asthma was 89% and 91% for EHV, and 75% and 86% for MCT, respectively. Conclusion EVH and MCT can be used to identify, but especially exclude asthma in Paralympic athletes. PMID:23845126

2013-01-01

365

Assessing the effect of community health nursing care management at home on war-worn soldiers' physical problems suffering from spinal cord complications (urinary infection, bedsore)  

PubMed Central

BACKGROUND: Veterans are among the highly-susceptible and highly-esteemed groups of the society. there is no correct, principled, and comprehensive programming with respect to home-nursing care for them. METHODS: In this quasi-experimental study, 26 veterans with spinal cord complications, with a 70-percent damage who were resident of Najaf Abad, Iran were concluded. The data were gathered by a checklist consisted of two parts, the first part included the demographic data and the second part consisted of Para-clinical (clinical findings) assessment of the veterans suffering from urinary infection, laboratorial assessments, and assessing the bedsores. The researcher visited all the veterans and completed the checklist by interviewing them. RESULTS: The mean age of the veterans was 45 (5.1) years and the highest frequency (53.8%) belonged to the age range of 40-44 years. The mean number of the family members was 4.4 people. The veterans who had paraplegia damage included 88.6%. Considering the damage rate, the highest frequency (69.2%) belonged to thoracic vertebra level. all the 26 veterans had been suffering from urinal infection before the managerial intervention; however 20 subjects (76.9%) had urinal infection after the intervention. CONCLUSIONS: It can be stated that pressure wounds are preventable and these caring measures can be offered to susceptible groups of the community in a better and cheaper way if more studies are done with a closer contact and a higher number of samples in addition to have unison among the community-based systems. PMID:22069406

Rastegari, Mohammad; Dehkordi, Akbar Jaafariyan; Sabouhi, Fakhri; Ghalriz, Parvin

2010-01-01

366

Posterior short segment pedicle screw fixation and TLIF for the treatment of unstable thoracolumbar/lumbar fracture  

PubMed Central

Background Currently, Posterior Short Segment Pedicle Screw Fixation is a popular procedure for treating unstable thoracolumbar/lumbar burst fracture. But progressive kyphosis and a high rate of hardware failure because of lack of the anterior column support remains a concern. The efficacy of different methods remains debatable and each technique has its advantages and disadvantages. Methods A consecutive series of 20 patients with isolated thoracolumbar/lumbar burst fractures were treated by posterior short segment pedicle screw fixation and transforaminal thoracolumbar/lumbar interbody fusion (TLIF) between January 2005 and December 2007. All patients were followed up for a minimum of 2 years. Demographic data, neurologic status, anterior vertebral body heights, segmental Cobb angle and treatment-related complications were evaluated. Results The mean operative time was 167 minutes (range, 150–220). Blood loss was 450 ~ 1200 ml, an average of 820 ml. All patients recovered with solid fusion of the intervertebral bone graft, without main complications like misplacement of the pedicle screw, nerve or vessel lesion or hard ware failure. The post-operative radiographs demonstrated a good fracture reduction and it was well maintained until the bone graft fusion. Neurological recovery of one to three Frankel grade was seen in 14 patients with partial neurological deficit, three grades of improvement was seen in one patient, two grades of improvement was observed in 6 patients and one grade of improvement was found in 6 patients. All the 6 patients with no paraplegia on admission remained neurological intact, and in one patient with Frankel D on admission no improvement was observed. Conclusion Posterior short-segment pedicle fixation in conjunction with TLIF seems to be a feasible option in the management of selected thoracolumbar/lumbar burst fractures, thereby addressing all the three columns through a single approach with less trauma and good results. PMID:24517217

2014-01-01

367

Evaluation of Role of Anterior Debridement and Decompression of Spinal Cord and Instrumentation in Treatment of Tubercular Spondylitis  

PubMed Central

Study Design Prospective study with simple randomization. Purpose To evaluate the results of anterior spinal instrumentation, debridement and decompression of cord and compare it with results of a similar procedure done without the use of anterior instrumentation. Overview of Literature Use of anterior spinal instrumentation in treatment of tubercular spondylitis is still an infrequently followed modality of treatment and data regarding its usefulness are still emerging. Methods Thirty-two patients of tubercular paraplegia with involvement of dorsal and dorso-lumbar vertebrae were operated with anterior spinal cord decompression, autofibular strut grafting with anterior instrumentation in 18 patients and no implant in 14 patients. Results were compared on the basis of improvement in Frankel grade, correction of local kyphosis, decrease in canal compromise and further progression of kyphosis. Results The mean local kyphosis correction in the immediate postoperative period was 24.1° in the instrumented group and was 6.1° in the non instrumented group. The mean late loss of correction of local kyphosis at 3 years follow-up was 1.7° in the instrumented and 6.7° in the non instrumented group. The mean improvement in canal compression was 39.5% in the instrumented group and 34.8% in the non instrumented group. Conclusions In treatment of tubercular spondylitis by anterior debridement and decompression of the spinal cord and autofibular strut grafting, the use of instrumentation has no relation with the improvement in neurological status, however the correction of local kyphosis and prevention of further progression of local kyphosis was better with the use anterior spinal instrumentation. PMID:22977698

Singh, Saurabh; Kumaraswamy, Vinay; Saraf, Shyam Kumar; Khare, Ghanshyam Narayan

2012-01-01

368

Spinal Cord Injury in the Pediatric Population: A Systematic Review of the Literature  

PubMed Central

Abstract Spinal Cord Injury (SCI) in the pediatric population is relatively rare but carries significant psychological and physiological consequences. An interdisciplinary group of experts composed of medical and surgical specialists treating patients with SCI formulated the following questions: 1) What is the epidemiology of pediatric spinal cord injury and fractures?; 2) Are there unique features of pediatric SCI which distinguish the pediatric SCI population from adult SCI?; 3) Is there evidence to support the use of neuroprotective approaches, including hypothermia and steroids, in the treatment of pediatric SCI? A systematic review of the literature using multiple databases was undertaken to evaluate these three specific questions. A search strategy composed of specific search terms (Spinal Cord Injury, Paraplegia, Quadriplegia, tetraplegia, lapbelt injuries, seatbelt injuries, cervical spine injuries and Pediatrics) returned over 220 abstracts that were evaluated and by two observers. Relevant abstracts were then evaluated and papers were graded using the Downs and Black method. A table of evidence was then presented to a panel of experts using a modified Delphi approach and the following recommendation was then formulated using a consensus approach: Pediatric patients with traumatic SCI have different mechanisms of injury and have a better neurological recovery potential when compared to adults. Patients with SCI before their adolescent growth spurt have a high likelihood of developing scoliosis. Because of these differences, traumatic SCI should be highly suspected in the presence of abnormal neck or neurological exam, a high-risk mechanism of injury or a distracting injury even in the absence of radiological anomaly. PMID:21501096

Mac-Thiong, Jean-Marc; Roy-Beaudry, Marjolaine; Sosa, Jose Felix; Labelle, Hubert

2011-01-01

369

Pott's disease in children  

PubMed Central

Background: The incidence of tuberculosis is increasing, and skeletal tuberculosis accounts for 10-20% of all extrapulmonary cases. Spinal tuberculosis occurs mostly in children and young adults. It causes bone destruction, spinal deformity and neural complications. Materials and Methods: Our study includes 37 children (below 15 years of age) with spinal tuberculosis treated in our department in the last 6 years. The demographic data, clinical profile, surgical intervention and outcome of these children are reported. Results: The mean age ranged from 4 to 15 years, with an average of 9.1 years, and the male/female ratio was 1.8. Thirty patients (81%) had progressive inflammatory rachialgia and only six patients (16.2%) had neurological symptoms. The lumbar spine was mostly affected (23 cases). All patients have benefited from antituberculous chemotherapy (Regimen 2SRHZ/10RH) associated with spinal immobilization during 3 months. The surgical treatment was indicated in seven patients because of the presence of large bilateral abscess of the psoas muscle in one patient and the presence of severe neurological symptoms in the six remaining patients. The evolution was favorable in all cases, including those with neurological symptoms. There was no case of death and the length of follow-up for these patients ranged between 1 and 4 years. Conclusion: Spinal tuberculosis is still a prevalent disease in developing countries, mainly occurring in children. Complications of the disease can be devastating because of its ability to cause bone destruction, spinal deformity and paraplegia. Therefore, an early diagnosis and establishment of treatment are necessary to expect a good outcome. PMID:21297923

Benzagmout, Mohammed; Boujraf, Said; Chakour, Khalid; Chaoui, Mohammed El Faiz

2011-01-01

370

N-methyl-D-aspartate receptor antagonist MK-801 prevents apoptosis in rats that have undergone fetal spinal cord transplantation following spinal hemisection  

PubMed Central

Spinal cord injury is the main cause of paraplegia, but effective therapies for it are lacking. Embryonic spinal cord transplantation is able to repair spinal cord injury, albeit with a large amount of neuronal apoptosis remaining in the spinal cord. MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, is able to reduce cell death by decreasing the concentration of excitatory amino acids and preventing extracellular calcium ion influx. In this study, the effect of MK-801 on the apoptosis of spinal cord neurons in rats that have received a fetal spinal cord (FSC) transplant following spinal hemisection was investigated. Wistar rats were divided into three groups: Spinal cord hemisection injury with a combination of FSC transplantation and MK-801 treatment (group A); spinal cord hemisection injury with FSC transplantation (group B); and spinal cord injury with insertion of a Gelfoam pledget (group C). The rats were sacrificed 1, 3, 7 and 14 days after the surgery. Apoptosis in spinal slices from the injured spinal cord was examined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling reaction, and the expression of B-cell lymphoma-2 (Bcl-2) was measured by immunohistochemistry. The positive cells were quantitatively analyzed using a computer image analysis system. The rate of apoptosis and the positive expression of Bcl-2 protein in the spinal cord neurons in the three groups decreased in the following order: C>B>A (P<0.05) and A>B>C (P<0.05), respectively. This indicates that treatment with the NMDA receptor antagonist MK-801 prevents apoptosis in the spinal cord neurons of rats that have undergone FSC transplantation following spinal hemisection. PMID:25371724

ZHANG, QIANG; SHAO, YANG; ZHAO, CHANGSONG; CAI, JUAN; SUN, SHENG

2014-01-01

371

The Kinesin-3, Unc-104 Regulates Dendrite Morphogenesis and Synaptic Development in Drosophila  

PubMed Central

Kinesin-based transport is important for synaptogenesis, neuroplasticity, and maintaining synaptic function. In an anatomical screen of neurodevelopmental mutants, we identified the exchange of a conserved residue (R561H) in the forkhead-associated domain of the kinesin-3 family member Unc-104/KIF1A as the genetic cause for defects in synaptic terminal- and dendrite morphogenesis. Previous structure-based analysis suggested that the corresponding residue in KIF1A might be involved in stabilizing the activated state of kinesin-3 dimers. Herein we provide the first in vivo evidence for the functional importance of R561. The R561H allele (unc-104bris) is not embryonic lethal, which allowed us to investigate consequences of disturbed Unc-104 function on postembryonic synapse development and larval behavior. We demonstrate that Unc-104 regulates the reliable apposition of active zones and postsynaptic densities, possibly by controlling site-specific delivery of its cargo. Next, we identified a role for Unc-104 in restraining neuromuscular junction growth and coordinating dendrite branch morphogenesis, suggesting that Unc-104 is also involved in dendritic transport. Mutations in KIF1A/unc-104 have been associated with hereditary spastic paraplegia and hereditary sensory and autonomic neuropathy type 2. However, we did not observe synapse retraction or dystonic posterior paralysis. Overall, our study demonstrates the specificity of defects caused by selective impairments of distinct molecular motors and highlights the critical importance of Unc-104 for the maturation of neuronal structures during embryonic development, larval synaptic terminal outgrowth, and dendrite morphogenesis. PMID:23770702

Kern, Jeannine V.; Zhang, Yao V.; Kramer, Stella; Brenman, Jay E.

2013-01-01

372

Neurology and diving.  

PubMed

Diving exposes a person to the combined effects of increased ambient pressure and immersion. The reduction in pressure when surfacing can precipitate decompression sickness (DCS), caused by bubble formation within tissues due to inert gas supersaturation. Arterial gas embolism (AGE) can also occur due to pulmonary barotrauma as a result of breath holding during ascent or gas trapping due to disease, causing lung hyperexpansion, rupture and direct entry of alveolar gas into the blood. Bubble disease due to either DCS or AGE is collectively known as decompression illness. Tissue and intravascular bubbles can induce a cascade of events resulting in CNS injury. Manifestations of decompression illness can vary in severity, from mild (paresthesias, joint pains, fatigue) to severe (vertigo, hearing loss, paraplegia, quadriplegia). Particularly as these conditions are uncommon, early recognition is essential to provide appropriate management, consisting of first aid oxygen, targeted fluid resuscitation and hyperbaric oxygen, which is the definitive treatment. Less common neurologic conditions that do not require hyperbaric oxygen include rupture of a labyrinthine window due to inadequate equalization of middle ear pressure during descent, which can precipitate vertigo and hearing loss. Sinus and middle ear overpressurization during ascent can compress the trigeminal and facial nerves respectively, causing temporary facial hypesthesia and lower motor neuron facial weakness. Some conditions preclude safe diving, such as seizure disorders, since a convulsion underwater is likely to be fatal. Preventive measures to reduce neurologic complications of diving include exclusion of individuals with specific medical conditions and safe diving procedures, particularly related to descent and ascent. PMID:24365363

Massey, E Wayne; Moon, Richard E

2014-01-01

373

Gene dosage-dependent rescue of HSP neurite defects in SPG4 patients' neurons.  

PubMed

The hereditary spastic paraplegias (HSPs) are a heterogeneous group of motorneuron diseases characterized by progressive spasticity and paresis of the lower limbs. Mutations in Spastic Gait 4 (SPG4), encoding spastin, are the most frequent cause of HSP. To understand how mutations in SPG4 affect human neurons, we generated human induced pluripotent stem cells (hiPSCs) from fibroblasts of two patients carrying a c.1684C>T nonsense mutation and from two controls. These SPG4 and control hiPSCs were able to differentiate into neurons and glia at comparable efficiency. All known spastin isoforms were reduced in SPG4 neuronal cells. The complexity of SPG4 neurites was decreased, which was paralleled by an imbalance of axonal transport with less retrograde movement. Prominent neurite swellings with disrupted microtubules were present in SPG4 neurons at an ultrastructural level. While some of these swellings contain acetylated and detyrosinated tubulin, these tubulin modifications were unchanged in total cell lysates of SPG4 neurons. Upregulation of another microtubule-severing protein, p60 katanin, may partially compensate for microtubuli dynamics in SPG4 neurons. Overexpression of the M1 or M87 spastin isoforms restored neurite length, branching, numbers of primary neurites and reduced swellings in SPG4 neuronal cells. We conclude that neurite complexity and maintenance in HSP patient-derived neurons are critically sensitive to spastin gene dosage. Our data show that elevation of single spastin isoform levels is sufficient to restore neurite complexity and reduce neurite swellings in patient cells. Furthermore, our human model offers an ideal platform for pharmacological screenings with the goal to restore physiological spastin levels in SPG4 patients. PMID:24381312

Havlicek, Steven; Kohl, Zacharias; Mishra, Himanshu K; Prots, Iryna; Eberhardt, Esther; Denguir, Naime; Wend, Holger; Plötz, Sonja; Boyer, Leah; Marchetto, Maria C N; Aigner, Stefan; Sticht, Heinrich; Groemer, Teja W; Hehr, Ute; Lampert, Angelika; Schlötzer-Schrehardt, Ursula; Winkler, Jürgen; Gage, Fred H; Winner, Beate

2014-05-15

374

A Novel Mouse Model for Multiple Myeloma (MOPC315.BM) That Allows Noninvasive Spatiotemporal Detection of Osteolytic Disease  

PubMed Central

Multiple myeloma (MM) is a lethal human cancer characterized by a clonal expansion of malignant plasma cells in bone marrow. Mouse models of human MM are technically challenging and do not always recapitulate human disease. Therefore, new mouse models for MM are needed. Mineral-oil induced plasmacytomas (MOPC) develop in the peritoneal cavity of oil-injected BALB/c mice. However, MOPC typically grow extramedullary and are considered poor models of human MM. Here we describe an in vivo-selected MOPC315 variant, called MOPC315.BM, which can be maintained in vitro. When injected i.v. into BALB/c mice, MOPC315.BM cells exhibit tropism for bone marrow. As few as 104 MOPC315.BM cells injected i.v. induced paraplegia, a sign of spinal cord compression, in all mice within 3–4 weeks. MOPC315.BM cells were stably transfected with either firefly luciferase (MOPC315.BM.Luc) or DsRed (MOPC315.BM.DsRed) for studies using noninvasive imaging. MOPC315.BM.Luc cells were detected in the tibiofemoral region already 1 hour after i.v. injection. Bone foci developed progressively, and as of day 5, MM cells were detected in multiple sites in the axial skeleton. Additionally, the spleen (a hematopoietic organ in the mouse) was invariably affected. Luminescent signals correlated with serum myeloma protein concentration, allowing for easy tracking of tumor load with noninvasive imaging. Affected mice developed osteolytic lesions. The MOPC315.BM model employs a common strain of immunocompetent mice (BALB/c) and replicates many characteristics of human MM. The model should be suitable for studies of bone marrow tropism, development of osteolytic lesions, drug testing, and immunotherapy in MM. PMID:23284805

Bommert, Kurt; Huard, Bertrand; Caers, Jo; Carlsen, Harald; Schwarzer, Rolf; Schunemann, Nicole; Jundt, Franziska; Lindeberg, Mona M.; Bogen, Bjarne

2012-01-01

375

Skeletal Manifestations of Hydatid Disease in Serbia: Demographic Distribution, Site Involvement, Radiological Findings, and Complications  

PubMed Central

Although Serbia is recognized as an endemic country for echinococcosis, no information about precise incidence in humans has been available. The aim of this study was to investigate the skeletal manifestations of hydatid disease in Serbia. This retrospective study was conducted by reviewing the medical database of Institute for Pathology (Faculty of Medicine in Belgrade), a reference institution for bone pathology in Serbia. We reported a total of 41 patients with bone cystic echinococcosis (CE) during the study period. The mean age of 41 patients was 40.9±18.8 years. In 39% of patients, the fracture line was the only visible radiological sign, followed by cyst and tumefaction. The spine was the most commonly involved skeletal site (55.8%), followed by the femur (18.6%), pelvis (13.9%), humerus (7.0%), rib (2.3%), and tibia (2.3%). Pain was the symptom in 41.5% of patients, while some patients demonstrated complications such as paraplegia (22.0%), pathologic fracture (48.8%), and scoliosis (9.8%). The pathological fracture most frequently affected the spine (75.0%) followed by the femur (20.0%) and tibia (5.0%). However, 19.5% of patients didn't develop any complication or symptom. In this study, we showed that bone CE is not uncommon in Serbian population. As reported in the literature, therapy of bone CE is controversial and its results are poor. In order to improve the therapy outcome, early diagnosis, before symptoms and complications occur, can be contributive. PMID:24039289

Bracanovic, Djurdja; Sopta, Jelena; Djonic, Danijela; Lujic, Nenad

2013-01-01

376

Skeletal manifestations of hydatid disease in Serbia: demographic distribution, site involvement, radiological findings, and complications.  

PubMed

Although Serbia is recognized as an endemic country for echinococcosis, no information about precise incidence in humans has been available. The aim of this study was to investigate the skeletal manifestations of hydatid disease in Serbia. This retrospective study was conducted by reviewing the medical database of Institute for Pathology (Faculty of Medicine in Belgrade), a reference institution for bone pathology in Serbia. We reported a total of 41 patients with bone cystic echinococcosis (CE) during the study period. The mean age of 41 patients was 40.9±18.8 years. In 39% of patients, the fracture line was the only visible radiological sign, followed by cyst and tumefaction. The spine was the most commonly involved skeletal site (55.8%), followed by the femur (18.6%), pelvis (13.9%), humerus (7.0%), rib (2.3%), and tibia (2.3%). Pain was the symptom in 41.5% of patients, while some patients demonstrated complications such as paraplegia (22.0%), pathologic fracture (48.8%), and scoliosis (9.8%). The pathological fracture most frequently affected the spine (75.0%) followed by the femur (20.0%) and tibia (5.0%). However, 19.5% of patients didn't develop any complication or symptom. In this study, we showed that bone CE is not uncommon in Serbian population. As reported in the literature, therapy of bone CE is controversial and its results are poor. In order to improve the therapy outcome, early diagnosis, before symptoms and complications occur, can be contributive. PMID:24039289

Bracanovic, Djurdja; Djuric, Marija; Sopta, Jelena; Djonic, Danijela; Lujic, Nenad

2013-08-01

377

The Collateral Network Concept: A Reassessment of the Anatomy of Spinal Cord Perfusion  

PubMed Central

OBJECTIVE Prevention of paraplegia following repair of thoracoabdominal aortic aneurysms (TAAA) requires understanding the anatomy and physiology of the blood supply to the spinal cord. Recent laboratory studies and clinical observations suggest that a robust collateral network must exist to explain preservation of spinal cord perfusion when segmental vessels are interrupted. An anatomical study was undertaken. METHODS Twelve juvenile Yorkshire pigs underwent aortic cannulation and infusion of a low-viscosity acrylic resin at physiological pressures. After curing of the resin and digestion of all organic tissue, the anatomy of the blood supply to the spinal cord was studied grossly and using light and electron microscopy. RESULTS All vascular structures ? 8?m in diameter were preserved. Thoracic and lumbar segmental arteries (SAs) give rise not only to the anterior spinal artery (ASA), but to an extensive paraspinous network feeding the erector spinae, iliopsoas, and associated muscles. The ASA, mean diameter 134±20 ?m, is connected at multiple points to repetitive circular epidural arteries with mean diameters of 150±26 ?m. The capacity of the paraspinous muscular network is 25-fold the capacity of the circular epidural arterial network and ASA combined. Extensive arterial collateralization is apparent between the intraspinal and paraspinous networks, and within each network. Only 75% of all SAs provide direct ASA-supplying branches. CONCLUSIONS The ASA is only one component of an extensive paraspinous and intraspinal collateral vascular network. This network provides an anatomic explanation of the physiological resiliency of spinal cord perfusion when SAs are sacrificed during TAAA repair. PMID:21419903

Etz, Christian D.; Kari, Fabian A.; Mueller, Christoph S.; Silovitz, Daniel; Brenner, Robert; Lin, Hung-Mo; Griepp, Randall B.

2010-01-01

378

Skin thickness on bony prominences measured by ultrasonography in patients with spinal cord injury  

PubMed Central

Objective The detailed assessment of soft tissues over bony prominences and identification of methods of predicting pressure sores would improve the quality of care for patients with spinal cord injury (SCI). Comparing skin thicknesses on bony prominences in patients with SCI to those in healthy individuals will represent, to our knowledge, the first study aimed at determining whether differences in skin thicknesses between these groups can be detected by ultrasound. Design In both patients and controls, skin thicknesses on the sites at risk for pressure ulcers – sacrum, greater trochanter, and ischium – were evaluated using high-frequency ultrasound. The waist was also evaluated by the same method for control as it was considered to be a pressure-free region. Participants Thirty-two patients with complete thoracic SCI and 34 able-bodied individuals. Results The skin was significantly thinner over the sacrum and ischial tuberosity in individuals with SCI compared with healthy individuals. No significant differences were observed in skin thicknesses over the greater trochanter or the waist between the two groups. Conclusions Protecting skin integrity in patients with paraplegia is challenging due to many contributing factors, such as prolonged pressure, frictional/shearing forces, and poor nutrition. Thinning of the skin can increase the risk of soft tissue damage, leading to pressure ulcers. The significant differences in skin thickness at the sacrum and ischium provide the basis for establishing the early signs of pressure damage. Measuring skin thickness by ultrasound is a reliable non-invasive method that could be a promising tool for predicting pressure ulcers. PMID:23809593

Yalcin, Elif; Akyuz, Mufit; Onder, Burcu; Unalan, Halil; Degirmenci, Ibrahim

2013-01-01

379

Evacuation preparedness in full-time wheelchair users with spinal cord injury  

PubMed Central

Objective To analyze and evaluate the efficacy of evacuation plans described by individuals with spinal cord injury (SCI). Design Descriptive study from a convenience sample. Setting Outpatient population center in Pittsburgh, PA, USA. Methods Twenty-one individuals with SCI who previously indicated that they had a plan of evacuation from either their homes, places of work, or towns/cities were contacted via telephone and asked to describe their evacuation plans. The number of critical elements (scale of 0–10 with 10 indicating a more thorough plan) and assistive technology (AT) devices were recorded. Outcome measures The number of critical elements (scale of 0–10 with 10 indicating a more thorough plan) and AT devices were recorded. Results Median home and town/city evacuation scores were both 3.00 (ranges: 1.0–4.0 and 0.0–8.0, respectively). Median evacuation scores of individuals with paraplegia were higher in home (P = 0.05, r = 0.44) and town/city (P = 0.045, r = 0.63) than individuals with tetraplegia. Median evacuation scores of subjects who were employed were higher in home (P = 0.036, r = 0.47) and town/city (P = 0.064, r = 0.59) than unemployed. Conclusion Low scores indicate that individuals with SCI who believe that they have plans are not adequately prepared for an emergency evacuation. Interventions are needed to improve evacuation readiness and lack of preparedness in a catastrophe should be considered by emergency personnel when responding. PMID:23820144

Hogaboom, Nathan S.; Oyster, Michelle L.; Riggins, Melissa S.; Boninger, Michael L.

2013-01-01

380

A pharmacogenetic study of docetaxel and thalidomide in patients with castration-resistant prostate cancer using the DMET genotyping platform.  

PubMed

The anticancer agent docetaxel shows significant inter-individual variation in its pharmacokinetic and toxicity profile. Thalidomide is an active anticancer agent and also shows wide pharmacological variation. Past pharmacogenetic research has not explained this variation. Patients with prostate cancer enrolled in a randomized phase II trial using docetaxel and thalidomide versus docetaxel alone were genotyped using the Affymetrix DMET 1.0 platform, which tests for 1256 genetic variations in 170 drug disposition genes. Genetic polymorphisms were analyzed for associations with clinical response and toxicity. In all, 10 single-nucleotide polymorphisms (SNPs) in three genes were potentially associated with response to therapy: peroxisome proliferator-activated receptor-delta (PPAR-delta), sulfotransferase family, cytosolic, 1C, member 2 (SULT1C2) and carbohydrate (chondroitin 6) sulfotransferase 3 (CHST3). In addition, 11 SNPs in eight genes were associated with toxicities to treatment: spastic paraplegia 7 (pure and complicated autosomal recessive) (SPG7), CHST3, cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6), N-acetyltransferase 2 (arylamine N-acetyltransferase) (NAT2), ATP-binding cassette, sub-family C (CFTR/MRP), member 6 (ABCC6), ATPase, Cu++ transporting, alpha polypeptide (ATP7A), cytochrome P450, family 4, subfamily B, polypeptide 1 (CYP4B1) and solute carrier family 10 (sodium/bile acid cotransporter family), member 2 (SLC10A2). Genotyping results between drug metabolizing enzymes and transporters (DMET) and direct sequencing showed >96% of concordance. These findings highlight the role that non-CYP450 metabolizing enzymes and transporters may have in the pharmacology of docetaxel and thalidomide. PMID:20038957

Deeken, J F; Cormier, T; Price, D K; Sissung, T M; Steinberg, S M; Tran, K; Liewehr, D J; Dahut, W L; Miao, X; Figg, W D

2010-06-01

381

Mutations in B4GALNT1 (GM2 synthase) underlie a new disorder of ganglioside biosynthesis  

PubMed Central

Glycosphingolipids are ubiquitous constituents of eukaryotic plasma membranes, and their sialylated derivatives, gangliosides, are the major class of glycoconjugates expressed by neurons. Deficiencies in their catabolic pathways give rise to a large and well-studied group of inherited disorders, the lysosomal storage diseases. Although many glycosphingolipid catabolic defects have been defined, only one proven inherited disease arising from a defect in ganglioside biosynthesis is known. This disease, because of defects in the first step of ganglioside biosynthesis (GM3 synthase), results in a severe epileptic disorder found at high frequency amongst the Old Order Amish. Here we investigated an unusual neurodegenerative phenotype, most commonly classified as a complex form of hereditary spastic paraplegia, present in families from Kuwait, Italy and the Old Order Amish. Our genetic studies identified mutations in B4GALNT1 (GM2 synthase), encoding the enzyme that catalyzes the second step in complex ganglioside biosynthesis, as the cause of this neurodegenerative phenotype. Biochemical profiling of glycosphingolipid biosynthesis confirmed a lack of GM2 in affected subjects in association with a predictable increase in levels of its precursor, GM3, a finding that will greatly facilitate diagnosis of this condition. With the description of two neurological human diseases involving defects in two sequentially acting enzymes in ganglioside biosynthesis, there is the real possibility that a previously unidentified family of ganglioside deficiency diseases exist. The study of patients and animal models of these disorders will pave the way for a greater understanding of the role gangliosides play in neuronal structure and function and provide insights into the development of effective treatment therapies. PMID:24103911

Lehman, Anna; Chioza, Barry; Baple, Emma L.; Maroofian, Reza; Cross, Harold; Sreekantan-Nair, Ajith; Priestman, David A.; Al-Turki, Saeed; McEntagart, Meriel E.; Proukakis, Christos; Royle, Louise; Kozak, Radoslaw P.; Bastaki, Laila; Patton, Michael; Wagner, Karin; Coblentz, Roselyn; Price, Joy; Mezei, Michelle; Schlade-Bartusiak, Kamilla; Hurles, Matthew E.

2013-01-01

382

Intravenous colistin-induced acute respiratory failure: A case report and a review of literature  

PubMed Central

The emergence of multi-drug-resistant gram negative bacillary infections has regained popularity of ancient drugs such as polymyxins. We report a case of acute respiratory failure induced by use of intravenous colistimethate, which is one of the forms of polymyxin. The patient is a 31 year old female with paraplegia due to spina bifida who underwent excisional debridement of large lumbosacral decubitus ulcer with osteomyelitis infected with pan-resistant Pseudomonas aeruginosa and MRSA. Six days after initiation of intravenous colistimethate and vancomycin, she developed acute respiratory failure requiring mechanical ventilation. Pan-culture was negative including a chest radiograph. V/Q scan showed low probability for pulmonary embolism. Echocardiogram showed normal right ventricle with no strain or pulmonary hypertension. Colistimethate was discontinued. Within 24 hours, she was extubated. In the early years after introduction of polymyxin, there were several reports of acute respiratory paralysis. The mechanism is thought to be noncompetitive myoneuronal presynaptic blockade of acetylcholine release. Though a direct causal relationship for respiratory failure is often difficult to establish in current era with multiple co morbidities, the timeframe of apnea, acuity of onset as well as rapid recovery in our case clearly point out the causal relationship. In addition, our patient also developed acute renal failure, presumably due to colistimethate induced nephrotoxicity, a possible contributing factor for her acute respiratory failure. In summary, colistimethate can induce acute neurotoxicity including respiratory muscular weakness and acute respiratory failure. Clinicians should consider its toxicity in the differential diagnosis of acute respiratory failure especially in critically ill patients.

Shrestha, Amardeep; Soriano, Sheryll Mae; Song, Mingchen; Chihara, Shingo

2014-01-01

383

Physical strain of handcycling: An evaluation using training guidelines for a healthy lifestyle as defined by the American College of Sports Medicine  

PubMed Central

Objective Developments in assistive technology such as handcycling provide attractive possibilities to pursue a healthy lifestyle for patients with spinal cord injury. The objective of the study is to evaluate physical stress and strain of handcycling against training guidelines as defined by the American College of Sports Medicine (ACSM). Design Seven able-bodied males conducted an incremental peak exercise handcycling test on a treadmill. In addition, two indoor treadmill (1.3 m/second with an inclination of 0.7% and 1.0 m/second with an inclination of 4.8%) and three outdoor over ground exercise bouts were performed (1.7, 3.3, and 5.0 m/second). One individual handcycled a representative 8-km-distance outdoors. Outcome measures Physical stress and strain were described in terms of absolute and relative power output, oxygen uptake (VO2), gross efficiency (GE), and heart rate (HR). Also, local perceived discomfort (LPD) was determined. Results Relative handcycling exercise intensities varied between 23.3 ± 4.2 (below the ACSM lower limit of 46%VO2peak) and 72.5 ± 15.1%VO2peak (well above the ACSM lower limit), with GE ranging from 6.0 ± 1.5% at the lower to 13.0 ± 2.6% at the higher exercise intensities. Exercise intensities were performed at 49.8 ± 4.2 to 80.1 ± 10.5%HRpeak. LPD scores were low to moderate (<27 ± 7). Conclusion Handcycling is relatively efficient and exercise intensities > 46%VO2peak were elicited. However, exercise load seems to be underestimated using %HRpeak. LPD was not perceived as limiting. Physiological stress and strain in able-bodied individuals appear to be comparable to individuals with a paraplegia. To understand individualize and optimize upper-body training, different training programs must be evaluated. PMID:23820153

Hettinga, Florentina J.; de Groot, Sonja; van Dijk, Frank; Kerkhof, Faes; Woldring, Ferry; van der Woude, Luc

2013-01-01

384

Hybrid Repair of Complex Thoracic Aortic Arch Pathology: Long-Term Outcomes of Extra-anatomic Bypass Grafting of the Supra-aortic Trunk  

SciTech Connect

Hybrid repair constitutes supra-aortic debranching before thoracic endovascular aortic repair (TEVAR). It offers improved short-term outcome compared with open surgery; however, longer-term studies are required to assess patient outcomes and patency of the extra-anatomic bypass grafts. A prospectively maintained database of 380 elective and urgent patients who had undergone TEVAR (1997-2011) was analyzed retrospectively. Fifty-one patients (34 males; 17 females) underwent hybrid repair. Median age was 71 (range, 18-90) years with mean follow-up of 15 (range, 0-61) months. Perioperative complications included death: 10 % (5/51), stroke: 12 % (6/51), paraplegia: 6 % (3/51), endoleak: 16 % (8/51), rupture: 4 % (2/51), upper-limb ischemia: 2 % (1/51), bypass graft occlusion: 4 % (2/51), and cardiopulmonary complications in 14 % (7/51). Three patients (6 %) required emergency intervention for retrograde dissection: (2 aortic root repairs; 2 innominate stents). Early reintervention was performed for type 1 endoleak in two patients (2 proximal cuff extensions). One patient underwent innominate stenting and revision of their bypass for symptomatic restenosis. At 48 months, survival was 73 %. Endoleak was detected in three (6 %) patients (type 1 = 2; type 2 = 1) requiring debranching with proximal stent graft (n = 2) and proximal extension cuff (n = 1). One patient had a fatal rupture of a mycotic aneurysm and two arch aneurysms expanded. No bypass graft occluded after the perioperative period. Hybrid operations to treat aortic arch disease can be performed with results comparable to open surgery. The longer-term outcomes demonstrate low rates of reintervention and high rates of graft patency.

Lotfi, S., E-mail: shamim.lotfi@kcl.ac.uk; Clough, R. E.; Ali, T. [Guy's and St. Thomas' NHS Trust, Vascular Surgery (United Kingdom)] [Guy's and St. Thomas' NHS Trust, Vascular Surgery (United Kingdom); Salter, R. [Guy's and St. Thomas' NHS Trust, Interventional Radiology (United Kingdom)] [Guy's and St. Thomas' NHS Trust, Interventional Radiology (United Kingdom); Young, C. P. [Guy's and St. Thomas' NHS Trust, Cardiac Surgery (United Kingdom)] [Guy's and St. Thomas' NHS Trust, Cardiac Surgery (United Kingdom); Bell, R.; Modarai, B.; Taylor, P., E-mail: peter.taylor@gstt.nhs.uk [Guy's and St. Thomas' NHS Trust, Vascular Surgery (United Kingdom)

2013-02-15

385

Inflammation-mediating cytokine response to acute handcycling exercise with/without functional electrical stimulation-evoked lower-limb cycling.  

PubMed

This feasibility study compared the plasma inflammation-mediating cytokine response to an acute bout of handcycling (HC) with and without the addition of functional electrical stimulation (FES)-evoked lower-limb cycling. On two separate occasions, five recreationally active, community-based participants with motor complete paraplegia (thoracic 5- 7) performed 30 min HC and hybrid exercise (HYB) at a fixed power output. Venous blood samples were collected at rest, immediately postexercise, 1 h postexercise (post+1) and 2 h postexercise (post+2). Plasma interleukin (IL)-6, IL-10, IL-1 receptor antagonist (IL-1ra), adrenaline, and cortisol concentrations were determined via enzyme-linked immunoassay. Plasma IL-6 concentrations were significantly (p < 0.04) elevated (~2.5-fold) at post+1 and post+2 in HYB only. A small (0.5-fold), nonsignificant (p > 0.05) increase in IL-6 was observed at post+1 in HC, with concentrations significantly higher in HYB at post+2 (p < 0.02). Plasma IL-1ra was unaffected in both trials. Although not reaching statistical significance (p = 0.15), a ~1-fold increase in IL-10 concentration was seen in HYB at post+2. In contrast, increases in adrenaline (p < 0.04) and cortisol (p = 0.08) were observed immediately postexercise in HC and HYB. Initial findings suggest paralyzed skeletal muscle releases IL-6 in response to FES-evoked contractions. HYB may provide a greater anti-inflammatory potential in individuals with a thoracic spinal cord injury compared with HC alone. PMID:25144177

Paulson, Thomas A W; Bishop, Nicolette C; Smith, Brett M; Goosey-Tolfrey, Victoria L

2014-07-01

386

Longitudinal relationship between wheelchair exercise capacity and life satisfaction in patients with spinal cord injury: A cohort study in the Netherlands.  

PubMed

Objective To examine the relationship between wheelchair exercise capacity and life satisfaction in persons with spinal cord injury from the start of active inpatient rehabilitation up to 5 years after discharge. Design Prospective cohort study. Subjects Persons with spinal cord injury, aged 18-65 years, and wheelchair dependent at least for long distances. Method Measurements at the start of active rehabilitation, after 3 months, at discharge from inpatient rehabilitation, and 1 and 5 years after discharge. A peak wheelchair exercise test was performed to record peak oxygen uptake (VO2peak) and peak power output (POpeak). Life satisfaction was measured as current life satisfaction and change of life satisfaction in comparison with life after spinal cord injury. Relationships between (changes in) exercise capacity and (changes in) life satisfaction were analyzed random coefficient analysis, corrected for possible confounders (age, gender, level of lesion, functional status, secondary impairments, pain, and sports activity) if necessary. Results Of 225 persons included, 130 attended two or more peak exercise tests, who were include in the analyses. Mean age at start was 39 years, 75% were male, 73% had paraplegia, and 76% had a traumatic lesion. Mean POpeak increased during the study from 32.9 to 55.9 Watts, mean VO2peak from 1.02  to 1.38 l/minute, and mean life satisfaction from 5.7 to 7.8. An increase of POpeak with 10 W was associated with a 0.3-point increase of life satisfaction (P = 0.01). An increase of VO2peak with 0.1 l/minute was associated with a 0.1-point increase of life satisfaction (P = 0.049). Conclusion High(er) wheelchair exercise capacity is related to high(er) life satisfaction in spinal cord injury patients. PMID:24621019

van Koppenhagen, Casper Floris; Post, Marcel; de Groot, Sonja; van Leeuwen, Christel; van Asbeck, Floris; Stolwijk-Swüste, Janneke; van der Woude, Lucas; Lindeman, Eline

2014-05-01

387

Gap junction disorders of myelinating cells.  

PubMed

Gap junctions (GJs) are channels that allow the diffusion of ions and small molecules across apposed cell membranes. In peripheral nerves, Schwann cells express the GJ proteins connexin32 (Cx32) and Cx29, which have distinct localizations. Cx32 forms GJs through non-compact myelin areas, whereas Cx29 forms hemichannels in the innermost layers of myelin apposing axonal Shaker-type K+ channels. In the CNS, rodent oligodendrocytes express Cx47, Cx32 and Cx29. Cx47 is expressed by all types of oligodendrocytes both in the white and grey matter and forms GJs on cell bodies and proximal processes, as well as most of the intercellular channels with astrocytes. Cx32 is expressed mostly by white matter oligodendrocytes and is localized in the myelin sheath of large diameter fibers. Cx29, and its human ortholog Cx31.3, appear to be restricted to oligodendrocytes that myelinate small caliber fibers, likely forming hemichannels. The importance of intercellular and intracellular GJs in myelinating cells are demonstrated by human disorders resulting from mutations affecting GJ proteins. The X-linked Charcot Marie Tooth disease (CMT1X) is caused by hundreds of mutations affecting Cx32. Patients with CMT1X present mainly with a progressive peripheral neuropathy, which may be accompanied by CNS myelin dysfunction. Mutations in Cx47 may cause a devastating leukodystrophy called Pelizaeus-Merzbacher-like disease or a milder spastic paraplegia. In addition, CNS demyelination may be caused by defects in genes expressing astrocytic GJ proteins, which are essential for oligodendrocytes. Findings from in vitro and in vivo models of these disorders developed over the last decade indicate that most mutations cause loss of function and an inability of the mutant connexins to form functional GJs. Here we review the clinical, genetic, and neurobiological aspects of GJ disorders affecting the PNS and CNS myelinating cells. PMID:21280457

Kleopa, Kleopas A; Orthmann-Murphy, Jennifer; Sargiannidou, Irene

2010-01-01

388

Polymeric biomaterials for nerve regeneration applications: From promoting cellular organization to the delivery of bioactive molecules  

NASA Astrophysics Data System (ADS)

Thousands of new cases of injury to the central nervous system (CNS) occur each year in the USA and all over the world. However, despite recent advances, at present there is no cure for the resulting paraplegia or quadriplegia. This research is directed towards engineering biomaterial platforms to promote cellular organization at the surface of polymer scaffolds that will be conducive to proper regeneration of injured CNS. In addition, the formulation of a delivery system for neuroactive molecules using polymer-based materials will be evaluated to establish its potential to treat CNS disorders. Initial studies involved the chemical modification of an electrospun nonwoven matrix of nanofibers with fibroblast growth factor 2 (FGF-2). Nanofibers alone up-regulated FGF-2, albeit to a lesser extent than nanofibers covalently modified with FGF-2. These results underscore the importance of both surface topography and growth factor presentation on cellular function. Moreover, that FGF-2 modified nanofibrillar scaffolds may demonstrate utility in tissue engineering applications for replacement and regeneration of damaged tissue following CNS injury or disease. Subsequent research efforts focused on a novel micropatterning technique called microscale plasma-initiated patterning (microPIP). This patterning method uses a polydimethylsiloxane (PDMS) stamp to selectively protect regions of an underlying substrate from oxygen plasma treatment resulting in hydrophobic and hydrophilic regions. FGF-2 and laminin-1 were applied to an electrospun polyamide nanofibrillar matrix following plasma treatment. In this work it, was possible to demonstrate that textured surfaces, such as nanofibrillar scaffolds, can be micropatterned to provide external chemical cues for cellular organization. Finally, a microsphere system capable of encapsulating proteins while minimizing the mechanisms of protein degradation and providing a controlled release was investigated. Microspheres were comprised of a salicylic-acid based poly(anhydride-ester) (PAE), a biodegradable polymer that incorporates salicylic acid into the polymer backbone (PolyAspirin). The use of microspheres formulated from PolyAspirin as a delivery vehicle can be advantageous due its ability of performing a dual delivery; biomolecule (protein) and drug. By combining these two properties, it will be possible to release neurotrophic factors to induce a biological response while mitigating inflammatory pathways due to the localized delivery of salicylic acid.

Delgado-Rivera, Roberto L.

389

Providers' Perceptions of Spinal Cord Injury Pressure Ulcer Guidelines  

PubMed Central

Background/Objective: Pressure ulcers are a serious complication for people with spinal cord injury (SCI). The Consortium for Spinal Cord Medicine (CSCM) published clinical practice guidelines (CPGs) that provided guidance for pressure ulcer prevention and treatment after SCI. The aim of this study was to assess providers' perceptions for each of the 32 CPG recommendations regarding their agreement with CPGs, degree of CPG implementation, and CPG implementation barriers and facilitators. Methods: This descriptive mixed-methods study included both qualitative (focus groups) and quantitative (survey) data collection approaches. The sample (n = 60) included 24 physicians and 36 nurses who attended the 2004 annual national conferences of the American Paraplegia Society or American Association of Spinal Cord Injury Nurses. This sample drew from two sources: a purposive sample from a list of preregistered participants and a convenience sample of conference attendee volunteers. We analyzed quantitative data using descriptive statistics and qualitative data using a coding scheme to capture barriers and facilitators. Results: The focus groups agreed unanimously on the substance of 6 of the 32 recommendations. Nurse and physician focus groups disagreed on the degree of CGP implementation at their sites, with nurses as a group perceiving less progress in implementation of the guideline recommendations. The focus groups identified only one recommendation, complications of surgery, as being fully implemented at their sites. Categories of barriers and facilitators for implementation of CPGs that emerged from the qualitative analysis included (a) characteristics of CPGs: need for research/evidence, (b) characteristics of CPGs: complexity of design and wording, (c) organizational factors, (d) lack of knowledge, and (e) lack of resources. Conclusions: Although generally SCI physicians and nurses agreed with the CPG recommendations as written, they did not feel these recommendations were fully implemented in their respective clinical settings. The focus groups identified multiple barriers to the implementation of the CPGs and suggested several facilitators/solutions to improve implementation of these guidelines in SCI. Participants identified organizational factors and the lack of knowledge as the most substantial systems/issues that created barriers to CPG implementation. PMID:17591223

Thomason, Susan S; Evitt, Celinda P; Harrow, Jeffrey J; Love, Linda; Moore, D. Helen; Mullins, Maria A; Powell-Cope, Gail; Nelson, Audrey L

2007-01-01

390

Ten-Year Follow-Up of Endovascular Aneurysm Treatment with Talent Stent-Grafts  

SciTech Connect

The purpose of this study was to evaluate the clinical results, complications, and secondary interventions during long-term follow-up after endovascular aneurysm repair (EVAR) and to investigate the impact of endoleak sizes on aneurysm shrinkage. From 1997 to March 2007, 127 patients (12 female, 115 male; age, 73.0 {+-} 7.2 years) with abdominal aortic aneurysms were treated with Talent stent-grafts. Follow-up included clinical visits, contrast-enhanced MDCT, and radiographs at 3, 6, and 12 months and then annually. Results were analyzed with respect to clinical outcome, secondary interventions, endoleak rate and management, and change in aneurysm size. There was no need for primary conversion surgery. Thirty-day mortality was 1.6% (two myocardial infarctions). Procedure-related morbidity was 2.4% (paraplegia, partial infarction of one kidney, and inguinal bleeding requiring surgery). Mean follow-up was 47.7 {+-} 34.2 months (range, 0-123 months). Thirty-nine patients died during follow-up; three of the deaths were related to aneurysm (aneurysm rupture due to endoleak, n = 1; secondary surgical reintervention n = 2). During follow-up, a total of 29 secondary procedures were performed in 19 patients, including 14 percutaneous procedures (10 patients) and 15 surgical procedures (12 patients), including 4 cases with late conversion to open aortic repair (stent-graft infection, n = 1; migration, endoleak, or endotension, n = 3). Overall mean survival was 84.5 {+-} 4.7 months. Mean survival and freedom from any event was 66.7 {+-} 4.5 months. MRI depicted significantly more endoleaks compared to MDCT (23.5% vs. 14.3%; P < 0.01). Patients in whom all aneurysm side branches were occluded prior to stent-grafting showed a significantly reduced incidence of large endoleaks. Endoleaks >10% of the aneurysm area were associated with reduced aneurysm shrinkage compared to no endoleaks or <10% endoleaks ({Delta} at 3 years, -1.8% vs. -12.0%; P < 0.05). In conclusion, endovascular aneurysm treatment with Talent stent-grafts demonstrated encouraging long-term results with moderate secondary intervention rates. Primary occlusion of all aortic side branches reduced the incidence of large endoleaks. Large endoleaks significantly impaired aneurysm shrinkage, whereas small endoleaks did not.

Pitton, Michael B., E-mail: pitton@radiologie.klinik.uni-mainz.de; Scheschkowski, Tobias; Ring, Markus; Herber, Sascha; Oberholzer, Katja; Leicher-Dueber, Annegret [University Hospital of Mainz, Johannes Gutenberg University of Mainz, Department of Diagnostic and Interventional Radiology (Germany); Neufang, Achim; Schmiedt, Walther [University Hospital of Mainz, Johannes Gutenberg University of Mainz, Department of Cardiovascular and Thoracic Surgery (Germany); Dueber, Christoph [University Hospital of Mainz, Johannes Gutenberg University of Mainz, Department of Diagnostic and Interventional Radiology (Germany)

2009-09-15

391

[Infantile neuro-axonal dystrophy: anatomo clinical study of one case (author's transl)].  

PubMed

A case of Seitelberger's infantile neuroaxonal dystrophy (a rare familial neurologic disease of childhood) is described. The clinical picture is characterized by a progressive deterioration of psychomotor functions leading to flaccid paraplegia with hypotonia of axial muscles, complete involution of language, and total loss of communication with the external world; death due to recurrent unassociated disease occurred at the age of 4 years. Histology showed numerous axonal spheroids mainly in the gray matter of the C.N.S. and plurisystemic degenerations of the motor and sensory systems, of the cerebellum, of the basal ganglia, and of specific sensory system such as the optic and (reported here for the first time) of the olfactory and acoustic systems. In particular, the main histopathological findings included: 1) a characteristic distribution of axonal swellings prevailing in the posterior horn of the spinal cord and in the dorsolateral portions of the medulla oblongata, mainly at the level of the sensory nuclei; 2) demyelinization of the pyramidal tracts and of the ascendings pathways of the sensory system with fibrillar gliosis and myelin breakdown products in some areas (internal capsule, pes pedunculi, VPL thalamic nuclei); 3) severe cerebellar atrophy with almost complete loss of granule and Purkinje cells and marked fibrillary gliosis; 4) presence of enormous amount of sudanophilic lipids in the striatum and pallidum; 5) optic, acoustic and olfactory system degeneration with demyelinization and gliosis at all levels examined and, in particular, sudanophilic lipid deposition in the optic radiations, trigone, and olfactory striae. The discussion emphasized the dying-back type of evolution of the degenerative process insofar as a) the spheroids represent a peculiar alteration of presynaptic endings (as demonstrated by electron microscopy) prevailing at the first sensory neuron, and b) in all systems involved, the degeneration is most marked at distal levels. The striato-pallidal lipophanerosis suggests that the sudanophilic lipids are, here as in other systems, parenchymal degeneration products. On the other hand, there are still many unresolved problems in this rare and complex disease, such as a) the predilection of the lesions for the sensory systems which in our case involved all three special senses; b) the extreme cerebellar atrophy; and c) the etiopathogenetic substrate of the process. All biochemical and histochemical studies have not yielded any results up to the present. PMID:1235007

Onnis, L; Nardelli, E; Buonanno, F; Galiazzo-Rizzuto, S; Panizon, F; Rizzuto, N

1975-01-01

392

Altered Behavioral Performance and Live Imaging of Circuit-Specific Neural Deficiencies in a Zebrafish Model for Psychomotor Retardation  

PubMed Central

The mechanisms and treatment of psychomotor retardation, which includes motor and cognitive impairment, are indefinite. The Allan-Herndon-Dudley syndrome (AHDS) is an X-linked psychomotor retardation characterized by delayed development, severe intellectual disability, muscle hypotonia, and spastic paraplegia, in combination with disturbed thyroid hormone (TH) parameters. AHDS has been associated with mutations in the monocarboxylate transporter 8 (mct8/slc16a2) gene, which is a TH transporter. In order to determine the pathophysiological mechanisms of AHDS, MCT8 knockout mice were intensively studied. Although these mice faithfully replicated the abnormal serum TH levels, they failed to exhibit the neurological and behavioral symptoms of AHDS patients. Here, we generated an mct8 mutant (mct8?/?) zebrafish using zinc-finger nuclease (ZFN)-mediated targeted gene editing system. The elimination of MCT8 decreased the expression levels of TH receptors; however, it did not affect the expression of other TH-related genes. Similar to human patients, mct8?/? larvae exhibited neurological and behavioral deficiencies. High-throughput behavioral assays demonstrated that mct8?/? larvae exhibited reduced locomotor activity, altered response to external light and dark transitions and an increase in sleep time. These deficiencies in behavioral performance were associated with altered expression of myelin-related genes and neuron-specific deficiencies in circuit formation. Time-lapse imaging of single-axon arbors and synapses in live mct8?/? larvae revealed a reduction in filopodia dynamics and axon branching in sensory neurons and decreased synaptic density in motor neurons. These phenotypes enable assessment of the therapeutic potential of three TH analogs that can enter the cells in the absence of MCT8. The TH analogs restored the myelin and axon outgrowth deficiencies in mct8?/? larvae. These findings suggest a mechanism by which MCT8 regulates neural circuit assembly, ultimately mediating sensory and motor control of behavioral performance. We also propose that the administration of TH analogs early during embryo development can specifically reduce neurological damage in AHDS patients. PMID:25255244

Lerer-Goldshtein, Tali; Vatine, Gad David; Appelbaum, Lior

2014-01-01

393

Further evidence for genetic heterogeneity of distal HMN type V, CMT2 with predominant hand involvement and Silver syndrome  

PubMed Central

Objective Distal hereditary motor neuropathy type V (dHMN-V) and Charcot–Marie–Tooth syndrome (CMT) type 2 presenting with predominant hand involvement, also known as CMT2D and Silver syndrome (SS) are rare phenotypically overlapping diseases which can be caused by mutations in the Berardinelli–Seip Congenital Lipodystrophy 2 (BSCL2) and in the glycyl-tRNA synthetase encoding (GARS) genes. Mutations in the heat-shock proteins HSPB1 and HSPB8 can cause related distal hereditary motor neuropathies (dHMN) and are considered candidates for dHMN-V, CMT2, and SS. Design To define the frequency and distribution of mutations in the GARS, BSCL2, HSPB1 and HSPB8 genes we screened 33 unrelated sporadic and familial patients diagnosed as either dHMN-V, CMT2D or SS. Exon 3 of the BSCL2 gene was screened in further 69 individuals with an unclassified dHMN phenotype or diagnosed as hereditary spastic paraplegia (HSP) complicated by pure motor neuropathy. Results Four patients diagnosed with dHMN-Vor SS carried known heterozygous BSCL2 mutations (N88S and S90L). In one dHMN-V patient we detected a putative GARS mutation (A57V). No mutations were detected in HSPB1 and HSPB8. The diagnostic yield gained in the series of 33 probands was 12% for BSCL2 mutations and 3% for GARS mutations. In the series of unclassified dHMN and complicated HSP cases no mutations were found. Conclusions Our data confirm that most likely only two mutations (N88S, S90L) in exon 3 of BSCL2 may lead to dHMN-V or SS phenotypes. Mutations in GARS, HSPB1 and HSPB8. are not a common cause of dHMN-V, SS and CMT2D. We would therefore suggest that a genetic testing of dHMN-V and SS patients should begin with screening of exon 3 of the BSCL2 gene. Screening of the GARS gene is useful in patients with CMT2 with predominant hand involvement and dHMN-V. The rather low frequencies of BSCL2, GARS, HSPB1 and HSPB8 mutations in dHMN-V, CMT2D and SS patients strongly point to further genetic heterogeneity of these related disorders. PMID:17663003

Rohkamm, Barbara; Reilly, Mary M.; Lochmüller, Hanns; Schlotter-Weigel, Beate; Barisic, Nina; Schöls, Ludger; Nicholson, Garth; Pareyson, Davide; Laurà, Matilde; Janecke, Andreas R.; Miltenberger-Miltenyi, Gabriel; John, Elisabeth; Fischer, Carina; Grill, Franz; Wakeling, William; Davis, Mary; Pieber, Thomas R.; Auer-Grumbach, Michaela

2011-01-01

394

Type I and Type II hybrid aortic arch replacement: postoperative and mid-term outcome analysis  

PubMed Central

Background Hybrid aortic arch replacement has emerged as a safe treatment modality for arch aneurysms, especially in patients of old age and with greater comorbid burden. We assessed our institutional outcomes in patients undergoing Types I and II hybrid aortic arch replacement. Methods From 2005 to 2012, 685 patients underwent thoracic endovascular repair (TEVAR), of whom 104 had hybrid arch repair (open + endovascular approach). 47 of these patients had treatment for aortic arch aneurysm ± proximal ascending aortic aneurysm. The hybrid repair entailed aortic arch vessel debranching and concomitant/delayed antegrade ± retrograde TEVAR stent grafting of the arch. Type III patients were excluded from the analysis. Data was prospectively maintained. Results 28 patients had Type I repair, 8 had Type II repair, and 11 had Type III repair. Mean age was 71±8 years. Primary aortic pathology was aneurysm (81%), followed by chronic arch dissection (11%). 14% of patients required reoperative cardiac surgery. Stent graft deployment rate was 100% after arch vessel debranching. Postoperative endoleak rate was zero. Average cardiopulmonary bypass time was 215±64 minutes, with crossclamp time of 70±55 minutes, and circulatory arrest time of 50±17 minutes. Paraplegia rate was 5.5% (n=2), with stroke rate of 8% (n=3) and renal failure rate of 3% (n=1) requiring hemodialysis. In-hospital mortality was 8% (n=3). Mean length of stay was 17.2±14 days. Median follow-up was 30±21 months. Freedom from all-cause mortality was 71%, 60%, and 48% at 1, 3, and 5 years respectively. Aortic reoperation rate was 2.7% (n=1). No patient had Type I or III endoleak at follow-up. Freedom from mortality was improved in cases performed more recently (July 2008 to 2012) than during our early experience (2005 to June 2008) (81% versus 44% at 3 years, P=0.05). Conclusions Hybrid aortic arch replacement can be performed with good postoperative and midterm results in a cohort of old patients with significant comorbidity. With greater experience, early and midterm outcomes continue to improve. The hybrid arch technique may represent a technical advancement in the field of aortic arch surgery. PMID:23977595

Vallabhajosyula, Prashanth; Szeto, Wilson; Desai, Nimesh

2013-01-01

395

Pattern of neurological admissions in the tropics: Experience at Kano, Northwestern Nigeria  

PubMed Central

Background: Kano is the most populated state in Nigeria with a population totaling 9,383,682. The pattern of neurologic diseases in this area is not known. Objective: To determine the of pattern of neurologic diseases warranting admission in a tertiary hospital in Kano and compare it with those elsewhere in the country with the view to using the data generated as a baseline for planning purposes and for future studies. Materials and Methods: The medical records of all cases admitted with neurologic diseases in the Aminu Kano Teaching Hospital, Kano between January 2005 and September 2008, were retrospectively reviewed and the frequency of neurologic diseases, sex, age, and outcome of these diseases analyzed. Result: Stroke, predominantly ischemic, accounted for 77.6% of the neurological cases for the period of study. Central nervous system infections, comprising mainly of meningitis and tetanus, accounted for 6.6% (64) and 3% (29) of cases, respectively. The myelopathies were the cause of neurologic admissions in 5.4% (53) with paraplegia and quadriplegia resulting from myelopathies accounting for 5% (49) and 0.4% (4) of the cases. Hypertensive encephalopathy and status epilepticus as the causes of admissions accounted for 1.6% each. Gullain Barre syndrome, Parkinson’s disease, and cerebral malaria were relatively rare causes of neurologic admissions in this study. The average duration of hospitalization was 25 days, and regarding outcome, 219 (22.4%) of these cases died. Conclusions: Stroke appeared to be the most common neurologic admission and the most common cause of neurologic and medical death in Kano as observed in other regions of the country and a little over one-fifths of stroke patients die. Central nervous system infections mainly meningitis and tetanus are the next common cause of admission. In view of these findings, the provision of a regional stroke unit, the improvement of the sanitary conditions of the home and environment; the widespread use of immunizations against meningitis, tetanus cannot be over-emphasized. These interventions will go a long way to reduce morbidity and mortality of stroke and neurologic infections. PMID:21085525

Owolabi, L. F.; Shehu, M. Y.; Shehu, M. N.; Fadare, J.

2010-01-01

396

Comorbidity and repeat admission to hospital for adverse drug reactions in older adults: retrospective cohort study  

PubMed Central

Objectives To identify factors that predict repeat admission to hospital for adverse drug reactions (ADRs) in older adults. Design Population based retrospective cohort study. Setting All public and private hospitals in Western Australia. Participants 28?548 patients aged ?60 years with an admission for an ADR during 1980-2000 followed for three years using the Western Australian data linkage system. Results 5056 (17.7%) patients had a repeat admission for an ADR. Repeat ADRs were associated with sex (hazard ratio 1.08, 95% confidence interval 1.02 to 1.15, for men), first admission in 1995-9 (2.34, 2.00 to 2.73), length of hospital stay (1.11, 1.05 to 1.18, for stays ?14 days), and Charlson comorbidity index (1.71, 1.46 to 1.99, for score ?7); 60% of comorbidities were recorded and taken into account in analysis. In contrast, advancing age had no effect on repeat ADRs. Comorbid congestive cardiac failure (1.56, 1.43 to 1.71), peripheral vascular disease (1.27, 1.09 to 1.48), chronic pulmonary disease (1.61, 1.45 to 1.79), rheumatological disease (1.65, 1.41 to 1.92), mild liver disease (1.48, 1.05 to 2.07), moderate to severe liver disease (1.85, 1.18 to 2.92), moderate diabetes (1.18, 1.07 to 1.30), diabetes with chronic complications (1.91, 1.65 to 2.22), renal disease (1.93, 1.71 to 2.17), any malignancy including lymphoma and leukaemia (1.87, 1.68 to 2.09), and metastatic solid tumours (2.25, 1.92 to 2.64) were strong predictive factors. Comorbidities requiring continuing care predicted a reduced likelihood of repeat hospital admissions for ADRs (cerebrovascular disease 0.85, 0.73 to 0.98; dementia 0.62, 0.49 to 0.78; paraplegia 0.73, 0.59 to 0.89). Conclusions Comorbidity, but not advancing age, predicts repeat admission for ADRs in older adults, especially those with comorbidities often managed in the community. Awareness of these predictors can help clinicians to identify which older adults are at greater risk of admission for ADRs and, therefore, who might benefit from closer monitoring. PMID:19129307

2009-01-01

397

Efficacy of extended DOTS category I chemotherapy in spinal tuberculosis based on MRI-based healed status  

PubMed Central

Background: Duration of treatment in tuberculosis of spine has always been debatable in the absence of marker of healing. The objective of the study was to evaluate the efficacy of extended DOTS regimen (2 months of intensive phase and 6 months of continuation phase) as recommended by WHO, by using MRI observations as the healing marker. Materials and Methods: 51 (Group A -28 prospective and Group B- 23 retrospective) patients of spine TB with mean age of 26.8 years (range 15-54 years) diagnosed clinico radiologically/imaging (n=36), histopathology or by PCR (n=15) were enrolled for the study. They were treated by extended DOTS regimen (2 months of HRZE and 6 months of HR) administered alternate day. The serial blood investigations and X-rays were done every 2 months. Contrast MRI was done at the end of 8 months and healing changes were recorded. Criteria of healing on the basis of MRI being: complete resolution of pre and paravertebral collections, resolution of marrow edema of vertebral body (VB), replacement of marrow edema by fat or by calcification suggested by iso- intense T1 and T2 weighted images in contrast enhanced MRI. Patients with non healed status, but, responding lesion on MRI after 8 months of treatment were continued on INH and rifampicin alternate day and contrast MRI was done subsequently at 12 months and 18 months till the healed status was achieved . Results: 9 patients had paraplegia and required surgical intervention out of which 1 did not recover neurologically. All patients have completed 8 months of extended DOTS regime