A case of acute paraplegia that improved with dialysis.

PubMed

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

2008-01-01

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.

Mechanistic basis of an epistatic interaction reducing age at onset in hereditary spastic paraplegia.

PubMed

Newton, Timothy; Allison, Rachel; Edgar, James R; Lumb, Jennifer H; Rodger, Catherine E; Manna, Paul T; Rizo, Tania; Kohl, Zacharias; Nygren, Anders O H; Arning, Larissa; Schüle, Rebecca; Depienne, Christel; Goldberg, Lisa; Frahm, Christiane; Stevanin, Giovanni; Durr, Alexandra; Schöls, Ludger; Winner, Beate; Beetz, Christian; Reid, Evan

2018-05-01

Many genetic neurological disorders exhibit variable expression within affected families, often exemplified by variations in disease age at onset. Epistatic effects (i.e. effects of modifier genes on the disease gene) may underlie this variation, but the mechanistic basis for such epistatic interactions is rarely understood. Here we report a novel epistatic interaction between SPAST and the contiguous gene DPY30, which modifies age at onset in hereditary spastic paraplegia, a genetic axonopathy. We found that patients with hereditary spastic paraplegia caused by genomic deletions of SPAST that extended into DPY30 had a significantly younger age at onset. We show that, like spastin, the protein encoded by SPAST, the DPY30 protein controls endosomal tubule fission, traffic of mannose 6-phosphate receptors from endosomes to the Golgi, and lysosomal ultrastructural morphology. We propose that additive effects on this pathway explain the reduced age at onset of hereditary spastic paraplegia in patients who are haploinsufficient for both genes.

A case of acute paraplegia that improved with dialysis

PubMed Central

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

2008-01-01

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

Functional MR imaging and traumatic paraplegia: preliminary report.

PubMed

Sabbah, P; Lévêque, C; Pfefer, F; Nioche, C; Gay, S; Sarrazin, J L; Barouti, H; Tadie, M; Cordoliani, Y S

2000-12-01

To evaluate residual activity in the sensorimotor cortex of the lower limbs in paraplegia. 5 patients suffering from a complete paralysis after traumatic medullar lesion (ASIA=A). Clinical evaluation of motility and sensitivity. 1. Control functional MR study of the sensorimotor cortex during simultaneous movements of hands, imaginary motor task and passive hands stimulation. 2. Concerning the lower limbs, 3 fMRI conditions: 1-patient attempts to move his toes with flexion-extension, 2-mental imagery task of the same movement, 3-peripheral passive proprio-somesthesic stimulation (squeezing) of the big toes. Activations were observed in the primary sensorimotor cortex (M1), premotor regions and in the supplementary motor area (SMA) during movement and mental imaginary tasks in the control study and during attempt to move and mental imaginary tasks in the study concerning the lower limbs. Passive somesthesic stimulation generated activation posterior to the central sulcus for 2 patients. Activations in the sensorimotor cortex of the lower limbs can be generated either by attempting to move or mental evocation. In spite of a clinical evaluation of complete paraplegia, fMRI can show a persistence of sensitive anatomic conduction, confirmed by Somesthesic Evoked Potentials.

Co-segregation of Huntington disease and hereditary spastic paraplegia in 4 generations.

PubMed

Panas, Marios; Karadima, Georgia; Kalfakis, Nikolaos; Vassilopoulos, Dimitris

2011-07-01

Huntington disease (HD) is an autosomal dominant neurodegenerative disease characterized by choreic hyperkinesias, cognitive decline, and psychiatric manifestations, caused by an increased number of CAG repeats in the IT15 gene on chromosome 4p16.3. Silver syndrome is a rare autosomal dominant form of complicated hereditary spastic paraplegia, characterized by lower limb spasticity in addition to amyotrophy of the small muscles of the hands. In addition to the previously identified locus SPG17 on chromosome 11q12-q14, a new locus (SPG38) on chromosome 4p16-p15 has been recently identified, a region that includes the HD gene. We present a Greek family with 5 members diagnosed with HD in 4 generations. All affected members also presented with clinical features of Silver syndrome showing severe spastic paraplegia and prominent atrophy of all small hand muscles bilaterally. None of the other family members showed features of either HD or spastic paraplegia. The reported coexistence of Silver syndrome with HD in 4 generations is not fortuitous, suggesting that these 2 distinct genetic disorders are in linkage disequilibrium. Although rare, it is reasonable to expect additional similar cases. Clinical neurologists should perhaps investigate this possibility in cases combining features of HD and involvement of the upper and lower motor neurons.

Hereditary spastic paraplegia.

PubMed

Blackstone, Craig

2018-01-01

The hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurologic disorders with the common feature of prominent lower-extremity spasticity, resulting from a length-dependent axonopathy of corticospinal upper motor neurons. The HSPs exist not only in "pure" forms but also in "complex" forms that are associated with additional neurologic and extraneurologic features. The HSPs are among the most genetically diverse neurologic disorders, with well over 70 distinct genetic loci, for which about 60 mutated genes have already been identified. Numerous studies elucidating the molecular pathogenesis underlying HSPs have highlighted the importance of basic cellular functions - especially membrane trafficking, mitochondrial function, organelle shaping and biogenesis, axon transport, and lipid/cholesterol metabolism - in axon development and maintenance. An encouragingly small number of converging cellular pathogenic themes have been identified for the most common HSPs, and some of these pathways present compelling targets for future therapies. Copyright © 2018 Elsevier B.V. All rights reserved.

Cellular pathways of hereditary spastic paraplegia.

PubMed

Blackstone, Craig

2012-01-01

Human voluntary movement is controlled by the pyramidal motor system, a long CNS pathway comprising corticospinal and lower motor neurons. Hereditary spastic paraplegias (HSPs) are a large, genetically diverse group of inherited neurologic disorders characterized by a length-dependent distal axonopathy of the corticospinal tracts, resulting in lower limb spasticity and weakness. A range of studies are converging on alterations in the shaping of organelles, particularly the endoplasmic reticulum, as well as intracellular membrane trafficking and distribution as primary defects underlying the HSPs, with clear relevance for other long axonopathies affecting peripheral nerves and lower motor neurons.

[A case of leptomeningeal melanomatosis with acute paraplegia and multiple cranial nerve palsies].

PubMed

Hattori, Kasumi; Matsuda, Nozomu; Murakami, Takenobu; Ito, Eiichi; Ugawa, Yoshikazu

2017-12-27

A 62-year-old man with acute paraplegia was transferred to our hospital. He had flaccid paraplegia and multiple cranial nerve palsies, such as mydriasis of the left pupil, abduction palsy of the left eye, hoarseness and dysphagia, but no meningeal irritation signs. MRI of the spinal canal showed swellings of the conus medullaris and the cauda equine, and also contrast enhancement of the spinal meninges. The cerebrospinal fluid (CSF) showed pleocytosis and protein increment. The lymph node was swollen in his right axilla. The biopsy specimen from the right axillary lymph node revealed metastasis of malignant melanoma histologically. Careful check-up of his whole body found a malignant melanoma in the subungual region of the right ring finger. Repeated cytological examination revealed melanoma cells in the CSF, confirming the diagnosis of leptomeningeal melanomatosis. His consciousness was gradually deteriorated. His family members chose supportive care instead of chemotherapy or surgical therapy after full information about his conditions. Finally, he died 60 days after transfer to our hospital. This is a rare case of leptomenigeal melanomatosis presenting with acute paraplegia and multiple cranial nerve palsies. Careful follow-up and repeated studies are vital for the early diagnosis of leptomenigeal melanomatosis in spite of atypical clinical presentation.

Hereditary spastic paraplegia: clinical principles and genetic advances.

PubMed

Fink, John K

2014-07-01

Hereditary spastic paraplegia (HSP) refers to inherited disorders in which spastic gait is either the only feature or is a major syndrome feature. There are more than 70 genetic types of HSP. Neuropathological studies, albeit limited to only a few genetic types of HSP, have identified axon degeneration involving the distal ends of the corticospinal tracts and fasciculus gracilis fibers. In this review, the author highlights the clinical and genetic features of HSP. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Loss-of-function mutations in the ATP13A2/PARK9 gene cause complicated hereditary spastic paraplegia (SPG78)

PubMed Central

Estrada-Cuzcano, Alejandro; Martin, Shaun; Chamova, Teodora; Synofzik, Matthis; Timmann, Dagmar; Holemans, Tine; Andreeva, Albena; Reichbauer, Jennifer; De Rycke, Riet; Chang, Dae-In; van Veen, Sarah; Samuel, Jean; Schöls, Ludger; Pöppel, Thorsten; Mollerup Sørensen, Danny; Asselbergh, Bob; Klein, Christine; Zuchner, Stephan; Jordanova, Albena; Vangheluwe, Peter; Tournev, Ivailo; Schüle, Rebecca

2017-01-01

Abstract Hereditary spastic paraplegias are heterogeneous neurodegenerative disorders characterized by progressive spasticity of the lower limbs due to degeneration of the corticospinal motor neurons. In a Bulgarian family with three siblings affected by complicated hereditary spastic paraplegia, we performed whole exome sequencing and homozygosity mapping and identified a homozygous p.Thr512Ile (c.1535C > T) mutation in ATP13A2. Molecular defects in this gene have been causally associated with Kufor-Rakeb syndrome (#606693), an autosomal recessive form of juvenile-onset parkinsonism, and neuronal ceroid lipofuscinosis (#606693), a neurodegenerative disorder characterized by the intracellular accumulation of autofluorescent lipopigments. Further analysis of 795 index cases with hereditary spastic paraplegia and related disorders revealed two additional families carrying truncating biallelic mutations in ATP13A2. ATP13A2 is a lysosomal P5-type transport ATPase, the activity of which critically depends on catalytic autophosphorylation. Our biochemical and immunocytochemical experiments in COS-1 and HeLa cells and patient-derived fibroblasts demonstrated that the hereditary spastic paraplegia-associated mutations, similarly to the ones causing Kufor-Rakeb syndrome and neuronal ceroid lipofuscinosis, cause loss of ATP13A2 function due to transcript or protein instability and abnormal intracellular localization of the mutant proteins, ultimately impairing the lysosomal and mitochondrial function. Moreover, we provide the first biochemical evidence that disease-causing mutations can affect the catalytic autophosphorylation activity of ATP13A2. Our study adds complicated hereditary spastic paraplegia (SPG78) to the clinical continuum of ATP13A2-associated neurological disorders, which are commonly hallmarked by lysosomal and mitochondrial dysfunction. The disease presentation in our patients with hereditary spastic paraplegia was dominated by an adult-onset lower

Progressive Paraplegia from Spinal Cord Stimulator Lead Fibrotic Encapsulation: A Case Report.

PubMed

Benfield, Jon; Maknojia, Asif; Epstein, Franklin

2016-03-01

Ten years after placement of a spinal cord stimulator (SCS) and resolution of pain, this patient presented with progressive paraplegia, worsening thoracic radicular pain at the same dermatome level of the electrodes, and bowel and bladder incontinence. Computed tomographic myelogram confirmed thoracic spinal cord central canal stenosis at the level of electrodes. After removal of the fibrotic tissue and electrodes, the patient had resolution of his thoracic radicular pain and a return of his pre-SCS pain and minimal neurologic and functional return. To the authors' knowledge, no studies have been identified with thoracic SCS lead fibrosis in the United States causing permanent paraplegia. Only one other case has been reported in Madrid, Spain. Patients with SCS presenting with loss of pain relief, new-onset radicular or neuropathic pain in same dermatome(s) as SCS electrodes, worsening neuromuscular examination, or new bladder or bowel incontinence need to be evaluated for complications regarding SCS implantation causing spinal stenosis and subsequent cord compression to avoid permanent neurologic deficits.

Converging cellular themes for the hereditary spastic paraplegias.

PubMed

Blackstone, Craig

2018-05-10

Hereditary spastic paraplegias (HSPs) are neurologic disorders characterized by prominent lower-extremity spasticity, resulting from a length-dependent axonopathy of corticospinal upper motor neurons. They are among the most genetically-diverse neurologic disorders, with >80 distinct genetic loci and over 60 identified genes. Studies investigating the molecular pathogenesis underlying HSPs have emphasized the importance of converging cellular pathogenic themes in the most common forms of HSP, providing compelling targets for therapy. Most notably, these include organelle shaping and biogenesis as well as membrane and cargo trafficking. Published by Elsevier Ltd.

Autosomal recessive mutilating sensory neuropathy with spastic paraplegia maps to chromosome 5p15.31-14.1.

PubMed

Bouhouche, Ahmed; Benomar, Ali; Bouslam, Naima; Ouazzani, Reda; Chkili, Taïeb; Yahyaoui, Mohamed

2006-02-01

Autosomal recessive ulcero-mutilating neuropathy with spastic paraplegia is a very rare disease since only few cases were described up to date. We report in this study a consanguineous Moroccan family with four affected males with this syndrome. The disease onset was in early infancy, with spastic paraplegia and sensory loss leading to mutilating acropathy. Electrophysiological studies revealed a severe axonal sensory neuropathy, magnetic resonance imaging ruled out compression of spinal cord and biological investigations showed decreased levels of Apo B, total cholesterol and triglycerides. A genomewide search was conducted in this family and linkage was found to chromosome 5p. Analysis of recombination events and LOD score calculation map the responsible gene in a 25 cM genetic interval between markers D5S2054 and D5S648. A maximum LOD score value of 3.92 was obtained for all markers located in this candidate interval. This study establishes the presence of a locus for autosomal recessive mutilating sensory neuropathy with spastic paraplegia on chromosome 5p15.31-14.1.

Sudden-onset paraplegia during pregnancy caused by haemorrhage in a spinal cord haemangioblastoma: A case report.

PubMed

Gormeli, Cemile Ayse; Sarac, Kaya; Ozdemir, Zeynep Maras; Gormeli, Gokay; Kahraman, Aysegul Sagir; Kahraman, Bayram; Oztanir, Mustafa Namik; Karadag, Nese

2016-09-01

Spinal cord haemangioblastomas are rare central nervous systems tumours, and haemorrhage.It is an uncommon occurance. We report a 28-year-old pregnant patient who presented with paraplegia due to acute haemorrhage of a spinal haemangioblastoma. Magnetic resonance imaging showed extensive syrinx cavities, an intramedullary lesion at the T4-T5 spinal cord level e, and a subarachnoid haemorrhage. Digital subtraction angiography showed the feeding artery and dilated tortuous draining vein within the dural sac. The lesion was deemed a haemangioblastoma. The histopathological examination confirmed the diagnosis. Postoperatively, the paraplegia improved and the patient was able to walk within 2 weeks. Imaging is important for early diagnosis to prevent patients persistent neurological deficits.

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

PubMed

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

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.

Serial casting for neuromuscular flatfoot and vertical talus in an adolescent with hereditary spastic paraplegia.

PubMed

Sweet, Laurene A; OʼNeill, Lindsey M; Dobbs, Matthew B

2014-01-01

The purpose of this report is to explore assessment and serial casting intervention for painful rigid flatfoot deformities with vertical talus in an adolescent girl with hereditary spastic paraplegia who was nonambulatory. The participant's right foot underwent 2 phases of casting with correction first toward hindfoot inversion and then dorsiflexion. Because of a vertical talus, her left foot required an intermediate casting toward plantar flexion, inversion, and forefoot adduction prior to casting toward dorsiflexion. The patient improved despite the underlying progressive neuromuscular disorder. Pain ameliorated and she returned to supported standing and transfers. Spasticity decreased bilaterally and the flexibility of her foot deformities improved to allow orthotic fabrication in subtalar neutral. Results were maintained at 12 and 16 months. Individualized multiphase serial casting requires further investigation with patients such as those with hereditary spastic paraplegia.

[Risk factors for the development of rotator cuff tears in individuals with paraplegia : A cross-sectional study].

PubMed

Pepke, W; Brunner, M; Abel, R; Almansour, H; Gerner, H J; Hug, A; Zeifang, F; Kentar, Y; Bruckner, T; Akbar, M

2018-02-27

Shoulder pain and rotator cuff tears are highly prevalent among wheelchair dependent individuals with paraplegia. The purpose of this study was to identify potential risk factors associated with the development of rotator cuff tears in this population. A total of 217 wheelchair dependent individuals with paraplegia were included in this cross-sectional study (level of evidence III). The mean age of this population was 47.9 years and the mean duration of wheelchair dependence was 24.1 years. Each individual was asked to complete a questionnaire designed to identify risk factors for rotator cuff tears and underwent a standardized clinical examination with the documentation of the Constant-Murley shoulder outcome score and magnetic resonance imaging (MRI) of both shoulder joints. MRI analysis revealed at least one rotator cuff tear in 93 patients (43%). Multiple logistic regression analysis identified the following factors to be associated with the presence of rotator cuff tear: patient age, duration of spinal cord injury/wheelchair dependence, gender, and wheelchair athletic activity. Neither BMI nor the level of spinal cord injury was found to pose a risk factor in the population studied. With respect to patient age, the risk of developing a rotator cuff tear increased by 11% per annum. In terms of duration of spinal cord injury, the analysis revealed a 6% increased risk per year of wheelchair dependence (OR = 1.06). Females had a 2.6-fold higher risk of developing rotator cuff tears than males and wheelchair sport activity increased the risk 2.3-fold. There is a high prevalence of rotator cuff tears in wheel-chair dependent persons with paraplegia. Risk factors such as age, gender, duration of paraplegia, and wheel chair sport activity seem to play an important role in the development of rotator cuff tears.

A spastic paraplegia mouse model reveals REEP1-dependent ER shaping

PubMed Central

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.

2013-01-01

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

Effects of walkbot gait training on kinematics, kinetics, and clinical gait function in paraplegia and quadriplegia.

PubMed

Hwang, Jongseok; Shin, Yongil; Park, Ji-Ho; Cha, Young Joo; You, Joshua Sung H

2018-04-07

The robotic-assisted gait training (RAGT) system has gained recognition as an innovative, effective paradigm to improve functional ambulation and activities of daily living in spinal cord injury and stroke. However, the effects of the Walkbot robotic-assisted gait training system with a specialized hip-knee-ankle actuator have never been examined in the paraplegia and quadriplegia population. The aim of this study was to determine the long-term effects of Walkbot training on clinical for hips and knee stiffness in individuals with paraplegia or quadriplegia. Nine adults with subacute or chronic paraplegia resulting from spinal cord injury or quadriplegia resulting from cerebral vascular accident (CVA) and/or hypoxia underwent progressive conventional gait retraining combined with the Walkbot RAGT for 5 days/week over an average of 43 sessions for 8 weeks. Clinical outcomes were measured with the Functional Ambulation Category (FAC), Modified Rankin Scale (MRS), Korean version of the Modified Barthel Index (K-MBI), Modified Ashworth Scale (MAS). Kinetic and kinematic data were collected via a built-in Walkbot program. Wilcoxon signed-rank tests showed significant positive intervention effects on K-MBI, maximal hip flexion and extension, maximal knee flexion, active torque in the knee joint, resistive torque, and stiffness in the hip joint (P <  0.05). These findings suggest that the Walkbot RAGT was effective for improving knee and hip kinematics and the active knee joint moment while decreasing hip resistive force. These improvements were associated with functional recovery in gait, balance, mobility and daily activities. These findings suggest that the Walkbot RAGT was effective for improving knee and hip kinematics and the active knee joint moment while decreasing hip resistive force. This is the first clinical evidence for intensive, long-term effects of the Walkbot RAGT on active or resistive moments and stiffness associated with spasticity and functional

Quantitative and Functional Analyses of Spastin in the Nervous System: Implications for Hereditary Spastic Paraplegia

DTIC Science & Technology

2008-02-27

equivalent levels of expression of the spastin constructs, as assessed by fluorescence intensity of the Sp/AAA antibody staining. Microtu- bule levels...Errico A, Ballabio A, Rugarli EI (2002) Spastin, the protein mutated in au- tosomal dominant hereditary spastic paraplegia, is involved in microtu- bule

GPT2 mutations cause developmental encephalopathy with microcephaly and features of complicated hereditary spastic paraplegia.

PubMed

Hengel, H; Keimer, R; Deigendesch, W; Rieß, A; Marzouqa, H; Zaidan, J; Bauer, P; Schöls, L

2018-06-07

Various genetic defects can cause intellectual and developmental disabilities (IDD). Often IDD is a symptom of a more complex neurodevelopmental or neurodegenerative syndrome. Identifying syndromic patterns is substantive for diagnostics and for understanding the pathomechanism of a disease. Recessive GPT2 mutations have recently been associated with IDD in four families. Here, we report a novel recessive GPT2 stop mutation p.Gln24* causing a complex IDD phenotype in a homozygous state in five patients from two consanguineous Arab families. By compiling clinical information of these individuals and previously described GPT2 patients a recognizable neurodevelopmental and potentially neurodegenerative phenotype can be assigned consisting of intellectual disability, pyramidal tract affection with spastic paraplegia, microcephaly and frequently epilepsy. Due to the consistent presence of pyramidal tract affection in GPT2 patients, we further suggest that GPT2 mutations should be considered in cases with complex hereditary spastic paraplegia. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Hereditary spastic paraplegias: membrane traffic and the motor pathway

PubMed Central

Blackstone, Craig; O’Kane, Cahir J.; Reid, Evan

2017-01-01

Voluntary movement is a fundamental way in which animals respond to, and interact with, their environment. In mammals, the main CNS pathway controlling voluntary movement is the corticospinal tract, which encompasses connections between the cerebral motor cortex and the spinal cord. Hereditary spastic paraplegias (HSPs) are a group of genetic disorders that lead to a length-dependent, distal axonopathy of fibres of the corticospinal tract, causing lower limb spasticity and weakness. Recent work aimed at elucidating the molecular cell biology underlying the HSPs has revealed the importance of basic cellular processes — especially membrane trafficking and organelle morphogenesis and distribution — in axonal maintenance and degeneration. PMID:21139634

Hereditary spastic paraplegias: membrane traffic and the motor pathway.

PubMed

Blackstone, Craig; O'Kane, Cahir J; Reid, Evan

2011-01-01

Voluntary movement is a fundamental way in which animals respond to, and interact with, their environment. In mammals, the main CNS pathway controlling voluntary movement is the corticospinal tract, which encompasses connections between the cerebral motor cortex and the spinal cord. Hereditary spastic paraplegias (HSPs) are a group of genetic disorders that lead to a length-dependent, distal axonopathy of fibres of the corticospinal tract, causing lower limb spasticity and weakness. Recent work aimed at elucidating the molecular cell biology underlying the HSPs has revealed the importance of basic cellular processes — especially membrane trafficking and organelle morphogenesis and distribution— in axonal maintenance and degeneration.

REEP1 Mutation Spectrum and Genotype/Phenotype Correlation in Hereditary Spastic Paraplegia Type 31

ERIC Educational Resources Information Center

Beetz, Christian; Schule, Rebecca; Deconinck, Tine; Tran-Viet, Khanh-Nhat; Zhu, Hui; Kremer, Berry P. H.; Frints, Suzanna G. M.; van Zelst-Stams, Wendy A. G.; Byrne, Paula; Otto, Susanne; Nygren, Anders O. H.; Baets, Jonathan; Smets, Katrien; Ceulemans, Berten; Dan, Bernard; Nagan, Narasimhan; Kassubek, Jan; Klimpe, Sven; Klopstock, Thomas; Stolze, Henning; Smeets, Hubert J. M.; Schrander-Stumpel, Constance T. R. M.; Hutchinson, Michael; van de Warrenburg, Bart P.; Braastad, Corey; Deufel, Thomas; Pericak-Vance, Margaret; Schols, Ludger; de Jonghe, Peter; Zuchner, Stephan

2008-01-01

Mutations in the receptor expression enhancing protein 1 (REEP1) have recently been reported to cause autosomal dominant hereditary spastic paraplegia (HSP) type SPG31. In a large collaborative effort, we screened a sample of 535 unrelated HSP patients for "REEP1" mutations and copy number variations. We identified 13 novel and 2 known "REEP1"…

A large primary vaginal calculus in a woman with paraplegia.

PubMed

Avsar, Ayse Filiz; Keskin, Huseyin Levent; Catma, Tuba; Kaya, Basak; Sivaslioglu, Ahmet Akın

2013-01-01

The study aimed to report a primary vaginal stone, an extremely rare entity, without vesicovaginal fistula in a woman with disability. We describe the case of a large primary vaginal calculus in a 22-year-old woman with paraplegia, which, surprisingly, was not diagnosed until she was examined under general anesthesia during a preparation for laparoscopy for an adnexal mass. The stone had not been identified by physical examination with the patient in a recumbent position or by transabdominal ultrasonography and pelvic tomography during the preoperative preparation. Vaginoscopy was not performed because the vagina was completely filled with the mass. As a result of its size and hard consistency, a right-sided episiotomy was performed and a 136-g stone was removed using ring forceps. A vesicovaginal fistula was excluded. There was no evidence of a foreign body or other nidus on the cut section of the stone, and it was determined to be composed of 100% struvite (ammonium magnesium phosphate). Culture of urine obtained via catheter showed Escherichia coli. After the surgical removal of the calculus without complications, a program of intermittent catheterization was started. The follow-up period was uneventful, and the patient was symptom free at 6 months after the operation. We postulate that the calculus formed as a consequence of urinary contamination of the vagina in association with incontinence and prolonged maintenance in a recumbent posture. This report is important because it highlights that, although vaginal stones are very rare, their possibility should be considered in the differential diagnosis of individuals with long-term paraplegia.

Multigeneration family with dominant SPG30 hereditary spastic paraplegia.

PubMed

Roda, Ricardo H; Schindler, Alice B; Blackstone, Craig

2017-11-01

Autosomal recessive KIF1A missense mutations cause hereditary spastic paraplegia (HSP) type SPG30, while recessive truncations lead to sensory and autonomic neuropathy (HSN2C) and many de novo missense mutations are associated with cognitive impairment. Here, we describe family members across three generations with pure HSP. A heterozygous p.Ser69Leu KIF1A mutation segregates with those afflicted. The same variant was previously reported in a Finnish father and son with pure HSP as well as four members of a Sicilian kindred with more intrafamilial phenotypic variability. This further validates the pathogenicity of the p.Ser69Leu mutation and suggests that it may represent a mutation hot spot.

Spectrum of X-linked hydrocephalus (HSAS), MASA syndrome, and complicated spastic paraplegia (SPG1): Clincal review with six additional families

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schrander-Stumpel, C.; Hoeweler, C.; Jones, M.

X-linked hydrocephalus (HSAS) (MIM{sup *}307000), MASA syndrome (MIM {sup *}303350), and complicated spastic paraplegia (SPG1) (MIM {sup *}3129000) are closely related. Soon after delineation, SPG1 was incorporated into the spectrum of MASA syndrome. HSAS and MASA syndrome show great clinical overlap; DNA linkage analysis places the loci at Xq28. In an increasing number of families with MASA syndrome or HSAS, mutations in L1CAM, a gene located at Xq28, have been reported. In order to further delineate the clinical spectrum, we studied 6 families with male patients presenting with MASA syndrome, HSAS, or a mixed phenotype. We summarized data from previousmore » reports and compared them with our data. Clinical variability appears to be great, even within families. Problems in genetic counseling and prenatal diagnosis, the possible overlap with X-linked corpus callosum agenesis and FG syndrome, and the different forms of X-linked complicated spastic paraplegia are discussed. Since adducted thumbs and spastic paraplegia are found in 90% of the patients, the condition may be present in males with nonspecific mental retardation. We propose to abandon the designation MASA syndrome and use the term HSAS/MASA spectrum, incorporating SPG1. 79 refs., 6 figs., 2 tabs.« less

A comparison of 2 circuit exercise training techniques for eliciting matched metabolic responses in persons with paraplegia.

PubMed

Nash, Mark S; Jacobs, Patrick L; Woods, Jeffrey M; Clark, James E; Pray, Tanya A; Pumarejo, Alex E

2002-02-01

To test whether acute metabolic (VO(2)), chronotropic (heart rate), and perceptual (rating of perceived exertion; RPE) responses to exercise by persons with paraplegia differ when the exercise is on a multistation isoinertial exercise system (MultiGym) or on a customized system of Thera-Band resistance bands (ElasticGym). Within-subjects comparison of 2 treatments. Academic medical center. Sixteen men and 1 woman with complete paraplegia (T4-L1), as defined by the American Spinal Injury Association. A circuit resistance training (CRT) program for persons with paraplegia was adapted to both a MultiGym and a customized ElasticGym. Exercises used for training and testing used 6 resistance maneuvers at 50% of the 1-repetition maximum (1-RM), with interposed rapid arm spinning. Subjects were habituated to both conditions for 2 weeks before testing on randomized nonconsecutive days. VO(2) (L/min) was measured by portable spirometry, heart rate (beats/min) by a chest strap monitor, and RPE by the Borg Scale of Perceived Exertion (6-20). No significant effects of test condition on average VO(2) or heart rate were observed, with differences between conditions reflecting only .08L/min and 6.4 beats/min, respectively. Average RPE was significantly higher in testing under the ElasticGym condition (P < .05). CRT on a customized ElasticGym system elicited acute metabolic and chronotropic responses that did not differ from responses to exercise on a MultiGym, though RPE was greater with the ElasticGym. Copyright 2002 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

In Vivo Evidence for Lysosome Depletion and Impaired Autophagic Clearance in Hereditary Spastic Paraplegia Type SPG11

PubMed Central

Varga, Rita-Eva; Khundadze, Mukhran; Damme, Markus; Nietzsche, Sandor; Hoffmann, Birgit; Stauber, Tobias; Koch, Nicole; Hennings, J. Christopher; Franzka, Patricia; Huebner, Antje K.; Kessels, Michael M.; Biskup, Christoph; Jentsch, Thomas J.; Qualmann, Britta; Braulke, Thomas; Kurth, Ingo; Beetz, Christian; Hübner, Christian A.

2015-01-01

Hereditary spastic paraplegia (HSP) is characterized by a dying back degeneration of corticospinal axons which leads to progressive weakness and spasticity of the legs. SPG11 is the most common autosomal-recessive form of HSPs and is caused by mutations in SPG11. A recent in vitro study suggested that Spatacsin, the respective gene product, is needed for the recycling of lysosomes from autolysosomes, a process known as autophagic lysosome reformation. The relevance of this observation for hereditary spastic paraplegia, however, has remained unclear. Here, we report that disruption of Spatacsin in mice indeed causes hereditary spastic paraplegia-like phenotypes with loss of cortical neurons and Purkinje cells. Degenerating neurons accumulate autofluorescent material, which stains for the lysosomal protein Lamp1 and for p62, a marker of substrate destined to be degraded by autophagy, and hence appears to be related to autolysosomes. Supporting a more generalized defect of autophagy, levels of lipidated LC3 are increased in Spatacsin knockout mouse embryonic fibrobasts (MEFs). Though distinct parameters of lysosomal function like processing of cathepsin D and lysosomal pH are preserved, lysosome numbers are reduced in knockout MEFs and the recovery of lysosomes during sustained starvation impaired consistent with a defect of autophagic lysosome reformation. Because lysosomes are reduced in cortical neurons and Purkinje cells in vivo, we propose that the decreased number of lysosomes available for fusion with autophagosomes impairs autolysosomal clearance, results in the accumulation of undegraded material and finally causes death of particularly sensitive neurons like cortical motoneurons and Purkinje cells in knockout mice. PMID:26284655

In Vivo Evidence for Lysosome Depletion and Impaired Autophagic Clearance in Hereditary Spastic Paraplegia Type SPG11.

PubMed

Varga, Rita-Eva; Khundadze, Mukhran; Damme, Markus; Nietzsche, Sandor; Hoffmann, Birgit; Stauber, Tobias; Koch, Nicole; Hennings, J Christopher; Franzka, Patricia; Huebner, Antje K; Kessels, Michael M; Biskup, Christoph; Jentsch, Thomas J; Qualmann, Britta; Braulke, Thomas; Kurth, Ingo; Beetz, Christian; Hübner, Christian A

2015-08-01

Hereditary spastic paraplegia (HSP) is characterized by a dying back degeneration of corticospinal axons which leads to progressive weakness and spasticity of the legs. SPG11 is the most common autosomal-recessive form of HSPs and is caused by mutations in SPG11. A recent in vitro study suggested that Spatacsin, the respective gene product, is needed for the recycling of lysosomes from autolysosomes, a process known as autophagic lysosome reformation. The relevance of this observation for hereditary spastic paraplegia, however, has remained unclear. Here, we report that disruption of Spatacsin in mice indeed causes hereditary spastic paraplegia-like phenotypes with loss of cortical neurons and Purkinje cells. Degenerating neurons accumulate autofluorescent material, which stains for the lysosomal protein Lamp1 and for p62, a marker of substrate destined to be degraded by autophagy, and hence appears to be related to autolysosomes. Supporting a more generalized defect of autophagy, levels of lipidated LC3 are increased in Spatacsin knockout mouse embryonic fibrobasts (MEFs). Though distinct parameters of lysosomal function like processing of cathepsin D and lysosomal pH are preserved, lysosome numbers are reduced in knockout MEFs and the recovery of lysosomes during sustained starvation impaired consistent with a defect of autophagic lysosome reformation. Because lysosomes are reduced in cortical neurons and Purkinje cells in vivo, we propose that the decreased number of lysosomes available for fusion with autophagosomes impairs autolysosomal clearance, results in the accumulation of undegraded material and finally causes death of particularly sensitive neurons like cortical motoneurons and Purkinje cells in knockout mice.

Clinical and genetic study of hereditary spastic paraplegia in Canada.

PubMed

Chrestian, Nicolas; Dupré, Nicolas; Gan-Or, Ziv; Szuto, Anna; Chen, Shiyi; Venkitachalam, Anil; Brisson, Jean-Denis; Warman-Chardon, Jodi; Ahmed, Sohnee; Ashtiani, Setareh; MacDonald, Heather; Mohsin, Noreen; Mourabit-Amari, Karim; Provencher, Pierre; Boycott, Kym M; Stavropoulos, Dimitri J; Dion, Patrick A; Ray, Peter N; Suchowersky, Oksana; Rouleau, Guy A; Yoon, Grace

2017-02-01

To describe the clinical, genetic, and epidemiologic features of hereditary spastic paraplegia (HSP) in Canada and to determine which clinical, radiologic, and genetic factors determine functional outcomes for patients with HSP. We conducted a multicenter observational study of patients who met clinical criteria for the diagnosis of HSP in the provinces of Alberta, Ontario, and Quebec from 2012 to 2015. Characteristics of the participants were analyzed using descriptive statistics. The main outcome measure for a subset of the cohort (n = 48) was the Spastic Paraplegia Rating Scale. We also used the SPATAX-EUROSPA disability stage (disability score) to assess disability (n = 65). A total of 526 patients were identified with HSP across the country, and 150 patients had a confirmed genetic diagnosis. Mutations were identified in 15 different genes; the most common were SPAST (SPG4, 48%), ATL1 (SPG3A, 16%), SPG11 (8%), SPG7 (7%), and KIAA0196 (SPG8, 5%). The diagnosis of SPG4 was associated with older age at symptom onset ( p = 0.0017). SPG4 and SPG3A were less associated with learning disabilities compared to other subtypes of HSP, and SPG11 was strongly associated with progressive cognitive deficits (odds ratio 87.75, 95% confidence interval 14.04-548.24, p < 0.0001). SPG3A was associated with better functional outcomes compared to other HSP subtypes ( p = 0.04) on multivariate analysis. The strongest predictor of significant disability was abnormal brain MRI ( p = 0.014). The most important predictors of disability in our HSP cohort were SPG11 mutations and abnormal brain MRI. Accurate molecular characterization of well-phenotyped cohorts and international collaboration are essential to establish the natural history of these rare neurodegenerative disorders.

Overlapping molecular pathological themes link Charcot-Marie-Tooth neuropathies and hereditary spastic paraplegias.

PubMed

Timmerman, Vincent; Clowes, Virginia E; Reid, Evan

2013-08-01

In this review we focus on Charcot-Marie-Tooth (CMT) neuropathies and hereditary spastic paraplegias (HSPs). Although these diseases differ in whether they primarily affect the peripheral or central nervous system, both are genetically determined, progressive, long axonopathies that affect motor and sensory pathways. This commonality suggests that there might be similarities in the molecular pathology underlying these conditions, and here we compare the molecular genetics and cellular pathology of the two groups. Copyright © 2012 Elsevier Inc. All rights reserved.

Relationship Between Hand Contact Angle and Shoulder Loading During Manual Wheelchair Propulsion by Individuals with Paraplegia

PubMed Central

Mulroy, Sara J.; Ruparel, Puja; Hatchett, Patricia E.; Haubert, Lisa Lighthall; Eberly, Valerie J.; Gronley, JoAnne K.

2015-01-01

Background: Shoulder loading during manual wheelchair propulsion (WCP) contributes to the development of shoulder pain in individuals with spinal cord injury (SCI). Objective: To use regression analysis to investigate the relationships between the hand contact angle (location of the hand on the pushrim at initial contact and release during the push phase of the WCP cycle) with propulsion characteristics, pushrim forces, and shoulder kinetics during WCP in individuals with paraplegia. Methods: Biomechanical data were collected from 222 individuals (198 men and 24 women) with paraplegia from SCI during WCP on a stationary ergometer at a self-selected speed. The average age of participants was 34.7 years (±9.3), mean time since SCI was 9.3 years (±6.1), and average body weight was 74.4 kg (±15.9). The majority (n = 127; 56%) of participants had lower level paraplegia (T8 to L5) and 95 (42%) had high paraplegia (T2 to T7). Results: Increased push arc (mean = 75.3°) was associated with greater velocity (R = 0.384, P < .001) and cycle distance (R = 0.658, P < .001) and reduced cadence (R = -0.419, P < .001). Initial contact angle and hand release angles were equally associated with cycle distance and cadence, whereas a more anterior release angle was associated with greater velocity (R = 0.372, P < .001). When controlling for body weight, a more posterior initial contact angle was associated with greater posterior shoulder net joint force (R = 0.229, P = .001) and greater flexor net joint moment (R = 0.204, P = .002), whereas a more anterior hand release angle was significantly associated with increased vertical (R = 0.270, P < .001) and greater lateral (R = .293, P < .001) pushrim forces; greater shoulder net joint forces in all 3 planes — posterior (R = 0.164, P = .015), superior (R = 0.176, P = .009), and medial (R = 0.284, P < .001); and greater external rotator (R = 0.176, P = .009) and adductor (R = 0.259, P = .001) net joint moments. Conclusions: Current

Relationship Between Hand Contact Angle and Shoulder Loading During Manual Wheelchair Propulsion by Individuals with Paraplegia.

PubMed

Requejo, Philip Santos; Mulroy, Sara J; Ruparel, Puja; Hatchett, Patricia E; Haubert, Lisa Lighthall; Eberly, Valerie J; Gronley, JoAnne K

2015-01-01

Shoulder loading during manual wheelchair propulsion (WCP) contributes to the development of shoulder pain in individuals with spinal cord injury (SCI). To use regression analysis to investigate the relationships between the hand contact angle (location of the hand on the pushrim at initial contact and release during the push phase of the WCP cycle) with propulsion characteristics, pushrim forces, and shoulder kinetics during WCP in individuals with paraplegia. Biomechanical data were collected from 222 individuals (198 men and 24 women) with paraplegia from SCI during WCP on a stationary ergometer at a self-selected speed. The average age of participants was 34.7 years (±9.3), mean time since SCI was 9.3 years (±6.1), and average body weight was 74.4 kg (±15.9). The majority (n = 127; 56%) of participants had lower level paraplegia (T8 to L5) and 95 (42%) had high paraplegia (T2 to T7). Increased push arc (mean = 75.3°) was associated with greater velocity (R = 0.384, P < .001) and cycle distance (R = 0.658, P < .001) and reduced cadence (R = -0.419, P <.001). Initial contact angle and hand release angles were equally associated with cycle distance and cadence, whereas a more anterior release angle was associated with greater velocity (R = 0.372, P < .001). When controlling for body weight, a more posterior initial contact angle was associated with greater posterior shoulder net joint force (R = 0.229, P = .001) and greater flexor net joint moment (R = 0.204, P = .002), whereas a more anterior hand release angle was significantly associated with increased vertical (R = 0.270, P < .001) and greater lateral (R = .293, P < .001) pushrim forces; greater shoulder net joint forces in all 3 planes - posterior (R = 0.164, P = .015), superior (R = 0.176, P = .009), and medial (R = 0.284, P < .001); and greater external rotator (R = 0.176, P = .009) and adductor (R = 0.259, P = .001) net joint moments. Current clinical practice guidelines recommend using long, smooth

Spastic Paraplegia Type 7 Is Associated with Multiple Mitochondrial DNA Deletions

PubMed Central

Wedding, Iselin Marie; Koht, Jeanette; Tran, Gia Tuong; Misceo, Doriana; Selmer, Kaja Kristine; Holmgren, Asbjørn; Frengen, Eirik; Bindoff, Laurence; Tallaksen, Chantal M. E.; Tzoulis, Charalampos

2014-01-01

Spastic paraplegia 7 is an autosomal recessive disorder caused by mutations in the gene encoding paraplegin, a protein located at the inner mitochondrial membrane and involved in the processing of other mitochondrial proteins. The mechanism whereby paraplegin mutations cause disease is unknown. We studied two female and two male adult patients from two Norwegian families with a combination of progressive external ophthalmoplegia and spastic paraplegia. Sequencing of SPG7 revealed a novel missense mutation, c.2102A>C, p.H 701P, which was homozygous in one family and compound heterozygous in trans with a known pathogenic mutation c.1454_1462del in the other. Muscle was examined from an additional, unrelated adult female patient with a similar phenotype caused by a homozygous c.1047insC mutation in SPG7. Immunohistochemical studies in skeletal muscle showed mosaic deficiency predominantly affecting respiratory complex I, but also complexes III and IV. Molecular studies in single, microdissected fibres showed multiple mitochondrial DNA deletions segregating at high levels (38–97%) in respiratory deficient fibres. Our findings demonstrate for the first time that paraplegin mutations cause accumulation of mitochondrial DNA damage and multiple respiratory chain deficiencies. While paraplegin is not known to be directly associated with the mitochondrial nucleoid, it is known to process other mitochondrial proteins and it is possible therefore that paraplegin mutations lead to mitochondrial DNA deletions by impairing proteins involved in the homeostasis of the mitochondrial genome. These studies increase our understanding of the molecular pathogenesis of SPG7 mutations and suggest that SPG7 testing should be included in the diagnostic workup of autosomal recessive, progressive external ophthalmoplegia, especially if spasticity is present. PMID:24466038

Voluntary Ambulation by Upper Limb-Triggered HAL® in Patients with Complete Quadri/Paraplegia Due to Chronic Spinal Cord Injury.

PubMed

Shimizu, Yukiyo; Kadone, Hideki; Kubota, Shigeki; Suzuki, Kenji; Abe, Tetsuya; Ueno, Tomoyuki; Soma, Yuichiro; Sankai, Yoshiyuki; Hada, Yasushi; Yamazaki, Masashi

2017-01-01

Patients with complete paraplegia after spinal cord injury (SCI) are unable to stand or walk on their own. Standing exercise decreases the risk of decubitus ulcers, osteoporosis, and joint deformities in patients with SCI. Conventional gait training for complete paraplegia requires excessive upper limb usage for weight bearing and is difficult in cases of complete quadriplegia. The purpose of this study was to describe voluntary ambulation triggered by upper limb activity using the Hybrid Assistive Limb® (HAL) in patients with complete quadri/paraplegia after chronic SCI. Four patients (3 men, 1 woman) were enrolled in this study. The mean patient age ± standard deviation was 37.2 ± 17.8 (range, 20-67) years. Clinical evaluation before intervention revealed the following findings: case 1, neurological level C6, American Spinal Cord Injury Association impairment scale (AIS) grade B; case 2, T6, AIS A; case 3, T10 AIS A; and case 4, T11, AIS A. The HAL intervention consisted of 10 sessions. Each HAL session lasted 60-90 min. The HAL electrodes for hip and knee flexion-extension were placed on the anterior and posterior sides of the upper limbs contralaterally corresponding to each of the lower limbs. Surface electromyography (EMG) was used to evaluate muscle activity of the tensor fascia lata and quadriceps femoris (Quad) in synchronization with a Vicon motion capture system. The modified Ashworth scale (mAs) score was also evaluated before and after each session. All participants completed all 10 sessions. Cases 1, 2, and 3 demonstrated significant decreases in mAs score after the sessions compared to pre-session measurements. In all cases, EMG before the intervention showed no apparent activation in either Quad. However, gait phase dependent activity of the lower limb muscles was seen during voluntarily triggered ambulation driven by upper limb muscle activities. In cases 3 and 4, active contraction in both Quads was observed after intervention. These findings

Voluntary Ambulation by Upper Limb-Triggered HAL® in Patients with Complete Quadri/Paraplegia Due to Chronic Spinal Cord Injury

PubMed Central

Shimizu, Yukiyo; Kadone, Hideki; Kubota, Shigeki; Suzuki, Kenji; Abe, Tetsuya; Ueno, Tomoyuki; Soma, Yuichiro; Sankai, Yoshiyuki; Hada, Yasushi; Yamazaki, Masashi

2017-01-01

Patients with complete paraplegia after spinal cord injury (SCI) are unable to stand or walk on their own. Standing exercise decreases the risk of decubitus ulcers, osteoporosis, and joint deformities in patients with SCI. Conventional gait training for complete paraplegia requires excessive upper limb usage for weight bearing and is difficult in cases of complete quadriplegia. The purpose of this study was to describe voluntary ambulation triggered by upper limb activity using the Hybrid Assistive Limb® (HAL) in patients with complete quadri/paraplegia after chronic SCI. Four patients (3 men, 1 woman) were enrolled in this study. The mean patient age ± standard deviation was 37.2 ± 17.8 (range, 20–67) years. Clinical evaluation before intervention revealed the following findings: case 1, neurological level C6, American Spinal Cord Injury Association impairment scale (AIS) grade B; case 2, T6, AIS A; case 3, T10 AIS A; and case 4, T11, AIS A. The HAL intervention consisted of 10 sessions. Each HAL session lasted 60–90 min. The HAL electrodes for hip and knee flexion-extension were placed on the anterior and posterior sides of the upper limbs contralaterally corresponding to each of the lower limbs. Surface electromyography (EMG) was used to evaluate muscle activity of the tensor fascia lata and quadriceps femoris (Quad) in synchronization with a Vicon motion capture system. The modified Ashworth scale (mAs) score was also evaluated before and after each session. All participants completed all 10 sessions. Cases 1, 2, and 3 demonstrated significant decreases in mAs score after the sessions compared to pre-session measurements. In all cases, EMG before the intervention showed no apparent activation in either Quad. However, gait phase dependent activity of the lower limb muscles was seen during voluntarily triggered ambulation driven by upper limb muscle activities. In cases 3 and 4, active contraction in both Quads was observed after intervention. These

Active lower limb orthosis with one degree of freedom for people with paraplegia.

PubMed

Gloger, Michal; Obinata, Goro; Genda, Eiichi; Babjak, Jan; Pei, Yanling

2017-07-01

The main challenges of designing devices for paraplegic walking can be summarized into three groups, stability and comfort, high efficiency or low energy consumption, dimensions and weight. A new economical device for people with paraplegia which tackles all problems of the three groups is introduced in this paper. The main idea of this device is based on HALO mechanism. HALO is compact passive medial hip joint orthosis with contralateral hip and ankle linkage, which keeps the feet always parallel to the ground and assists swinging the leg. The medial hip joint is equipped with one actuator in the new design and the new orthosis is called @halo. Due to this update, we can achieve more stable and smoother walking patterns with decreased energy consumption of the users, yet maintain its compact and lightweight features. It is proven by the results from preliminary experiments with able-bodied subjects during which the same device with and without actuator was evaluated. Waddling and excessive vertical elevation of the center of gravity were decreased by 40% with significantly smaller standard deviations in case of the active orthosis. There was 52% less energy spent by the user wearing @halo which was calculated from the vertical excursion difference. There was measured 38.5% bigger impulse in crutches while using passive orthosis. The new @halo device is the first active orthosis for lower limbs with just one actuated degree of freedom for users with paraplegia.

Late-onset spastic paraplegia: Aberrant SPG11 transcripts generated by a novel splice site donor mutation.

PubMed

Kawarai, Toshitaka; Miyamoto, Ryosuke; Mori, Atsuko; Oki, Ryosuke; Tsukamoto-Miyashiro, Ai; Matsui, Naoko; Miyazaki, Yoshimichi; Orlacchio, Antonio; Izumi, Yuishin; Nishida, Yoshihiko; Kaji, Ryuji

2015-12-15

We identified a novel homozygous mutation in the splice site donor (SSD) of intron 30 (c.5866+1G>A) in consanguineous Japanese SPG11 siblings showing late-onset spastic paraplegia using the whole-exome sequencing. Phenotypic variability was observed, including age-at-onset, dysarthria and pes cavus. Coding DNA sequencing revealed that the mutation affected the recognition of the constitutive SSD of intron 30, splicing upstream onto a nearby cryptic SSD in exon 30. The use of constitutive splice sites of intron 29 was confirmed by sequencing. The mutant transcripts are mostly subject to degradation by the nonsense-mediated mRNA decay system. SPG11 transcripts, escaping from the nonsense-mediated mRNA decay pathway, would generate a truncated protein (p.Tyr1900Phefs5X) containing the first 1899 amino acids and followed by 4 aberrant amino acids. This study showed a successful clinical application of whole-exome sequencing in spastic paraplegia and demonstrated a further evidence of allelic heterogeneity in SPG11. The confirmation of aberrant transcript by splice site mutation is a prerequisite for a more precise molecular diagnosis. Copyright © 2015 Elsevier B.V. All rights reserved.

The effect of low-magnitude whole body vibration on bone density and microstructure in men and women with chronic motor complete paraplegia.

PubMed

Wuermser, Lisa-Ann; Beck, Lisa A; Lamb, Jeffry L; Atkinson, Elizabeth J; Amin, Shreyasee

2015-03-01

To examine the effect of low-magnitude whole body vibration on bone density and microstructure in women and men with chronic motor complete paraplegia. We studied nine subjects (four women and five men) with motor complete paraplegia of 2 years duration or more, age 20-50 years. Subjects were instructed to stand on a low-magnitude vibration plate within a standing frame for 20 minutes per day, 5 days a week, and for 6 months. Bone density at the proximal femur by dual-energy X-ray absorptiometry and bone microstructure at the distal tibia by high-resolution peripheral quantitative computed tomography were assessed at four timepoints over 12 months (baseline, at 3 months and 6 months while on intervention, and after 6 months off intervention). Standing on the low-magnitude vibration plate with a standing frame was well tolerated by participants. However, most subjects did not show an improvement in bone density or microstructure after 6 months of intervention, or any relevant changes 6 months following the discontinuation of the low-magnitude vibration. We were unable to identify an improvement in either bone density or microstructure following 6 months use of a low-magnitude vibration plate in women or men with chronic motor complete paraplegia. Longer duration of use may be necessary, or it is possible that this intervention is of limited benefit following chronic spinal cord injury.

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

PubMed

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

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. 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.

Lysosomal abnormalities in hereditary spastic paraplegia types SPG15 and SPG11

PubMed Central

Renvoisé, Benoît; 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

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

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

ERIC Educational Resources Information Center

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

2013-01-01

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…

Hemorrhagic thoracic schwannoma presenting with intradural hematoma and acute paraplegia after spinal manipulation therapy.

PubMed

Hdeib, Alia; Goodwin, C Rory; Sciubba, Daniel; Bydon, Ali; Wolinsky, Jean-Paul; Witham, Timothy; Gokaslan, Ziya L

2016-01-01

Hemorrhagic conversion of spinal schwannomas represents a rare occurrence; also rare is the development of a spinal intradural hematoma after spinal manipulation therapy. We report a unique presentation of paraplegia in a patient who underwent spinal manipulation therapy and was found to have a hemorrhagic thoracic schwannoma at time of surgery in the setting of anti-platelet therapy use. In patients with spinal schwannomas, tumor hemorrhage is a rare occasion, which can be considered in the setting of additive effects of spinal manipulation therapy and antiplatelet therapy.

Autosomal dominant spastic paraplegia with peripheral neuropathy maps to chr12q23-24.

PubMed

Schüle, R; Bonin, M; Dürr, A; Forlani, S; Sperfeld, A D; Klimpe, S; Mueller, J C; Seibel, A; van de Warrenburg, B P; Bauer, P; Schöls, L

2009-06-02

Hereditary spastic paraplegias (HSP) are genetically exceedingly heterogeneous. To date, 37 genetic loci for HSP have been described (SPG1-41), among them 16 loci for autosomal dominant disease. Notwithstanding, further genetic heterogeneity is to be expected in HSP, as various HSP families do not link to any of the known HSP loci. In this study, we aimed to map the disease locus in a German family segregating autosomal dominant complicated HSP. A genome-wide linkage analysis was performed using the GeneChip Mapping 10Kv2.0 Xba Array containing 10,204 SNP markers. Suggestive loci were further analyzed by mapping of microsatellite markers. One locus on chromosome 12q23-24, termed SPG36, was confirmed by high density microsatellite fine mapping with a significant LOD score of 3.2. SPG36 is flanked by markers D12S318 and D12S79. Linkage to SPG36 was excluded in >20 additional autosomal dominant HSP families. Candidate genes were selected and sequenced. No disease-causing mutations were identified in the coding regions of ATXN2, HSPB8, IFT81, Myo1H, UBE3B, and VPS29. SPG36 is complicated by a sensory and motor neuropathy; it is therefore the eighth autosomal dominant subtype of complicated HSP. We report mapping of a new locus for autosomal dominant hereditary spastic paraplegia (HSP) (SPG36) on chromosome 12q23-24 in a German family with autosomal dominant HSP complicated by peripheral neuropathy.

Mutations in the KIAA0196 Gene at the SPG8 Locus Cause Hereditary Spastic Paraplegia

PubMed Central

Valdmanis, Paul N.; Meijer, Inge A.; Reynolds, Annie; Lei, Adrienne; MacLeod, Patrick; Schlesinger, David; Zatz, Mayana; Reid, Evan; Dion, Patrick A.; Drapeau, Pierre; Rouleau, Guy A.

2007-01-01

Hereditary spastic paraplegia (HSP) is a progressive upper-motor neurodegenerative disease. The eighth HSP locus, SPG8, is on chromosome 8p24.13. The three families previously linked to the SPG8 locus present with relatively severe, pure spastic paraplegia. We have identified three mutations in the KIAA0196 gene in six families that map to the SPG8 locus. One mutation, V626F, segregated in three large North American families with European ancestry and in one British family. An L619F mutation was found in a Brazilian family. The third mutation, N471D, was identified in a smaller family of European origin and lies in a spectrin domain. None of these mutations were identified in 500 control individuals. Both the L619 and V626 residues are strictly conserved across species and likely have a notable effect on the structure of the protein product strumpellin. Rescue studies with human mRNA injected in zebrafish treated with morpholino oligonucleotides to knock down the endogenous protein showed that mutations at these two residues impaired the normal function of the KIAA0196 gene. However, the function of the 1,159-aa strumpellin protein is relatively unknown. The identification and characterization of the KIAA0196 gene will enable further insight into the pathogenesis of HSP. PMID:17160902

The effect of low-magnitude whole body vibration on bone density and microstructure in men and women with chronic motor complete paraplegia

PubMed Central

Wuermser, Lisa-Ann; Beck, Lisa A.; Lamb, Jeffry L.; Atkinson, Elizabeth J.; Amin, Shreyasee

2015-01-01

Objective To examine the effect of low-magnitude whole body vibration on bone density and microstructure in women and men with chronic motor complete paraplegia. Methods We studied nine subjects (four women and five men) with motor complete paraplegia of 2 years duration or more, age 20–50 years. Subjects were instructed to stand on a low-magnitude vibration plate within a standing frame for 20 minutes per day, 5 days a week, and for 6 months. Bone density at the proximal femur by dual-energy X-ray absorptiometry and bone microstructure at the distal tibia by high-resolution peripheral quantitative computed tomography were assessed at four timepoints over 12 months (baseline, at 3 months and 6 months while on intervention, and after 6 months off intervention). Results Standing on the low-magnitude vibration plate with a standing frame was well tolerated by participants. However, most subjects did not show an improvement in bone density or microstructure after 6 months of intervention, or any relevant changes 6 months following the discontinuation of the low-magnitude vibration. Conclusion We were unable to identify an improvement in either bone density or microstructure following 6 months use of a low-magnitude vibration plate in women or men with chronic motor complete paraplegia. Longer duration of use may be necessary, or it is possible that this intervention is of limited benefit following chronic spinal cord injury. PMID:24621040

Short-term effects of upper extremity circuit resistance training on muscle strength and functional independence in patients with paraplegia.

PubMed

Yildirim, Adem; Sürücü, Gülseren Dost; Karamercan, Ayşe; Gedik, Dilay Eken; Atci, Nermin; Dülgeroǧlu, Deniz; Özgirgin, Neşe

2016-11-21

A number of exercises to strengthen the upper extremities are recommended to increase functional independence and quality of life (QoL) in patients with paraplegia. Circuit resistance training (CRT) is a type of progressive resistive exercise performed repeatedly at fixed mechanical exercise stations. The aim of this study was to investigate the potential benefits of CRT for upper extremity muscle strength, functional independence, and QoL in patients with paraplegia. Twenty-six patients with paraplegia who were participating in a conventional rehabilitation program at a tertiary education and research hospital were enrolled in this study. The participants were randomly assigned to two groups. The exercise group participated in the CRT program, which consisted of repetitive exercises for the upper extremities performed at fixed mechanical stations 5 sessions per week for 6 weeks, in addition to conventional rehabilitation. Participants in the control group received only conventional rehabilitation over the same period. We compared the groups with respect to QoL, as well as isokinetic muscle test outcomes in the upper extremities, using the Functional Independence Measure (FIM) and Borg's scale. We observed significant increases in scores on the physical component of the FIM, Borg's scale, and QoL in both the exercise and control groups. Furthermore, the large majority of isokinetic values were significantly more improved in the exercise group compared to the control group. When post-treatment outcomes were compared between the groups, improvements in scores on the physical component of the FIM and in most isokinetic values were significantly greater in the exercise group. This study showed that CRT has positive effects on muscle strength in the upper extremities and the physical disability components of the FIM when added to conventional rehabilitation programs for paraplegic patients. However, we observed no significant improvement in QoL scores after adding CRT

A novel ABCD1 mutation detected by next generation sequencing in presumed hereditary spastic paraplegia: A 30-year diagnostic delay caused by misleading biochemical findings.

PubMed

Koutsis, Georgios; Lynch, David S; Tucci, Arianna; Houlden, Henry; Karadima, Georgia; Panas, Marios

2015-08-15

To present a Greek family in which 5 male and 2 female members developed progressive spastic paraplegia. Plasma very long chain fatty acids (VLCFA) were reportedly normal at first testing in an affected male and for over 30 years the presumed diagnosis was hereditary spastic paraplegia (HSP). Targeted next generation sequencing (NGS) was used as a further diagnostic tool. Targeted exome sequencing in the proband, followed by Sanger sequencing confirmation; mutation segregation testing in multiple family members and plasma VLCFA measurement in the proband. NGS of the proband revealed a novel frameshift mutation in ABCD1 (c.1174_1178del, p.Leu392Serfs*7), bringing an end to diagnostic uncertainty by establishing the diagnosis of adrenomyeloneuropathy (AMN), the myelopathic phenotype of X-linked adrenoleukodystrophy (ALD). The mutation segregated in all family members and the diagnosis of AMN/ALD was confirmed by plasma VLCFA measurement. Confounding factors that delayed the diagnosis are presented. This report highlights the diagnostic utility of NGS in patients with undiagnosed spastic paraplegia, establishing a molecular diagnosis of AMN, allowing proper genetic counseling and management, and overcoming the diagnostic delay that can be rarely caused by false negative VLCFA analysis. Copyright © 2015 Elsevier B.V. All rights reserved.

A Telerehabilitation Approach to Enhance Quality of Life Through Exercise Among Adults With Paraplegia: Study Protocol.

PubMed

Sweet, Shane Norman; Rocchi, Meredith; Arbour-Nicitopoulos, Kelly; Kairy, Dahlia; Fillion, Brigitte

2017-10-19

Despite compelling evidence linking physical activity and quality of life among adults with spinal cord injury (SCI), exercise participation rates are extremely low in this population. Unfortunately, a lack of behavioral exercise interventions, in particular theory-based randomized controlled trials (RCT), exists within the SCI literature. A pilot RCT is needed to first examine the feasibility to conduct such interventions and determine the appropriate effect size to inform future full-scale interventions. The overall goal of this pilot RCT is to test an 8-week innovative, video-based telerehabilitation intervention based on self-determination theory and aimed at enhancing the basic psychological needs, motivation, exercise participation, and quality of life‒related outcomes of adults with paraplegia. The objectives are to (1) determine if individuals in the intervention group have greater increases in their basic psychological needs and autonomous motivation and a decrease in controlled motivation compared to the control group, (2) determine whether the intervention group reports greater increases in exercise participation and quality of life‒related variables (eg, life satisfaction, participation in daily/social activities, depressive symptoms) compared to the control group, and (3) examine if adults with paraplegia who received the intervention report improved scores on psychosocial predictors of exercise (eg, action planning) and well-being (eg, positive affect) compared to the control group. We also aimed to examine the implementation characteristics of the intervention (eg, satisfaction with the technology, counselor's ability to foster the psychological needs). Adults with paraplegia (N=24) living in the community will be recruited. All participants will be invited to complete assessments of their psychological needs, motivation, exercise, and quality of life‒related variables at three time points (baseline, 6, and 10 weeks). Following the baseline

NIPA1 Gene Mutations Cause Autosomal Dominant Hereditary Spastic Paraplegia (SPG6)

PubMed Central

Rainier, Shirley; Chai, Jing-Hua; Tokarz, Debra; Nicholls, Robert D.; Fink, John K.

2003-01-01

The hereditary spastic paraplegias (HSPs) are genetically heterogeneous disorders characterized by progressive lower-extremity weakness and spasticity. The molecular pathogenesis is poorly understood. We report discovery of a dominant negative mutation in the NIPA1 gene in a kindred with autosomal dominant HSP (ADHSP), linked to chromosome 15q11-q13 (SPG6 locus); and precisely the same mutation in an unrelated kindred with ADHSP that was too small for meaningful linkage analysis. NIPA1 is highly expressed in neuronal tissues and encodes a putative membrane transporter or receptor. Identification of the NIPA1 function and ligand will aid an understanding of axonal neurodegeneration in HSP and may have important therapeutic implications. PMID:14508710

Car Transfer and Wheelchair Loading Techniques in Independent Drivers with Paraplegia

PubMed Central

Haubert, Lisa Lighthall; Mulroy, Sara J.; Hatchett, Patricia E.; Eberly, Valerie J.; Maneekobkunwong, Somboon; Gronley, Joanne K.; Requejo, Philip S.

2015-01-01

Car transfers and wheelchair (WC) loading are crucial for independent community participation in persons with complete paraplegia from spinal cord injury, but are complex, physically demanding, and known to provoke shoulder pain. This study aimed to describe techniques and factors influencing car transfer and WC loading for individuals with paraplegia driving their own vehicles and using their personal WCs. Sedans were the most common vehicle driven (59%). Just over half (52%) of drivers place their right leg only into the vehicle prior to transfer. Overall, the leading hand was most frequently placed on the driver’s seat (66%) prior to transfer and the trailing hand was most often place on the WC seat (48%). Vehicle height influenced leading hand placement but not leg placement such that drivers of higher profile vehicles were more likely to place their hand on the driver’s seat than those who drove sedans. Body lift time was negatively correlated with level of injury and age and positively correlated with vehicle height and shoulder abduction strength. Drivers who transferred with their leading hand on the steering wheel had significantly higher levels of shoulder pain than those who placed their hand on the driver’s seat or overhead. The majority of participants used both hands (62%) to load their WC frame, and overall, most loaded their frame into the back (62%) vs. the front seat. Sedan drivers were more likely to load their frame into the front seat than drivers of higher profile vehicles (53 vs. 17%). Average time to load the WC frame (10.7 s) was 20% of the total WC loading time and was not related to shoulder strength, frame weight, or demographic characteristics. Those who loaded their WC frame into the back seat had significantly weaker right shoulder internal rotators. Understanding car transfers and WC loading in independent drivers is crucial to prevent shoulder pain and injury and preserve community participation. PMID:26442253

Clinical indicators of paraplegia underplay universal spinal cord neuronal injury from transient aortic occlusion.

PubMed

Bell, Marshall T; Puskas, Ferenc; Bennett, Daine T; Cleveland, Joseph C; Herson, Paco S; Mares, Joshua M; Meng, Xainzhong; Weyant, Michael J; Fullerton, David A; Brett Reece, T

2015-08-27

Paraplegia following complex aortic intervention relies on crude evaluation of lower extremity strength such as whether the patient can lift their legs or flex the ankle. Little attention has been given to the possible long-term neurologic sequelae following these procedures in patients appearing functionally normal. We hypothesize that mice subjected to minimal ischemic time will have functional and histological changes despite the gross appearance of normal function. Male mice underwent 3 min of aortic occlusion (n=14) or sham surgery (n=4) via a median sternotomy. Neurologic function was graded by Basso Motor Score (BMS) preoperatively and at 24h intervals after reperfusion. Mice appearing functionally normal and sham mice were placed on a walking beam and recorded on high-definition, for single-frame motion analysis. After 96 hrs, spinal cords were removed for histological analysis. Following 3 min of ischemia, functional outcomes were split evenly with either mice displaying almost normal function n=7 or near complete paraplegia n=7. Additionally, single-frame motion analysis revealed significant changes in gait. Histologically, there was a significant stepwise reduction of neuronal viability, with even the normal function ischemic group demonstrating significant loss of neurons. Despite the appearance of normal function, temporary ischemia induced marked cyto-architectural changes and neuronal degeneration. Furthermore high-definition gait analysis revealed significant changes in gait and activity following thoracic aortic occlusion. These data suggest that all patients undergoing procedures, even with short ischemic times, may have spinal cord injury that is not evident clinically. Copyright © 2015 Elsevier B.V. All rights reserved.

Identification of two novel KIF5A mutations in hereditary spastic paraplegia associated with mild peripheral neuropathy.

PubMed

López, Eva; Casasnovas, Carlos; Giménez, Javier; Santamaría, Raúl; Terrazas, Jesús M; Volpini, Víctor

2015-11-15

Spastic paraplegia type 10 (SPG10) is a rare form of autosomal dominant hereditary spastic paraplegia (AD-HSP) due to mutations in KIF5A, a gene encoding the neuronal kinesin heavy-chain involved in axonal transport. KIF5A mutations have been associated with a wide clinical spectrum, ranging from pure HSP to isolated peripheral nerve involvement or complicated HSP phenotypes. Most KIF5A mutations are clustered in the motor domain of the protein that is necessary for microtubule interaction. Here we describe two Spanish families with an adult onset complicated AD-HSP in which neurological studies revealed a mild sensory neuropathy. Intention tremor was also present in both families. Molecular genetic analysis identified two novel mutations c.773 C>T and c.833 C>T in the KIF5A gene resulting in the P258L and P278L substitutions respectively. Both were located in the highly conserved kinesin motor domain of the protein which has previously been identified as a hot spot for KIF5A mutations. This study adds to the evidence associating the known occurrence of mild peripheral neuropathy in the adult onset SPG10 type of AD-HSP. Copyright © 2015 Elsevier B.V. All rights reserved.

Loss of Function of Glucocerebrosidase GBA2 Is Responsible for Motor Neuron Defects in Hereditary Spastic Paraplegia

PubMed Central

Martin, Elodie; Schüle, Rebecca; Smets, Katrien; Rastetter, Agnès; Boukhris, Amir; Loureiro, José L.; Gonzalez, Michael A.; Mundwiller, Emeline; Deconinck, Tine; Wessner, Marc; Jornea, Ludmila; Oteyza, Andrés Caballero; Durr, Alexandra; Martin, Jean-Jacques; Schöls, Ludger; Mhiri, Chokri; Lamari, Foudil; Züchner, Stephan; De Jonghe, Peter; Kabashi, Edor; Brice, Alexis; Stevanin, Giovanni

2013-01-01

Spastic paraplegia 46 refers to a locus mapped to chromosome 9 that accounts for a complicated autosomal-recessive form of hereditary spastic paraplegia (HSP). With next-generation sequencing in three independent families, we identified four different mutations in GBA2 (three truncating variants and one missense variant), which were found to cosegregate with the disease and were absent in controls. GBA2 encodes a microsomal nonlysosomal glucosylceramidase that catalyzes the conversion of glucosylceramide to free glucose and ceramide and the hydrolysis of bile acid 3-O-glucosides. The missense variant was also found at the homozygous state in a simplex subject in whom no residual glucocerebrosidase activity of GBA2 could be evidenced in blood cells, opening the way to a possible measurement of this enzyme activity in clinical practice. The overall phenotype was a complex HSP with mental impairment, cataract, and hypogonadism in males associated with various degrees of corpus callosum and cerebellar atrophy on brain imaging. Antisense morpholino oligonucleotides targeting the zebrafish GBA2 orthologous gene led to abnormal motor behavior and axonal shortening/branching of motoneurons that were rescued by the human wild-type mRNA but not by applying the same mRNA containing the missense mutation. This study highlights the role of ceramide metabolism in HSP pathology. PMID:23332916

Modeling of axonal endoplasmic reticulum network by spastic paraplegia proteins.

PubMed

Yalçın, Belgin; Zhao, Lu; Stofanko, Martin; O'Sullivan, Niamh C; Kang, Zi Han; Roost, Annika; Thomas, Matthew R; Zaessinger, Sophie; Blard, Olivier; Patto, Alex L; Sohail, Anood; Baena, Valentina; Terasaki, Mark; O'Kane, Cahir J

2017-07-25

Axons contain a smooth tubular endoplasmic reticulum (ER) network that is thought to be continuous with ER throughout the neuron; the mechanisms that form this axonal network are unknown. Mutations affecting reticulon or REEP proteins, with intramembrane hairpin domains that model ER membranes, cause an axon degenerative disease, hereditary spastic paraplegia (HSP). We show that Drosophila axons have a dynamic axonal ER network, which these proteins help to model. Loss of HSP hairpin proteins causes ER sheet expansion, partial loss of ER from distal motor axons, and occasional discontinuities in axonal ER. Ultrastructural analysis reveals an extensive ER network in axons, which shows larger and fewer tubules in larvae that lack reticulon and REEP proteins, consistent with loss of membrane curvature. Therefore HSP hairpin-containing proteins are required for shaping and continuity of axonal ER, thus suggesting roles for ER modeling in axon maintenance and function.

Paraplegia after myocardial revascularization. Case report.

PubMed

Nigro Neto, Caetano; Iza, Milton Patricio Chango; Tardelli, Maria Angela

2010-01-01

Developments in anesthesiology have improved safety indices. Several techniques and agents are used to control the hemodynamic response and minimize adverse effects triggered by surgical stimuli in patients undergoing cardiac procedures. This is a 70 years old male patient, 1.74 m, 75 kg, ASA III, and NYHA II. The patient had controlled dyslipedemia, type II diabetes mellitus, and hypertension; history of smoking, peripheral vascular disease, and myocardial infarction 20 years ago. The patient underwent revascularization with the left internal mammary artery and saphenous grafts with extracorporeal circulation with intermittent clamping of the aorta. During the first 24 hours in the ICU, the patient developed hemodynamic instability, sudden hypotension, and atrial fibrillation. Twenty-six hours after the end of the surgery, the patient was awake, hemodynamically stable, and with good respiratory dynamics, being extubated. The patient was talkative and oriented, but immobile and negative reflexes in the lower limbs. Neurological evaluation showed: cranial nerves without changes, no complaints of pain below the hips, preserved superficial and deep sensitivity, adequate distal perfusion without edema, and flaccid paraplegia below T8. The echocardiogram did not show any changes. CT scan of the lumbosacral spine was negative for compressive mass in the epidural space or adjacent to it. Anterior spinal artery syndrome should be considered in procedures with manipulation of the aorta. Prevention, especially in patients at risk, is necessary. Computed tomography, for the differential diagnosis, and MRI, to localize the lesion, are important.

The DALY, context and the determinants of the severity of disease: an exploratory comparison of paraplegia in Australia and Cameroon.

PubMed

Allotey, Pascale; Reidpath, Daniel; Kouamé, Aka; Cummins, Robert

2003-09-01

This paper summarises the findings of an empirical investigation of some of the technical and social assumptions on which the disability adjusted life year (DALY) is based. The objectives of the study were to examine the notion that the burden of disease is broadly similar without regard to country, environment, gender or socio-economic status and to develop detailed descriptions of the experiences of the burden of disease as they related to these contextual factors. The study was a multi-factorial exploratory study employing qualitative and quantitative techniques to obtain data on the effects of country (development), environment (urban versus rural), gender and socio-economic status on people with paraplegia. The data provided an extensive and detailed compilation of context rich descriptions of living with paraplegia. Striking features of the data were the differences between countries with respect to the impact of the health conditions on functioning and highlight a context in which paraplegia of like clinical severity can be fatal in one environment and not in another. While there has been some focus on the control of social determinants of disease, there has been little work on the social determinants of the severity of disease. The underlying assumptions of the DALY, which ignore context in the assessment of the burden of disease, risk exacerbating inequalities by undervaluing the burden of disease in less-developed countries. There is a need to continue to subject the development of indicators to rigorous debate to determine a balance between the assumption of a global "average social milieu" and the treatment of each individual as belonging to their own context in the assessment of population health in order for indicators to be meaningful cross-culturally.

Voluntary ambulation using voluntary upper limb muscle activity and Hybrid Assistive Limb® (HAL®) in a patient with complete paraplegia due to chronic spinal cord injury: A case report.

PubMed

Shimizu, Yukiyo; Kadone, Hideki; Kubota, Shigeki; Suzuki, Kenji; Saotome, Kousaku; Ueno, Tomoyuki; Abe, Tetsuya; Marushima, Aiki; Watanabe, Hiroki; Endo, Ayumu; Tsurumi, Kazue; Ishimoto, Ryu; Matsushita, Akira; Koda, Masao; Matsumura, Akira; Sankai, Yoshiyuki; Hada, Yasushi; Yamazaki, Masashi

2018-01-19

We sought to describe our experience with the Hybrid Assistive Limb® (HAL®) for active knee extension and voluntary ambulation with remaining muscle activity in a patient with complete paraplegia after spinal cord injury. A 30-year-old man with complete paraplegia used the HAL® for 1 month (10 sessions) using his remaining muscle activity, including hip flexor and upper limb activity. Electromyography was used to evaluate muscle activity of the gluteus maximus, tensor fascia lata, quadriceps femoris, and hamstring muscles in synchronization with the Vicon motion capture system. A HAL® session included a knee extension session with the hip flexor and voluntary gait with upper limb activity. After using the HAL® for one month, the patient's manual muscle hip flexor scores improved from 1/5 to 2/5 for the right and from 2/5 to 3/5 for the left knee, and from 0/5 to 1/5 for the extension of both knees. Knee extension sessions with HAL®, and hip flexor and upper-limb-triggered HAL® ambulation seem a safe and feasible option in a patient with complete paraplegia due to spinal cord injury.

Spastic paraplegia proteins spastizin and spatacsin mediate autophagic lysosome reformation

PubMed Central

Chang, Jaerak; Lee, Seongju; Blackstone, Craig

2014-01-01

Autophagy allows cells to adapt to changes in their environment by coordinating the degradation and recycling of cellular components and organelles to maintain homeostasis. Lysosomes are organelles critical for terminating autophagy via their fusion with mature autophagosomes to generate autolysosomes that degrade autophagic materials; therefore, maintenance of the lysosomal population is essential for autophagy-dependent cellular clearance. Here, we have demonstrated that the two most common autosomal recessive hereditary spastic paraplegia gene products, the SPG15 protein spastizin and the SPG11 protein spatacsin, are pivotal for autophagic lysosome reformation (ALR), a pathway that generates new lysosomes. Lysosomal targeting of spastizin required an intact FYVE domain, which binds phosphatidylinositol 3-phosphate. Loss of spastizin or spatacsin resulted in depletion of free lysosomes, which are competent to fuse with autophagosomes, and an accumulation of autolysosomes, reflecting a failure in ALR. Moreover, spastizin and spatacsin were essential components for the initiation of lysosomal tubulation. Together, these results link dysfunction of the autophagy/lysosomal biogenesis machinery to neurodegeneration. PMID:25365221

Modeling of axonal endoplasmic reticulum network by spastic paraplegia proteins

PubMed Central

Yalçın, Belgin; Zhao, Lu; Stofanko, Martin; O'Sullivan, Niamh C; Kang, Zi Han; Roost, Annika; Thomas, Matthew R; Zaessinger, Sophie; Blard, Olivier; Patto, Alex L; Sohail, Anood; Baena, Valentina; Terasaki, Mark; O'Kane, Cahir J

2017-01-01

Axons contain a smooth tubular endoplasmic reticulum (ER) network that is thought to be continuous with ER throughout the neuron; the mechanisms that form this axonal network are unknown. Mutations affecting reticulon or REEP proteins, with intramembrane hairpin domains that model ER membranes, cause an axon degenerative disease, hereditary spastic paraplegia (HSP). We show that Drosophila axons have a dynamic axonal ER network, which these proteins help to model. Loss of HSP hairpin proteins causes ER sheet expansion, partial loss of ER from distal motor axons, and occasional discontinuities in axonal ER. Ultrastructural analysis reveals an extensive ER network in axons, which shows larger and fewer tubules in larvae that lack reticulon and REEP proteins, consistent with loss of membrane curvature. Therefore HSP hairpin-containing proteins are required for shaping and continuity of axonal ER, thus suggesting roles for ER modeling in axon maintenance and function. DOI: http://dx.doi.org/10.7554/eLife.23882.001 PMID:28742022

Spastic paraplegia proteins spastizin and spatacsin mediate autophagic lysosome reformation.

PubMed

Chang, Jaerak; Lee, Seongju; Blackstone, Craig

2014-12-01

Autophagy allows cells to adapt to changes in their environment by coordinating the degradation and recycling of cellular components and organelles to maintain homeostasis. Lysosomes are organelles critical for terminating autophagy via their fusion with mature autophagosomes to generate autolysosomes that degrade autophagic materials; therefore, maintenance of the lysosomal population is essential for autophagy-dependent cellular clearance. Here, we have demonstrated that the two most common autosomal recessive hereditary spastic paraplegia gene products, the SPG15 protein spastizin and the SPG11 protein spatacsin, are pivotal for autophagic lysosome reformation (ALR), a pathway that generates new lysosomes. Lysosomal targeting of spastizin required an intact FYVE domain, which binds phosphatidylinositol 3-phosphate. Loss of spastizin or spatacsin resulted in depletion of free lysosomes, which are competent to fuse with autophagosomes, and an accumulation of autolysosomes, reflecting a failure in ALR. Moreover, spastizin and spatacsin were essential components for the initiation of lysosomal tubulation. Together, these results link dysfunction of the autophagy/lysosomal biogenesis machinery to neurodegeneration.

The influence of shoulder pain on functional limitation, perceived health, and depressive mood in patients with traumatic paraplegia

PubMed Central

Wang, Jia-Chi; Chan, Rai-Chi; Tsai, Yun-An; Huang, Wen-Cheng; Cheng, Henrich; Wu, Han-Lin

2015-01-01

Objective To assess whether functional activity, perceived health, and depressive symptoms differ between individuals with traumatic paraplegia with and without shoulder pain. Design Cross sectional and comparative investigation using the unified questionnaire. Setting Neural Regeneration and Repair Division unit of Taipei Veterans General Hospital in Taiwan. Participants Seventy-six patients with paraplegia (23 with and 53 without shoulder pain) who had experienced spinal cord injury at American Spinal Injury Association Impairment Scale T2 to T12 neurologic level (at least 6 months previously). Outcome measures Spinal Cord Independence Measure (SCIM), a single item from the Medical Outcomes Study 36-Item Short-Form Health Survey, and Patient Health Questionnaire-9 (PHQ-9) depression scale. Results Shoulder pain was prevalent in 30% patients. Patients with shoulder pain had significantly worse perceived health and greater depressive symptoms than those without. No significant difference was found in functional ability between groups. Greater shoulder pain intensity was related to higher depressive scores (r = 0.278, P = 0.017) and lower self-perceived health scores (r = −0.433, P < 0.001) but not SCIM scores (P = 0.342). Conclusion Although shoulder pain was unrelated to functional limitation, it was associated with lower perceived health and higher depressive mood levels. PMID:25296991

Using Rasch motor FIM individual growth curves to inform clinical decisions for persons with paraplegia.

PubMed

Pretz, C R; Kozlowski, A J; Charlifue, S; Chen, Y; Heinemann, A W

2014-09-01

A longitudinal retrospective study. To better understand individual-level temporal change in functional status for participants with paraplegia in the National Spinal Cord Injury Database (NSCID), as measured by Rasch Transformed Motor Functional Indepedence Measure (FIM) scores. Multicenter/Multistate longitudinal study across the United States. Non-linear random effects modeling, that is, individual growth curve analysis of retrospective data obtained from the National Institute on Disability and Rehabilitation Research (NIDRR) NSCID. We generated non-linear individual level trajectories of recovery for Rasch Transformed Motor FIM scores that rise rapidly from inpatient rehabilitation admission to a plateau. Trajectories are based on relationships between growth parameters and patient and injury factors: race, gender, level of education at admission, age at injury, neurological level at discharge, American Spinal Injury Association Impairment Scale (AIS) at discharge, days from injury to first system inpatient rehabilitation admission, rehabilitation length of stay, marital status and etiology. On the basis of study results, an interactive tool was developed to represent individual level longitudinal outcomes as trajectories based upon an individual's given baseline characteristics, that is, information supplied by the covariates and provides a robust description of temporal change for those with paraplegia within the NSCID. This methodology allows researchers and clinicians to generate and better understand patient-specific trajectories through the use of an automated interactive tool where a nearly countless number of longitudinal paths of recovery can be explored. Projected trajectories holds promise in facilitating planning for inpatient and outpatient services, which could positively impact long term outcomes.

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

PubMed

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

2014-05-09

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.

Loss of function of glucocerebrosidase GBA2 is responsible for motor neuron defects in hereditary spastic paraplegia.

PubMed

Martin, Elodie; Schüle, Rebecca; Smets, Katrien; Rastetter, Agnès; Boukhris, Amir; Loureiro, José L; Gonzalez, Michael A; Mundwiller, Emeline; Deconinck, Tine; Wessner, Marc; Jornea, Ludmila; Oteyza, Andrés Caballero; Durr, Alexandra; Martin, Jean-Jacques; Schöls, Ludger; Mhiri, Chokri; Lamari, Foudil; Züchner, Stephan; De Jonghe, Peter; Kabashi, Edor; Brice, Alexis; Stevanin, Giovanni

2013-02-07

Spastic paraplegia 46 refers to a locus mapped to chromosome 9 that accounts for a complicated autosomal-recessive form of hereditary spastic paraplegia (HSP). With next-generation sequencing in three independent families, we identified four different mutations in GBA2 (three truncating variants and one missense variant), which were found to cosegregate with the disease and were absent in controls. GBA2 encodes a microsomal nonlysosomal glucosylceramidase that catalyzes the conversion of glucosylceramide to free glucose and ceramide and the hydrolysis of bile acid 3-O-glucosides. The missense variant was also found at the homozygous state in a simplex subject in whom no residual glucocerebrosidase activity of GBA2 could be evidenced in blood cells, opening the way to a possible measurement of this enzyme activity in clinical practice. The overall phenotype was a complex HSP with mental impairment, cataract, and hypogonadism in males associated with various degrees of corpus callosum and cerebellar atrophy on brain imaging. Antisense morpholino oligonucleotides targeting the zebrafish GBA2 orthologous gene led to abnormal motor behavior and axonal shortening/branching of motoneurons that were rescued by the human wild-type mRNA but not by applying the same mRNA containing the missense mutation. This study highlights the role of ceramide metabolism in HSP pathology. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

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

PubMed

Fink, John K

2013-09-01

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 of diverse ethnic groups with prevalence estimates ranging from 1.2 to 9.6 per 100,000. 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. Postmortem 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 (1) axon transport (e.g. SPG30/KIF1A, SPG10/KIF5A and possibly SPG4/Spastin); (2) endoplasmic reticulum morphology (e.g. SPG3A/Atlastin, SPG4/Spastin, SPG12/reticulon 2, and SPG31/REEP1, all of which interact); (3) 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), "mutilating sensory neuropathy with spastic paraplegia" owing 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

Audio-visual distraction as an adjunct to standby anaesthesia in persons with paraplegia: a case series of five operations.

PubMed

Ayub, Khurram; Corrigan, Ruth A; Misra, Jyoti; Galitzine, Svetlana

2018-01-01

Persons with paraplegia present complex challenges to anaesthetists. Complications experienced by these patients can require major orthoplastic surgery such as excision of infected bone and soft tissue due to pressure sores and soft tissue reconstruction. Anaesthetic strategies deemed both safe and acceptable to this population are essential. We report a case series of five procedures in four patients with complete chronic spinal cord injury (CSCI) who underwent operations in lateral position under standby anaesthesia and audio-visual distraction (AVD) with minimal sedation. Patients' experience was formally assessed as part of the ongoing AVD service evaluation in our institution. All stated that they were not concerned in the operating theatre and felt "comfortable" or "very comfortable" throughout. All patients rated the experience as "better" than their previous experience with general anaesthesia and felt "very satisfied" with their anaesthetic. Importantly, all patients would recommend sedation with AVD to other patients. To our knowledge, this is the first report of AVD application as an adjunct to standby anaesthesia during major surgery in persons with paraplegia. Patient feedback was extremely positive, therefore it is likely that by making standby anaesthesia more acceptable to patients the use of AVD could reduce anaesthetic risk in this complex patient group.

Study on the Effectiveness of Virtual Reality Game-Based Training on Balance and Functional Performance in Individuals with Paraplegia

PubMed Central

Khurana, Meetika; Walia, Shefali

2017-01-01

Objective: To determine whether there is any difference between virtual reality game–based balance training and real-world task-specific balance training in improving sitting balance and functional performance in individuals with paraplegia. Methods: The study was a pre test–post test experimental design. There were 30 participants (28 males, 2 females) with traumatic spinal cord injury randomly assigned to 2 groups (group A and B). The levels of spinal injury of the participants were between T6 and T12. The virtual reality game–based balance training and real-world task-specific balance training were used as interventions in groups A and B, respectively. The total duration of the intervention was 4 weeks, with a frequency of 5 times a week; each training session lasted 45 minutes. The outcome measures were modified Functional Reach Test (mFRT), t-shirt test, and the self-care component of the Spinal Cord Independence Measure–III (SCIM-III). Results: There was a significant difference for time (p = .001) and Time × Group effect (p = .001) in mFRT scores, group effect (p = .05) in t-shirt test scores, and time effect (p = .001) in the self-care component of SCIM-III. Conclusions: Virtual reality game–based training is better in improving balance and functional performance in individuals with paraplegia than real-world task-specific balance training. PMID:29339902

Study on the Effectiveness of Virtual Reality Game-Based Training on Balance and Functional Performance in Individuals with Paraplegia.

PubMed

Khurana, Meetika; Walia, Shefali; Noohu, Majumi M

2017-01-01

Objective: To determine whether there is any difference between virtual reality game-based balance training and real-world task-specific balance training in improving sitting balance and functional performance in individuals with paraplegia. Methods: The study was a pre test-post test experimental design. There were 30 participants (28 males, 2 females) with traumatic spinal cord injury randomly assigned to 2 groups (group A and B). The levels of spinal injury of the participants were between T6 and T12. The virtual reality game-based balance training and real-world task-specific balance training were used as interventions in groups A and B, respectively. The total duration of the intervention was 4 weeks, with a frequency of 5 times a week; each training session lasted 45 minutes. The outcome measures were modified Functional Reach Test (mFRT), t-shirt test, and the self-care component of the Spinal Cord Independence Measure-III (SCIM-III). Results: There was a significant difference for time ( p = .001) and Time × Group effect ( p = .001) in mFRT scores, group effect ( p = .05) in t-shirt test scores, and time effect ( p = .001) in the self-care component of SCIM-III. Conclusions: Virtual reality game-based training is better in improving balance and functional performance in individuals with paraplegia than real-world task-specific balance training.

Weight bearing through lower limbs in a standing frame with and without arm support and low-magnitude whole-body vibration in men and women with complete motor paraplegia.

PubMed

Bernhardt, Kathie A; Beck, Lisa A; Lamb, Jeffry L; Kaufman, Kenton R; Amin, Shreyasee; Wuermser, Lisa-Ann

2012-04-01

The aim of the study was to determine the proportion of body weight borne through the lower limbs in persons with complete motor paraplegia using a standing frame, with and without the support of their arms. We also examined the effect of low-magnitude whole-body vibration on loads borne by the lower limbs. Vertical ground reaction forces (GRFs) were measured in 11 participants (six men and five women) with paraplegia of traumatic origin (injury level T3-T12) standing on a low-magnitude vibrating plate using a standing frame. GRFs were measured in four conditions: (1) no vibration with arms on standing frame tray, (2) no vibration with arms at side, (3) vibration with arms on tray, and (4) vibration with arms at side. GRF with arms on tray, without vibration, was 0.76 ± 0.07 body weight. With arms at the side, GRF increased to 0.85 ± 0.12 body weight. With vibration, mean GRF did not significantly differ from no-vibration conditions for either arm positions. Oscillation of GRF with vibration was significantly different from no-vibration conditions (P < 0.001) but similar in both arm positions. Men and women with paraplegia using a standing frame bear most of their weight through their lower limbs. Supporting their arms on the tray reduces the GRF by approximately 10% body weight. Low-magnitude vibration provided additional oscillation of the load-bearing forces and was proportionally similar regardless of arm position.

Weight Bearing through Lower Limbs in a Standing Frame with and without Arm Support and Low-Magnitude Whole Body Vibration in Men and Women with Complete Motor Paraplegia

PubMed Central

Bernhardt, Kathie A.; Beck, Lisa A.; Lamb, Jeffry L.; Kaufman, Kenton R.; Amin, Shreyasee; Wuermser, Lisa-Ann

2014-01-01

Objective To determine the proportion of body weight (BW) borne through the lower limbs in persons with complete, motor paraplegia using a standing frame, with and without support of their arms. We also examined the effect of low-magnitude whole body vibration on loads borne by the lower extremities. Design Vertical ground reaction forces (GRF) were measured in 11 participants (6 men and 5 women) with paraplegia of traumatic origin (injury level T3 to T12) standing on a low-magnitude vibrating plate using a standing frame. GRF were measured in four conditions: 1) no vibration with arms on standing frame tray; 2) no vibration with arms at side; 3) vibration with arms on tray; 4) vibration with arms at side. Results GRF with arms on tray, without vibration, was 0.76 ± 0.07 BW. With arms at the side, GRF increased to 0.85 ± 0.12 BW. With vibration, mean GRF did not significantly differ from no-vibration conditions for either arm positions. Oscillation of GRF with vibration was significantly different from no-vibration conditions (p<0.001) but similar in both arm positions. Conclusion Men and women with paraplegia using a standing frame bear the majority of their weight through their lower limbs. Supporting their arms on the tray reduces the GRF by ~10% BW. Low-magnitude vibration provided additional oscillation of the load-bearing forces and was proportionally similar regardless of arm position. PMID:22407161

Energy Cost of Lower Body Dressing, Pop-Over Transfers, and Manual Wheelchair Propulsion in People with Paraplegia Due to Motor-Complete Spinal Cord Injury

PubMed Central

McCormick, Zachary; Liem, Brian; Jacobs, Geneva; Hwang, Peter; Hornby, Thomas George; Rydberg, Leslie; Roth, Elliot J.

2015-01-01

Background: Energy required for able-bodied individuals to perform common activities is well documented, whereas energy associated with daily activities among people with spinal cord injury (SCI) is less understood. Objective: To determine energy expended during several basic physical tasks specific to individuals with paraplegia due to motor-complete SCI. Methods: Sixteen adults with motor-complete SCI below T2 level and duration of paraplegia greater than 3 months were included. Oxygen consumption (VO2), caloric expenditure, and heart rate were measured at rest and while participants performed lower body dressing (LBD), pop-over transfers (POTs), and manual wheelchair propulsion (MWP) at a self-selected pace. These data were used to calculate energy expenditure in standard metabolic equivalents (METs), as defined by 1 MET = 3.5 mL O2/kg/min, and in SCI METs using the conversion 1 SCI MET = 2.7 mL O2/kg/min. Results: VO2 at rest was 3.0 ± 0.9 mL O2/kg/min, which equated to 0.9 ± 0.3 standard METs and 1.1 ± 0.4 SCI METs in energy expenditure. LBD required 3.2 ± 0.7 METs and 4.1 ± 0.9 SCI METs; POTs required 3.4 ± 1.0 METs and 4.5 ± 1.3 SCI METs; and MWP required 2.4 ± 0.6 METs and 3.1 ± 0.7 SCI METs. Conclusion: Resting VO2 for adults with motor-complete paraplegia is 3.0 mL O2/kg/min, which is lower than standard resting VO2 in able-bodied individuals. Progressively more energy is required to perform MWP, LBD, and POTs, respectively. Use of the standard METs formula may underestimate the level of intensity an individual with SCI uses to perform physical activities. PMID:26364283

Effects of prandial challenge on triglyceridemia, glycemia, and pro-inflammatory activity in persons with chronic paraplegia

PubMed Central

Ellenbroek, Dennis; Kressler, Jochen; Cowan, Rachel E.; Burns, Patricia A.; Mendez, Armando J.; Nash, Mark S.

2015-01-01

Context/Objective Exaggerated postprandial lipemia has been reported after spinal cord injury (SCI). We examined metabolite and accompanying pro-inflammatory biomarker responses to repeat feeding of typical high-fat meals in individuals with chronic paraplegia. Design Descriptive trial. Methods Metabolites (triglycerides, glucose, and insulin) and inflammatory biomarkers (interleukin-6 and high-sensitivity C-reactive protein (hsCRP)) were measured under fasting conditions in 11 recreationally active individuals with chronic (>1 year) paraplegia. Subjects received high-fat meals at time point 0 and again at minute 240. Antecubital venous blood was obtained at time points −30 (fasting), 0 (first meal), 30, 60, 90, 120, 240 (second meal), 360, and 480 minutes. Correlations were examined among the study variables. Exploratory subgroup analysis was performed for subjects with levels of postprandial glucose greater than >200 mg/dl. Results Triglycerides showed a significant rise 4 hours after eating. Basal inflammatory markers were elevated, and did not undergo additional change during the testing. Additionally, subjects with excessive postprandial glucose responses showed higher hsCRP levels than those having typical glucose responses both for fasting (11.8 ± 6.5 vs. 2.9 ± 2.7 mg/l, P = 0.064) and postprandial (11.1 ± 4.9 vs. 3.7 ± 3.8 mg/l, P = 0.018) values. Conclusions Despite elevations in metabolic response markers, inflammatory markers did not change significantly after consumption of population-representative (i.e. hypercaloric) mixed-nutrient meals. Levels of fasting CRP in the high-risk range are consistent with other reports in persons with SCI and continue to pose concern for their cardiovascular disease risk. The possible association between postprandial metabolic responses and inflammatory states warrants further investigation to identify individual component risks for this secondary health hazard. PMID:24617559

Spastic paraplegia gene 7 in patients with spasticity and/or optic neuropathy

PubMed Central

Klebe, Stephan; Depienne, Christel; Gerber, Sylvie; Challe, Georges; Anheim, Mathieu; Charles, Perrine; Fedirko, Estelle; Lejeune, Elodie; Cottineau, Julien; Brusco, Alfredo; Dollfus, Hélène; Chinnery, Patrick F.; Mancini, Cecilia; Ferrer, Xavier; Sole, Guilhem; Destée, Alain; Mayer, Jean-Michel; Fontaine, Bertrand; de Seze, Jérôme; Clanet, Michel; Ollagnon, Elisabeth; Busson, Philippe; Cazeneuve, Cécile; Stevanin, Giovanni; Kaplan, Josseline; Rozet, Jean-Michel; Brice, Alexis

2012-01-01

Mutations in the spastic paraplegia 7 (SPG7) gene encoding paraplegin are responsible for autosomal recessive hereditary spasticity. We screened 135 unrelated index cases, selected in five different settings: SPG7-positive patients detected during SPG31 analysis using SPG31/SPG7 multiplex ligation-dependent probe amplification (n = 7); previously reported ambiguous SPG7 cases (n = 5); patients carefully selected on the basis of their phenotype (spasticity of the lower limbs with cerebellar signs and/or cerebellar atrophy on magnetic resonance imaging/computer tomography scan and/or optic neuropathy and without other signs) (n = 24); patients with hereditary spastic paraparesis referred consecutively from attending neurologists and the national reference centre in a diagnostic setting (n = 98); and the index case of a four-generation family with autosomal dominant optic neuropathy but no spasticity linked to the SPG7 locus. We identified two SPG7 mutations in 23/134 spastic patients, 21% of the patients selected according to phenotype but only 8% of those referred directly. Our results confirm the pathogenicity of Ala510Val, which was the most frequent mutation in our series (65%) and segregated at the homozygous state with spastic paraparesis in a large family with autosomal recessive inheritance. All SPG7-positive patients tested had optic neuropathy or abnormalities revealed by optical coherence tomography, indicating that abnormalities in optical coherence tomography could be a clinical biomarker for SPG7 testing. In addition, the presence of late-onset very slowly progressive spastic gait (median age 39 years, range 18–52 years) associated with cerebellar ataxia (39%) or cerebellar atrophy (47%) constitute, with abnormal optical coherence tomography, key features pointing towards SPG7-testing. Interestingly, three relatives of patients with heterozygote SPG7 mutations had cerebellar signs and atrophy, or peripheral neuropathy, but no spasticity of the lower

A novel mutation in KIF5A in a Malian family with spastic paraplegia and sensory loss.

PubMed

Guinto, Cheick O; Diarra, Salimata; Diallo, Salimata; Cissé, Lassana; Coulibaly, Thomas; Diallo, Seybou H; Taméga, Abdoulaye; Chen, Ke-Lian; Schindler, Alice B; Bagayoko, Koumba; Simaga, Assiatou; Blackstone, Craig; Fischbeck, Kenneth H; Landouré, Guida

2017-04-01

Hereditary spastic paraplegias (HSPs) are well-characterized disorders but rarely reported in Africa. We evaluated a Malian family in which three individuals had HSP and distal muscle atrophy and sensory loss. HSP panel testing identified a novel heterozygous missense mutation in KIF5A (c.1086G>C, p.Lys362Asn) that segregated with the disease (SPG10). Lys362 is highly conserved across species and Lys362Asn is predicted to be damaging. This study shows that HSPs are present in sub-Saharan Africa, although likely underdiagnosed. Increasing efficiency and decreasing costs of DNA sequencing will make it more feasible to diagnose HSPs in developing countries.

Conserved pharmacological rescue of hereditary spastic paraplegia-related phenotypes across model organisms

PubMed Central

Julien, Carl; Lissouba, Alexandra; Madabattula, Surya; Fardghassemi, Yasmin; Rosenfelt, Cory; Androschuk, Alaura; Strautman, Joel; Wong, Clement; Bysice, Andrew; O'sullivan, Julia; Rouleau, Guy A.; Drapeau, Pierre; Parker, J. Alex; Bolduc, François V.

2016-01-01

Hereditary spastic paraplegias (HSPs) are a group of neurodegenerative diseases causing progressive gait dysfunction. Over 50 genes have now been associated with HSP. Despite the recent explosion in genetic knowledge, HSP remains without pharmacological treatment. Loss-of-function mutation of the SPAST gene, also known as SPG4, is the most common cause of HSP in patients. SPAST is conserved across animal species and regulates microtubule dynamics. Recent studies have shown that it also modulates endoplasmic reticulum (ER) stress. Here, utilizing null SPAST homologues in C. elegans, Drosophila and zebrafish, we tested FDA-approved compounds known to modulate ER stress in order to ameliorate locomotor phenotypes associated with HSP. We found that locomotor defects found in all of our spastin models could be partially rescued by phenazine, methylene blue, N-acetyl-cysteine, guanabenz and salubrinal. In addition, we show that established biomarkers of ER stress levels correlated with improved locomotor activity upon treatment across model organisms. Our results provide insights into biomarkers and novel therapeutic avenues for HSP. PMID:26744324

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

PubMed Central

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

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

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

PubMed

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

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.

Physical therapists' perceptions about patients with incomplete post-traumatic paraplegia adherence to recommended home exercises: a qualitative study.

PubMed

Serpanou, Ismini; Sakellari, Evanthia; Psychogiou, Maria; Zyga, Sofia; Sapountzi-Krepia, Despina

2018-06-08

The overall purpose of physical therapy for patients with spinal cord injury is to improve health-related quality of life. However, poor adherence is a problem in physical therapy and may have negative impact on outcomes. To explore the physical therapists' perspectives about patients with incomplete post-traumatic paraplegia adherence to recommended home exercises. A qualitative content analysis was conducted. Data were collected in a convenience sample using semi-structured interviews. Thirteen registered physical therapists in Athens area participated in the study. Five categories emerged from the data: (1) reasons to recommend home exercise by the physical therapist; (2) obstacles to recommend home exercise by the physical therapist; (3) methods addressing these obstacles; (4) the family's role in the adherence to recommended home exercise; and (5) the impact of financial crisis in adherence to recommended home exercise. All participants found the recommended home exercises essential to rehabilitation and health maintenance, and they value their benefits. They also expressed the obstacles that need to be faced during rehabilitation process in order to promote adherence. Physical therapists should take into account the different obstacles that may prevent patients with incomplete post-traumatic paraplegia adherence to recommended home exercises. These involve the patients and their families, while, financial crisis has also an impact in adherence. In order to overcome these obstacles and increase adherence, communication with patient and family while taking into account the individual's needs, capacities, and resources are essential. Copyright © 2018 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

A non-randomised, controlled clinical trial of an innovative device for negative pressure wound therapy of pressure ulcers in traumatic paraplegia patients.

PubMed

Srivastava, Rajeshwar N; Dwivedi, Mukesh K; Bhagat, Amit K; Raj, Saloni; Agarwal, Rajiv; Chandra, Abhijit

2016-06-01

The conventional methods of treatment of pressure ulcers (PUs) by serial debridement and daily dressings require prolonged hospitalisation, associated with considerable morbidity. There is, however, recent evidence to suggest that negative pressure wound therapy (NPWT) accelerates healing. The commercial devices for NPWT are costly, cumbersome, and electricity dependent. We compared PU wound healing in traumatic paraplegia patients by conventional dressing and by an innovative negative pressure device (NPD). In this prospective, non-randomised trial, 48 traumatic paraplegia patients with PUs of stages 3 and 4 were recruited. Patients were divided into two groups: group A (n = 24) received NPWT with our NPD, and group B (n = 24) received conventional methods of dressing. All patients were followed up for 9 weeks. At week 9, all patients on NPD showed a statistically significant improvement in PU healing in terms of slough clearance, granulation tissue formation, wound discharge and culture. A significant reduction in wound size and ulcer depth was observed in NPD as compared with conventional methods at all follow-up time points (P = 0·0001). NPWT by the innovative device heals PUs at a significantly higher rate than conventional treatment. The device is safe, easy to apply and cost-effective. © 2014 The Authors. International Wound Journal © 2014 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

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

PubMed Central

Féron, 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

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

Anterior spinal artery syndrome. Paraplegia following segmental ischaemic injury to the spinal cord after oesophagectomy.

PubMed

Djurberg, H; Haddad, M

1995-04-01

A case of unexpected paraplegia after oesophageal resection under general anaesthesia combined with epidural analgesia and intra-operative intercostal block is described. Patients with compromised cardiovascular and respiratory function undergoing thoracic or major abdominal surgery can benefit significantly intra-operatively from a combination of general anaesthesia and regional analgesia. The continued use of regional analgesia into the postoperative period offers even more advantages. General anaesthesia administered before regional analgesia may, however, mask complications related to the regional technique and delay the instigation of corrective measures. The blood supply to the anterior part of the spinal cord, through the artery of Adamkiewicz, may be impaired intra-operatively leading to neurological sequelae known as the anterior spinal artery syndrome, characterised by loss of motor function with intact or partially intact sensory function. Patients at risk of developing the syndrome can be identified pre-operatively.

Impaired Mitochondrial Dynamics Underlie Axonal Defects in Hereditary Spastic Paraplegias.

PubMed

Denton, Kyle; Mou, Yongchao; Xu, Chong-Chong; Shah, Dhruvi; Chang, Jaerak; Blackstone, Craig; Li, Xue-Jun

2018-05-02

Mechanisms by which long corticospinal axons degenerate in hereditary spastic paraplegia (HSP) are largely unknown. Here, we have generated induced pluripotent stem cells (iPSCs) from patients with two autosomal recessive forms of HSP, SPG15 and SPG48, which are caused by mutations in the ZFYVE26 and AP5Z1 genes encoding proteins in the same complex, the spastizin and AP5Z1 proteins, respectively. In patient iPSC-derived telencephalic glutamatergic and midbrain dopaminergic neurons, neurite number, length and branching are significantly reduced, recapitulating disease-specific phenotypes. We analyzed mitochondrial morphology and noted a significant reduction in both mitochondrial length and their densities within axons of these HSP neurons. Mitochondrial membrane potential was also decreased, confirming functional mitochondrial defects. Notably, mdivi-1, an inhibitor of the mitochondrial fission GTPase DRP1, rescues mitochondrial morphology defects and suppresses the impairment in neurite outgrowth and late-onset apoptosis in HSP neurons. Furthermore, knockdown of these HSP genes causes similar axonal defects, also mitigated by treatment with mdivi-1. Finally, neurite outgrowth defects in SPG15 and SPG48 cortical neurons can be rescued by knocking down DRP1 directly. Thus, abnormal mitochondrial morphology caused by an imbalance of mitochondrial fission and fusion underlies specific axonal defects and serves as a potential therapeutic target for SPG15 and SPG48.

Cannabinoids for spasticity due to multiple sclerosis or paraplegia: A systematic review and meta-analysis of randomized clinical trials.

PubMed

da Rovare, Victoria P; Magalhães, Gabriel P A; Jardini, Guilherme D A; Beraldo, Matheus L; Gameiro, Mariel O; Agarwal, Arnav; Luvizutto, Gustavo José; Paula-Ramos, Lucas; Camargo, Samira Esteves Afonso; de Oliveira, Luciane Dias; Bazan, Rodrigo; El Dib, Regina

2017-10-01

Spasticity remains highly prevalent in patients with spinal cord injury and multiple sclerosis. To summarize the effects of cannabinoids compared with usual care, placebo for spasticity due to multiple sclerosis (MS) or paraplegia. Searches of MEDLINE, EMBASE, CENTRAL and LILACS to March 2017 were performed to identify randomized controlled trials. The primary outcomes were spasticity and spasm frequency. The criteria were any patient with MS and spasticity affecting upper or lower limbs or both, and that had a confirmed diagnosis of MS based on validated criteria, or however defined by the authors of the included studies. 16 trials including 2597 patients were eligible. Moderate-certainty evidence suggested a non-statistically significant decrease in spasticity (standardized mean difference (SMD) 0.36 [confidential interval (CI) 95% -0.17 to 0.88; p=0.18; I2=88%]), and spasm frequency (SMD 0.04 [CI 95% -0.15 to 0.22]). There was an increase in adverse events such as dizziness (risk ratio (RR) 3.45 [CI 95% 2.71-4.4; p=0.20; I2=23%]), somnolence (RR 2.9 [CI 95% 1.98-4.23; p=0.77; I2=0%]), and nausea (RR 2.25 [CI 95% 1.62-3.13; p=0.83; I2=0%]). There is moderate certainty evidence regarding the impact of cannabinoids in spasticity (average 0.36 more spasticity; 0.17 fewer to 0.88 more) due to multiple sclerosis or paraplegia, and in adverse events such as dizziness (419 more dizziness/1000 over 19 weeks), somnolence (127 more somnolence/1000 over 19 weeks), and nausea (125 more somnolence/1000 over 19 weeks). Copyright © 2017. Published by Elsevier Ltd.

Complicated spastic paraplegia in patients with AP5Z1 mutations (SPG48)

PubMed Central

Hirst, Jennifer; Madeo, Marianna; Smets, Katrien; Edgar, James R.; Schols, Ludger; Li, Jun; Yarrow, Anna; Deconinck, Tine; Baets, Jonathan; Van Aken, Elisabeth; De Bleecker, Jan; Datiles, Manuel B.; Roda, Ricardo H.; Liepert, Joachim; Züchner, Stephan; Mariotti, Caterina; De Jonghe, Peter; Blackstone, Craig

2016-01-01

Objective: Biallelic mutations in the AP5Z1 gene encoding the AP-5 ζ subunit have been described in a small number of patients with hereditary spastic paraplegia (HSP) (SPG48); we sought to define genotype–phenotype correlations in patients with homozygous or compound heterozygous sequence variants predicted to be deleterious. Methods: We performed clinical, radiologic, and pathologic studies in 6 patients with biallelic mutations in AP5Z1. Results: In 4 of the 6 patients, there was complete loss of AP-5 ζ protein. Clinical features encompassed not only prominent spastic paraparesis but also sensory and motor neuropathy, ataxia, dystonia, myoclonus, and parkinsonism. Skin fibroblasts from affected patients tested positive for periodic acid Schiff and autofluorescent storage material, while electron microscopic analysis demonstrated lamellar storage material consistent with abnormal storage of lysosomal material. Conclusions: Our findings expand the spectrum of AP5Z1-associated neurodegenerative disorders and point to clinical and pathophysiologic overlap between autosomal recessive forms of HSP and lysosomal storage disorders. PMID:27606357

Evaluation of a training program for persons with SCI paraplegia using the Parastep 1 ambulation system: part 4. Effect on physical self-concept and depression.

PubMed

Guest, R S; Klose, K J; Needham-Shropshire, B M; Jacobs, P L

1997-08-01

To determine whether persons with spinal cord injury (SCI) paraplegia who participated in an electrical stimulation walking program experienced changes in measures of physical self-concept and depression. Before-after trial. Human SCI applied research laboratory. Volunteer sample of 12 men and 3 women with SCI paraplegia, mean age 28.75 +/- 6.6yrs and mean duration of injury 3.8 +/- 3.2yrs. Thirty-two FNS ambulation training sessions using a commercially available system (Parastep 1). The hybrid system consists of a microprocessor-controlled stimulator and a modified walking frame with finger-operated switches that permit the user to control the stimulation parameters and activate the stepping. The Tennessee Self-Concept Scale (TSCS) and the Beck Depression Inventory (BDI) were administered before and after training. Only the Physical Self subscale of the TSCS was analyzed. After training, individual interviews were performed to assess participants' subjective reactions to the training program. A repeated measures analysis of variance indicated that desired directional and statistically significant changes occurred on the Physical Self subscale of the TSCS (F(1,14) = 8.54, p < .011) and on the BDI (F(1,14) = 5.42, p < .035). Subsequent to the ambulation training program there were statistically significant increases in physical self-concept scores and decreases in depression scores.

A muscle-driven approach to restore stepping with an exoskeleton for individuals with paraplegia.

PubMed

Chang, Sarah R; Nandor, Mark J; Li, Lu; Kobetic, Rudi; Foglyano, Kevin M; Schnellenberger, John R; Audu, Musa L; Pinault, Gilles; Quinn, Roger D; Triolo, Ronald J

2017-05-30

Functional neuromuscular stimulation, lower limb orthosis, powered lower limb exoskeleton, and hybrid neuroprosthesis (HNP) technologies can restore stepping in individuals with paraplegia due to spinal cord injury (SCI). However, a self-contained muscle-driven controllable exoskeleton approach based on an implanted neural stimulator to restore walking has not been previously demonstrated, which could potentially result in system use outside the laboratory and viable for long term use or clinical testing. In this work, we designed and evaluated an untethered muscle-driven controllable exoskeleton to restore stepping in three individuals with paralysis from SCI. The self-contained HNP combined neural stimulation to activate the paralyzed muscles and generate joint torques for limb movements with a controllable lower limb exoskeleton to stabilize and support the user. An onboard controller processed exoskeleton sensor signals, determined appropriate exoskeletal constraints and stimulation commands for a finite state machine (FSM), and transmitted data over Bluetooth to an off-board computer for real-time monitoring and data recording. The FSM coordinated stimulation and exoskeletal constraints to enable functions, selected with a wireless finger switch user interface, for standing up, standing, stepping, or sitting down. In the stepping function, the FSM used a sensor-based gait event detector to determine transitions between gait phases of double stance, early swing, late swing, and weight acceptance. The HNP restored stepping in three individuals with motor complete paralysis due to SCI. The controller appropriately coordinated stimulation and exoskeletal constraints using the sensor-based FSM for subjects with different stimulation systems. The average range of motion at hip and knee joints during walking were 8.5°-20.8° and 14.0°-43.6°, respectively. Walking speeds varied from 0.03 to 0.06 m/s, and cadences from 10 to 20 steps/min. A self-contained muscle

Shoulder Strength and Physical Activity Predictors of Shoulder Pain in People With Paraplegia From Spinal Injury: Prospective Cohort Study

PubMed Central

Hatchett, Patricia; Eberly, Valerie J.; Lighthall Haubert, Lisa; Conners, Sandy; Requejo, Philip S.

2015-01-01

Background Shoulder joint pain is a frequent secondary complaint for people following spinal cord injury (SCI). Objective The purpose of this study was to determine predictors of shoulder joint pain in people with paraplegia. Methods/Design A 3-year longitudinal study was conducted. Participants were people with paraplegia who used a manual wheelchair for at least 50% of their mobility and were asymptomatic for shoulder pain at study entry. Participants were classified as having developed shoulder pain if they experienced an increase of ≥10 points on the Wheelchair User's Shoulder Pain Index in the 3-year follow-up period. Measurements of maximal isometric shoulder torques were collected at study entry (baseline), 18 months, and 3 years. Daily activity was measured using a wheelchair odometer, and self-reported daily transfer and raise frequency data were collected by telephone every 6 weeks. Results Two hundred twenty-three participants were enrolled in the study; 39.8% developed shoulder pain over the 3-year follow-up period. Demographic variables and higher activity levels were not associated with shoulder pain onset. Baseline maximal isometric torque (normalized by body weight) in all shoulder muscle groups was 10% to 15% lower in participants who developed shoulder pain compared with those who remained pain-free. Lower shoulder adduction torque was a significant predictor of shoulder pain development (log-likelihood test=11.38), but the model explained only 7.5% of shoulder pain onset and consequently is of limited clinical utility. Limitations Time since SCI varied widely among participants, and transfer and raise activity was measured by participant recall. Conclusions Participants who developed shoulder pain had decreased muscle strength, particularly in the shoulder adductors, and lower levels of physical activity prior to the onset of shoulder pain. Neither factor was a strong predictor of shoulder pain onset. PMID:25721123

Late onset Pott's paraplegia in patients with upper thoracic sharp kyphosis.

PubMed

Zhang, Zhengfeng

2012-02-01

The purpose of this study was to determine the clinical results of patients with late onset upper thoracic sharp Pott's kyphosis and to predict the prognosis for Pott's paraplegics. The study included five patients who developed late onset upper thoracic (T1-T4) sharp Pott's kyphosis/kyphoscoliosis within a period from 19 to 37 years after the active disease was healed. The kyphosis angle of the patients ranged from 95° to 105°. Among them, three patients suffered onset of paraplegia ranging from 26 to 31 years after spinal tuberculosis was healed. The duration of neurological deterioration before surgery ranged from four to five years. All patients underwent decompressive surgery with an attempt to correct the curve. Neurological status was evaluated using the ASIA impairment classification and the motor score. Postoperatively, kyphosis correction ranged from 20° to 30° for five patients. No neurological deficit occurred in two patients with normal neurological status. Two ASIA D paraplegics remained unchanged after surgery and no further improvement was found at one year follow-up. One ASIA C paralysis deteriorated neurologically to ASIA B after surgery and persisted to a deterioration of neurological status at one year follow-up. Upper thoracic sharp Pott's kyphosis and neurological deficits occur progressively. The neurological recovery or improvement of Pott's paraplegics with upper thoracic severe sharp kyphosis results in poor prognosis after decompressive surgery.

Differential changes in the spinal segmental locomotor output in Hereditary Spastic Paraplegia.

PubMed

Martino, G; Ivanenko, Y; Serrao, M; Ranavolo, A; Draicchio, F; Rinaldi, M; Casali, C; Lacquaniti, F

2018-03-01

A comprehensive treatment of Hereditary Spastic Paraplegia (HSP) should consider the specific pathophysiological changes in the spinal cord. Here we reported a detailed characterization of the spinal motoneuronal output in HSP during locomotion. We recorded kinematics and electromyographic (EMG) activity of 12 leg muscles in 29 patients with pure forms of HSP and compared them with 30 controls while walking at matched speeds. We assessed the spinal locomotor output by evaluating EMG patterns and by mapping them onto the rostrocaudal location of the spinal motoneuron pools. The activity profiles of muscles innervated from the sacral segments were significantly wider in patients. Similarly, spinal maps revealed a tendency for spreading the main loci of activation, involving initially the sacral segments and, at more severe stages, the lumbar segments. The degeneration of the corticospinal tract in HSP is associated with a widening of spinal locomotor output spreading from caudal to rostral segments. The findings highlight pathophysiologically relevant differential changes in the spinal locomotor output in HSP related to the specific innervation of muscles in the spinal cord, and might be helpful for developing future therapeutic strategies and identifying physiological markers of the disease. Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Recessive loss-of-function mutations in AP4S1 cause mild fever-sensitive seizures, developmental delay and spastic paraplegia through loss of AP-4 complex assembly

PubMed Central

Hardies, Katia; May, Patrick; Djémié, Tania; Tarta-Arsene, Oana; Deconinck, Tine; Craiu, Dana; Helbig, Ingo; Suls, Arvid; Balling, Rudy; Weckhuysen, Sarah; De Jonghe, Peter; Hirst, Jennifer; Afawi, Zaid; Barisic, Nina; Baulac, Stéphanie; Caglayan, Hande; Depienne, Christel; De Kovel, Carolien G.F.; Dimova, Petia; Guerrero-López, Rosa; Guerrini, Renzo; Hjalgrim, Helle; Hoffman-Zacharska, Dorota; Jahn, Johanna; Klein, Karl Martin; Koeleman, Bobby P.C.; Leguern, Eric; Lehesjoki, Anna-Elina; Lemke, Johannes; Lerche, Holger; Marini, Carla; Muhle, Hiltrud; Rosenow, Felix; Serratosa, Jose M.; Møller, Rikke S.; Stephani, Ulrich; Striano, Pasquale; Talvik, Tiina; Von Spiczak, Sarah; Weber, Yvonne; Zara, Federico

2015-01-01

We report two siblings with infantile onset seizures, severe developmental delay and spastic paraplegia, in whom whole-genome sequencing revealed compound heterozygous mutations in the AP4S1 gene, encoding the σ subunit of the adaptor protein complex 4 (AP-4). The effect of the predicted loss-of-function variants (p.Gln46Profs*9 and p.Arg97*) was further investigated in a patient's fibroblast cell line. We show that the premature stop mutations in AP4S1 result in a reduction of all AP-4 subunits and loss of AP-4 complex assembly. Recruitment of the AP-4 accessory protein tepsin, to the membrane was also abolished. In retrospect, the clinical phenotype in the family is consistent with previous reports of the AP-4 deficiency syndrome. Our study reports the second family with mutations in AP4S1 and describes the first two patients with loss of AP4S1 and seizures. We further discuss seizure phenotypes in reported patients, highlighting that seizures are part of the clinical manifestation of the AP-4 deficiency syndrome. We also hypothesize that endosomal trafficking is a common theme between heritable spastic paraplegia and some inherited epilepsies. PMID:25552650

SPG3A-linked hereditary spastic paraplegia associated with cerebral glucose hypometabolism.

PubMed

Terada, Tatsuhiro; Kono, Satoshi; Ouchi, Yasuomi; Yoshida, Kenichi; Hamaya, Yasushi; Kanaoka, Shigeru; Miyajima, Hiroaki

2013-04-01

SPG3A-linked hereditary spastic paraplegia (HSP) is a rare autosomal dominant motor disorder caused by a mutation in the SPG3A gene, and is characterized by progressive motor weakness and spasticity in the lower limbs, without any other neurological abnormalities. SPG3A-linked HSP caused by a R239C mutation has been reported to present a pure phenotype confined to impairment of the corticospinal tract. However, there is still a debate about the etiology of this motor deficit with regard to whether it is peripheral or central. We herein report two patients who were heterozygous for a R239C mutation in the SPG3A gene. Two middle-aged Japanese sisters had been suffering from a pure phenotype of HSP since their childhood. Both patients had a significant decrease in glucose metabolism in the frontal cortex medially and dorsolaterally in a [(18)F]-fluorodeoxyglucose (FDG) positron emission photography (PET) study and low scores on the Frontal Assessment Battery. A real-time PCR analysis in normal subjects showed the frontal cortex to be the major location where SPG3A mRNA is expressed. The present finding that the frontal glucose hypometabolism was associated with frontal cognitive impairment indicates that widespread neuropathology associated with mutations in the SPG3A gene may be present more centrally than previously assumed.

Infusion of autologous adipose tissue derived neuronal differentiated mesenchymal stem cells and hematopoietic stem cells in post-traumatic paraplegia offers a viable therapeutic approach.

PubMed

Thakkar, Umang G; Vanikar, Aruna V; Trivedi, Hargovind L; Shah, Veena R; Dave, Shruti D; Dixit, Satyajit B; Tiwari, Bharat B; Shah, Harda H

2016-01-01

Spinal cord injury (SCI) is not likely to recover by current therapeutic modalities. Stem cell (SC) therapy (SCT) has promising results in regenerative medicine. We present our experience of co-infusion of autologous adipose tissue derived mesenchymal SC differentiated neuronal cells (N-Ad-MSC) and hematopoietic SCs (HSCs) in a set of patients with posttraumatic paraplegia. Ten patients with posttraumatic paraplegia of mean age 3.42 years were volunteered for SCT. Their mean age was 28 years, and they had variable associated complications. They were subjected to adipose tissue resection for in vitro generation of N-Ad-MSC and bone marrow aspiration for generation of HSC. Generated SCs were infused into the cerebrospinal fluid (CSF) below injury site in all patients. Total mean quantum of SC infused was 4.04 ml with a mean nucleated cell count of 4.5 × 10(4)/μL and mean CD34+ of 0.35%, CD45-/90+ and CD45-/73+ of 41.4%, and 10.04%, respectively. All of them expressed transcription factors beta-3 tubulin and glial fibrillary acid protein. No untoward effect of SCT was noted. Variable and sustained improvement in Hauser's index and American Spinal Injury Association score was noted in all patients over a mean follow-up of 2.95 years. Mean injury duration was 3.42 years against the period of approximately 1-year required for natural recovery, suggesting a positive role of SCs. Co-infusion of N-Ad-MSC and HSC in CSF is safe and viable therapeutic approach for SCIs.

Mutation in the epsilon subunit of the cytosolic chaperonin-containing t-complex peptide-1 (Cct5) gene causes autosomal recessive mutilating sensory neuropathy with spastic paraplegia.

PubMed

Bouhouche, A; Benomar, A; Bouslam, N; Chkili, T; Yahyaoui, M

2006-05-01

Mutilating sensory neuropathy with spastic paraplegia is a very rare disease with both autosomal dominant and recessive modes of inheritance. We previously mapped the locus of the autosomal recessive form to a 25 cM interval between markers D5S2048 and D5S648 on chromosome 5p. In this candidate interval, the Cct5 gene encoding the epsilon subunit of the cytosolic chaperonin-containing t-complex peptide-1 (CCT) was the most obvious candidate gene since mutation in the Cct4 gene encoding the CCT delta subunit has been reported to be associated with autosomal recessive mutilating sensory neuropathy in mutilated foot (mf) rat mutant. A consanguineous Moroccan family with four patients displaying mutilating sensory neuropathy associated with spastic paraplegia was investigated. To identify the disease causing gene, the 11 coding exons of the Cct5 gene were screened for mutations by direct sequencing in all family members including the four patients, parents, and six at risk relatives. Sequence analysis of the Cct5 gene revealed a missense A492G mutation in exon 4 that results in the substitution of a highly conserved histidine for arginine amino acid 147. Interestingly, R147 was absent in 384 control matched chromosomes tested. This is the first disease causing mutation that has been identified in the human CCT subunit genes; the mf rat mutant could serve as an animal model for studying these chaperonopathies.

Clinical phenotype of hereditary spastic paraplegia due to KIF1C gene mutations across life span.

PubMed

Yücel-Yılmaz, Didem; Yücesan, Emrah; Yalnızoğlu, Dilek; Oğuz, Kader Karlı; Sağıroğlu, Mahmut Şamil; Özbek, Uğur; Serdaroğlu, Esra; Bilgiç, Başar; Erdem, Sevim; İşeri, Sibel Aylin Uğur; Hanağası, Haşmet; Gürvit, Hakan; Özgül, Rıza Köksal; Dursun, Ali

2018-06-01

Hereditary spastic paraplegias (HSPs) are a group of genetic disorders resulting in pyramidal tract impairment, predominantly in lower limbs. KIF1C gene has recently been identified as one of the genetic causes of HSP and associated with pure or complicated HSP. We present three patients with complicated HSP from two unrelated families, who had early onset progressive cerebellar signs and developed pyramidal tract signs during follow-up. Whole exome sequencing in these patients followed by segregation analysis identified novel truncating KIF1C mutations (c.463C> T; p.R155 ∗ and c.2478delA; p.Ala828Argfs ∗ 13). Neuroimaging findings showed cerebral and upper cervical spinal atrophy, bilateral symmetrical pyramidal tract involvement, and focal cerebral white matter lesions. Patients with KIF1C mutations may present with cerebellar signs and pyramidal findings may emerge later, therefore complicated HSP should be considered in the differential diagnosis of unidentified cases with cerebellar dysfunction. Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

[When a patient falls (asleep) and can't get up: conversion disorder - paraplegia following general anesthesia].

PubMed

Mason, Chawla LaToya

This case report describes the rare occurrence of paraplegia caused by conversion disorder in a woman who received general anesthesia for breast surgery. A 46-year-old healthy woman received general anesthesia for excision of a left breast fibroepithelial lesion. In the post-anesthesia care unit, she reported bilateral loss of both sensation and motor function below the knees. Physical signs and symptoms did not correlate with any anatomical or neurological patterns; imaging revealed no abnormalities. Psychiatric consultation was performed wherein familial stressor circumstances were identified, leading to diagnosis and management of conversion disorder. Conversion disorder is characterized by alteration of physical function due to expression of an underlying psychological ailment. Its diagnosis requires thorough evaluation including appropriate workup to exclude organic causes. The meshing together of anesthesiology and psychiatry - as demonstrated by this case report - offers an opportunity to highlight important information pertaining to the definition, diagnosis, and management of conversion disorder as it may be encountered in the postanesthesia recovery period. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Hereditary Spastic Paraplegia-Linked REEP1 Modulates ER-Mitochondria Contacts

PubMed Central

Lim, Youngshin; Cho, Il-Taeg; Schoel, Leah J.; Cho, Ginam; Golden, Jeffrey A.

2015-01-01

Objective Mutations in receptor expression enhancing protein 1 (REEP1) are associated with hereditary spastic paraplegias (HSPs). Although axonal degeneration is thought to be a predominant feature in HSP, the role of REEP1 mutations in degeneration is largely unknown. Previous studies have implicated a role for REEP1 in the ER, whereas others localized REEP1 with mitochondria. We sought to resolve the cellular localization of REEP1 and to further elucidate the pathobiology underlying REEP1 mutations in patients. Methods A combination of cellular imaging and biochemical approaches was used to refine the cellular localization of REEP1. Next, Reep1 mutations associated with HSP were functionally tested in neuritic growth and degeneration assays using mouse cortical culture. Finally, a novel assay was developed and used with wild type and mutant Reep1s to measure the interactions between the ER and mitochondria. Results We found that REEP1 is present at the ER-mitochondria interface, and it contains subdomains for mitochondrial as well as ER localization. Knockdown of Reep1 and the expression of pathological Reep1 mutations resulted in neuritic growth defects and degeneration. Finally, using our novel split-RLuc8 assay, we show REEP1 facilitates ER-mitochondria interactions, a function diminished by disease-associated mutations. Interpretation Our data potentially reconcile the current conflicting reports regarding REEP1 being either an ER or a mitochondrial protein. Furthermore, our results connect, for the first time, the disrupted ER-mitochondria interactions to a failure in maintaining health of long axons in HSPs. Finally, the split-RLuc8 assay offers a new tool to identify potential drugs for multiple neurodegenerative diseases with ER-mitochondria interaction defects. PMID:26201691

Unusual Presentation of a Primary Ewing's Sarcoma of the Spine with Paraplegia: A Case Report.

PubMed

Kannan, Karthik Kailash; Sundarapandian, Rajkumar Jayachandran; Surulivel, Vignesh Jayabalan

2015-03-01

Ewing's sarcoma is a primary malignancy of the bone affecting individuals in the second decade of life. Primary sarcomas of the spine are rare and the occurrence of Primary Ewing's sarcoma in the spine is very rare. Ewing's sarcoma occurring in the spine is divided into two types, Ewing's sarcoma of sacral spine which are very aggressive with poor prognosis and Ewing's sarcoma of the non sacral spine which is an extremely rare occurrence. Patient may present with neurological deficit when the tumour extends into the spinal canal causing spinal cord compression. Magnetic resonance imaging (MRI) is very sensitive in diagnosing the tumour and defining the extent of the tumour. Here we report an 18-year-old boy who presented with back pain and complete paraplegia of two months duration. The MRI gave a differential diagnosis of infective pathology due to the fluid collection in the paraspinal region, followed by primary malignancy as the second diagnosis. Patient underwent posterior spinal decompression and stabilization, and intaoperatively there was significant collection of pus whose culture showed no growth. The histopathology and immunohistochemistry studies confirmed the diagnosis of Ewing's sarcoma and patient was started on combination chemotherapy and radiotherapy.

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

PubMed Central

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

2012-01-01

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

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

PubMed

Dubé, M P; Mlodzienski, M A; Kibar, Z; Farlow, M R; Ebers, G; Harper, P; Kolodny, E H; Rouleau, G A; Figlewicz, D A

1997-03-01

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.

Autosomal dominant hereditary spastic paraplegia with axonal sensory motor polyneuropathy maps to chromosome 21q 22.3.

PubMed

Peddareddygari, Leema Reddy; Hanna, Philip A; Igo, Robert P; Luo, Yuqun A; Won, Sungho; Hirano, Michio; Grewal, Raji P

2016-01-01

Hereditary spastic paraplegia (HSP) are a genetically and clinically heterogeneous group of disorders. At present, 19 autosomal dominant loci for HSP have been mapped. We ascertained an American family of European descent segregating an autosomal dominant HSP associated with peripheral neuropathy. A genome wide scan was performed with 410 microsatellite repeat marker (Weber lab screening set 16) and following linkage and haplotype analysis, fine mapping was performed. Established genes or loci for HSP were excluded by direct sequencing or haplotype analysis. All established loci for HSP were excluded. Fine mapping suggested a locus on chromosome 21q22.3 flanked by markers D21S1411 and D21S1446 with a maximum logarithm of odds score of 2.05 and was supported by haplotype analysis. A number of candidate genes in this region were analyzed and no disease-producing mutations were detected. We present the clinical and genetic analysis of an American family with autosomal dominant HSP with axonal sensory motor polyneuropathy mapping to a novel locus on chromosome 21q22.3 designated SPG56.

Burn from car seat heater in a man with paraplegia: case report

PubMed Central

Benjamin, Cheryl; Gittler, Michelle; Lee, Ray

2011-01-01

Objective/background Heated car seats are a common feature in newer automobiles. They are increasingly being recognized as potential hazards as there have been multiple reports of significant burns to its users. The potential for harm is considerably increased in those with impaired sensation with the possibility of a devastating injury. Methods Case report and literature review. Results A 26-year-old male with a T8 ASIA A paraplegia presented to the outpatient clinic for management of a hip burn. Two weeks prior to his visit he was driving a 2004 Jeep Cherokee for approximately 30 minutes. He was unaware that the driver's side seat warmer was set on high. He denied that his seat belt was in direct contact with the skin of his right hip. He presented to an acute care hospital that evening with a hip burn where he was prescribed silver sulfadiazine cream and instructed to apply it until his scheduled follow-up clinic visit. In clinic, the hip wound was unstageable with approximately 95% eschar. A dressing of bismuth tribromophenate in petrolatum was applied to the wound and he was instructed to change the dressing daily. This was later changed to an antimicrobial alginate dressing. The ulcer eventually healed. Conclusions This case illustrates the significant risk of car seat heaters in individuals with spinal cord injuries or neurological impairment who have decreased sensation. Additionally, it highlights an atypical area of potential for burn. Furthermore, it emphasizes the need for a heightened awareness for this unique and dangerous situation. PMID:21756574

Kinematic gait deficits at the trunk and pelvis: characteristic features in children with hereditary spastic paraplegia.

PubMed

Adair, Brooke; Rodda, Jillian; McGinley, Jennifer L; Graham, H Kerr; Morris, Meg E

2016-08-01

To examine the kinematic gait deviations at the trunk and pelvis of children with hereditary spastic paraplegia (HSP). This exploratory observational study quantified gait kinematics for the trunk and pelvis from 11 children with HSP (7 males, 4 females) using the Gait Profile Score and Gait Variable Scores (GVS), and compared the kinematics to data from children with typical development using a Mann-Whitney U test. Children with HSP (median age 11y 4mo, interquartile range 4y) demonstrated large deviations in the GVS for the trunk and pelvis in the sagittal and coronal planes when compared to the gait patterns of children with typical development (p=0.010-0.020). Specific deviations included increased range of movement for the trunk in the coronal plane and increased excursion of the trunk and pelvis in the sagittal plane. In the transverse plane, children with HSP demonstrated later peaks in posterior pelvic rotation. The kinematic gait deviations identified in this study raise questions about the contribution of muscle weakness in HSP. Further research is warranted to determine contributing factors for gait dysfunction in HSP, especially the relative influence of spasticity and weakness. © 2016 Mac Keith Press.

Hereditary spastic paraplegia type 43 (SPG43) is caused by mutation in C19orf12

PubMed Central

Landouré, Guida; Zhu, Peng-Peng; Lourenço, Charles M.; Johnson, Janel O.; Toro, Camilo; Bricceno, Katherine V.; Rinaldi, Carlo; Meilleur, Katherine G.; Sangaré, Modibo; Diallo, Oumarou; Pierson, Tyler M.; Ishiura, Hiroyuki; Tsuji, Shoji; Hein, Nichole; Fink, John K.; Stoll, Marion; Nicholson, Garth; Gonzalez, Michael; Speziani, Fiorella; Dürr, Alexandra; Stevanin, Giovanni; Biesecker, Leslie G.; Accardi, John; Landis, Dennis M. D.; Gahl, William A.; Traynor, Bryan J.; Marques, Wilson; Züchner, Stephan; Blackstone, Craig; Fischbeck, Kenneth H.; Burnett, Barrington G.

2013-01-01

We report here the genetic basis for a form of progressive hereditary spastic paraplegia (SPG43) previously described in two Malian sisters. Exome sequencing revealed a homozygous missense variant (c.187G>C; p.Ala63Pro) in C19orf12, a gene recently implicated in neurodegeneration with brain iron accumulation (NBIA). The same mutation was subsequently also found in a Brazilian family with features of NBIA, and we identified another NBIA patient with a three-nucleotide deletion (c.197_199del; p.Gly66del). Haplotype analysis revealed that the p.Ala63Pro mutations have a common origin, but MRI scans showed no brain iron deposition in the Malian SPG43 subjects. Heterologous expression of these SPG43 and NBIA variants resulted in similar alterations in the subcellular distribution of C19orf12. The SPG43 and NBIA variants reported here as well as the most common C19orf12 missense mutation reported in NBIA patients are found within a highly-conserved, extended hydrophobic domain in C19orf12, underscoring the functional importance of this domain. PMID:23857908

Autosomal dominant familial spastic paraplegia: Tight linkage to chromosome 15q

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fink, J.K.; Wu, C.T.B.; Jones, S.M.

1994-09-01

Familial spastic paraplegia (FSP) (MIM No.18260) constitutes a clinically and genetically diverse group of disorders that share the primary feature of progressive, severe, lower extremity spasticity. FSP is classified according to the mode of inheritance and whether progressive spasticity occurs in isolation ({open_quotes}uncomplicated FSP{close_quotes}) or with other neurologic abnormalities ({open_quotes}complicated FSP{close_quotes}), including optic neuropathy, retinopathy, extrapyramidal disturbance, dementia, ataxia, ichthyosis, mental retardation, or deafness. Recently, autosomal dominant, uncomplicated FSP was shown to be genetically heterogeneous and tightly linked to a group of microsatellite markers on chromosome 14q in one large kindred. We examined 126 members of a non-consanguineous North Americanmore » kindred of Irish descent. FSP was diagnosed in 31 living subjects who developed insidiously progressive gait disturbance between ages 12 and 35 years. Using genetic linkage analysis to microsatellite DNA polymorphisms, we showed that the FSP locus on chromosome 14q was exluded from linkage with the disorder in our family. Subsequently, we searched for genetic linkage between the disorder and microsatellite DNA polymorphisms spanning approximately 50% of the genome. We observed significantly positive, two-point maximum lod scores (Z) for markers on chromosome 15q: D15S128 (Z=9.70, {theta}=0.05), D15S165 (Z=3.30, {theta}=0.10), and UT511 (Z=3.86, {theta}=0.10). Our data clearly establishes that one locus for autosomal dominant, uncomplicated FSP is mapped to the pericentric region of chromosome 15q. Identifying genes responsible for chromosome 15q-linked and chromosome 14q-linked FSP will greatly advance our understanding of this condition and hopefully other inherited and degenerative brain and spinal cord disorders that are also characterized by axonal degeneration.« less

Modeling Axonal Defects in Hereditary Spastic Paraplegia with Human Pluripotent Stem Cells

PubMed Central

Denton, Kyle R.; Xu, Chongchong; Shah, Harsh; Li, Xue-Jun

2016-01-01

BACKGROUND Cortical motor neurons, also known as upper motor neurons, are large projection neurons whose axons convey signals to lower motor neurons to control the muscle movements. Degeneration of cortical motor neuron axons is implicated in several debilitating disorders, including hereditary spastic paraplegia (HSP) and amyotrophic lateral sclerosis (ALS). Since the discovery of the first HSP gene, SPAST that encodes spastin, over 70 distinct genetic loci associated with HSP have been identified. How the mutations of these functionally diverse genes result in axonal degeneration and why certain axons are affected in HSP remains largely unknown. The development of induced pluripotent stem cell (iPSC) technology has provided researchers an excellent resource to generate patient-specific human neurons to model human neuropathologic processes including axonal defects. METHODS In this article, we will frst review the pathology and pathways affected in the common forms of HSP subtypes by searching the PubMed database. We will then summurize the findings and insights gained from studies using iPSC-based models, and discuss the challenges and future directions. RESULTS HSPs, a heterogeneous group of genetic neurodegenerative disorders, are characterized by lower extremity weakness and spasticity that result from retrograde axonal degeneration of cortical motor neurons. Recently, iPSCs have been generated from several common forms of HSP including SPG4, SPG3A, and SPG11 patients. Neurons derived from HSP iPSCs exhibit disease-relevant axonal defects, such as impaired neurite outgrowth, increased axonal swellings, and reduced axonal transport. CONCLUSION These patient-derived neurons offer unique tools to study the pathogenic mechanisms and explore the treatments for rescuing axonal defects in HSP, as well as other diseases involving axonopathy. PMID:27956894

Loss of Association of REEP2 with Membranes Leads to Hereditary Spastic Paraplegia

PubMed Central

Esteves, Typhaine; Durr, Alexandra; Mundwiller, Emeline; Loureiro, José L.; Boutry, Maxime; Gonzalez, Michael A.; Gauthier, Julie; El-Hachimi, Khalid H.; Depienne, Christel; Muriel, Marie-Paule; Acosta Lebrigio, Rafael F.; Gaussen, Marion; Noreau, Anne; Speziani, Fiorella; Dionne-Laporte, Alexandre; Deleuze, Jean-François; Dion, Patrick; Coutinho, Paula; Rouleau, Guy A.; Zuchner, Stephan; Brice, Alexis; Stevanin, Giovanni; Darios, Frédéric

2014-01-01

Hereditary spastic paraplegias (HSPs) are clinically and genetically heterogeneous neurological conditions. Their main pathogenic mechanisms are thought to involve alterations in endomembrane trafficking, mitochondrial function, and lipid metabolism. With a combination of whole-genome mapping and exome sequencing, we identified three mutations in REEP2 in two families with HSP: a missense variant (c.107T>A [p.Val36Glu]) that segregated in the heterozygous state in a family with autosomal-dominant inheritance and a missense change (c.215T>A [p.Phe72Tyr]) that segregated in trans with a splice site mutation (c.105+3G>T) in a family with autosomal-recessive transmission. REEP2 belongs to a family of proteins that shape the endoplasmic reticulum, an organelle that was altered in fibroblasts from an affected subject. In vitro, the p.Val36Glu variant in the autosomal-dominant family had a dominant-negative effect; it inhibited the normal binding of wild-type REEP2 to membranes. The missense substitution p.Phe72Tyr, in the recessive family, decreased the affinity of the mutant protein for membranes that, together with the splice site mutation, is expected to cause complete loss of REEP2 function. Our findings illustrate how dominant and recessive inheritance can be explained by the effects and nature of mutations in the same gene. They have also important implications for genetic diagnosis and counseling in clinical practice because of the association of various modes of inheritance to this new clinico-genetic entity. PMID:24388663

Novel Compound Heterozygous Spatacsin Mutations in a Greek Kindred with Hereditary Spastic Paraplegia SPG11 and Dementia.

PubMed

Fraidakis, Matthew J; Brunetti, Maura; Blackstone, Craig; Filippi, Massimo; Chiò, Adriano

2016-01-01

SPG11 belongs to the autosomal recessive hereditary spastic paraplegias (HSP) and presents during childhood or puberty with a complex clinical phenotype encompassing learning difficulties, ataxia, peripheral neuropathy, amyotrophy, and mental retardation. We hereby present the case of a 30-year-old female patient with complex autosomal recessive HSP with thinning of the corpus callosum (TCC) and dementia that was compound heterozygous with two novel mutations in the SPG11 gene. Sequence analysis of the SPG11 gene revealed two novel mutations in a compound heterozygous state in the index patient (c.2431C>T/p.Gln811Ter and c.6755_6756insT/p.Glu2252Aspfs*88). MRI showed abnormal TCC, white matter (WM) hyperintensities periventricularly, and the 'ears of the lynx' sign. Diffusion tensor imaging showed a mild-to-moderate decrease in fractional anisotropy and an increase in mean diffusivity in WM compared to age-matched controls, while magnetic resonance spectroscopy showed abnormal findings in affected WM with a decrease in N-acetyl-aspartate in WM regions of interest. This is the first SPG11 kindred from the Greek population to be reported in the medical literature. © 2016 S. Karger AG, Basel.

Silver syndrome variant of hereditary spastic paraplegia: A locus to 4p and allelism with SPG4.

PubMed

Orlacchio, A; Patrono, C; Gaudiello, F; Rocchi, C; Moschella, V; Floris, R; Bernardi, G; Kawarai, T

2008-05-20

To perform a clinical and genetic study of two large Italian families (RM-36 and RM-51) showing the cardinal clinical features of Silver syndrome (SS), a rare dominantly inherited form of hereditary spastic paraplegia (HSP) complicated by amyotrophy of the small hand muscles. Clinical assessment including neurophysiologic, neuropsychological, and neuroimaging evaluations. Genetic studies included linkage and sequence analyses. Using a genome-wide survey in the RM-36 family, a novel locus (SPG38) has been identified and mapped within the 13.1-cM region on chromosome 4p16-p15 between markers D4S432 and D4S1599. The RM-51 family was linked to the SPG4 locus at 2p21-p24 and sequence analysis of SPG4 showed a novel frameshift mutation p.Asp321GlyfsX6. Clinical examination of the affected members carrying the mutation showed high frequency of additional clinical features including decreased vibration sense, pes cavus, temporal lobe epilepsy, and cognitive impairment. This study demonstrates evidence of a novel locus SPG38 for Silver syndrome (SS) and suggests that genetic defects in SPG4 might lead to broad clinical features overlapped with those of SS.

Unusual Presentation of a Primary Ewing’s Sarcoma of the Spine with Paraplegia: A Case Report

PubMed Central

Sundarapandian, Rajkumar Jayachandran; Surulivel, Vignesh Jayabalan

2015-01-01

Ewing’s sarcoma is a primary malignancy of the bone affecting individuals in the second decade of life. Primary sarcomas of the spine are rare and the occurrence of Primary Ewing’s sarcoma in the spine is very rare. Ewing’s sarcoma occurring in the spine is divided into two types, Ewing’s sarcoma of sacral spine which are very aggressive with poor prognosis and Ewing’s sarcoma of the non sacral spine which is an extremely rare occurrence. Patient may present with neurological deficit when the tumour extends into the spinal canal causing spinal cord compression. Magnetic resonance imaging (MRI) is very sensitive in diagnosing the tumour and defining the extent of the tumour. Here we report an 18-year-old boy who presented with back pain and complete paraplegia of two months duration. The MRI gave a differential diagnosis of infective pathology due to the fluid collection in the paraspinal region, followed by primary malignancy as the second diagnosis. Patient underwent posterior spinal decompression and stabilization, and intaoperatively there was significant collection of pus whose culture showed no growth. The histopathology and immunohistochemistry studies confirmed the diagnosis of Ewing’s sarcoma and patient was started on combination chemotherapy and radiotherapy. PMID:25954672

Hereditary spastic paraplegia in Greece: characterisation of a previously unexplored population using next-generation sequencing

PubMed Central

Lynch, David S; Koutsis, Georgios; Tucci, Arianna; Panas, Marios; Baklou, Markella; Breza, Marianthi; Karadima, Georgia; Houlden, Henry

2016-01-01

Hereditary Spastic Paraplegia (HSP) is a syndrome characterised by lower limb spasticity, occurring alone or in association with other neurological manifestations, such as cognitive impairment, seizures, ataxia or neuropathy. HSP occurs worldwide, with different populations having different frequencies of causative genes. The Greek population has not yet been characterised. The purpose of this study was to describe the clinical presentation and molecular epidemiology of the largest cohort of HSP in Greece, comprising 54 patients from 40 families. We used a targeted next-generation sequencing (NGS) approach to genetically assess a proband from each family. We made a genetic diagnosis in >50% of cases and identified 11 novel variants. Variants in SPAST and KIF5A were the most common causes of autosomal dominant HSP, whereas SPG11 and CYP7B1 were the most common cause of autosomal recessive HSP. We identified a novel variant in SPG11, which led to disease with later onset and may be unique to the Greek population and report the first nonsense mutation in KIF5A. Interestingly, the frequency of HSP mutations in the Greek population, which is relatively isolated, was very similar to other European populations. We confirm that NGS approaches are an efficient diagnostic tool and should be employed early in the assessment of HSP patients. PMID:26374131

Hereditary spastic paraplegia in Greece: characterisation of a previously unexplored population using next-generation sequencing.

PubMed

Lynch, David S; Koutsis, Georgios; Tucci, Arianna; Panas, Marios; Baklou, Markella; Breza, Marianthi; Karadima, Georgia; Houlden, Henry

2016-06-01

Hereditary Spastic Paraplegia (HSP) is a syndrome characterised by lower limb spasticity, occurring alone or in association with other neurological manifestations, such as cognitive impairment, seizures, ataxia or neuropathy. HSP occurs worldwide, with different populations having different frequencies of causative genes. The Greek population has not yet been characterised. The purpose of this study was to describe the clinical presentation and molecular epidemiology of the largest cohort of HSP in Greece, comprising 54 patients from 40 families. We used a targeted next-generation sequencing (NGS) approach to genetically assess a proband from each family. We made a genetic diagnosis in >50% of cases and identified 11 novel variants. Variants in SPAST and KIF5A were the most common causes of autosomal dominant HSP, whereas SPG11 and CYP7B1 were the most common cause of autosomal recessive HSP. We identified a novel variant in SPG11, which led to disease with later onset and may be unique to the Greek population and report the first nonsense mutation in KIF5A. Interestingly, the frequency of HSP mutations in the Greek population, which is relatively isolated, was very similar to other European populations. We confirm that NGS approaches are an efficient diagnostic tool and should be employed early in the assessment of HSP patients.

Subjective Measures of Exercise Intensity to Gauge Substrate Partitioning in Persons With Paraplegia

PubMed Central

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

2012-01-01

Background: The Borg Rating of Perceived Exertion (RPE) Scale and talk test (TT) are commonly recommended for persons to gauge exercise intensity. It is not known whether they are suitable to estimate substrate partitioning between carbohydrate and fat in persons with SCI. Objective: Investigate substrate partitioning/utilization patterns associated with RPE and TT. Methods: Twelve participants with chronic paraplegia underwent 2 arm crank exercise tests on nonconsecutive days within 2 weeks. Test 1 was a graded exercise test (GXT) to volitional exhaustion. Test 2 was a 15-minute self-selected steady state (SS) voluntary arm exercise bout simulating a brief, yet typical exercise session. Results: For the GXT, very light intensity exercise (RPE < 9) and TT stage before last positive were associated with highest contribution of fat oxidation (~35%-50%) to total energy expenditure (TEE). Fat oxidation was low at all stages, with the highest rate (0.13 ± 0.07 g/min) occurring at stage 1 (10 W). Corresponding average RPE was 7 ± 2 and the TT was positive for all participants at this stage. For the SS, fuel partitioning throughout exercise was dominated by carbohydrate oxidation (1.47 ± 0.08 g/min), accounting for almost all (~94%) of TEE with only a minute contribution from fat oxidation (0.02 ± 0.004 g/min). A positive TT was associated with an average contribution of fat oxidation of ~10%. Conclusions: RPE but not the TT appears suitable to predict exercise intensities associated with the highest levels of fat oxidation. However, such intensities are below authoritative intensity thresholds for cardiorespiratory fitness promotion, and therefore the applicability of such a prediction for exercise prescriptions is likely limited to individuals with low exercise tolerance. PMID:23459243

Autosomal recessive spastic paraplegia (SPG30) with mild ataxia and sensory neuropathy maps to chromosome 2q37.3.

PubMed

Klebe, Stephan; Azzedine, Hamid; Durr, Alexandra; Bastien, Patrick; Bouslam, Naima; Elleuch, Nizar; Forlani, Sylvie; Charon, Celine; Koenig, Michel; Melki, Judith; Brice, Alexis; Stevanin, Giovanni

2006-06-01

The hereditary spastic paraplegias (HSPs) are a clinically and genetically heterogeneous group of neurodegenerative diseases characterized by progressive spasticity in the lower limbs. Twenty-nine different loci (SPG) have been mapped so far, and 11 responsible genes have been identified. Clinically, one distinguishes between pure and complex HSP forms which are variably associated with numerous combinations of neurological and extra-neurological signs. Less is known about autosomal recessive forms (ARHSP) since the mapped loci have been identified often in single families and account for only a small percentage of patients. We report a new ARHSP locus (SPG30) on chromosome 2q37.3 in a consanguineous family with seven unaffected and four affected members of Algerian origin living in Eastern France with a significant multipoint lod score of 3.8. Ten other families from France (n = 4), Tunisia (n = 2), Algeria (n = 3) and the Czech Republic (n = 1) were not linked to the newly identified locus thus demonstrating further genetic heterogeneity. The phenotype of the linked family consists of spastic paraparesis and peripheral neuropathy associated with slight cerebellar signs confirmed by cerebellar atrophy on one CT scan.

Heterozygous KIDINS220/ARMS nonsense variants cause spastic paraplegia, intellectual disability, nystagmus, and obesity.

PubMed

Josifova, Dragana J; Monroe, Glen R; Tessadori, Federico; de Graaff, Esther; van der Zwaag, Bert; Mehta, Sarju G; Harakalova, Magdalena; Duran, Karen J; Savelberg, Sanne M C; Nijman, Isaäc J; Jungbluth, Heinz; Hoogenraad, Casper C; Bakkers, Jeroen; Knoers, Nine V; Firth, Helen V; Beales, Philip L; van Haaften, Gijs; van Haelst, Mieke M

2016-06-01

We identified de novo nonsense variants in KIDINS220/ARMS in three unrelated patients with spastic paraplegia, intellectual disability, nystagmus, and obesity (SINO). KIDINS220 is an essential scaffold protein coordinating neurotrophin signal pathways in neurites and is spatially and temporally regulated in the brain. Molecular analysis of patients' variants confirmed expression and translation of truncated transcripts similar to recently characterized alternative terminal exon splice isoforms of KIDINS220 KIDINS220 undergoes extensive alternative splicing in specific neuronal populations and developmental time points, reflecting its complex role in neuronal maturation. In mice and humans, KIDINS220 is alternative spliced in the middle region as well as in the last exon. These full-length and KIDINS220 splice variants occur at precise moments in cortical, hippocampal, and motor neuron development, with splice variants similar to the variants seen in our patients and lacking the last exon of KIDINS220 occurring in adult rather than in embryonic brain. We conducted tissue-specific expression studies in zebrafish that resulted in spasms, confirming a functional link with disruption of the KIDINS220 levels in developing neurites. This work reveals a crucial physiological role of KIDINS220 in development and provides insight into how perturbation of the complex interplay of KIDINS220 isoforms and their relative expression can affect neuron control and human metabolism. Altogether, we here show that de novo protein-truncating KIDINS220 variants cause a new syndrome, SINO. This is the first report of KIDINS220 variants causing a human disease. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A rodent brain-machine interface paradigm to study the impact of paraplegia on BMI performance.

PubMed

Bridges, Nathaniel R; Meyers, Michael; Garcia, Jonathan; Shewokis, Patricia A; Moxon, Karen A

2018-05-31

Most brain machine interfaces (BMI) focus on upper body function in non-injured animals, not addressing the lower limb functional needs of those with paraplegia. A need exists for a novel BMI task that engages the lower body and takes advantage of well-established rodent spinal cord injury (SCI) models to study methods to improve BMI performance. A tilt BMI task was designed that randomly applies different types of tilts to a platform, decodes the tilt type applied and rights the platform if the decoder correctly classifies the tilt type. The task was tested on female rats and is relatively natural such that it does not require the animal to learn a new skill. It is self-rewarding such that there is no need for additional rewards, eliminating food or water restriction, which can be especially hard on spinalized rats. Finally, task difficulty can be adjusted by making the tilt parameters. This novel BMI task bilaterally engages the cortex without visual feedback regarding limb position in space and animals learn to improve their performance both pre and post-SCI.Comparison with Existing Methods: Most BMI tasks primarily engage one hemisphere, are upper-body, rely heavily on visual feedback, do not perform investigations in animal models of SCI, and require nonnaturalistic extrinsic motivation such as water rewarding for performance improvement. Our task addresses these gaps. The BMI paradigm presented here will enable researchers to investigate the interaction of plasticity after SCI and plasticity during BMI training on performance. Copyright © 2018. Published by Elsevier B.V.

[Difficulties in the diagnosis in the case of subacute paraplegia in a woman with Addison-Biermer disease].

PubMed

Szupień, Elzbieta; Ositek, Bozena; Pniewski, Jarosław

2004-01-01

The following paper presents a case of presently rare serious and non-typical subacutely progressing neurological complications in Addison-Biermer disease in a period before the diagnosis, and effective treatment with vitamin B12 in the advanced process of the nervous system impairment. The patient was a 52-year-old woman with the following (increasingly severe) symptoms occurring over a period of 5 weeks, after an earlier non-related operation: paresis of lower limbs (up to paraplegia), slight paresis of upper limbs, sphincters disorder, numbness and the loss of sensation in the upper and lower limbs, and finally mental deterioration. The woman was admitted to a neurological clinic with the suspected Guillain-Bare syndrome. After an interview and medical examination, with the help of some additional tests and resulting clinical picture, it was diagnosed as the Addison-Biermer disorder. A typical treatment was started with vitamin B12 injections, with a neurological improvement within a week, and further gradual improvement over the following 5 weeks of treatment in the clinic (improvement in the strength, sensation in the limbs, functionality of the sphincters, and normalization of the cognitive functions). After 2 months of continuous pharmacological treatment and physical rehabilitation, the patient started to walk with the help of a walker, and after further 2 months, she was able to walk on her own with a crutch.

Quality of life and self-esteem of persons with paraplegia living in São Paulo, Brazil.

PubMed

Blanes, Leila; Carmagnani, Maria Isabel S; Ferreira, Lydia M

2009-02-01

To evaluate the quality of life (QoL) and self-esteem of paraplegic persons. The sample consisted of 60 outpatients with traumatic paraplegia living in São Paulo, Brazil, from whom clinical and demographic data were obtained. QoL was assessed by the 36-item Short-Form (SF-36) health survey questionnaire, and self-esteem was measured by Rosenberg's Self-Esteem (RSE) scale. Statistical analysis was performed using Student's t-test, analysis of variance and Fisher's least significant difference (LSD) test at a significance level of 5%. Participants were predominately men (86.7%) with a mean age of 32.9 (standard deviation [SD] = 9.47) years, low education level and low income. The SF-36 dimensions that received the lowest scores were physical functioning, role physical and role emotional. Cronbach's alpha for the SF-36 questionnaire was 0.80. A significant statistical difference was found between the presence of pressure ulcers and low scores on mental health (P = 0.001), as determined by Student's t-test. The mean self-esteem score was 8.35 and there was a significant statistical difference between low self-esteem scores and occupation (P = 0.008). Participants reported low QoL and self-esteem. The results provide background information that may be useful in the development of strategies to reduce the impact of spinal cord injury (SCI) on the life and health of persons with SCI, improving their QoL.

Brain magnetic resonance imaging findings and auditory brainstem response in a child with spastic paraplegia 2 due to a PLP1 splice site mutation.

PubMed

Kubota, Kazuo; Saito, Yoshiaki; Ohba, Chihiro; Saitsu, Hirotomo; Fukuyama, Tetsuhiro; Ishiyama, Akihiko; Saito, Takashi; Komaki, Hirofumi; Nakagawa, Eiji; Sugai, Kenji; Sasaki, Masayuki; Matsumoto, Naomichi

2015-01-01

A boy with spastic paraplegia type 2 (SPG2) due to a novel splice site mutation of PLP1 presented with progressive spasticity of lower limbs, which was first observed during late infancy, when he gained the ability to walk with support. His speech was slow and he had dysarthria. The patient showed mildly delayed intellectual development. Subtotal dysmyelination in the central nervous system was revealed, which was especially prominent in structures known to be myelinated during earlier period, whereas structures that are myelinated later were better myelinated. These findings on the brain magnetic resonance imaging were unusual for subjects with PLP1 mutations. Peaks I and II of the auditory brainstem response (ABR) were normally provoked, but peaks III-V were not clearly demarcated, similarly to the findings in Pelizaeus-Merzbacher disease. These findings of brain MRI and ABR may be characteristic for a subtype of SPG2 patients. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

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

PubMed Central

Fink, John K.

2014-01-01

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

Reep1 null mice reveal a converging role for hereditary spastic paraplegia proteins in lipid droplet regulation.

PubMed

Renvoisé, Benoît; Malone, Brianna; Falgairolle, Melanie; Munasinghe, Jeeva; Stadler, Julia; Sibilla, Caroline; Park, Seong H; Blackstone, Craig

2016-12-01

Hereditary spastic paraplegias (HSPs; SPG1-76 plus others) are length-dependent disorders affecting long corticospinal axons, and the most common autosomal dominant forms are caused by mutations in genes that encode the spastin (SPG4), atlastin-1 (SPG3A) and REEP1 (SPG31) proteins. These proteins bind one another and shape the tubular endoplasmic reticulum (ER) network throughout cells. They also are involved in lipid droplet formation, enlargement, or both in cells, though mechanisms remain unclear. Here we have identified evidence of partial lipoatrophy in Reep1 null mice in addition to prominent spastic paraparesis. Furthermore, Reep1-/- embryonic fibroblasts and neurons in the cerebral cortex both show lipid droplet abnormalities. The apparent partial lipodystrophy in Reep1 null mice, although less severe, is reminiscent of the lipoatrophy phenotype observed in the most common form of autosomal recessive lipodystrophy, Berardinelli-Seip congenital lipodystrophy. Berardinelli-Seip lipodystrophy is caused by autosomal recessive mutations in the BSCL2 gene that encodes an ER protein, seipin, that is also mutated in the autosomal dominant HSP SPG17 (Silver syndrome). Furthermore, REEP1 co-immunoprecipitates with seipin in cells. This strengthens the link between alterations in ER morphogenesis and lipid abnormalities, with important pathogenic implications for the most common forms of HSP. Published by Oxford University Press 2016. This work is written by US Government employees and is in the public domain in the US.

Pott disease in the thoracolumbar spine with marked kyphosis and progressive paraplegia necessitating posterior vertebral column resection and anterior reconstruction with a cage.

PubMed

Pappou, Ioannis P; Papadopoulos, Elias C; Swanson, Andrew N; Mermer, Matthew J; Fantini, Gary A; Urban, Michael K; Russell, Linda; Cammisa, Frank P; Girardi, Federico P

2006-02-15

Case report. To report on a patient with Pott disease, progressive neurologic deficit, and severe kyphotic deformity, who had medical treatment fail and required posterior/anterior decompression with instrumented fusion. Treatment options will be discussed. Tuberculous spondylitis is an increasingly common disease worldwide, with an estimated prevalence of 800,000 cases. Surgical treatment consisting of extensive posterior decompression/instrumented fusion and 3-level posterior vertebral column resection, followed by anterior debridement/fusion with cage reconstruction. Neurologic improvement at 6-month follow-up (Frankel B to Frankel D), with evidence of radiographic fusion. A 70-year-old patient with progressive Pott paraplegia and severe kyphotic deformity, for whom medical treatment failed is presented. A posterior vertebral column resection, multiple level posterior decompression, and instrumented fusion, followed by an anterior interbody fusion with cage was used to decompress the spinal cord, restore sagittal alignment, and debride the infection. At 6-month follow-up, the patient obtained excellent pain relief, correction of deformity, elimination of the tuberculous foci, and significant recovery of neurologic function.

Structural annotation of Beta-1,4-N-acetyl galactosaminyltransferase 1 (B4GALNT1) causing Hereditary Spastic Paraplegia 26.

PubMed

Dad, Rubina; Malik, Uzma; Javed, Aneela; Minassian, Berge A; Hassan, Muhammad Jawad

2017-08-30

Beta-1,4-N-acetyl galactosaminyltransferase 1, B4GALNT1, is a GM2/GD2 synthase, involved in the expression of glycosphingolipids (GSLs) containing sialic acid. Mutations in the gene B4GALNT1 cause Hereditary Spastic Paraplegia 26 (HSP26). In present study we have made attempt to predict the potential structural of the human B4GALNT1 protein. The results illustrated that the amino acid sequences of B4GALNT1 are not 100% conserved among selected twenty species. One signal peptide and one transmembrane domain predicted in human wild type B4GALNT1 protein with aliphatic index of 92.76 and theoretical (iso-electric point) pI of 8.93. It was a kind of unstable protein with Grand average of hydropathicity (GRAVY) of -0.127. Various post-translational modifications were also predicted to exist in B4GALNT1 and predicted to interact with different proteins including ST8SIA5, SLC33A1, GLB1 and others. In the final round, reported missense mutations have shown the further decrease in stability of the protein. This in-silico analysis of B4GALNT1 protein will provide the basis for the further studies on structural variations and biological pathways involving B4GALNT1 in the HSP26. Copyright © 2017. Published by Elsevier B.V.

The mechanism of neurofeedback training for treatment of central neuropathic pain in paraplegia: a pilot study.

PubMed

Hassan, Muhammad Abul; Fraser, Matthew; Conway, Bernard A; Allan, David B; Vuckovic, Aleksandra

2015-10-13

Central neuropathic pain has a prevalence of 40% in patients with spinal cord injury. Electroencephalography (EEG) studies showed that this type of pain has identifiable signatures, that could potentially be targeted by a neuromodulation therapy. The aim of the study was to investigate the putative mechanism of neurofeedback training on central neuropathic pain and its underlying brain signatures in patients with chronic paraplegia. Patients' EEG activity was modulated from the sensory-motor cortex, electrode location C3/Cz/C4/P4 in up to 40 training sessions Results. Six out of seven patients reported immediate reduction of pain during neurofeedback training. Best results were achieved with suppressing Ɵ and higher β (20-30 Hz) power and reinforcing α power at C4. Four patients reported clinically significant long-term reduction of pain (>30%) which lasted at least a month beyond the therapy. EEG during neurofeedback revealed a wide spread modulation of power in all three frequency bands accompanied with changes in the coherence most notable in the beta band. The standardized low resolution electromagnetic tomography analysis of EEG before and after neurofeedback therapy showed the statistically significant reduction of power in beta frequency band in all tested patients. Areas with reduced power included the Dorsolateral Prefrontal Cortex, the Anterior Cingulate Cortex and the Insular Cortex. Neurofeedback training produces both immediate and longer term reduction of central neuropathic pain that is accompanied with a measurable short and long term modulation of cortical activity. Controlled trials are required to confirm the efficacy of this neurofeedback protocol on treatment of pain. The study is a registered UKCRN clinical trial Nr 9824.

Activation of lower back muscles via FES for pressure sores prevention in paraplegia: a case study.

PubMed

Vanoncini, M; Holderbaum, W; Andrews, B J

2010-04-01

The aim of this paper is to show the feasibility of the use of functional electrical stimulation (FES) applied to the lower back muscles for pressure sores prevention in paraplegia. The hypothesis under study is that FES induces a change in the pressure distribution on the contact area during sitting. Tests were conducted on a paraplegic subject (T5), sitting on a standard wheelchair and cushion. Trunk extensors (mainly the erector spinae) were stimulated using surface electrodes placed on the skin. A pressure mapping system was used to measure the pressure on the sitting surface in four situations: (a) no stimulation; (b) stimulation on one side of the spine only; (c) stimulation on both sides, at different levels; and (d) stimulation at the same level on both sides, during pressure-relief manoeuvres. A session of prolonged stimulation was also conducted. The experimental results show that the stimulation of the erector spinae on one side of the spine can induce a trunk rotation on the sagittal plane, which causes a change in the pressure distribution. A decrease of pressure on the side opposite to the stimulation was recorded. The phenomenon is intensified when different levels of stimulation are applied to the two sides, and such change can be sustained for a considerable time (around 5 minutes). The stimulation did not induce changes during pressure-relief manoeuvres. Finally, from this research we can conclude that the stimulation of the trunk extensors can be a useful tool for pressure sores prevention, and can potentially be used in a routine for pressure sores prevention based on periodical weight shifts.

Massive sequencing of 70 genes reveals a myriad of missing genes or mechanisms to be uncovered in hereditary spastic paraplegias

PubMed Central

Morais, Sara; Raymond, Laure; Mairey, Mathilde; Coutinho, Paula; Brandão, Eva; Ribeiro, Paula; Loureiro, José Leal; Sequeiros, Jorge; Brice, Alexis; Alonso, Isabel; Stevanin, Giovanni

2017-01-01

Hereditary spastic paraplegias (HSP) are neurodegenerative disorders characterized by lower limb spasticity and weakness that can be complicated by other neurological or non-neurological signs. Despite a high genetic heterogeneity (>60 causative genes), 40–70% of the families remain without a molecular diagnosis. Analysis of one of the pioneer cohorts of 193 HSP families generated in the early 1990s in Portugal highlighted that SPAST and SPG11 are the most frequent diagnoses. We have now explored 98 unsolved families from this series using custom next generation sequencing panels analyzing up to 70 candidate HSP genes. We identified the likely disease-causing variant in 20 of the 98 families with KIF5A being the most frequently mutated gene. We also found 52 variants of unknown significance (VUS) in 38% of the cases. These new diagnoses resulted in 42% of solved cases in the full Portuguese cohort (81/193). Segregation of the variants was not always compatible with the presumed inheritance, indicating that the analysis of all HSP genes regardless of the inheritance mode can help to explain some cases. Our results show that there is still a large set of unknown genes responsible for HSP and most likely novel mechanisms or inheritance modes leading to the disease to be uncovered, but this will require international collaborative efforts, particularly for the analysis of VUS. PMID:28832565

Paraplegia-quadriplegia Independently Increases All Percutaneous Nephrolithotomy Complications: A Comparative Study Using the Modified Clavien System.

PubMed

Danawala, Zeeshan A; Singh, Dinesh

2015-05-01

To investigate the perioperative complication rates for paraplegic-quadriplegic patients (PQPs) undergoing percutaneous nephrolithotomy (PCNL) as compared with non-PQPs using a standardized method of complication reporting via the Clavien system. Two hundred thirteen consecutive PCNLs performed by a single surgeon were analyzed. There were 31 and 115 patients separated into PQP and non-PQP groups, respectively. Data collection included demographic and clinical factors, as well as perioperative and delayed complications. Complications were organized by the Clavien grade. All- and initial-procedure complications were analyzed. The rate of adverse events for each Clavien grade was calculated, and statistical comparisons were made. The relationship between PQP and complication severity was investigated using univariate and multivariate analyses. There were 38 and 43 initial-procedure complications in the PQP and non-PQP groups, respectively. The rate of adverse events was higher across the spectrum of Clavien grades for the PQP group, specifically grade 1 (48.4% vs 20.2%; P = .002), grade 2 (22.6% vs 5.3%; P = .004), grade 3b (12.9% vs 2.6%; P = .038), grade 4a (6.5% vs 0%), and grade 4b (9.7% vs 1.8%; P = .066). Approximately 51.6% and 31.5% of PQPs and non-PQPs experienced ≥ 1 complications, respectively (odds ratio = 2.34; P = .05). Multivariate analysis demonstrated paraplegia or quadriplegia status to be an independent risk factor for the development of perioperative complications after adjusting for confounding factors (odds ratio = 2.91; P = .040). PCNL complication rates are higher in PQPs compared with non-PQPs. This study is one of the first in PCNL to use a standardized reporting system to highlight high-risk individuals within the stone population. Copyright © 2015 Elsevier Inc. All rights reserved.

Gait phenotypes in paediatric hereditary spastic paraplegia revealed by dynamic time warping analysis and random forests

PubMed Central

Martín-Gonzalo, Juan Andrés; Rodríguez-Andonaegui, Irene; López-López, Javier; Pascual-Pascual, Samuel Ignacio

2018-01-01

The Hereditary Spastic Paraplegias (HSP) are a group of heterogeneous disorders with a wide spectrum of underlying neural pathology, and hence HSP patients express a variety of gait abnormalities. Classification of these phenotypes may help in monitoring disease progression and personalizing therapies. This is currently managed by measuring values of some kinematic and spatio-temporal parameters at certain moments during the gait cycle, either in the doctor´s surgery room or after very precise measurements produced by instrumental gait analysis (IGA). These methods, however, do not provide information about the whole structure of the gait cycle. Classification of the similarities among time series of IGA measured values of sagittal joint positions throughout the whole gait cycle can be achieved by hierarchical clustering analysis based on multivariate dynamic time warping (DTW). Random forests can estimate which are the most important isolated parameters to predict the classification revealed by DTW, since clinicians need to refer to them in their daily practice. We acquired time series of pelvic, hip, knee, ankle and forefoot sagittal angular positions from 26 HSP and 33 healthy children with an optokinetic IGA system. DTW revealed six gait patterns with different degrees of impairment of walking speed, cadence and gait cycle distribution and related with patient’s age, sex, GMFCS stage, concurrence of polyneuropathy and abnormal visual evoked potentials or corpus callosum. The most important parameters to differentiate patterns were mean pelvic tilt and hip flexion at initial contact. Longer time of support, decreased values of hip extension and increased knee flexion at initial contact can differentiate the mildest, near to normal HSP gait phenotype and the normal healthy one. Increased values of knee flexion at initial contact and delayed peak of knee flexion are important factors to distinguish GMFCS stages I from II-III and concurrence of polyneuropathy

Cold temperature improves mobility and survival in Drosophila models of autosomal-dominant hereditary spastic paraplegia (AD-HSP).

PubMed

Baxter, Sally L; Allard, Denise E; Crowl, Christopher; Sherwood, Nina Tang

2014-08-01

Autosomal-dominant hereditary spastic paraplegia (AD-HSP) is a crippling neurodegenerative disease for which effective treatment or cure remains unknown. Victims experience progressive mobility loss due to degeneration of the longest axons in the spinal cord. Over half of AD-HSP cases arise from loss-of-function mutations in spastin, which encodes a microtubule-severing AAA ATPase. In Drosophila models of AD-HSP, larvae lacking Spastin exhibit abnormal motor neuron morphology and function, and most die as pupae. Adult survivors display impaired mobility, reminiscent of the human disease. Here, we show that rearing pupae or adults at reduced temperature (18°C), compared with the standard temperature of 24°C, improves the survival and mobility of adult spastin mutants but leaves wild-type flies unaffected. Flies expressing human spastin with pathogenic mutations are similarly rescued. Additionally, larval cooling partially rescues the larval synaptic phenotype. Cooling thus alleviates known spastin phenotypes for each developmental stage at which it is administered and, notably, is effective even in mature adults. We find further that cold treatment rescues larval synaptic defects in flies with mutations in Flower (a protein with no known relation to Spastin) and mobility defects in flies lacking Kat60-L1, another microtubule-severing protein enriched in the CNS. Together, these data support the hypothesis that the beneficial effects of cold extend beyond specific alleviation of Spastin dysfunction, to at least a subset of cellular and behavioral neuronal defects. Mild hypothermia, a common neuroprotective technique in clinical treatment of acute anoxia, might thus hold additional promise as a therapeutic approach for AD-HSP and, potentially, for other neurodegenerative diseases. © 2014. Published by The Company of Biologists Ltd.

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

PubMed Central

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

2014-01-01

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 α-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 α-tubulin in patient-derived ONS cells. Drug doses that restored acetylated α-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 α-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 α-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

Identification of a Heterozygous SPG11 Mutation by Clinical Exome Sequencing in a Patient With Hereditary Spastic Paraplegia: A Case Report.

PubMed

Oh, Ja-Young; Do, Hyun Jung; Lee, Seungok; Jang, Ja-Hyun; Cho, Eun-Hae; Jang, Dae-Hyun

2016-12-01

Next-generation sequencing, such as whole-genome sequencing, whole-exome sequencing, and targeted panel sequencing have been applied for diagnosis of many genetic diseases, and are in the process of replacing the traditional methods of genetic analysis. Clinical exome sequencing (CES), which provides not only sequence variation data but also clinical interpretation, aids in reaching a final conclusion with regards to genetic diagnosis. Sequencing of genes with clinical relevance rather than whole exome sequencing might be more suitable for the diagnosis of known hereditary disease with genetic heterogeneity. Here, we present the clinical usefulness of CES for the diagnosis of hereditary spastic paraplegia (HSP). We report a case of patient who was strongly suspected of having HSP based on her clinical manifestations. HSP is one of the diseases with high genetic heterogeneity, the 72 different loci and 59 discovered genes identified so far. Therefore, traditional approach for diagnosis of HSP with genetic analysis is very challenging and time-consuming. CES with TruSight One Sequencing Panel, which enriches about 4,800 genes with clinical relevance, revealed compound heterozygous mutations in SPG11 . One workflow and one procedure can provide the results of genetic analysis, and CES with enrichment of clinically relevant genes is a cost-effective and time-saving diagnostic tool for diseases with genetic heterogeneity, including HSP.

Mutation in CPT1C Associated With Pure Autosomal Dominant Spastic Paraplegia

PubMed Central

Rinaldi, Carlo; Schmidt, Thomas; Situ, Alan J.; Johnson, Janel O.; Lee, Philip R.; Chen, Ke-lian; Bott, Laura C.; Fadó, Rut; Harmison, George H.; Parodi, Sara; Grunseich, Christopher; Renvoisé, Benoît; Biesecker, Leslie G.; De Michele, Giuseppe; Santorelli, Filippo M.; Filla, Alessandro; Stevanin, Giovanni; Dürr, Alexandra; Brice, Alexis; Casals, Núria; Traynor, Bryan J.; Blackstone, Craig; Ulmer, Tobias S.; Fischbeck, Kenneth H.

2017-01-01

IMPORTANCE The family of genes implicated in hereditary spastic paraplegias (HSPs) is quickly expanding, mostly owing to the widespread availability of next-generation DNA sequencing methods. Nevertheless, a genetic diagnosis remains unavailable for many patients. OBJECTIVE To identify the genetic cause for a novel form of pure autosomal dominant HSP. DESIGN, SETTING, AND PARTICIPANTS We examined and followed up with a family presenting to a tertiary referral center for evaluation of HSP for a decade until August 2014. Whole-exome sequencing was performed in 4 patients from the same family and was integrated with linkage analysis. Sanger sequencing was used to confirm the presence of the candidate variant in the remaining affected and unaffected members of the family and screen the additional patients with HSP. Five affected and 6 unaffected participants from a 3-generation family with pure adult-onset autosomal dominant HSP of unknown genetic origin were included. Additionally, 163 unrelated participants with pure HSP of unknown genetic cause were screened. MAIN OUTCOME AND MEASURE Mutation in the neuronal isoform of carnitine palmitoyl-transferase (CPT1C) gene. RESULTS We identified the nucleotide substitution c.109C>T in exon 3 of CPT1C, which determined the base substitution of an evolutionarily conserved Cys residue for an Arg in the gene product. This variant strictly cosegregated with the disease phenotype and was absent in online single-nucleotide polymorphism databases and in 712 additional exomes of control participants. We showed that CPT1C, which localizes to the endoplasmic reticulum, is expressed in motor neurons and interacts with atlastin-1, an endoplasmic reticulum protein encoded by the ATL1 gene known to be mutated in pure HSPs. The mutation, as indicated by nuclear magnetic resonance spectroscopy studies, alters the protein conformation and reduces the mean (SD) number (213.0 [46.99] vs 81.9 [14.2]; P < .01) and size (0.29 [0.01] vs 0.26 [0

Hereditary spastic paraplegias: identification of a novel SPG57 variant affecting TFG oligomerization and description of HSP subtypes in Sudan.

PubMed

Elsayed, Liena E O; Mohammed, Inaam N; Hamed, Ahlam A A; Elseed, Maha A; Johnson, Adam; Mairey, Mathilde; Mohamed, Hassab Elrasoul S A; Idris, Mohamed N; Salih, Mustafa A M; El-Sadig, Sarah M; Koko, Mahmoud E; Mohamed, Ashraf Y O; Raymond, Laure; Coutelier, Marie; Darios, Frédéric; Siddig, Rayan A; Ahmed, Ahmed K M A; Babai, Arwa M A; Malik, Hiba M O; Omer, Zulfa M B M; Mohamed, Eman O E; Eltahir, Hanan B; Magboul, Nasr Aldin A; Bushara, Elfatih E; Elnour, Abdelrahman; Rahim, Salah M Abdel; Alattaya, Abdelmoneim; Elbashir, Mustafa I; Ibrahim, Muntaser E; Durr, Alexandra; Audhya, Anjon; Brice, Alexis; Ahmed, Ammar E; Stevanin, Giovanni

2016-01-01

Hereditary spastic paraplegias (HSP) are the second most common type of motor neuron disease recognized worldwide. We investigated a total of 25 consanguineous families from Sudan. We used next-generation sequencing to screen 74 HSP-related genes in 23 families. Linkage analysis and candidate gene sequencing was performed in two other families. We established a genetic diagnosis in six families with autosomal recessive HSP (SPG11 in three families and TFG/SPG57, SACS and ALS2 in one family each). A heterozygous mutation in a gene involved in an autosomal dominant HSP (ATL1/SPG3A) was also identified in one additional family. Six out of seven identified variants were novel. The c.64C>T (p.(Arg22Trp)) TFG/SPG57 variant (PB1 domain) is the second identified that underlies HSP, and we demonstrated its impact on TFG oligomerization in vitro. Patients did not present with visual impairment as observed in a previously reported SPG57 family (c.316C>T (p.(Arg106Cys)) in coiled-coil domain), suggesting unique contributions of the PB1 and coiled-coil domains in TFG complex formation/function and a possible phenotype correlation to variant location. Some families manifested marked phenotypic variations implying the possibility of modifier factors complicated by high inbreeding. Finally, additional genetic heterogeneity is expected in HSP Sudanese families. The remaining families might unravel new genes or uncommon modes of inheritance.

Hereditary spastic paraplegias: identification of a novel SPG57 variant affecting TFG oligomerization and description of HSP subtypes in Sudan

PubMed Central

Elsayed, Liena E O; Mohammed, Inaam N; Hamed, Ahlam A A; Elseed, Maha A; Johnson, Adam; Mairey, Mathilde; Mohamed, Hassab Elrasoul S A; Idris, Mohamed N; Salih, Mustafa A M; El-sadig, Sarah M; Koko, Mahmoud E; Mohamed, Ashraf Y O; Raymond, Laure; Coutelier, Marie; Darios, Frédéric; Siddig, Rayan A; Ahmed, Ahmed K M A; Babai, Arwa M A; Malik, Hiba M O; Omer, Zulfa M B M; Mohamed, Eman O E; Eltahir, Hanan B; Magboul, Nasr Aldin A; Bushara, Elfatih E; Elnour, Abdelrahman; Rahim, Salah M Abdel; Alattaya, Abdelmoneim; Elbashir, Mustafa I; Ibrahim, Muntaser E; Durr, Alexandra; Audhya, Anjon; Brice, Alexis; Ahmed, Ammar E; Stevanin, Giovanni

2017-01-01

Hereditary spastic paraplegias (HSP) are the second most common type of motor neuron disease recognized worldwide. We investigated a total of 25 consanguineous families from Sudan. We used next-generation sequencing to screen 74 HSP-related genes in 23 families. Linkage analysis and candidate gene sequencing was performed in two other families. We established a genetic diagnosis in six families with autosomal recessive HSP (SPG11 in three families and TFG/SPG57, SACS and ALS2 in one family each). A heterozygous mutation in a gene involved in an autosomal dominant HSP (ATL1/SPG3A) was also identified in one additional family. Six out of seven identified variants were novel. The c.64C>T (p.(Arg22Trp)) TFG/SPG57 variant (PB1 domain) is the second identified that underlies HSP, and we demonstrated its impact on TFG oligomerization in vitro. Patients did not present with visual impairment as observed in a previously reported SPG57 family (c.316C>T (p.(Arg106Cys)) in coiled-coil domain), suggesting unique contributions of the PB1 and coiled-coil domains in TFG complex formation/function and a possible phenotype correlation to variant location. Some families manifested marked phenotypic variations implying the possibility of modifier factors complicated by high inbreeding. Finally, additional genetic heterogeneity is expected in HSP Sudanese families. The remaining families might unravel new genes or uncommon modes of inheritance. PMID:27601211

ATPase-deficient mitochondrial inner membrane protein ATAD3A disturbs mitochondrial dynamics in dominant hereditary spastic paraplegia

PubMed Central

Cooper, Helen M.; Yang, Yang; Ylikallio, Emil; Khairullin, Rafil; Woldegebriel, Rosa; Lin, Kai-Lan; Euro, Liliya; Palin, Eino; Wolf, Alexander; Trokovic, Ras; Isohanni, Pirjo; Kaakkola, Seppo; Auranen, Mari; Lönnqvist, Tuula; Wanrooij, Sjoerd

2017-01-01

Abstract De novo mutations in ATAD3A (ATPase family AAA-domain containing protein 3A) were recently found to cause a neurological syndrome with developmental delay, hypotonia, spasticity, optic atrophy, axonal neuropathy, and hypertrophic cardiomyopathy. Using whole-exome sequencing, we identified a dominantly inherited heterozygous variant c.1064G > A (p.G355D) in ATAD3A in a mother presenting with hereditary spastic paraplegia (HSP) and axonal neuropathy and her son with dyskinetic cerebral palsy, both with disease onset in childhood. HSP is a clinically and genetically heterogeneous disorder of the upper motor neurons. Symptoms beginning in early childhood may resemble spastic cerebral palsy. The function of ATAD3A, a mitochondrial inner membrane AAA ATPase, is yet undefined. AAA ATPases form hexameric rings, which are catalytically dependent on the co-operation of the subunits. The dominant-negative patient mutation affects the Walker A motif, which is responsible for ATP binding in the AAA module of ATAD3A, and we show that the recombinant mutant ATAD3A protein has a markedly reduced ATPase activity. We further show that overexpression of the mutant ATAD3A fragments the mitochondrial network and induces lysosome mass. Similarly, we observed altered dynamics of the mitochondrial network and increased lysosomes in patient fibroblasts and neurons derived through differentiation of patient-specific induced pluripotent stem cells. These alterations were verified in patient fibroblasts to associate with upregulated basal autophagy through mTOR inactivation, resembling starvation. Mutations in ATAD3A can thus be dominantly inherited and underlie variable neurological phenotypes, including HSP, with intrafamiliar variability. This finding extends the group of mitochondrial inner membrane AAA proteins associated with spasticity. PMID:28158749

Effects of paraplegia on quality of life and family economy among patients with spinal cord injuries in selected hospitals of Sri Lanka.

PubMed

Kalyani, H H N; Dassanayake, S; Senarath, U

2015-06-01

The study was conducted with the aim of assessing the effects of paraplegia caused by spinal cord injuries on the quality of life of patients and their family economy. A descriptive cross-sectional study. The study was carried out in Accident Service, Orthopedic and Neurosurgery Units of the National Hospital of Sri Lanka and the Spinal Injury Unit of Rehabilitation Hospital Ragama. One hundred traumatic paraplegic patients were included as the study sample. Modified Ferrans and Powers quality of life index: spinal cord injury version was used to measure the quality of life. Pre- and post-family economic data were collected using an interviewer-administered questionnaire. Quality of Life was calculated under four major components. Paraplegics' family component (mean=3.50) and social, economic aspects (mean=3.24) are considerably good when compared with health and functioning (mean=2.83) and psychological (mean=2.78) components. Also the study revealed that expenditures are significantly high (P=0.001) and income is significantly less (P=0.001) after injury than before. Quality of life is relatively good on family and social aspects, whereas the physical and psychological aspects are somewhat poor. Regarding family economy, expenses are significantly high and earnings are significantly less after the injury. Contribution to the income from self-employment shows the most significant decline. Findings suggest that the family economy of such patients should be supported.

Ancient observation of spinal cord injury: the case of the Assiryan lion.

PubMed

Luvizutto, Gustavo J; Siqueira, Emerson G; Hamamoto Filho, Pedro Tadao; Zétola, Viviane F; Lange, Marcos C; Theive, Hélio A; Resende, Luiz A; Bazan, Rodrigo

2018-05-19

The description of paraplegia is considered a milestone in the history of neurology. The Egyptians provided excellent descriptions of spinal cord injuries, the Bible has several references to paraplegia, and, more recently, the pioneers of neurology described the classic syndromes related to spinal injuries and paraplegia. Here, we describe an ancient observation by the Assyrian people of paraplegia in an animal. In ancient Assyria, lion hunting was a ritualized activity conducted for political and religious purposes. The Lion Hunt of Ashurbanipal, a series of Assyrian palace reliefs from the North Palace at Nineveh dating from approximately 645 BCE, which is now in the British Museum in London, UK, shows King Ashurbanipal hunting lions. Applying modern knowledge of mammalian dermatomes to the images, we reveal a detailed and precise observation of paraplegia following spinal cord injury. Copyright © 2018 Elsevier Inc. All rights reserved.

Augmentation of systemic blood pressure during spinal cord ischemia to prevent postoperative paraplegia after aortic surgery in a rabbit model.

PubMed

Izumi, So; Okada, Kenji; Hasegawa, Tomomi; Omura, Atsushi; Munakata, Hiroshi; Matsumori, Masamichi; Okita, Yutaka

2010-05-01

Paraplegia from spinal cord ischemia remains an unresolved complication in thoracoabdominal aortic surgery, with high morbidity and mortality. This study investigated postoperative effects of systemic blood pressure augmentation during ischemia. Spinal cord ischemia was induced in rabbits by infrarenal aortic occlusion for 15 minutes with infused phenylephrine (high blood pressure group, n = 8) or nitroprusside (low blood pressure group, n = 8) or without vasoactive agent (control, n = 8). Spinal cord blood flow, transcranial motor evoked potentials, neurologic outcome, and motor neuron cell damage (apoptosis, necrosis, superoxide generation, myeloperoxidase activity) were evaluated. Mean arterial pressures during ischemia were controlled at 121.9 +/- 2.8, 50.8 +/- 4.3, and 82.3 +/- 10.7 mm Hg in high blood pressure, low blood pressure, and control groups, respectively. In high blood pressure group, high spinal cord blood flow (P < .01), fast recovery of transcranial motor evoked potentials (P < .01), and high neurologic score (P < .05) were observed after ischemia relative to low blood pressure and control groups. At 48 hours after ischemia, there were significantly more viable neurons, fewer terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling-positive neurons, and less alpha-fodrin expression in high blood pressure group than low blood pressure and control groups. Superoxide generation and myeloperoxidase activity at 3 hours after ischemia were suppressed in high blood pressure group relative to low blood pressure group. Augmentation of systemic blood pressure during spinal cord ischemia can reduce ischemic insult and postoperative neurologic adverse events. 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

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

PubMed Central

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

2010-01-01

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

Effect of exoskeletal joint constraint and passive resistance on metabolic energy expenditure: Implications for walking in paraplegia

PubMed Central

Kobetic, Rudi; Triolo, Ronald J.

2017-01-01

An important consideration in the design of a practical system to restore walking in individuals with spinal cord injury is to minimize metabolic energy demand on the user. In this study, the effects of exoskeletal constraints on metabolic energy expenditure were evaluated in able-bodied volunteers to gain insight into the demands of walking with a hybrid neuroprosthesis after paralysis. The exoskeleton had a hydraulic mechanism to reciprocally couple hip flexion and extension, unlocked hydraulic stance controlled knee mechanisms, and ankles fixed at neutral by ankle-foot orthoses. These mechanisms added passive resistance to the hip (15 Nm) and knee (6 Nm) joints while the exoskeleton constrained joint motion to the sagittal plane. The average oxygen consumption when walking with the exoskeleton was 22.5 ± 3.4 ml O2/min/kg as compared to 11.7 ± 2.0 ml O2/min/kg when walking without the exoskeleton at a comparable speed. The heart rate and physiological cost index with the exoskeleton were at least 30% and 4.3 times higher, respectively, than walking without it. The maximum average speed achieved with the exoskeleton was 1.2 ± 0.2 m/s, at a cadence of 104 ± 11 steps/min, and step length of 70 ± 7 cm. Average peak hip joint angles (25 ± 7°) were within normal range, while average peak knee joint angles (40 ± 8°) were less than normal. Both hip and knee angular velocities were reduced with the exoskeleton as compared to normal. While the walking speed achieved with the exoskeleton could be sufficient for community ambulation, metabolic energy expenditure was significantly increased and unsustainable for such activities. This suggests that passive resistance, constraining leg motion to the sagittal plane, reciprocally coupling the hip joints, and weight of exoskeleton place considerable limitations on the utility of the device and need to be minimized in future designs of practical hybrid neuroprostheses for walking after paraplegia. PMID:28817701

Effect of exoskeletal joint constraint and passive resistance on metabolic energy expenditure: Implications for walking in paraplegia.

PubMed

Chang, Sarah R; Kobetic, Rudi; Triolo, Ronald J

2017-01-01

An important consideration in the design of a practical system to restore walking in individuals with spinal cord injury is to minimize metabolic energy demand on the user. In this study, the effects of exoskeletal constraints on metabolic energy expenditure were evaluated in able-bodied volunteers to gain insight into the demands of walking with a hybrid neuroprosthesis after paralysis. The exoskeleton had a hydraulic mechanism to reciprocally couple hip flexion and extension, unlocked hydraulic stance controlled knee mechanisms, and ankles fixed at neutral by ankle-foot orthoses. These mechanisms added passive resistance to the hip (15 Nm) and knee (6 Nm) joints while the exoskeleton constrained joint motion to the sagittal plane. The average oxygen consumption when walking with the exoskeleton was 22.5 ± 3.4 ml O2/min/kg as compared to 11.7 ± 2.0 ml O2/min/kg when walking without the exoskeleton at a comparable speed. The heart rate and physiological cost index with the exoskeleton were at least 30% and 4.3 times higher, respectively, than walking without it. The maximum average speed achieved with the exoskeleton was 1.2 ± 0.2 m/s, at a cadence of 104 ± 11 steps/min, and step length of 70 ± 7 cm. Average peak hip joint angles (25 ± 7°) were within normal range, while average peak knee joint angles (40 ± 8°) were less than normal. Both hip and knee angular velocities were reduced with the exoskeleton as compared to normal. While the walking speed achieved with the exoskeleton could be sufficient for community ambulation, metabolic energy expenditure was significantly increased and unsustainable for such activities. This suggests that passive resistance, constraining leg motion to the sagittal plane, reciprocally coupling the hip joints, and weight of exoskeleton place considerable limitations on the utility of the device and need to be minimized in future designs of practical hybrid neuroprostheses for walking after paraplegia.

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

PubMed

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

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. Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Adaptor Protein Complex 4 Deficiency Causes Severe Autosomal-Recessive Intellectual Disability, Progressive Spastic Paraplegia, Shy Character, and Short Stature

PubMed Central

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

2011-01-01

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

Alu elements mediate large SPG11 gene rearrangements: further spatacsin mutations.

PubMed

Conceição Pereira, Maria; Loureiro, José Leal; Pinto-Basto, Jorge; Brandão, Eva; Margarida Lopes, Ana; Neves, Georgina; Dias, Pureza; Geraldes, Ruth; Martins, Isabel Pavão; Cruz, Vitor Tedim; Kamsteeg, Erik-Jan; Brunner, Han G; Coutinho, Paula; Sequeiros, Jorge; Alonso, Isabel

2012-01-01

Hereditary spastic paraplegias compose a group of neurodegenerative disorders with a large clinical and genetic heterogeneity. Among the autosomal recessive forms, spastic paraplegia type 11 is the most common. To better understand the spastic paraplegia type 11 mutation spectrum, we studied a group of 54 patients with hereditary spastic paraplegia. Mutation screening was performed by PCR amplification of SPG11 coding regions and intron boundaries, followed by sequencing. For the detection of large gene rearrangements, we performed multiplex ligation-dependent probe amplification. We report 13 families with spastic paraplegia type 11 carrying either novel or previously identified mutations. We describe a complex entire SPG11 rearrangement and show that large gene rearrangements are frequent among patients with spastic paraplegia type 11. Moreover, we mapped the deletion breakpoints of three different large SPG11 deletions and provide evidence for Alu microhomology-mediated exon deletion. Our analysis shows that the high number of repeated elements in SPG11 together with the presence of recombination hotspots and the high intrinsic instability of the 15q locus all contribute toward making this genomic region more prone to large gene rearrangements. These findings enlarge the amount of data relating repeated elements with neurodegenerative disorders and highlight their importance in human disease and genome evolution.

The temporal profile of the reaction of microglia, astrocytes, and macrophages in the delayed onset paraplegia after transient spinal cord ischemia in rabbits.

PubMed

Matsumoto, Satoshi; Matsumoto, Mishiya; Yamashita, Atsuo; Ohtake, Kazunobu; Ishida, Kazuyoshi; Morimoto, Yasuhiro; Sakabe, Takefumi

2003-06-01

In the present study, we sought to elucidate the temporal profile of the reaction of microglia, astrocytes, and macrophages in the progression of delayed onset motor dysfunction after spinal cord ischemia (15 min) in rabbits. At 2, 4, 8, 12, 24, and 48 h after reperfusion (9 animals in each), hind limb motor function was assessed, and the lumbar spinal cord was histologically examined. Delayed motor dysfunction was observed in most animals at 48 h after ischemia, which could be predicted by a poor recovery of segmental spinal cord evoked potentials at 15 min of reperfusion. In the gray matter of the lumbar spinal cord, both microglia and astrocytes were activated early (2 h) after reperfusion. Microglia were diffusely activated and engulfed motor neurons irrespective of the recovery of segmental spinal cord evoked potentials. In contrast, early astrocytic activation was confined to the area where neurons started to show degeneration. Macrophages were first detected at 8 h after reperfusion and mainly surrounded the infarction area later. Although the precise roles of the activation of microglia, astrocytes, and macrophages are to be further determined, the results indicate that understanding functional changes of astrocytes may be important in the mechanism of delayed onset motor dysfunction including paraplegia. Microglia and macrophages play a role in removing tissue debris after transient spinal cord ischemia. Disturbance of astrocytic defense mechanism, breakdown of the blood-spinal cord barrier, or both seemed to be involved in the development of delayed motor dysfunction.

Loss of spastin function results in disease-specific axonal defects in human pluripotent stem cell-based models of hereditary spastic paraplegia

PubMed Central

Denton, Kyle R.; Lei, Ling; Grenier, Jeremy; Rodionov, Vladimir; Blackstone, Craig; Li, Xue-Jun

2013-01-01

Human neuronal models of hereditary spastic paraplegias (HSP) that recapitulate disease-specific axonal pathology hold the key to understanding why certain axons degenerate in patients and to developing therapies. SPG4, the most common form of HSP, is caused by autosomal dominant mutations in the SPAST gene, which encodes the microtubule-severing ATPase spastin. Here, we have generated a human neuronal model of SPG4 by establishing induced pluripotent stem cells (iPSCs) from an SPG4 patient and differentiating these cells into telencephalic glutamatergic neurons. The SPG4 neurons displayed a significant increase in axonal swellings, which stained strongly for mitochondria and tau, indicating the accumulation of axonal transport cargoes. In addition, mitochondrial transport was decreased in SPG4 neurons, revealing that these patient iPSC-derived neurons recapitulate disease-specific axonal phenotypes. Interestingly, spastin protein levels were significantly decreased in SPG4 neurons, supporting a haploinsufficiency mechanism. Furthermore, cortical neurons derived from spastin-knockdown human embryonic stem cells (hESCs) exhibited similar axonal swellings, confirming that the axonal defects can be caused by loss of spastin function. These spastin-knockdown hESCs serve as an additional model for studying HSP. Finally, levels of stabilized acetylated-tubulin were significantly increased in SPG4 neurons. Vinblastine, a microtubule-destabilizing drug, rescued this axonal swelling phenotype in neurons derived from both SPG4 iPSCs and spastin-knockdown hESCs. Thus, this study demonstrates the successful establishment of human pluripotent stem cell-based neuronal models of SPG4, which will be valuable for dissecting the pathogenic cellular mechanisms and screening compounds to rescue the axonal degeneration in HSP. PMID:24123785

Neurological Complications Following Endoluminal Repair of Thoracic Aortic Disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morales, J. P.; Taylor, P. R.; Bell, R. E.

2007-09-15

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, generalmore » 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.« less

Ossified ligamentum flavum causing neurological deficit above the level of post-tuberculous kyphotic deformity.

PubMed

Subramani, Suresh; Shetty, Ajoy Prasad; Kanna, Rishi Mugesh; Shanmuganathan, Rajasekaran

2017-01-01

Late onset paraplegia is a rare complication of spinal tuberculosis. Disease reactivation and cord compression by internal gibbus are the common causes for neurological deficit. We report a patient with post-tubercular kyphotic deformity in whom the late onset paraplegia is caused by ossified ligamentum flavum above the level of kyphotic deformity. The deficit was attributable to the ossified ligamentum flavum and she recovered completely following posterior decompression and instrumented posterolateral fusion. To the best of our knowledge, this is the first report of this unusual cause of late onset paraplegia.

Effective Structured Query Formulation for Session Search

DTIC Science & Technology

2012-11-01

with top frequency are “type of paralysi”, “ quadriplegia paraplegia”, “paraplegia”, “spinal cord injury”, and “quadriplegic tetraplegic”, so the final... quadriplegia paraplegia) 0.004819 paraplegia 0.004819 #combine(spinal cord injury) 0.00241 #combine(quadriplegic tetraplegic) )”, where the

ATXN2 with intermediate-length CAG/CAA repeats does not seem to be a risk factor in hereditary spastic paraplegia.

PubMed

Nielsen, Troels Tolstrup; Svenstrup, Kirsten; Budtz-Jørgensen, Esben; Eiberg, Hans; Hasholt, Lis; Nielsen, Jørgen E

2012-10-15

Hereditary spastic paraplegia (HSP) confines a group of heterogeneous neurodegenerative disorders characterized by progressive spasticity and lower limb weakness. Age of onset is highly variable even in familial cases with known mutations suggesting that the disease is modulated by other yet unknown parameters. Although progressive gait disturbances, lower limb spasticity and extensor plantar responses are hallmarks of HSP these characteristics are also found in other neurodegenerative disorders, e.g. amytrophic lateral sclerosis (ALS). HSP has been linked to ALS and frontotemporal degeneration with motor neuron disease (FTD-MND), since TDP-43 positive inclusions have recently been found in an HSP subtype, and TDP-43 are found in abundance in pathological inclusions of both ALS and FTD-MND. Furthermore, ataxin-2 (encoded by the gene ATXN2), a polyglutamine containing protein elongated in spinocerebellar ataxia type 2, has been shown to be a modulator of TDP-43 induced toxicity in ALS animal and cell models. Finally, it has been shown that ATXN2 with non-pathogenic intermediate-length CAG/CAA repeat elongations (encoding the polyglutamine tract) is a genetic risk factor of ALS. Considering the similarities in the disease phenotype and the neuropathological link between ALS and HSP we hypothesized that intermediate-length CAG/CAA repeats in ATXN2 could be a modulator of HSP. We show that in a cohort of 181 HSP patients 4.9 % of the patients had intermediate-length CAG/CAA repeats in ATXN2 which was not significantly different from the frequencies in a Danish control cohort or in American and European control populations. However, the mean age of onset was significantly lower in HSP patients with intermediate-length CAG/CAA repeats in ATXN2 compared to patients with normal length repeats. Based on these results we conclude that ATXN2 is most likely not a risk factor of HSP, whereas it might serve as a modulator of age of onset. Copyright © 2012 Elsevier B.V. All

Interruption of spinal cord microglial signaling by alpha-2 agonist dexmedetomidine in a murine model of delayed paraplegia.

PubMed

Bell, Marshall T; Agoston, Viktor A; Freeman, Kirsten A; Puskas, Ferenc; Herson, Paco S; Mares, Joshua; Fullerton, David A; Reece, T Brett

2014-04-01

Despite investigation into preventable pharmacologic adjuncts, paraplegia continues to complicate thoracoabdominal aortic interventions. The alpha 2a adrenergic receptor agonist, dexmedetomidine, has been shown to preserve neurologic function and neuronal viability in a murine model of spinal cord ischemia reperfusion, although the mechanism remains elusive. We hypothesize that dexmedetomidine will blunt postischemic inflammation in vivo following thoracic aortic occlusion with in vitro demonstration of microglial inhibition following lipopolysaccharide (LPS) stimulation. Adult male C57BL/6 mice underwent 4 minutes of aortic occlusion. Mice received 25 μg/kg intraperitoneal dexmedetomidine (n = 8) or 0.9% normal saline (n = 7) at reperfusion and 12-hour intervals postoperatively until 48 hours. Additionally, sham mice (n = 3), which had aortic arch exposed with no occlusion, were included for comparison. Functional scoring was done at 6 hours following surgery and 12-hour intervals until 60 hours when spinal cords were removed and examined for neuronal viability and cytokine production. Additional analysis of microglia activation was done in 12 hours following surgery. Age- and sex-matched mice had spinal cord removed for microglial isolation culture. Cells were grown to confluence and stimulated with toll-like receptor-4 agonist LPS 100 ng/mL in presence of dexmedetomidine or vehicle control for 24 hours. Microglia and media were then removed for analysis of protein expression. Dexmedetomidine treatment at reperfusion significantly preserved neurologic function with mice in treatment group having a Basso Score of 6.3 in comparison to 2.3 in ischemic control group. Treatment was associated with a significant reduction in microglia activation and in interleukin-6 production. Microglial cells in isolation when stimulated with LPS had an increased production of proinflammatory cytokines and markers of activation. Treatment with dexmedetomidine significantly

Ambulatory and Non-Ambulatory Benefits of Lower Limb Exoskeleton Use, with and without FES, in Clinical and Community Settings

DTIC Science & Technology

2016-10-01

15. SUBJECT TERMS spinal cord injury, paraplegia, exoskeleton, physical medicine and rehabilitation, rehabilitation research, legged mobility...2. KEYWORDS • spinal cord injury • paraplegia • exoskeleton • physical medicine and rehabilitation • rehabilitation research • legged mobility...study protocol notebooks and record books have been assembled with session-by-session instructions and data entry. o Electronic data entry forms have

Electrical treatment of spinal cord injuries in the 18th and 19th centuries.

PubMed

Silver, John R; Weiner, M-F

2013-05-01

Two centuries ago, electricity was being used for the treatment of paraplegia and trials were taking place in France. This study aims to identify cases of traumatic paraplegia treated with electricity in the 19th century in order to assess the therapeutic benefit. Only four such cases were identified, none with a complete transection of the spinal cord since these patients would have died from pressure sores and urinary tract infections. The personalities involved, William Gull, William Erb, Guillaume Duchenne and Cyril Henry Golding Bird are portrayed and contemporaneous views on electrotherapy analysed. While the four patients apparently benefited from the treatment, the lack of follow-up and the incomplete data prevented a definitive conclusion on the therapeutic value of electrical treatment in traumatic paraplegia.

The effects of L-carnitine on spinal cord ischemia/reperfusion injury in rabbits.

PubMed

Tetik, O; Yagdi, T; Islamoglu, F; Calkavur, T; Posacioglu, H; Atay, Y; Ayik, F; Canpolat, L; Yuksel, M

2002-02-01

Paraplegia after distal aortic aneurysm repair remains a persistent clinical problem. We hypothesized that the tolerance of the spinal cord to an ischemic period could be improved with hypothermic Ringer's Lactate containing L-Carnitine. Twenty-eight New Zealand white rabbits were used as spinal cord ischemia models. We separated rabbits into four equal groups and clamped each animal's abdominal aorta distal to the left renal artery. We occluded the aortas above the iliac bifurcation for 30 minutes. In group I, the infrarenal aorta was clamped without infusing any solution. In group II, Ringer's Lactate solution was infused at + 25degrees C for 3 minutes at a rate of 5 ml/min into the isolated aortic segments immediately after cross-clamping and the last 3 minutes of ischemia. In group III, Ringer's Lactate solution at +3 degrees C was given in the same method as that of group II. In group IV, Ringer's Lactate solution at +3 degrees C plus 100 mg/kg of L-carnitine was infused using the same technique. We assessed the neurological status of the hind limbs 24 and 48 hours after operation according to Tarlov's criteria. All animals were sacrificed and spinal cords were harvested for histological analyses. The neurological status in groups III and IV was significantly superior to that of groups I and II. All the animals in group I had complete hind-limb paraplegia. Complete hind-limb paraplegia occurred in 5 rabbits in group II. Two of the 7 animals in group III had spastic paraplegia, and none at all in group IV. Histological analysis of the cross-clamped segments of the rabbits with paraplegia in group I, II and III revealed changes consistent with ischemic injury, while findings were normal for the normal animals in group III and IV. In this model, the infusion of hypothermic Ringer's Lactate contained L-carnitine provided sufficient spinal cord protection against ischemia. Clinically, this may be a useful adjunct for prevention of paraplegia during surgery of the

Reproducibility and effect of posture on impulse oscillation parameters in persons with spinal cord injury

PubMed Central

Cirnigliaro, Christopher M.; Lesser, Marvin; Moyer, Jeremy; Kirshblum, Steven C.; Bauman, William A.; Spungen, Ann M.

2012-01-01

Background The impulse oscillation system (IOS) offers significant value in the assessment of airway dynamics in persons with spinal cord injury (SCI) because of minimal patient effort but measurement reproducibility in SCI is unknown. Objective To evaluate between-day reproducibility and the effect of posture on airway resistance [respiratory resistances at 5 Hz (R5) and 20 Hz (R20)] in subjects with tetraplegia, paraplegia and able-bodied controls. Methods Ten subjects with tetraplegia, 10 subjects with paraplegia and 11 able-bodied individuals were evaluated using IOS. Three 30 second trials were obtained in each while in the seated and supine position on Day 1, and repeated on Day 2. Results The within-day coefficient of variation (CV%) for R5 and R20 were comparable in the 3 study groups in the seated and supine positions. Compared to controls, the between-day CV% for the combined data was higher in subjects with tetraplegia and paraplegia for R5 seated, and was higher in subjects with tetraplegia for R5 supine. Conclusions IOS has applicability to the study of within-day respiratory resistance in SCI. However, performing longer-term studies in subjects with tetraplegia and paraplegia may be problematic because of the greater variability for R5 when compared to able-bodied individuals. PMID:22330188

Marked hydronephrosis and hydroureter after distigmine therapy in an adult male patient with paraplegia due to spinal cord injury: a case report

PubMed Central

Mansour, Paul; Soni, Bakul M; Hughes, Peter L; Singh, Gurpreet; Oo, Tun

2009-01-01

Introduction Distigmine, a long-acting anti-cholinesterase, is associated with side effects such as Parkinsonism, cholinergic crisis, and rhabdomyolysis. We report a spinal cord injury patient, who developed marked hydronephrosis and hydroureter after distigmine therapy, which led to a series of complications over subsequent years. Case presentation A 38-year-old male developed T-9 paraplegia in 1989. Intravenous urography, performed in 1989, showed normal kidneys, ureters and bladder. He was prescribed distigmine bromide orally and was allowed to pass urine spontaneously. In 1992, intravenous urography showed bilateral marked hydronephrosis and hydroureter. Distigmine was discontinued. He continued to pass urine spontaneously. In 2006, intravenous urography showed moderate dilatation of both pelvicalyceal systems and ureters down to the level of urinary bladder. This patient was performing self-catheterisation only once a day. He was advised to do catheterisations at least three times a day. In December 2008, this patient developed haematuriawhich lasted for nearly four months.. He received trimethoprim, then cephalexin, followed by Macrodantin, amoxicillin and ciprofloxacin. In February 2009, intravenous urography showed calculus at the lower pole of left kidney. Both kidneys were moderately hydronephrotic. Ureters were dilated down to the bladder. Dilute contrast was seen in the bladder due to residual urine. This patient was advised to perform six catheterisations a day, and take propiverine hydrochloride 15 mg, three times a day. Microbiology of urine showed Klebsiella oxytoca, Pseudomonas aeruginosa, and Enterococcus faecalis. Cystoscopy revealed papillary lesions in bladder neck and trigone. Transurethral resection was performed. Histology showed marked chronic cystitis including follicular cystitis and papillary/polypoid cystitis. There was no evidence of malignancy. Conclusion Distigmine therapy resulted in marked bilateral hydronephrosis and hydroureter

Nutrient Intake and Body Habitus After Spinal Cord Injury: An Analysis by Sex and Level of Injury

PubMed Central

Groah, Suzanne L; Nash, Mark S; Ljungberg, Inger H; Libin, Alexander; Hamm, Larry F; Ward, Emily; Burns, Patricia A; Enfield, Gwen

2009-01-01

Background/Objectives: To examine nutrient intake and body mass index (BMI) in the spinal cord injury (SCI) population according to level of injury and sex. Design: Cross-sectional study conducted at 2 SCI treatment centers. Participants/Methods: Seventy-three community-dwelling individuals with C5-T12 ASIA Impairment Scale (AIS) A or B SCI. Subjects were divided into 4 groups: male tetraplegia (N = 24), male paraplegia (N = 37), female tetraplegia (N = 1), and female paraplegia (N = 11). Mean age was 38 years; 84% were male; 34% were white, 41% were African American, and 25% were Hispanic. Participants completed a 4-day food log examining habitual diet. Dietary composition was analyzed using Food Processor II v 7.6 software. Results: Excluding the 1 woman with tetraplegia, total calorie intake for the other 3 groups was below observed values for the general population. The female paraplegia group tended to have a lower total calorie intake than the other groups, although macronutrient intake was within the recommended range. The male tetraplegia group, male paraplegia group, and the 1 woman with tetraplegia all had higher than recommended fat intake. Intake of several vitamins, minerals, and macronutrients did not meet recommended levels or were excessively low, whereas sodium and alcohol intake were elevated. Using adjusted BMI tables, 74.0% of individuals with SCI were overweight or obese. Conclusions: Women with paraplegia tended to maintain healthier diets, reflected by lower caloric and fat intakes, fewer key nutrients falling outside recommended guidelines, and less overweight or obesity. Individuals with tetraplegia tended to take in more calories and had higher BMIs, and using adjusted BMI, the majority of the population was overweight or obese. The majority of people with SCI would benefit from nutritional counseling to prevent emerging secondary conditions as the population with SCI ages. PMID:19264046

Wheelchair-specific fitness of persons with a long-term spinal cord injury: cross-sectional study on effects of time since injury and physical activity level.

PubMed

de Groot, Sonja; van der Scheer, Jan W; Bakkum, Arjan J T; Adriaansen, Jacinthe J E; Smit, Christof A; Dijkstra, Catja; Post, Marcel W M; van der Woude, Lucas H V

2016-01-01

To study the impact of time since injury (TSI) and physical activity (PA) on fitness of persons with spinal cord injury (SCI). Cross-sectional study. Persons with SCI (N = 158) in three TSI strata: 10-19, 20-29 and ≥30 years after SCI and divided in an active and inactive group. Fitness [peak power output (POpeak) and peak oxygen uptake (VO2peak)] was assessed. In persons with tetraplegia, no significant relationship was found between TSI and fitness after controlling for confounders, while a higher activity level was related to a higher POpeak in this group. Active people with tetraplegia also showed less decline in POpeak with an increase in TSI compared to inactive people. In persons with paraplegia, after controlling for confounders, it was shown that TSI had a negative effect on POpeak, while PA was not significantly associated with fitness in people with paraplegia. In people with paraplegia, fitness was significantly lower in those with a longer TSI. Persons with a long TSI might need more attention to remain fit and PA might be an important element in that respect as shown by the results of the group with a tetraplegia. Wheelchair-specific fitness seems to diminish over time after paraplegia. An active lifestyle is related to wheelchair-specific fitness in persons with tetraplegia. Prevention of long-term deconditioning is very important.

Economic Values for Evaluation of Federal Aviation Administration Investment and Regulatory Programs

DTIC Science & Technology

1989-10-01

Classifications: Critical Spinal Cord Injury Resulting in Quadriplegia $ 2,210,000 Critical Head Injury Resulting in Total Disability $ 2,460,000...34 Table 8 Percentage Utility Loss Associated with Severe Injuries AIS 4 AIS 5 Quadriplegia Paraplegia Quadriplegia Paraplegia Spinal Cord 109% 46% 109... Quadriplegia : d Air Carrier Domestic Pass. 1,719,071 91,522 223,492 23,784 75.4% Int’l Pass. 1,719,071 237,261 225,049 23,915 4.8% Commuter 1,719,071

Paraplegia due to adrenomyeloneuropathy.

PubMed

Lamid, S; El Ghatit, A Z

1984-04-01

Only nine cases of adrenomyeloneuropathy have been reported in the literature. It manifested as adrenal insufficiency, spastic paraparesis, loss of bowel, bladder and sexual functions, and peripheral neuropathy. Our paper describes a patient with the diagnosis of adrenomyeloneuropathy who was admitted to our hospital for rehabilitation. Family and neurological history, physical examination and special laboratory studies such as ACTH stimulation test, electrodiagnostic findings, cystometrogram and sexual function evaluation were essential to establish the diagnosis of this disease. His rehabilitation consisted of bowel and bladder training, ambulation with long-leg braces and crutches, wheelchair mobilization and transfers, and independence of all activities of daily living.

Aspergillus spondylodiscitis in an immunocompetent paraplegic patient.

PubMed

Schubert, M; Schär, G; Curt, A; Dietz, V

1998-11-01

A case of an immunocompetent 60 year old patient is reported, who suffered extensive thoracic spinal injury and paraplegia after polytrauma. In the course of rehabilitation he developed aspergillus spondylodiscitis in a part of the thoraco-lumbar spine which was primarily uninjured. The diagnostic assessment and therapeutic approach of this rare disorder is elucidated and discussed in the context of paraplegia and polytrauma. Possible mechanisms of inoculation and spreading of the moulds as well as predisposing factors of the disease are discussed in this paper and a review of the recent literature is provided.

Inhibition of TFG function causes hereditary axon degeneration by impairing endoplasmic reticulum structure.

PubMed

Beetz, Christian; Johnson, Adam; Schuh, Amber L; Thakur, Seema; Varga, Rita-Eva; Fothergill, Thomas; Hertel, Nicole; Bomba-Warczak, Ewa; Thiele, Holger; Nürnberg, Gudrun; Altmüller, Janine; Saxena, Renu; Chapman, Edwin R; Dent, Erik W; Nürnberg, Peter; Audhya, Anjon

2013-03-26

Hereditary spastic paraplegias are a clinically and genetically heterogeneous group of gait disorders. Their pathological hallmark is a length-dependent distal axonopathy of nerve fibers in the corticospinal tract. Involvement of other neurons can cause additional neurological symptoms, which define a diverse set of complex hereditary spastic paraplegias. We present two siblings who have the unusual combination of early-onset spastic paraplegia, optic atrophy, and neuropathy. Genome-wide SNP-typing, linkage analysis, and exome sequencing revealed a homozygous c.316C>T (p.R106C) variant in the Trk-fused gene (TFG) as the only plausible mutation. Biochemical characterization of the mutant protein demonstrated a defect in its ability to self-assemble into an oligomeric complex, which is critical for normal TFG function. In cell lines, TFG inhibition slows protein secretion from the endoplasmic reticulum (ER) and alters ER morphology, disrupting organization of peripheral ER tubules and causing collapse of the ER network onto the underlying microtubule cytoskeleton. The present study provides a unique link between altered ER architecture and neurodegeneration.

[Neuro-urological diagnosis and therapy of lower urinary tract dysfunction in patients with spinal cord injury : S2k Guideline of the German-Speaking Medical Society of Paraplegia (DMGP), AWMF register no. 179/001].

PubMed

Böthig, R; Domurath, B; Kaufmann, A; Bremer, J; Vance, W; Kurze, I

2017-06-01

Most patients with spinal cord injury (SCI) suffer from neurogenic lower urinary tract dysfunction (NLUTD), bowel dysfunction and sexual dysfunction. If these remain untreated, severe medical complications and serious limitations (restrictions) in quality of life are imminent. In the long term, there are considerable differences in the treatment results of highly specialized centers versus other treatment facilities. Against this background, a consensus-based guideline, according to the AWMF (Association of the Scientific Medical Societies in Germany) criteria (S2k), was developed by the neuro-urology working group of the DMPG (German-Speaking Medical Society of Paraplegia). The guideline defines the principles and objectives of the neuro-urological care of patients with SCI and discusses in detail the principles of diagnosis and therapy of NLUTD. The need for video-urodynamic studies as a basis for the classification of the NLUTD and as a foundation for the development of a treatment strategy is emphasized. Both conservative and surgical therapy options and their indications are explained in detail. Possible complications and their prevention in the long-term course of SCI are presented with a particular consideration of the specific features of urinary tract infections and autonomic dysreflexia. Finally, the principles of the provision of urological appliances are discussed. The presented S2k guideline provides the current standards in the neuro-urological care of patients with NLUTD due to SCI. Their consistent implementation both in the acute and chronic phase as well as in the context of lifelong surveillance of SCI patients should prevent the impending complications of NLUTD.

Spinal cord ischemia following thoracotomy without epidural anesthesia.

PubMed

Raz, Aeyal; Avramovich, Aharon; Saraf-Lavi, Efrat; Saute, Milton; Eidelman, Leonid A

2006-06-01

Paraplegia is an uncommon yet devastating complication following thoracotomy, usually caused by compression or ischemia of the spinal cord. Ischemia without compression may be a result of global ischemia, vascular injury and other causes. Epidural anesthesia has been implicated as a major cause. This report highlights the fact that perioperative cord ischemia and paraplegia may be unrelated to epidural intervention. A 71-yr-old woman was admitted for a left upper lobectomy for resection of a non-small cell carcinoma of the lung. The patient refused epidural catheter placement and underwent a left T5-6 thoracotomy under general anesthesia. During surgery, she was hemodynamically stable and good oxygen saturation was maintained. Several hours following surgery the patient complained of loss of sensation in her legs. Neurological examination disclosed a complete motor and sensory block at the T5-6 level. Magnetic resonance imaging (MRI) revealed spinal cord ischemia. The patient received iv steroid treatment, but remained paraplegic. Five months following the surgery there was only partial improvement in her motor symptoms. A follow-up MRI study was consistent with a diagnosis of spinal cord ischemia. In this case of paraplegia following thoracic surgery for lung resection, epidural anesthesia/analgesia was not used. The MRI demonstrated evidence of spinal cord ischemia, and no evidence of cord compression. This case highlights that etiologies other than epidural intervention, such as injury to the spinal segmental arteries during thoracotomy, should be considered as potential causes of cord ischemia and resultant paraplegia in this surgical population.

34 CFR 350.5 - What definitions apply?

Code of Federal Regulations, 2014 CFR

2014-07-01

..., blindness, burn injury, cancer, cerebral palsy, cystic fibrosis, deafness, head injury, heart disease... epilepsy), paraplegia, quadriplegia, other spinal cord impairments, sickle cell anemia, specific learning...

34 CFR 350.5 - What definitions apply?

Code of Federal Regulations, 2013 CFR

2013-07-01

..., blindness, burn injury, cancer, cerebral palsy, cystic fibrosis, deafness, head injury, heart disease... epilepsy), paraplegia, quadriplegia, other spinal cord impairments, sickle cell anemia, specific learning...

Mobility Outcomes Following Five Training Sessions with a Powered Exoskeleton

PubMed Central

Hartigan, Clare; Kandilakis, Casey; Dalley, Skyler; Clausen, Mike; Wilson, Edgar; Morrison, Scott; Etheridge, Steven

2015-01-01

Background: Loss of legged mobility due to spinal cord injury (SCI) is associated with multiple physiological and psychological impacts. Powered exoskeletons offer the possibility of regained mobility and reversal or prevention of the secondary effects associated with immobility. Objective: This study was conducted to evaluate mobility outcomes for individuals with SCI after 5 gait-training sessions with a powered exoskeleton, with a primary goal of characterizing the ease of learning and usability of the system. Methods: Sixteen subjects with SCI were enrolled in a pilot clinical trial at Shepherd Center, Atlanta, Georgia, with injury levels ranging from C5 complete to L1 incomplete. An investigational Indego exoskeleton research kit was evaluated for ease of use and efficacy in providing legged mobility. Outcome measures of the study included the 10-meter walk test (10MWT) and the 6-minute walk test (6MWT) as well as measures of independence including donning and doffing times and the ability to walk on various surfaces. Results: At the end of 5 sessions (1.5 hours per session), average walking speed was 0.22 m/s for persons with C5-6 motor complete tetraplegia, 0.26 m/s for T1-8 motor complete paraplegia, and 0.45 m/s for T9-L1 paraplegia. Distances covered in 6 minutes averaged 64 meters for those with C5-6, 74 meters for T1-8, and 121 meters for T9-L1. Additionally, all participants were able to walk on both indoor and outdoor surfaces. Conclusions: Results after only 5 sessions suggest that persons with tetraplegia and paraplegia learn to use the Indego exoskeleton quickly and can manage a variety of surfaces. Walking speeds and distances achieved also indicate that some individuals with paraplegia can quickly become limited community ambulators using this system. PMID:26364278

[Motor evoked potentials in thoracoabdominal aortic surgery].

PubMed

Magro, Cátia; Nora, David; Marques, Miguel; Alves, Angela Garcia

2012-01-01

Thoracoabdominal aortic disease (aneurysm or dissection) has increased in recent decades. Surgery is the curative treatment but is associated to high perioperative morbidity and mortality risks. Paraplegia is one of the most severe complications, whose incidence has decreased significantly with the implementation of spinal cord protection strategies. No single method or combination of methods has proven to be fully effective in preventing paraplegia. This review is intended to analyse the scientific evidence available on the role of intraoperative monitoring with motor evoked potentials in the neurological outcome of patients undergoing thoracoabdominal aortic surgery. An online search (PubMed) was conducted. Relevant references were selected and reviewed. Intraoperative monitoring with motor evoked potentials (MEP) allows early detection of ischemic events and a targeted intervention to prevent the development of spinal cord injury, significantly reducing the incidence of postoperative paraplegia. MEP monitoring may undergo several intraoperative interferences which may compromise their interpretation. Neuromuscular blockade is the main limiting factor of anesthetic origin. It is essential to strike a balance between monitoring conditions and surgical and anesthetic needs as well as to evaluate the risks and benefits of the technique for each patient. MEP monitoring improves neurological outcome when integrated in a multidisciplinary strategy which must include multiple protective mechanisms that should be tailored to each hospital reality.

A rare cause of late onset neurological deficit in post tuberculous kyphotic deformity-case report.

PubMed

Subramani, Suresh; Shetty, Ajoy Prasad; Kanna, Rishi M; Rajasekaran, Shanmuganathan

2017-12-01

Late onset neurological deficit is a rare complication of spinal tuberculosis. Reactivation of the disease and compression by internal gibbus are the common causes for late onset neurological deficit. We report a rare cause of late onset paraplegia in a patient with post tubercular kyphotic deformity. The late onset neurological deficit was due to the adjacent segment degeneration proximal to the kyphotic deformity. Posterior hypertrophied ligamentum flavum and anterior disc osteophyte complex caused the cord compression. The increased stress for prolonged period at the end of the deformity was the reason for the accelerated degeneration. Patient underwent posterior decompression, posterolateral and interbody fusion. Deformity correction was not done. To our best knowledge, this is only the second report of this unusual cause of late onset paraplegia.

A rare cause of late onset neurological deficit in post tuberculous kyphotic deformity—case report

PubMed Central

Shetty, Ajoy Prasad; Kanna, Rishi M.; Rajasekaran, Shanmuganathan

2017-01-01

Late onset neurological deficit is a rare complication of spinal tuberculosis. Reactivation of the disease and compression by internal gibbus are the common causes for late onset neurological deficit. We report a rare cause of late onset paraplegia in a patient with post tubercular kyphotic deformity. The late onset neurological deficit was due to the adjacent segment degeneration proximal to the kyphotic deformity. Posterior hypertrophied ligamentum flavum and anterior disc osteophyte complex caused the cord compression. The increased stress for prolonged period at the end of the deformity was the reason for the accelerated degeneration. Patient underwent posterior decompression, posterolateral and interbody fusion. Deformity correction was not done. To our best knowledge, this is only the second report of this unusual cause of late onset paraplegia. PMID:29354759

Treatment of spinal fractures with paraplegia.

PubMed

Riska, E B; Myllynen, P

1981-01-01

Of 206 patients with vertebral fractures in the thoraco-lumbar spine with spinal cord injuries, an antero-lateral decompression with stabilization of the injured segment of the vertebral column was undertaken in 56 cases. In all these cases there was a compression of the spinal cord from the front. 8 patients made a complete recovery, 31 a good recovery, and 6 were improved. In 8 patients no improvement was noted. 2 patients developed pressure sores later and 1 patient died one year after the operation of uraemia. 22 patients out of 55 got a normal function of the bladder and 25 patients out of 54 a normal function of the anal sphincter. 16 patients out of 17 made a complete or good recovery after removal of a displaced rotated vertebral bony fragment from the spinal canal, and 7 patients out of 9 with wedge shaped fractures. In our clinic today, in cases of vertebral fractures with neural involvement, reduction and internal fixation with Harrington rods and fusion of the injured segment is undertaken as soon as possible, also during the night. If narrowing of the neural canal and compression of the spinal cord are verified, a decompression operation with interbody fusion is undertaken during the next days.

Instilling positive beliefs about disabilities: pilot testing a novel experiential learning activity for rehabilitation students.

PubMed

Silverman, Arielle M; Pitonyak, Jennifer S; Nelson, Ian K; Matsuda, Patricia N; Kartin, Deborah; Molton, Ivan R

2018-05-01

To develop and test a novel impairment simulation activity to teach beginning rehabilitation students how people adapt to physical impairments. Masters of Occupational Therapy students (n = 14) and Doctor of Physical Therapy students (n = 18) completed the study during the first month of their program. Students were randomized to the experimental or control learning activity. Experimental students learned to perform simple tasks while simulating paraplegia and hemiplegia. Control students viewed videos of others completing tasks with these impairments. Before and after the learning activities, all students estimated average self-perceived health, life satisfaction, and depression ratings among people with paraplegia and hemiplegia. Experimental students increased their estimates of self-perceived health, and decreased their estimates of depression rates, among people with paraplegia and hemiplegia after the learning activity. The control activity had no effect on these estimates. Impairment simulation can be an effective way to teach rehabilitation students about the adaptations that people make to physical impairments. Positive impairment simulations should allow students to experience success in completing activities of daily living with impairments. Impairment simulation is complementary to other pedagogical methods, such as simulated clinical encounters using standardized patients. Implication of Rehabilitation It is important for rehabilitation students to learn how people live well with disabilities. Impairment simulations can improve students' assessments of quality of life with disabilities. To be beneficial, impairment simulations must include guided exposure to effective methods for completing daily tasks with disabilities.

Exome sequencing and SNP analysis detect novel compound heterozygosity in fatty acid hydroxylase-associated neurodegeneration

PubMed Central

Pierson, Tyler Mark; Simeonov, Dimitre R; Sincan, Murat; Adams, David A; Markello, Thomas; Golas, Gretchen; Fuentes-Fajardo, Karin; Hansen, Nancy F; Cherukuri, Praveen F; Cruz, Pedro; Blackstone, Craig; Tifft, Cynthia; Boerkoel, Cornelius F; Gahl, William A

2012-01-01

Fatty acid hydroxylase-associated neurodegeneration due to fatty acid 2-hydroxylase deficiency presents with a wide range of phenotypes including spastic paraplegia, leukodystrophy, and/or brain iron deposition. All previously described families with this disorder were consanguineous, with homozygous mutations in the probands. We describe a 10-year-old male, from a non-consanguineous family, with progressive spastic paraplegia, dystonia, ataxia, and cognitive decline associated with a sural axonal neuropathy. The use of high-throughput sequencing techniques combined with SNP array analyses revealed a novel paternally derived missense mutation and an overlapping novel maternally derived ∼28-kb genomic deletion in FA2H. This patient provides further insight into the consistent features of this disorder and expands our understanding of its phenotypic presentation. The presence of a sural nerve axonal neuropathy had not been previously associated with this disorder and so may extend the phenotype. PMID:22146942

Shoulder Muscular Demand During Lever-Activated Vs Pushrim Wheelchair Propulsion in Persons With Spinal Cord Injury

PubMed Central

Requejo, Philip Santos; Lee, Sharon E; Mulroy, Sara J; Haubert, Lisa Lighthall; Bontrager, Ernest L; Gronley, JoAnne K; Perry, Jacquelin

2008-01-01

Background/Objective: The high demand on the upper limbs during manual wheelchair (WC) use contributes to a high prevalence of shoulder pathology in people with spinal cord injury (SCI). Lever-activated (LEVER) WCs have been presented as a less demanding alternative mode of manual WC propulsion. The objective of this study was to evaluate the shoulder muscle electromyographic activity and propulsion characteristics in manual WC users with SCI propelling a standard pushrim (ST) and LEVER WC design. Methods: Twenty men with complete injuries (ASIA A or B) and tetraplegia (C6, n = 5; C7, n = 7) or paraplegia (n = 8) secondary to SCI propelled ST and LEVER WCs at 3 propulsion conditions on a stationary ergometer: self-selected free, self-selected fast, and simulated graded resistance. Average velocity, cycle distance, and cadence; median and peak electromyographic intensity; and duration of electromyography of anterior deltoid, pectoralis major, supraspinatus, and infraspinatus muscles were compared between LEVER and ST WC propulsion. Results: Significant decreases in pectoralis major and supraspinatus activity were recorded during LEVER compared with ST WC propulsion. However, anterior deltoid and infraspinatus intensities tended to increase during LEVER WC propulsion. Participants with tetraplegia had similar or greater anterior deltoid, pectoralis major, and infraspinatus activity for both ST and LEVER WC propulsion compared with the men with paraplegia. Conclusions: Use of the LEVER WC reduced and shifted the shoulder muscular demands in individuals with paraplegia and tetraplegia. Further studies are needed to determine the impact of LEVER WC propulsion on long-term shoulder function. PMID:19086715

Correlation of diffusion tensor imaging parameters with neural status in Pott's spine.

PubMed

Jain, Nikhil; Saini, Namita Singh; Kumar, Sudhir; Rajagopalan, Mukunth; Chakraborti, Kanti Lal; Jain, Anil Kumar

2016-04-29

Diffusion tensor imaging (DTI) has been used in cervical trauma and spondylotic myelopathy, and it has been found to correlate with neural deficit and prognosticate neural recovery. Such a correlation has not been studied in Pott's spine with paraplegia. Hence, this prospective study has been used to find correlation of DTI parameters with neural deficit in these patients. Thirty-four patients of spinal TB were enrolled and DTI was performed before the start of treatment and after six months. Fractional anisotropy (FA), Mean diffusivity (MD), and Tractography were studied. Neurological deficit was graded by the Jain and Sinha scoring. Changes in FA and MD at and below the site of lesion (SOL) were compared to above the SOL (control) using the unpaired t-test. Pre-treatment and post-treatment values were also compared using the paired t-test. Correlation of DTI parameters with neurological score was done by Pearson's correlation. Subjective assessment of Tractography images was done. Mean average FA was not significantly decreased at the SOL in patients with paraplegia as compared to control. After six months of treatment, a significant decrease (p = 0.02) in mean average FA at the SOL compared to pre-treatment was seen. Moderate positive correlation (r = 0.49) between mean average FA and neural score after six months of treatment was found. Tractography images were not consistent with severity of paraplegia. Unlike spondylotic myelopathy and trauma, epidural collection and its organized inflammatory tissue in Pott's spine precludes accurate assessment of diffusion characteristics of the compressed cord.

Swimming for the Handicapped Child and Adult: Occasional Papers No. 10.

ERIC Educational Resources Information Center

Neishloss, Lou

Outlined are physiological and psychological values of swimming for the handicapped, basic principles and teaching procedures for instructing physically handicapped persons, and specific suggestions for teaching swimming to persons with the following conditions; amputations, polio, paraplegia, cerebral palsy, spina bifida, Legg-Perthes Disease,…

Genetics Home Reference: tetrasomy 18p

MedlinePlus

... parental origin and different mechanisms of formation. Eur J Hum Genet. 1996;4(3):160-7. Erratum in: Eur J Hum Genet 1996;4(5):291. Citation on ... paraplegia as a feature of tetrasomy 18p. Am J Med Genet A. 2010 Sep;152A(9):2173- ...

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

PubMed

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

1975-01-01

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.

Duration and functional outcome of spinal cord injury rehabilitation in the Netherlands.

PubMed

Post, Marcel W M; Dallmeijer, Annet J; Angenot, Edmond L D; van Asbeck, Floris W A; van der Woude, Lucas H V

2005-01-01

This study describes the length of stay (LOS) and functional outcome of spinal cord injury (SCI) in the Netherlands and its determinants. Data of 157 patients from eight rehabilitation centers were available. Mean age was 40.0 years and 76.4% were traumatic injuries, 39.8% had tetraplegia, and 69.9% had a motor complete SCI. Median LOS was 240 days (interquartile range 164-322). Median motor Functional Independence Measure (FIM) scores at discharge were 37.3 for persons with complete tetraplegia and 69.7 for persons with complete paraplegia. Level and completeness of injury, bed rest because of pressure sores, and LOS were predictors of motor FIM scores. Duration of SCI rehabilitation in the Netherlands is long compared with the literature. Functional outcome appears slightly better in persons with complete tetraplegia, but not in persons with complete paraplegia when compared with data from the United States. International studies are necessary to reveal strengths and weaknesses of SCI rehabilitation systems in different countries.

Genetics Home Reference: spastic paraplegia type 11

MedlinePlus

... Inheritance Pattern This condition is inherited in an autosomal recessive pattern , which means both copies of the ... mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the ...

Acute progressive paraplegia in heroin-associated myelopathy.

PubMed

Mahoney, Kyle W; Romba, Meghan; Gailloud, Philippe; Izbudak, Izlem; Saylor, Deanna

2018-05-01

As the opioid epidemic continues, understanding manifestations of abuse, including heroin-associated myelopathy remains essential. Here we describe a young man with a past medical history significant for polysubstance abuse who developed acute-onset, rapidly progressive myelopathy after resumption of intravenous heroin use. He had significant spinal cord involvement with findings suggestive of heroin-associated myelopathy. The salient features of this case include diffusion imaging of the spine and spinal angiography supporting a possible vasculopathy as the pathophysiologic mechanism underlying heroin-associated myelopathy. Additionally, CSF studies showed the transition from a neutrophilic pleocytosis to a lymphocytic pleocytosis suggesting an inflammatory component. Copyright © 2018 Elsevier Ltd. All rights reserved.

Genetics Home Reference: spastic paraplegia type 15

MedlinePlus

... This protein is important in a process called autophagy, in which worn-out cell parts and unneeded ... As a result, functional autophagosomes are not produced, autophagy cannot occur, and recycling of materials within cells ...

Genetics Home Reference: spastic paraplegia type 4

MedlinePlus

... 2005 Jul 7. Review. Citation on PubMed Yip AG, Dürr A, Marchuk DA, Ashley-Koch A, Hentati ... qualified healthcare professional . About Selection Criteria for Links Data Files & API Site Map Subscribe Customer Support USA. ...

Relationship of physical therapy inpatient rehabilitation interventions and patient characteristics to outcomes following spinal cord injury: The SCIRehab project

PubMed Central

Teeter, Laura; Gassaway, Julie; Taylor, Sally; LaBarbera, Jacqueline; McDowell, Shari; Backus, Deborah; Zanca, Jeanne M.; Natale, Audrey; Cabrera, Jordan; Smout, Randall J.; Kreider, Scott E. D.; Whiteneck, Gale

2012-01-01

Background/objective Examine associations of type and quantity of physical therapy (PT) interventions delivered during inpatient spinal cord injury (SCI) rehabilitation and patient characteristics with outcomes at the time of discharge and at 1 year post-injury. Methods Physical therapists delivering routine care documented details of PT interventions provided. Regression modeling was used to predict outcomes at discharge and 1 year post-injury for a 75% subset; models were validated with the remaining 25%. Injury subgroups also were examined: motor complete low tetraplegia, motor complete paraplegia, and American Spinal Injury Association (ASIA) Impairment Scale (AIS) D motor incomplete tetra-/paraplegia. Results PT treatment variables explain more variation in three functionally homogeneous subgroups than in the total sample. Among patients with motor complete low tetraplegia, higher scores for the transfer component of the discharge motor Functional Independence Measure () are strongly associated with more time spent working on manual wheelchair skills. Being male is the most predictive variable for the motor FIM score at discharge for patients with motor complete paraplegia. Admission ASIA lower extremity motor score (LEMS) and change in LEMS were the factors most predictive for having the primary locomotion mode of “walk” or “both (walk and wheelchair)” on the discharge motor FIM for patients with AIS D injuries. Conclusion Injury classification influences type and quantity of PT interventions during inpatient SCI rehabilitation and is a strong predictor of outcomes at discharge and 1 year post-injury. The impact of PT treatment increases when patient groupings become more homogeneous and outcomes become specific to the groupings. Note This is the second of nine articles in the SCIRehab series. PMID:23318034

Alpha-2 agonist attenuates ischemic injury in spinal cord neurons.

PubMed

Freeman, Kirsten A; Puskas, Ferenc; Bell, Marshall T; Mares, Joshua M; Foley, Lisa S; Weyant, Michael J; Cleveland, Joseph C; Fullerton, David A; Meng, Xianzhong; Herson, Paco S; Reece, T Brett

2015-05-01

Paraplegia secondary to spinal cord ischemia-reperfusion injury remains a devastating complication of thoracoabdominal aortic intervention. The complex interactions between injured neurons and activated leukocytes have limited the understanding of neuron-specific injury. We hypothesize that spinal cord neuron cell cultures subjected to oxygen-glucose deprivation (OGD) would simulate ischemia-reperfusion injury, which could be attenuated by specific alpha-2a agonism in an Akt-dependent fashion. Spinal cords from perinatal mice were harvested, and neurons cultured in vitro for 7-10 d. Cells were pretreated with 1 μM dexmedetomidine (Dex) and subjected to OGD in an anoxic chamber. Viability was determined by MTT assay. Deoxyuridine-triphosphate nick-end labeling staining and lactate dehydrogenase (LDH) assay were used for apoptosis and necrosis identification, respectively. Western blot was used for protein analysis. Vehicle control cells were only 59% viable after 1 h of OGD. Pretreatment with Dex significantly preserves neuronal viability with 88% viable (P < 0.05). Dex significantly decreased apoptotic cells compared with that of vehicle control cells by 50% (P < 0.05). Necrosis was not significantly different between treatment groups. Mechanistically, Dex treatment significantly increased phosphorylated Akt (P < 0.05), but protective effects of Dex were eliminated by an alpha-2a antagonist or Akt inhibitor (P < 0.05). Using a novel spinal cord neuron cell culture, OGD mimics neuronal metabolic derangement responsible for paraplegia after aortic surgery. Dex preserves neuronal viability and decreases apoptosis in an Akt-dependent fashion. Dex demonstrates clinical promise for reducing the risk of paraplegia after high-risk aortic surgery. Copyright © 2015 Elsevier Inc. All rights reserved.

Perceptions of Shared Decision Making Among Patients with Spinal Cord Injuries/Disorders.

PubMed

Locatelli, Sara M; Etingen, Bella; Heinemann, Allen; Neumann, Holly DeMark; Miskovic, Ana; Chen, David; LaVela, Sherri L

2016-01-01

Background: Individuals with spinal cord injuries/disorders (SCI/D) are interested in, and benefit from, shared decision making (SDM). Objective: To explore SDM among individuals with SCI/D and how demographics and health and SCI/D characteristics are related to SDM. Method: Individuals with SCI/D who were at least 1 year post injury, resided in the Chicago metropolitan area, and received SCI care at a Veterans Affairs (VA; n = 124) or an SCI Model Systems facility ( n = 326) completed a mailed survey measuring demographics, health and SCI/D characteristics, physical and mental health status, and perceptions of care, including SDM, using the Combined Outcome Measure for Risk Communication and Treatment Decision-Making Effectiveness (COMRADE) that assesses decision-making effectiveness (effectiveness) and risk communication (communication). Bivariate analyses and multiple linear regression were used to identify variables associated with SDM. Results: Participants were mostly male (83%) and White (70%) and were an average age of 54 years ( SD = 14.3). Most had traumatic etiology, 44% paraplegia, and 49% complete injury. Veteran/civilian status and demographics were unrelated to scores. Bivariate analyses showed that individuals with tetraplegia had better effectiveness scores than those with paraplegia. Better effectiveness was correlated with better physical and mental health; better communication was correlated with better mental health. Multiple linear regressions showed that tetraplegia, better physical health, and better mental health were associated with better effectiveness, and better mental health was associated with better communication. Conclusion: SCI/D and health characteristics were the only variables associated with SDM. Interventions to increase engagement in SDM and provider attention to SDM may be beneficial, especially for individuals with paraplegia or in poorer physical and mental health.

Surgical outcome of traumatic aortic disruption of the thoracic aorta in Songklanagarind Hospital.

PubMed

Chittithavorn, Voravit; Vasinanukorn, Prasert; Rergkliang, Chareonkiat; Chetpaophan, Apirak

2004-09-01

This retrospective study collected data from 11 patients who underwent TDTA' repair from February 1987 to June 2003, 10 patients were men (90.9%) and 1 was a woman (9.09%) with a mean age of 32 years. All patients had a blunt injury from a violent motor vehicle accident. None of them required thoracotomy at the emergency room. Standard chest x-ray was done in every patient and the widening of the upper mediastinum was mainly found in 10 patients (90.9%), hemothorax in 8 patients, blurred aortic knob in 7 patients, lower left main bronchus in 3 patients, pleural apical cap in 2 patients and pneumothorax in 1 patient, 8 patients were investigated by CT scan and presented a positive study. 3 patients (27.27%) were diagnosed by both aortogram and CT scan anda pseudo-false aneurysm was found Multi organ system injury was mainly found in 10 patients (90.91%). 7 patients (63.64%) had hypovolumic shock on admission, 3 patients died postoperation and 2 of them had experience of postoperative paraplegia. Clamp and sew technique was used in 6 patients (54.54%). The duration of aortic cross clamp time ranged from 19-67 minutes (mean time = 39.30 min.) Pneumonia was the significant postoperative complication found in 3 patients, including acute renal failure, ARDS (all died) and paraplegia in 2 patients. The duration of the aortic cross clamp time that was used in the patients who presented with paraplegia was more than 40 minutes. 1 patient had delayed the aortic repair for 3 weeks resulting from severe brain contusion. 5 patients (45.45%) died in hospital. 1 patient died in the operating theatre, 4 of them (36.36%) died during postoperatively within 24 hours. The mainly cause of death which occurred in every patient was intraoperative cardiac arrest, the others were postoperative bleeding, ARDS and arrhythmias. The mean of length of stay in the intensive care unit was 6.94 days. The period of hospitalization ranged from 11 to 180 days (mean = 62.83 days). The small sample

Chemical Genetic Screens for TDP-43 Modifiers and ALS Drug Discovery

DTIC Science & Technology

2015-03-01

Blackstone , 2012). Recently, a large network including many of these genes have been identify and this network is highly similar to Parkinson’s, ALS and...10.1186/1750- 1326-8-30 Blackstone , C. (2012). Cellular pathways of hereditary spastic paraplegia. Annu. Rev. Neurosci. 35, 25–47. doi: 10.1146/annurev

One Hundred Ninety-five Cases of High-voltage Electric Injury

DTIC Science & Technology

2005-08-01

that level; and T4 to T5 paraplegia, secondary to fractures of T4 to T7. In 3 cases, frac- tures were not present: one case of a T11 to T12 sensory ...problems, including fractures, neurological inju- ries, ocular injuries, and complex reconstructive and re- habilitative needs, underscores the

Compressive myelopathy in severe angular kyphosis: a series of ten patients.

PubMed

Zhang, Zhengfeng; Wang, Honggang; Liu, Chao

2016-06-01

Compressive myelopathy in severe angular kyphosis is rare and challenging for surgical treatment. The goal of this retrospective study was to report a series of ten patients with compressive myelopathy in severe angular kyphosis and the results of surgical decompression and correction of kyphosis. Between 2010 and 2014, 10 patients were surgically treated for severe angular kyphosis with a progressive onset or a sudden onset of paraplegia in investigator group. In these ten patients (seven males and three females), the etiologic diagnosis included eight cases of congenital kyphosis and two of neurofibromatosis; the distribution of spine level was from C5 to T11; the duration from onset until surgery ranged from 1 to 120 months; follow-up ranged from 12 to 26 months (mean 18.5 months); the kyphosis angle of the patients ranged from 50° to 180°. Magnetic resonance imaging demonstrated the spinal cord thinning and compression at apex in most of patients. All patients underwent decompressive surgery by single-stage posterior vertebral column resection or both anterior corpectomy fusion and posterior fixation. Neurological status was evaluated using the ASIA impairment classification and the motor score. Postoperatively, all patients had different kyphosis correction rate from 24 to 100 %. Nine patients showed neurological improvement; one patient showed no improvement. Among them, one sudden onset ASIA A adolescent paraplegic patient improved to ASIA E within 1 year of follow-up. One ASIA C adolescent paraplegic patients deteriorated neurologically to ASIA A after surgery and improved to ASIA D with 12-month follow-up. Compressive myelopathy in severe angular congenital kyphosis is usually occurred high incidence rate at apex of upper thoracic spine (T1-T4). The duration from onset of paraplegia until surgery and the severity of paraplegia before surgery are two key factors for neurological prognosis after surgery.

Paralysis from sport and diving accidents.

PubMed

Schmitt, H; Gerner, H J

2001-01-01

To examine the causes of sport-related spinal cord injuries that developed into paraplegia or tetraplegia, and to compare data from different sports with previous studies in the same geographical region. A retrospective epidemiological study and comparison with previous studies. The Orthopedic Department, specializing in the treatment and rehabilitation of paralyzed patients, at the University of Heidelberg, Germany. Between 1985 and 1997, 1,016 cases of traumatic spinal cord injury presented at the Orthopedic Department at the University of Heidelberg: 6.8% were caused by sport and 7.7% by diving accidents. Sport-related spinal cord injuries with paralysis. A total of 1.016 cases of traumatic spinal cord injury were reviewed. Of these, 14.5% were caused by sport accidents (n = 69) or diving accidents (n = 78). Age of patients ranged from 9 to 52 years. 83% were male. 77% of the patients developed tetraplegia, and 23%, paraplegia. 16 of the sport accidents resulted from downhill skiing, 9 resulted from horseback riding, 7 from modern air sports, 6 from gymnastics, 5 from trampolining, and 26 from other sports. Previous analyses had revealed that paraplegia had mainly occurred from gymnastics, trampolining, or high diving accidents. More recently, however, the number of serious spinal injuries caused by risk-filled sports such as hang gliding and paragliding has significantly increased (p = 0.095), as it has for horseback riding and skiing. Examinations have shown that all patients who were involved in diving accidents developed tetraplegia. An analysis of injury from specific sports is still under way. Analysis of accidents resulting in damage to the spinal cord in respect to different sports shows that sports that have become popular during the last 10 years show an increasing risk of injury. Modern air sports hold the most injuries. Injury-preventing strategies also are presented.

Sensitivity of the SCI-FI/AT in Individuals With Traumatic Spinal Cord Injury.

PubMed

Keeney, Tamra; Slavin, Mary; Kisala, Pamela; Ni, Pengsheng; Heinemann, Allen W; Charlifue, Susan; Fyffe, Denise C; Marino, Ralph J; Morse, Leslie R; Worobey, Lynn A; Tate, Denise; Rosenblum, David; Zafonte, Ross; Tulsky, David; Jette, Alan M

2018-03-31

To examine the ability of the Spinal Cord Injury-Functional Index/Assistive Technology (SCI-FI/AT) measure to detect change in persons with spinal cord injury (SCI). Multisite longitudinal (12-mo follow-up) study. Nine SCI Model Systems programs. Adults (N=165) with SCI enrolled in the SCI Model Systems database. Not applicable. SCI-FI/AT computerized adaptive test (CAT) (Basic Mobility, Self-Care, Fine Motor Function, Wheelchair Mobility, and/or Ambulation domains) completed at discharge from rehabilitation and 12 months after SCI. For each domain, effect size estimates and 95% confidence intervals were calculated for subgroups with paraplegia and tetraplegia. The demographic characteristics of the sample were as follows: 46% (n=76) individuals with paraplegia, 76% (n=125) male participants, 57% (n=94) used a manual wheelchair, 38% (n=63) used a power wheelchair, 30% (n=50) were ambulatory. For individuals with paraplegia, the Basic Mobility, Self-Care, and Ambulation domains of the SCI-FI/AT detected a significantly large amount of change; in contrast, the Fine Motor Function and Wheelchair Mobility domains detected only a small amount of change. For those with tetraplegia, the Basic Mobility, Fine Motor Function, and Self-Care domains detected a small amount of change whereas the Ambulation item domain detected a medium amount of change. The Wheelchair Mobility domain for people with tetraplegia was the only SCI-FI/AT domain that did not detect significant change. SCI-FI/AT CAT item banks detected an increase in function from discharge to 12 months after SCI. The effect size estimates for the SCI-FI/AT CAT vary by domain and level of lesion. Findings support the use of the SCI-FI/AT CAT in the population with SCI and highlight the importance of multidimensional functional measures. Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

A Case of Mixed Germ Cell Tumor in the Intramedullary Spinal-cord.

PubMed

Nitta, Masahiro; Hoshi, Akio; Higure, Taro; Shimizu, Yuki; Nakajima, Nobuyuki; Hanai, Kazuya; Kawamura, Yoshiaki; Terachi, Toshiro

2016-09-20

A 28-year-old man was hospitalized with advancing paraplegia. Under the diagnosis of Guillain-Barre syndrome, steroid pulse therapy was administered and plasmapheresis was performed. However, the paraplegia gradually progressed. Subsequently, a spinal cord tumor was revealed by magnetic resonance imaging (MRI). The pathological diagnosis, obtained by open biopsy, confirmed a mixed germ cell tumor in the spinal cord. Multiple lung and lymph nodes metastases were also detected upon computed tomography, along with increased serum alpha-fetoprotein (33.9 ng/mL) and human chorionic gonadotropin (182.5 mIU/mL) levels. Consequently, he received chemotherapy comprising three courses of BEP (bleomycin, etoposide, and cisplatin) as first-line therapy, followed by four courses of TGN (paclitaxel, gemcitabine, and nedaplatin) as second-line treatment. As a result, the spinal cord lesion area was significantly decreased and the alpha-fetoprotein and human chorionic gonadotropin levels were normalized. Four years after chemotherapy, MRI revealed pituitary gland and pineal organ recurrence of the germ cell tumor and additional TGN chemotherapy was performed.

Stance control knee mechanism for lower-limb support in hybrid neuroprosthesis

PubMed Central

To, Curtis S.; Kobetic, Rudi; Bulea, Thomas C.; Audu, Musa L.; Schnellenberger, John R.; Pinault, Gilles; Triolo, Ronald J.

2014-01-01

A hydraulic stance control knee mechanism (SCKM) was developed to fully support the knee against flexion during stance and allow uninhibited motion during swing for individuals with paraplegia using functional neuromuscular stimulation (FNS) for gait assistance. The SCKM was optimized for maximum locking torque for body-weight support and minimum resistance when allowing for free knee motion. Ipsilateral and contralateral position and force feedback were used to control the SCKM. Through bench and nondisabled testing, the SCKM was shown to be capable of supporting up to 70 N-m, require no more than 13% of the torque achievable with FNS to facilitate free motion, and responsively and repeatedly unlock under an applied flexion knee torque of up to 49 N-m. Preliminary tests of the SCKM with an individual with paraplegia demonstrated that it could support the body and maintain knee extension during stance without the stimulation of the knee extensor muscles. This was achieved without adversely affecting gait, and knee stability was comparable to gait assisted by knee extensor stimulation during stance. PMID:21938668

Design and evaluation of Mina: a robotic orthosis for paraplegics.

PubMed

Neuhaus, Peter D; Noorden, Jerryll H; Craig, Travis J; Torres, Tecalote; Kirschbaum, Justin; Pratt, Jerry E

2011-01-01

Mobility options for persons suffering from paraplegia or paraparesis are limited to mainly wheeled devices. There are significant health, psychological, and social consequences related to being confined to a wheelchair. We present the Mina, a robotic orthosis for assisting mobility, which offers a legged mobility option for these persons. Mina is an overground robotic device that is worn on the back and around the legs to provide mobility assistance for people suffering from paraplegia or paraparesis. Mina uses compliant actuation to power the hip and knee joints. For paralyzed users, balance is provided with the assistance of forearm crutches. This paper presents the evaluation of Mina with two paraplegics (SCI ASIA-A). We confirmed that with a few hours of training and practice, Mina is currently able to provide paraplegics walking mobility at speeds of up to 0.20 m/s. We further confirmed that using Mina is not physically taxing and requires little cognitive effort, allowing the user to converse and maintain eye contact while walking. © 2011 IEEE

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

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

2009-01-01

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).…

A Randomized, Crossover Clinical Trial of Exoskeletal-Assisted Walking to Improve Mobility, Bowel Function, and Cardiometabolic Profiles in Persons with SCI

DTIC Science & Technology

2017-10-01

lipid profile, total testosterone, estradiol levels, and quality of life (QOL). 2. KEYWORDS: Powered exoskeletons, paraplegia, tetraplegia...high density lipoprotein, lipid profile, orthostatic tolerance, total testosterone, estradiol, quality of life , ReWalk, and Ekso 3. ACCOMPLISHMENTS...Nothing to Report What was the impact on society beyond science and technology? Nothing to Report 5. CHANGES/PROBLEMS: Nothing to Report

Walking and wheelchair energetics in persons with paraplegia.

PubMed

Cerny, D; Waters, R; Hislop, H; Perry, J

1980-09-01

The energetics of walking with orthoses and wheelchair propulsion at free velocity were tested in 10 adults with low-level spinal cord injuries. Eight were subjects who customarily used wheelchairs as their primary mode of locomotion; the other two used orthoses and had discontinued use of their wheelchairs. All required bilateral knee-ankle-foot orthoses to walk. A third habitual walker also was tested during walking only. Patients walked or propelled their wheelchairs around a 60.5-meter outdoor cement track. Heart rate, respiratory rate, and step frequency were recorded and transmitted by radiotelemetry. Expired air was collected for gas analysis in a polyethylene bag during the activity after a three-minute warm-up. During wheelchair propulsion all subjects demonstrated physiological responses within normal limits. Walking was significantly more difficult to perform than wheelchair propulsion (p < .005). Subjects who customarily used orthoses walked at a mean velocity of 59 +/- 5 m/min; those who primarily used wheelchairs had a mean walking velocity of 22 +/- 13 m/min. Oxygen uptake per minute was similar for both groups. These data suggest that the wheelchair will be the primary mode of locomotion for persons with spinal cord injury who need two knee-ankle-foot orthoses to walk, unless they are willing to work under anaerobic conditions and can walk at a velocity of 54 m/min or better.

Paraplegia in a thalassaemic patient with short stature.

PubMed

Campisi, Saveria; Mangiagli, Antonino; De Sanctis, Vincenzo; Giovannini, Michela

2011-03-01

Extramedullary hematopoiesis (EMH) is a normal compensatory reaction that occurs in almost all chronic hemolytic anemia, especially in transfusion independent thalassemia intermedia, and can involve many organs or tissues, including the epidural space leading to spinal cord compression syndrome. We present a case of EMH in a 29 year old woman with thalassemia major, regularly transfused since the time of diagnosis (age 21 months), who presented with sudden muscle weakness, difficulty walking and maintaining the upright position. Magnetic Resonance Imaging (MRI) of the thoracic spine showed spinal cord compression secondary to extramedullary hematopoiesis in the spinal canal, leading to early therapy. The neurosurgical treatment (decompressive laminectomy D3-D6) in our patient brought a significant and rapid recovery. The next two MRI of the spine (after 6 and 18 months) were both negative for recurrence.

Genetics Home Reference: spastic paraplegia type 5A

MedlinePlus

... Testing (2 links) Gasser T, Finsterer J, Baets J, Van Broeckhoven C, Di Donato S, Fontaine B, De Jonghe P, Lossos A, Lynch T, Mariotti C, Schöls L, ... M, Forlani S, Guyant-Maréchal L, Fontaine B, Guimarães J, Isidor B, ... D, Chevy F, Chinnery PF, Coutinho P, Azulay JP, Feki I, Mochel F, Wolf C, ...

Ambulatory and Non-Ambulatory Benefits of Lower Limb Exoskeleton Use, with and without FES, in Clinical and Community Settings

DTIC Science & Technology

2017-10-01

research investigates the extent to which regular walking in an exoskeleton will provide mobility, health , and recovery benefits to individuals with spinal...15. SUBJECT TERMS spinal cord injury, paraplegia, exoskeleton, physical medicine and rehabilitation, rehabilitation research, legged mobility...regular walking in an exoskeleton will provide mobility, health , and recovery benefits to individuals with spinal cord injury. The research is comprised

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

PubMed Central

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

2013-01-01

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

A lifestyle intervention program for successfully addressing major cardiometabolic risks in persons with SCI: a three-subject case series.

PubMed

Bigford, Gregory E; Mendez, Armando J; Betancourt, Luisa; Burns-Drecq, Patricia; Backus, Deborah; Nash, Mark S

2017-01-01

This study is a prospective case series analyzing the effects of a comprehensive lifestyle intervention program in three patients with chronic paraplegia having major risks for the cardiometabolic syndrome (CMS). Individuals underwent an intense 6-month program of circuit resistance exercise, nutrition using a Mediterranean diet and behavioral support, followed by a 6-month extension (maintenance) phase involving minimal support. The primary goal was a 7% reduction of body mass. Other outcomes analyzed insulin resistance using the HOMA-IR model, and plasma levels of fasting triglycerides and high-density lipoprotein cholesterol. All participants achieved the goal for 7% reduction of body mass and maintained the loss after the MP. Improvements were observed in 2/3 subjects for HOMA-IR and high-density lipoprotein cholesterol. All participants improved their risk for plasma triglycerides. We conclude, in a three-person case series of persons with chronic paraplegia, a lifestyle intervention program involving circuit resistance training, a calorie-restrictive Mediterranean-style diet and behavioral support, results in clinically significant loss of body mass and effectively reduced component risks for CMS and diabetes. These results were for the most part maintained after a 6-month MP involving minimal supervision.

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

PubMed

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

2014-01-01

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.

Syndrome of the anterior spinal artery as the primary manifestation of aspergillosis.

PubMed

Pfausler, B; Kampfl, A; Berek, K; Maier, H; Aichner, F; Schmutzhard, E

1995-01-01

Aspergillosis of the central nervous system (CNS) is an uncommon infection, mainly occurring in immunocompromised patients. Beside cerebral involvement spinal cord lesions are extremely rare. To our knowledge, aspergillosis initially presenting with acute paraplegia due to mycotic thrombosis of the anterior spinal artery in a formerly healthy patient has, so far, not been reported. Neither a primary focus nor an underlying disease had been detected.

Aculaser therapy: a comprehensive approach for the treatment of cerebral palsy

NASA Astrophysics Data System (ADS)

Anwar, Shahzad; Nazir Khan, Malik Muhammed; Nadeem Khan, Malik Mohammad; Munir Qazi, Faiza; Ahmed, Imtiaz; Awan, Abid Hareef

2006-10-01

A single, open and non comparative study was conducted at Anwar Shah's First C.P. & Paralysis Clinic and Research Center 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 (CP) and associated Neurological Disorders like epilepsy, cortical blindness, spasticity, hemiplegia, paraplegia, quadriplegia, paraplegia, monoplegia, sensory-neural deafness and speech disorders. In all 100 childern were treated and the data was gathered during a period of 18 months from December 2003 till June 2005. This article shows results of the treatment with ACULASER THERAPY in CP childern who were treated for minimum 6 weeks and more or had minimum of 10 treatment sessions and more. This paper also shows that those childern who were given a break in the treatment for 4-12 weeks did not show any reversal of the symptoms. These children were classified according to the associated Neurological Disorders. Analysis of the data showed that out of 81 children with Spasticity and Stiffness 69 showed marked improvement showing 85% improvement rate, out of 54 children with Epileptic fits there was a significant reduction in the intensity, frequency and duration of Epileptic fits in 34 children showing 63% success rate, out of 18 children with Cortical Blindness 13 children showed improvement accounting for 72% efficacy rate, out of 45 children with Hearing Difficulties, 31 showed marked improvement accounting for 69% improvement rate, out of 100 children with Speech Disorders 67 showed improvement reflecting 67 % improvement rate, out of 46 children with Hemiplegia 32 showed improvement in movement, tone and power accounting for 69% improvement rate, out of 36 children with Quadriplegia 25 showed improvement in gross and fine motor functions showing 69% success rate and out of 18 children with Paraplegia of lower limbs 12 showed improvement in weight bearing

Economic evaluation of open vs endovascular repair of blunt traumatic thoracic aortic injuries.

PubMed

Tong, Michael Zhen-Yu; Koka, Pavan; Forbes, Thomas L

2010-07-01

During the last decade, endovascular repair (EV) has replaced open surgical repair (OSR) as the preferred method of treatment of blunt traumatic thoracic aortic injuries (BTAIs) at many trauma centers. This has resulted in reductions in mortality, length of stay, and major complications, including paraplegia, with the added expense of the initial endograft, subsequent surveillance, and reinterventions. The purpose of this study was to conduct an economic evaluation comparing these two methods of repair. We performed an economic comparison of EV and OSR for the treatment of BTAI using a decision tree analysis with transition points derived from our institution's experience and through a review of the literature. Over a 15-year period (1991-2006), 28 patients with BTAI were treated at our center (15 EV, 13 OSR). Costs were obtained from our hospital's case costing center, the Ontario Case Costing Initiative, Ontario's Drug Benefit Formulary, and Ontario's Schedule of Benefits for physician costs. Our center's results were then combined with those from the literature to arrive at an economic model. These combined results revealed that EV, when compared to OSR, resulted in decreased early mortality (7.2% vs 22.5%), decreased composite outcome of mortality and paraplegia (7.7% vs 27.6%) and decreased composite outcome of mortality and major complication (42.5% vs 69.8%). Patients undergoing EV also had shorter intensive care unit stays (12.2 vs 15.3 days), total hospital length of stays (22.5 vs 28.6 days), and ventilator days (8.0 vs 9.2 days). Additionally, patients undergoing EV had decreased total 1-year costs compared with OSR ($70,442 vs $72,833). EV repair of BTAIs offers a survival advantage as well as a reduction in major morbidity, including paraplegia, compared with OSR, and results in a reduction in costs at 1 year. As a result, from the cost-effectiveness point of view, EV is the DOMINANT therapy over OSR for these injuries. Copyright (c) 2010 Society for

Traumatic spinal cord injuries in Ile-Ife, Nigeria, and its environs.

PubMed

Olasode, Babatunde J; Komolafe, I E; Komolafe, M; Olasode, Olayinka A

2006-07-01

In Ile-Ife, Nigeria, traumatic brain injuries are largely due to traffic accidents caused mainly by the bad maintenance of the roads and unsafe driving. Young men in the productive stage of their lives are those most affected. The resultant disabilities include quadriplegia (in more than half the patients) and paraplegia. The cost of treating and providing adequate facilities for these patients imposes a heavy economic burden upon developing countries.

[Continuous registration of the filling volume of the human urinary bladder].

PubMed

Preussner, P R

1991-11-01

A sensing system for continuous recording of bladder volume is described. The system is intended for use in particular in patients with paraplegia or bladder plastique. Owing to the very simple measuring procedure employed the implantable components can be designed for very low power consumption. Also, there is no need for an additional data transfer from inside the body to the exterior, because measurement and telemetry are physically the same procedures.

Evaluation of the physical activity scale for individuals with physical disabilities in people with spinal cord injury.

PubMed

de Groot, S; van der Woude, L H V; Niezen, A; Smit, C A J; Post, M W M

2010-07-01

Cross-sectional study. To evaluate the physical activity scale for individuals with physical disabilities (PASIPD) in people with spinal cord injury (SCI). Eight Dutch rehabilitation centers with a specialized SCI unit. The PASIPD was examined by comparing group scores of people with different personal (age, gender and body mass index) and lesion characteristics (level (paraplegia/tetraplegia), completeness, time since injury (TSI)) in 139 persons with SCI 1 year after discharge from in-patient rehabilitation. Relationships between PASIPD scores and measures of activities (wheelchair skills, Utrecht Activity List, mobility range and social behavior subscales of the SIP68) and fitness (peak oxygen uptake, peak power output and muscular strength) were determined. Persons with tetraplegia had significantly lower PASIPD scores than those with paraplegia (P<0.02). Persons with longer TSI had lower PASIPD scores than persons with shorter TSI (P<0.03). PASIPD scores showed moderate correlations with activities (0.36-0.51, P<0.01) and weak-to-moderate correlations with fitness parameters (0.25-0.36, P<0.05). In a fairly homogeneous group of persons with SCI, 1 year after in-patient rehabilitation, the PASIPD showed weak-to-moderate relationships with activity and fitness parameters. There seems to be a limited association between self-reported activity level and fitness in people with SCI.

A lifestyle intervention program for successfully addressing major cardiometabolic risks in persons with SCI: a three-subject case series

PubMed Central

Bigford, Gregory E; Mendez, Armando J; Betancourt, Luisa; Burns-Drecq, Patricia; Backus, Deborah; Nash, Mark S

2017-01-01

Introduction This study is a prospective case series analyzing the effects of a comprehensive lifestyle intervention program in three patients with chronic paraplegia having major risks for the cardiometabolic syndrome (CMS). Case presentation: Individuals underwent an intense 6-month program of circuit resistance exercise, nutrition using a Mediterranean diet and behavioral support, followed by a 6-month extension (maintenance) phase involving minimal support. The primary goal was a 7% reduction of body mass. Other outcomes analyzed insulin resistance using the HOMA-IR model, and plasma levels of fasting triglycerides and high-density lipoprotein cholesterol. All participants achieved the goal for 7% reduction of body mass and maintained the loss after the MP. Improvements were observed in 2/3 subjects for HOMA-IR and high-density lipoprotein cholesterol. All participants improved their risk for plasma triglycerides. Discussion: We conclude, in a three-person case series of persons with chronic paraplegia, a lifestyle intervention program involving circuit resistance training, a calorie-restrictive Mediterranean-style diet and behavioral support, results in clinically significant loss of body mass and effectively reduced component risks for CMS and diabetes. These results were for the most part maintained after a 6-month MP involving minimal supervision. PMID:28382218

Spinal tuberculosis, natural history of disease, classifications and principles of management with historical perspective.

PubMed

Kumar, Kush

2016-08-01

To describe the natural history spinal tuberculosis, classifications and principles of management based upon the grading of the neurological deficit. Review of literature was conducted with the aim to provide the clinico-radiological correlation of the natural history of spinal tuberculosis in different stages. Management strategy is developed based upon the severity of the neurological deficit. A five stage natural history of spinal tuberculosis is described. Stage of neurological involvement is further divided into 4 grades, predominantly on the basis of progressively increasing motor deficits as negligible, mild, moderate and severe with sensory and autonomic dysfunctions. Suitable principles of management with role of rest, braces, chemotherapy and surgery are discussed. Neurological deficit grading based management is developed. Grade 1 and 2, conservative treatment, grade 3, gray zone and grade 4, operative treatment is emphasized. The five stages of natural history of tuberculosis of spine have been developed from the clinician's point of view. Management of tuberculosis of spine, in general, it is no different than management of soft tissue tuberculosis, in HIV negative or positive patients. Role of surgery is very limited. Management of tubercular paraplegia, based upon the grading of paraplegia is simple, logical, efficient and easy to understand and remember by any orthopedic surgeon.

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

PubMed Central

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

2014-01-01

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

Motor exam of patients with spinal cord injury: a terminological imbroglio.

PubMed

Figueiredo, Nicandro

2017-07-01

The description of the motor deficit of patients with spinal cord injury (SCI) varies significantly, leading to confusion within the neurological terminology. This paper proposes a concise and easy to use terminology to describe the motor deficit of patients with SCI. A broad review of the origin of the nomenclature used to describe the motor deficit of patients with SCI was performed and discussed. The prefix: "hemi" should be used to describe paralysis of one half of the body; "mono" for one limb; "para" for lower limbs, di" for two symmetrical segments and/or parts in both sides of the body; "tri" for three limbs, or two limbs and one side of the face; and "tetra" for four limbs. The suffix: "plegia" should be used for total paralysis of a limb or part of the body, and "paresis" for partial paralysis. The term "brachial" refers to the upper limbs; and "podal" to the lower limbs. According to the spinal cord origin of the main key muscles for the limbs, patients with complete injury affecting spinal cord segments C1-5 usually presents with "tetraplegia"; C6-T1 presents with "paraplegia and brachial diparesis"; T2-L2 with "paraplegia"; and L3-S1 with "paraparesis".

Aspergillus vertebral osteomyelitis and epidural abscess.

PubMed

Tew, C W; Han, F C; Jureen, R; Tey, B H

2009-04-01

We present the first reported case of Aspergillus vertebral osteomyelitis and epidural abscess in Singapore in a 50-year-old man with post-tuberculous bronchiectasis. The patient presented with acute urinary retention and flaccid paraplegia. Despite surgical debridement and treatment with voriconazole, the patient developed multiorgan failure and died two weeks after presentation. Early diagnosis and prompt initiation of treatment are emphasised in the hope of improving the outcome of this aggressive condition.

Aspergillus osteomyelitis of the spine.

PubMed

Govender, S; Rajoo, R; Goga, I E; Charles, R W

1991-07-01

Aspergillosis involving either the vertebral body or the intervertebral disc is a rare cause of osteomyelitis of the spine. The following is a report of five cases of Aspergillus fumigatus infection of the spine treated successfully with amphotericin B and 5-flucytosine. In three patients, the diagnosis was established at closed-needle biopsy; two patients with paraplegia had an anterior decompression and fusion. The follow-up period ranged from 19 to 48 months.

Spinal cord aspergillus invasion--complication of an aspergilloma.

PubMed

Sheth, N K; Varkey, B; Wagner, D K

1985-12-01

Acute paraplegia developed in a 53-year-old man with pulmonary aspergilloma because of contiguous extension of Aspergillus infection to the epidural and subdural spaces and spinal cord. Histopathologic findings of the spinal cord showed Aspergillus hyphae penetrating the myelin sheath and myelomalacia, predominantly in the anterior and lateral columns. To the authors' knowledge, there have been no previous descriptions or illustrations of spinal cord involvement and the pathologic changes caused by Aspergillus infection.

Acute intraparenchymal spinal cord injury in a cat due to high-rise syndrome.

PubMed

Cruz-Arámbulo, Robert; Nykamp, Stephanie

2012-03-01

A 9-year-old spayed female Bengal Red cat was evaluated for high-rise syndrome. The cat had paraplegia of the hind limbs, intact reflexes and pain perception, and hyperesthesia in the caudal thoracic area. Mentation, cranial nerve function, forelimb proprioceptive responses, and spinal reflexes were normal. There were no abnormalities on radiographs or computed tomography scan, but magnetic resonance imaging revealed a hyperintense intraparenchymal spinal cord lesion on T2-weighted and T2 fat saturation images.

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

PubMed Central

Haley, Stephen M.

2013-01-01

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

A mutation of EPT1 (SELENOI) underlies a new disorder of Kennedy pathway phospholipid biosynthesis

PubMed Central

Ahmed, Mustafa Y.; Al-Khayat, Aisha; Al-Murshedi, Fathiya; Al-Futaisi, Amna; Chioza, Barry A.; Pedro Fernandez-Murray, J.; Self, Jay E.; Salter, Claire G.; Harlalka, Gaurav V.; Rawlins, Lettie E.; Al-Zuhaibi, Sana; Al-Azri, Faisal; Al-Rashdi, Fatma; Cazenave-Gassiot, Amaury; Wenk, Markus R.; Al-Salmi, Fatema; Patton, Michael A.; Silver, David L.; Baple, Emma L.; McMaster, Christopher R.; Crosby, Andrew H.

2017-01-01

Abstract Mutations in genes involved in lipid metabolism have increasingly been associated with various subtypes of hereditary spastic paraplegia, a highly heterogeneous group of neurodegenerative motor neuron disorders characterized by spastic paraparesis. Here, we report an unusual autosomal recessive neurodegenerative condition, best classified as a complicated form of hereditary spastic paraplegia, associated with mutation in the ethanolaminephosphotransferase 1 (EPT1) gene (now known as SELENOI), responsible for the final step in Kennedy pathway forming phosphatidylethanolamine from CDP-ethanolamine. Phosphatidylethanolamine is a glycerophospholipid that, together with phosphatidylcholine, constitutes more than half of the total phospholipids in eukaryotic cell membranes. We determined that the mutation defined dramatically reduces the enzymatic activity of EPT1, thereby hindering the final step in phosphatidylethanolamine synthesis. Additionally, due to central nervous system inaccessibility we undertook quantification of phosphatidylethanolamine levels and species in patient and control blood samples as an indication of liver phosphatidylethanolamine biosynthesis. Although this revealed alteration to levels of specific phosphatidylethanolamine fatty acyl species in patients, overall phosphatidylethanolamine levels were broadly unaffected indicating that in blood EPT1 inactivity may be compensated for, in part, via alternate biochemical pathways. These studies define the first human disorder arising due to defective CDP-ethanolamine biosynthesis and provide new insight into the role of Kennedy pathway components in human neurological function. PMID:28052917

A mutation of EPT1 (SELENOI) underlies a new disorder of Kennedy pathway phospholipid biosynthesis.

PubMed

Ahmed, Mustafa Y; Al-Khayat, Aisha; Al-Murshedi, Fathiya; Al-Futaisi, Amna; Chioza, Barry A; Pedro Fernandez-Murray, J; Self, Jay E; Salter, Claire G; Harlalka, Gaurav V; Rawlins, Lettie E; Al-Zuhaibi, Sana; Al-Azri, Faisal; Al-Rashdi, Fatma; Cazenave-Gassiot, Amaury; Wenk, Markus R; Al-Salmi, Fatema; Patton, Michael A; Silver, David L; Baple, Emma L; McMaster, Christopher R; Crosby, Andrew H

2017-03-01

Mutations in genes involved in lipid metabolism have increasingly been associated with various subtypes of hereditary spastic paraplegia, a highly heterogeneous group of neurodegenerative motor neuron disorders characterized by spastic paraparesis. Here, we report an unusual autosomal recessive neurodegenerative condition, best classified as a complicated form of hereditary spastic paraplegia, associated with mutation in the ethanolaminephosphotransferase 1 (EPT1) gene (now known as SELENOI), responsible for the final step in Kennedy pathway forming phosphatidylethanolamine from CDP-ethanolamine. Phosphatidylethanolamine is a glycerophospholipid that, together with phosphatidylcholine, constitutes more than half of the total phospholipids in eukaryotic cell membranes. We determined that the mutation defined dramatically reduces the enzymatic activity of EPT1, thereby hindering the final step in phosphatidylethanolamine synthesis. Additionally, due to central nervous system inaccessibility we undertook quantification of phosphatidylethanolamine levels and species in patient and control blood samples as an indication of liver phosphatidylethanolamine biosynthesis. Although this revealed alteration to levels of specific phosphatidylethanolamine fatty acyl species in patients, overall phosphatidylethanolamine levels were broadly unaffected indicating that in blood EPT1 inactivity may be compensated for, in part, via alternate biochemical pathways. These studies define the first human disorder arising due to defective CDP-ethanolamine biosynthesis and provide new insight into the role of Kennedy pathway components in human neurological function. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

Measurement properties of the Spinal Cord Injury-Functional Index (SCI-FI) short forms.

PubMed

Heinemann, Allen W; Dijkers, Marcel P; Ni, Pengsheng; Tulsky, David S; Jette, Alan

2014-07-01

To evaluate the psychometric properties of the Spinal Cord Injury-Functional Index (SCI-FI) short forms (basic mobility, self-care, fine motor, ambulation, manual wheelchair, and power wheelchair) based on internal consistency; correlations between short forms banks, full item bank forms, and a 10-item computer adaptive test version; magnitude of ceiling and floor effects; and test information functions. Cross-sectional cohort study. Six rehabilitation hospitals in the United States. Individuals with traumatic spinal cord injury (N=855) recruited from 6 national Spinal Cord Injury Model Systems facilities. Not applicable. SCI-FI full item bank, 10-item computer adaptive test, and parallel short form scores. The SCI-FI short forms (with separate versions for individuals with paraplegia and tetraplegia) demonstrate very good internal consistency, group-level reliability, excellent correlations between short forms and scores based on the total item bank, and minimal ceiling and floor effects (except ceiling effects for persons with paraplegia on self-care, fine motor, and power wheelchair ability and floor effects for persons with tetraplegia on self-care, fine motor, and manual wheelchair ability). The test information functions are acceptable across the range of scores where most persons in the sample performed. Clinicians and researchers should consider the SCI-FI short forms when computer adaptive testing is not feasible. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Effects of wheelchair sports on respiratory muscle strength and thoracic mobility of individuals with spinal cord injury.

PubMed

Moreno, Marlene Aparecida; Zamunér, Antonio Roberto; Paris, Juliana Viana; Teodori, Rosana Macher; Barros, Ricardo M L

2012-06-01

The aim of this study was to evaluate the effects of wheelchair sports on respiratory muscle strength and the thoracic mobility of individuals with spinal cord injury. Thirty male subjects with chronic spinal cord injury (American Spinal Injury Association Impairment Scale grade A) took part in the study and were divided into four groups: sedentary subjects with quadriplegia (S-QUAD, n = 7), wheelchair rugby athletes with quadriplegia (A-QUAD, n = 8), sedentary subjects with paraplegia (S-PARA, n = 6), and wheelchair basketball athletes with paraplegia (A-PARA, n = 9). The main outcome measures were maximal inspiratory and expiratory pressure and the respiratory coefficients at the axillary and xiphoid levels. A-QUAD group presented values significantly higher for all respiratory variables studied compared with the S-QUAD group. No significant differences in any of the respiratory variables were observed between S-PARA and A-PARA groups. There was a negative correlation between spinal cord injury level and respiratory variables for the S-QUAD and S-PARA groups. There were positive correlations in the A-QUAD group between time of training and maximal inspiratory pressure (adjusted R = 0.84; P = 0.001) and respiratory coefficients at the axillary level (adjusted R = 0.80; P = 0.002). Physical training seems to have a positive influence on respiratory muscle strength and thoracic mobility, especially in subjects with quadriplegia.

Litigation in nontraumatic aortic diseases--a tempest in the malpractice maelstrom.

PubMed

Elefteriades, John A; Barrett, Peter W; Kopf, Gary S

2008-01-01

Physicians are vulnerable to highly litigated thoracic aortic diseases. On the basis of a review of litigated cases, we aim to determine legally protective strategies for physicians and methods to improve treatment. Thirty-three nontraumatic, thoracic aorta-related legal cases were analyzed. Twenty-three patients (69.7%) had dissections (21 ascending, 2 descending), 8 (24.2%) had aneurysms and 2 had miscellaneous other phenomena (1 coarctation and 1 iatrogenic descending aortic rupture). The adverse event was death in 30 (90.9%) patients and paraplegia or stroke in 3 (9.1%). Allegations included: failure/delay in diagnosis (19), delay in surgery (4), error in surgical technique (5), failure to prevent paraplegia (2) and miscellaneous (3). Medical treatment was retrospectively judged suboptimal in 22 cases (66.6%) for reasons consonant with allegations. Aortic disease can be diagnostically elusive, as 'the great masquerader'. Emergency physicians must maintain a high index of suspicion for aneurysm and dissection. The D-dimer test can effectively rule out aortic dissection. 'Triple rule-out' CT scans should be performed liberally. CT scan readers must remember to evaluate the aorta. Operating room administrators must be aware that postponing a scheduled thoracic aortic case may result in interim rupture and consequent litigation. With virulent thoracic aortic diseases, adverse outcome itself does not imply substandard care. 2007 S. Karger AG, Basel

Adult Leigh disease without failure to thrive.

PubMed

Sakushima, Ken; Tsuji-Akimoto, Sachiko; Niino, Masaaki; Saitoh, Shinji; Yabe, Ichiro; Sasaki, Hidenao

2011-07-01

Most Leigh disease (LD) patients die before reaching adulthood, but there are reports of "adult LD." The clinical features of adult LD were quite different from those in infant or childhood cases. Here, we describe a normally developed patient with adult LD, who presented with spastic paraplegia that was followed several years later by acute encephalopathy. We also conducted a systemic literature search on adult LD and integrated its various manifestations to arrive at a diagnostic procedure for adult LD. A 26-year-old woman presented with acute encephalopathy after spastic paraplegia. On her first admission, she exhibited bilateral basal ganglia lesion on magnetic resonance images and normal serum lactate levels. On second admission, she had acute encephalopathy with lactic acidosis and bilateral basal ganglia and brainstem lesions. A muscle biopsy revealed cytochrome c oxidase deficiency, and a diagnosis of adult LD was made. Despite treatment in the intensive care unit, she died 9 days after admission. A review of the literature describing adult LD revealed that developmental delay, COX deficiency, serum lactate elevation, and basal ganglia lesions occurred less frequently than they did in children with LD. Cranial nerve disturbance, pyramidal signs, and cerebellar dysfunction were the primary symptoms in adult LD. Thus, the many differences between childhood and adult LD may be helpful for diagnosing adult LD.

[Athymhormic syndrome and progressive paraplegia disclosing adrenoleukomyeloneuropathy in an adult].

PubMed

Brosset, C; Ceccaldi, M; Pierlovisi, F; Poncet, M

1995-01-01

A 40-year-old man presented with both paraparesia and an athymhormic syndrome. Bicapsular lesions together with abnormal evoked motor potentials suggested cortical and spinal involvement in the deficiency syndrome. The neuropsychologic symptoms appeared to be secondary to bilateral pallidium lesions. Associated signs were adrenoleukocystrophy and adrenomyeloneuropathy suggesting the term, adrenoleukocyeloneuropathy.

Imaging diagnosis--Spontaneous subperiosteal vertebral hemorrhage in a greyhound.

PubMed

Theobald, Anita; Dennis, Ruth; Beltran, Elsa

2014-01-01

A 4-year-old, spayed female greyhound dog was presented with an acute onset of paraplegia. There was no known history of trauma or coagulopathy. Spinal cord compression was identified on MRI. Intra-operative evaluation revealed the presence of a large subperiosteal hematoma and a smaller epidural hematoma. To the authors' knowledge, this is the first report of a spinal subperiosteal hematoma diagnosed antemortem through MRI, with surgical exploration and successful treatment in a dog. © 2013 American College of Veterinary Radiology.

The clinical spectrum of mutations in L1, a neuronal cell adhesion molecule

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fransen, E.; Vits, L.; Van Camp, G.

1996-07-12

Mutations in the gene encoding the neuronal cell adhesion molecule L1 are responsible for several syndromes with clinical overlap, including X-linked hydrocephalus (XLH, HSAS), MASA (mental retardation, aphasia, shuffling gait, adducted thumbs) syndrome, complicated X-linked spastic paraplegia (SP 1), X-linked mental retardation-clasped thumb (MR-CT) syndrome, and some forms of X-linked agenesis of the corpus callosum (ACC). We review 34 L1 mutations in patients with these phenotypes. 22 refs., 3 figs., 4 tabs.

Spontaneous Spinal Epidural Hematoma Coexisting Guillan-Barré Syndrome in a Child: A Case Report

PubMed Central

Lee, Chi Hyung; Kim, Young Ha; Son, Dong Wuk; Lee, Sang Weon

2016-01-01

Spontaneous spinal epidural hematoma (SSEH) has been reported as a rare cause of spinal cord compression, especially in children. Clinical features are usually nonspecific, although cervicothoracic location of hematoma could be presented with progressive paraplegia. Guillian-Barré syndrome (GBS) is clinically defined as an acute peripheral neuropathy causing progressive limb weakness. Because SSEH and GBS have very similar signs and symptoms, SSEH could be misdiagnosed as GBS. Nevertheless, they can be presented together. We describe a rare case of SSEH coexisting with GBS. PMID:27800000

Spontaneous Spinal Epidural Hematoma Coexisting Guillan-Barré Syndrome in a Child: A Case Report.

PubMed

Lee, Chi Hyung; Song, Geun Sung; Kim, Young Ha; Son, Dong Wuk; Lee, Sang Weon

2016-09-01

Spontaneous spinal epidural hematoma (SSEH) has been reported as a rare cause of spinal cord compression, especially in children. Clinical features are usually nonspecific, although cervicothoracic location of hematoma could be presented with progressive paraplegia. Guillian-Barré syndrome (GBS) is clinically defined as an acute peripheral neuropathy causing progressive limb weakness. Because SSEH and GBS have very similar signs and symptoms, SSEH could be misdiagnosed as GBS. Nevertheless, they can be presented together. We describe a rare case of SSEH coexisting with GBS.

Impact of a film portrayal of a police officer with spinal cord injury on attitudes towards disability: a media effects experiment.

PubMed

Reinhardt, Jan D; Pennycott, Andrew; Fellinghauer, Bernd A G

2014-01-01

The portrayal of disabled people in the media can influence the public's perception of disability in both positive and negative ways. In this article, an experimental before and after design is used to determine the effects of a short film on the attitudes of non-disabled and disabled persons concerning employment and productivity of persons with disabilities. Three questions were posed to 480 study participants prior to and following a short film featuring a police officer with paraplegia. Linear mixed models were used to assess the effects of time point and disability status on the responses. The non-disabled participants' ratings of eligibility for employment of a paraplegic man and estimates of the employment rate of disabled people were significantly enhanced following the film. Nevertheless, the film had no significant effects on the ratings given by participants with disabilities in terms of eligibility, employment rate or productivity. This investigation highlights the potentially important influence of media portrayal and coverage of people with disabilities on attitudes of the public concerning disability. Restrictions in participation may result from an interaction of persons with impairments with an environment that is dominated by negative attitudes towards disability The portrayal of disabled people in the media can influence the public's attitudes towards disability in both positive and negative ways In this experimental study, attitudes of the general public were significantly improved following viewing a short film featuring a positive media portrayal of a police officer with paraplegia.

Challenge of handling a Charcot spinal arthropathy with a novel hybrid fibular autograft and expandable cage.

PubMed

Ohana, Nissim; Benharroch, Daniel; Sheinis, Dimitri

2018-04-13

A 26-year-old man, who was paraplegic for 6 years due to a motor vehicle accident, presented to the authors' clinic following his incapacity to withstand a sitting posture, the frequent sensation of "clicks" in his back, and a complaint of back pain while in his wheelchair. On imaging, his dorsal spine showed a complete arthrodesis of the primarily fused vertebrae. However, distal to this segment, a Charcot spinal arthropathy with subluxation of T12-L1 was evident. Repair of this complex, uncommon, late complication of his paraplegia by the frequently used fusion techniques was shown to be inappropriate. A novel and elaborate surgical procedure is presented by which a complete fusion of the affected spine was secured. A left retrodiaphragmatic approach was used. Complete corpectomy of both the T-12 and L-1 vertebrae to the preserved endplates was performed. Most of the patient's fibula was resected and shaped for engrafting. The segment of the fibula was introduced into a mesh cage, before its intramedullary implantation into the T-12 and L-1 vertebrae. This 2-step procedure combined the hybrid use of a fibular autograft and an expandable mesh cage, incorporated one into the other, in an innovative intramedullary position. This intervention allowed the patient to resume his former condition as an extremely physically active patient with paraplegia. Nine years later, an asymptomatic early-stage Charcot spine was found at L5-S1, but no treatment is planned at this point.

Endovascular treatment of patients with types A and B thoracic aortic dissection using Relay thoracic stent-grafts: results from the RESTORE Patient Registry.

PubMed

Zipfel, Burkhart; Czerny, Martin; Funovics, Martin; Coppi, Gioacchino; Ferro, Carlo; Rousseau, Hervé; Berti, Sergio; Tealdi, Domenico G; Riambau, Vincent; Mangialardi, Nicola; Sassi, Carlo

2011-04-01

To evaluate the safety and performance of Relay stent-grafts in patients with acute or chronic aortic dissections. Patients with types A or B aortic dissections suitable for treatment with Relay stent-grafts and followed for 2 years after thoracic endovascular aortic repair (TEVAR) were identified from a company-sponsored registry database established in January 2006. Ninety-one consecutive patients (69 men; mean age 65 years) underwent TEVAR with Relay stent-grafts for dissection. Most patients (76, 84%) had type B dissections; 61 of all patients were classified as chronic and 30 as acute. The technical success rate was 95% (97% in acute, 95% in chronic, and 93% in type B dissections). The type I endoleak rate was 7% (7% in acute and 8% in chronic dissections); all occurred in patients with type B dissections. Paraplegia, paraparesis, and stroke occurred in 4, 1, and 2 patients, respectively; 2 cases of paraplegia occurred in patients with acute type B dissections. Thirty-day mortality was 8% (13% in acute and 5% in chronic dissections); all deaths occurred in patients with type B dissections. The 2-year survival rate was 82% in the overall population and 84% in patients with type B dissections. The combination of Relay's features, such as stent conformability, radial force, atraumatic design, and controlled deployment and fixation, may contribute to the safety of the Relay stent-grafts for the treatment of thoracic aortic dissections, including acute and chronic type B dissections.

The risks of polypharmacy following spinal cord injury.

PubMed

Kitzman, Patrick; Cecil, Darrin; Kolpek, Jimmi Hatton

2017-03-01

The purpose of this study was to examine the overall prevalence of polypharmacy within the spinal cord injury (SCI) population, the level of polypharmacy with respect to seven classes of high-risk drugs commonly used to treat secondary conditions in the SCI population, and the overall risks for drug-related problems (DRP) related to polypharmacy. A retrospective case-control design. A commercially available claims dataset that included patient cases from 4800 hospitals in the USA between 2007 and 2009. Individuals with tetraplegia, paraplegia, and those with SCI but not specified as either tetraplegia or paraplegia as well as a control population of randomly selected, age- and sex-matched individuals without a diagnosis of SCI. The overall prevalence of polypharmacy, the prevalence of commonly prescribed high-risk medications, and the prevalence of reported DRPs. Overall, the patients in the SCI population were prescribed significantly more medications than their control counterparts. There was a higher rate of individuals being prescribed medications from multiple high-risk classes (e.g. analgesic-narcotics, anticonvulsant, antidepressant, and skeletal muscle relaxer), as well as multiple medications within each class (e.g. multiple analgesic-narcotics). The SCI group had a higher incidence of DRPs. Our results are some of the first to demonstrate the extent of polypharmacy in individuals with SCI, including commonly prescribed high-risk medications, leading to a higher rate of DPRs. The higher rate of polypharmacy and DRPs can impact rehabilitation goals and community integration following neurologic injury.

Aggressive hemangioma of the thoracic spine.

PubMed

Schrock, Wesley B; Wetzel, Raun J; Tanner, Stephanie C; Khan, Majid A

2011-01-01

Vertebral hemangiomas are common lesions and usually considered benign. A rare subset of them, however, are characterized by extra-osseous extension, bone expansion, disturbance of blood flow, and occasionally compression fractures and thereby referred to as aggressive hemangiomas. We present a case of a 67-year-old woman with progressive paraplegia and an infiltrative mass of T4 vertebra causing mass effect on the spinal cord. Multiple conventional imaging modalities were utilized to suggest the diagnosis of aggressive hemangioma. Final pathologic diagnosis after decompressive surgery confirmed the diagnosis of an osseous hemangioma.

Aggressive hemangioma of the thoracic spine

PubMed Central

Schrock, Wesley B.; Wetzel, Raun J.; Tanner, Stephanie C.; Khan, Majid A.

2011-01-01

Vertebral hemangiomas are common lesions and usually considered benign. A rare subset of them, however, are characterized by extra-osseous extension, bone expansion, disturbance of blood flow, and occasionally compression fractures and thereby referred to as aggressive hemangiomas. We present a case of a 67-year-old woman with progressive paraplegia and an infiltrative mass of T4 vertebra causing mass effect on the spinal cord. Multiple conventional imaging modalities were utilized to suggest the diagnosis of aggressive hemangioma. Final pathologic diagnosis after decompressive surgery confirmed the diagnosis of an osseous hemangioma. PMID:22470764

A Hybrid Neuromechanical Ambulatory Assist System

DTIC Science & Technology

2014-06-01

during swing. The exoskeleton is designed for easy fitting with adjustable uprights and hip abduction for donning for use in activities of daily...living for persons with paraplegia. 15. SUBJECT TERMS Exoskeleton , hydraulic, spinal cord injury, walking, rehabilitation, robotic 16. SECURITY...evaluation……………………………………………………….14 Hydraulic circuitry and evaluation…………………………………………………………….15 Supporting structure of the exoskeleton

A Hybrid Neuromechanical Ambulatory Assist System

DTIC Science & Technology

2015-06-01

during swing on an uneven terrain. The exoskeleton is designed for easy fitting with adjustable uprights and hip abduction for donning for use in...activities of daily living for persons with paraplegia. 15. SUBJECT TERMS Exoskeleton , hydraulic, spinal cord injury, walking 16. SECURITY...15 Design of Exoskeleton ………………………………………………………………………………17 Task 3 Implement control system to coordinate electrical stimulation with exoskeleton in

[Carcinomatous meningitis revealing a cancer: study of two cases].

PubMed

Samet, S; Belahsen, F; Triki, C; Masmoudi, H; Jlidi, R; Mhiri, C

2001-04-01

Meningeal Carcinomatosis (MC) is rare (4 to 5% of patients with solid tumors). We report two cases. The first case is a 53 year-old man presenting flaccid paraplegia and the second is a 76 year-old man presenting a clinical picture suggestive of normal pressure hydrocephalus. In the two cases, the diagnosis of MC was achieved by the demonstration of malignant cells in the CSF. Prognosis was poor in the two cases. The clinical presentation of MC is non specific and the diagnosis is only confirmed by demonstrating carcinomatous cells in CSF.

POSTURAL CONTROL ASSESSMENT IN PHYSICALLY ACTIVE AND SEDENTARY INDIVIDUALS WITH PARAPLEGIA.

PubMed

Magnani, Paola Errera; Cliquet, Alberto; de Abreu, Daniela Cristina Carvalho

2017-01-01

The aim of this study was to evaluate functional independence and trunk control during maximum-range tasks in individuals with spinal cord injuries, who were divided into sedentary (SSI, n=10) and physically active (PASI, n=10) groups . Anamnesis was conducted and level and type of injury were identified (according to the American Spinal Injury Association protocol, ASIA) and the Functional Independence Measure (FIM) questionnaire was applied. For the forward and lateral reach task, the subjects were instructed to reach as far as possible. Mean data were compared using the unpaired t test and Mann-Whitney test and differences were considered significant when p<0.05 . The PASI group performed better in self-care activities (PASI: 40.8±0.42 points, SSI: 38.0±3.58 points, p=0.01), sphincter control (PASI: 10.5±1.84 points, SSI: 8.2±3.04 points, p=0.02), transfers (PASI: 20.7±0.48 points, SSI: 16.9±4.27 points, p=0.04), and total FIM score (PASI: 104.0±2.30 points, SSI 105.1±8.56 points, p=0.01). On the maximum reach task, the PASI group had a greater average range in all directions evaluated (p<0.05) . The continuous practice of exercise increased motor function independence and trunk control in individuals with complete spinal cord injury. Level of Evidence II, Prospective Comparative Study.

POSTURAL CONTROL ASSESSMENT IN PHYSICALLY ACTIVE AND SEDENTARY INDIVIDUALS WITH PARAPLEGIA

PubMed Central

Magnani, Paola Errera; Cliquet, Alberto; de Abreu, Daniela Cristina Carvalho

2017-01-01

ABSTRACT Objective: The aim of this study was to evaluate functional independence and trunk control during maximum-range tasks in individuals with spinal cord injuries, who were divided into sedentary (SSI, n=10) and physically active (PASI, n=10) groups . Methods: Anamnesis was conducted and level and type of injury were identified (according to the American Spinal Injury Association protocol, ASIA) and the Functional Independence Measure (FIM) questionnaire was applied. For the forward and lateral reach task, the subjects were instructed to reach as far as possible. Mean data were compared using the unpaired t test and Mann-Whitney test and differences were considered significant when p<0.05 . Results: The PASI group performed better in self-care activities (PASI: 40.8±0.42 points, SSI: 38.0±3.58 points, p=0.01), sphincter control (PASI: 10.5±1.84 points, SSI: 8.2±3.04 points, p=0.02), transfers (PASI: 20.7±0.48 points, SSI: 16.9±4.27 points, p=0.04), and total FIM score (PASI: 104.0±2.30 points, SSI 105.1±8.56 points, p=0.01). On the maximum reach task, the PASI group had a greater average range in all directions evaluated (p<0.05) . Conclusion: The continuous practice of exercise increased motor function independence and trunk control in individuals with complete spinal cord injury. Level of Evidence II, Prospective Comparative Study. PMID:28955171

Functional electrical stimulation: cardiorespiratory adaptations and applications for training in paraplegia.

PubMed

Deley, Gaëlle; Denuziller, Jérémy; Babault, Nicolas

2015-01-01

Regular exercise can be broadly beneficial to health and quality of life in humans with spinal cord injury (SCI). However, exercises must meet certain criteria, such as the intensity and muscle mass involved, to induce significant benefits. SCI patients can have difficulty achieving these exercise requirements since the paralysed muscles cannot contribute to overall oxygen consumption. One solution is functional electrical stimulation (FES) and, more importantly, hybrid training that combines volitional arm and electrically controlled contractions of the lower limb muscles. However, it might be rather complicated for therapists to use FES because of the wide variety of protocols that can be employed, such as stimulation parameters or movements induced. Moreover, although the short-term physiological and psychological responses during different types of FES exercises have been extensively reported, there are fewer data regarding the long-term effects of FES. Therefore, the purpose of this brief review is to provide a critical appraisal and synthesis of the literature on the use of FES for exercise in paraplegic individuals. After a short introduction underlying the importance of exercise for SCI patients, the main applications and effects of FES are reviewed and discussed. Major findings reveal an increased physiological demand during FES hybrid exercises as compared with arms only exercises. In addition, when repeated within a training period, FES exercises showed beneficial effects on muscle characteristics, force output, exercise capacity, bone mineral density and cardiovascular parameters. In conclusion, there appears to be promising evidence of beneficial effects of FES training, and particularly FES hybrid training, for paraplegic individuals.

Developing physical activity interventions for adults with spinal cord injury. Part 2: motivational counseling and peer-mediated interventions for people intending to be active.

PubMed

Latimer-Cheung, Amy E; Arbour-Nicitopoulos, Kelly P; Brawley, Lawrence R; Gray, Casey; Justine Wilson, A; Prapavessis, Harry; Tomasone, Jennifer R; Wolfe, Dalton L; Martin Ginis, Kathleen A

2013-08-01

The majority of people with spinal cord injury (SCI) do not engage in sufficient leisure-time physical activity (LTPA) to attain fitness benefits; however, many have good intentions to be active. This paper describes two pilot interventions targeting people with SCI who are insufficiently active but intend to be active (i.e., "intenders"). Study 1 examined the effects of a single, telephone-based counseling session on self-regulatory efficacy, intentions, and action plans for LTPA among seven men and women with paraplegia or tetraplegia. Study 2 examined the effects of a home-based strength-training session, delivered by a peer and a fitness trainer, on strength-training task self-efficacy, intentions, action plans, and behavior. Participants were 11 men and women with paraplegia. The counseling session (Study 1) yielded medium- to large-sized increases in participants' confidence to set LTPA goals and intentions to be active. The home visit (Study 2) produced medium- to large-sized increases in task self-efficacy, barrier self-efficacy, intentions, action planning, and strength-training behavior from baseline to 4 weeks after the visit. Study 1 findings provide preliminary evidence that a single counseling session can impact key determinants of LTPA among intenders with SCI. Study 2 findings demonstrate the potential utility of a peer-mediated, home-based strength training session for positively influencing social cognitions and strength-training behavior. Together, these studies provide evidence and resources for intervention strategies to promote LTPA among intenders with SCI, a population for whom LTPA interventions and resources are scarcely available.

Modifications in Wheelchair Propulsion Technique with Speed.

PubMed

Russell, Ian M; Raina, Shashank; Requejo, Philip S; Wilcox, Rand R; Mulroy, Sara; McNitt-Gray, Jill L

2015-01-01

Repetitive loading of the upper limb joints during manual wheelchair (WC) propulsion (WCP) has been identified as a factor that contributes to shoulder pain, leading to loss of independence and decreased quality of life. The purpose of this study was to determine how individual manual WC users with paraplegia modify propulsion mechanics to accommodate expected increases in reaction forces (RFs) generated at the pushrim with self-selected increases in WCP speed. Upper extremity kinematics and pushrim RFs were measured for 40 experienced manual WC users with paraplegia while propelling on a stationary ergometer at self-selected free and fast propulsion speeds. Upper extremity kinematics and kinetics were compared within subject between propulsion speeds. Between group and within-subject differences were determined (α = 0.05). Increased propulsion speed was accompanied by increases in RF magnitude (22 of 40, >10 N) and shoulder net joint moment (NJM, 15 of 40, >10 Nm) and decreases in pushrim contact duration. Within-subject comparison indicated that 27% of participants modified their WCP mechanics with increases in speed by regulating RF orientation relative to the upper extremity segments. Reorientation of the RF relative to the upper extremity segments can be used as an effective strategy for mitigating rotational demands (NJM) imposed on the shoulder at increased propulsion speeds. Identification of propulsion strategies that individuals can use to effectively accommodate for increases in RFs is an important step toward preserving musculoskeletal health of the shoulder and improving health-related quality of life.

Pressure ulcer management in paraplegic patients with a novel negative pressure device: a randomised controlled trial.

PubMed

Dwivedi, M K; Srivastava, R N; Bhagat, A K; Agarwal, R; Baghel, K; Jain, A; Raj, S

2016-04-01

A randomised controlled trial to compare negative pressure wound therapy (NPWT) using our innovative negative pressure device (NPD) and the standard pressure ulcer (PU) wound dressing of in traumatic paraplegia patients. This study was conducted in the Department of Orthopaedic Surgery at King George's Medical University, Lucknow, India. Traumatic paraplegia patients with sacral pressure ulcers of stage 3 and 4 were randomised into two groups, receiving either standard wound dressings or NPWT with NPD. The outcomes monitored were length, width (surface area), depth of PU, exudates, discharge, tissue type (necrotic, slough and red granulating tissue), and cost-effectiveness during 0 to 9 weeks follow-up. Length and width were significantly (p<0.01) decreased in NPWT group as compared with standard care group at week 9. At weeks 1, 2 and 3, depth was significantly (p<0.05) higher in NPWT group, whereas at week 9 a significant reduction (p=0.01) was observed. Exudates were significantly (p=0.001) lower in NPWT group at weeks 4 and 9. Conversion of slough into red granulation tissue was significantly higher in NPWT group (p=0.001). Discharge became significantly (p=0.001) lower in NPWT at week 2 and no discharge was observed after week 6. In all parameters, decrease was larger in NPWT group compared with standard care, which was significant for exudates type (p=0.03) and tissue type (p=0.004). Our NPD is better than standard wound care procedures and cost-effective for management of PU.

Loss of AP-5 results in accumulation of aberrant endolysosomes: defining a new type of lysosomal storage disease

PubMed Central

Hirst, Jennifer; Edgar, James R.; Esteves, Typhaine; Darios, Frédéric; Madeo, Marianna; Chang, Jaerak; Roda, Ricardo H.; Dürr, Alexandra; Anheim, Mathieu; Gellera, Cinzia; Li, Jun; Züchner, Stephan; Mariotti, Caterina; Stevanin, Giovanni; Blackstone, Craig; Kruer, Michael C.; Robinson, Margaret S.

2015-01-01

Adaptor proteins (AP 1–5) are heterotetrameric complexes that facilitate specialized cargo sorting in vesicular-mediated trafficking. Mutations in AP5Z1, encoding a subunit of the AP-5 complex, have been reported to cause hereditary spastic paraplegia (HSP), although their impact at the cellular level has not been assessed. Here we characterize three independent fibroblast lines derived from skin biopsies of patients harbouring nonsense mutations in AP5Z1 and presenting with spastic paraplegia accompanied by neuropathy, parkinsonism and/or cognitive impairment. In all three patient-derived lines, we show that there is complete loss of AP-5 ζ protein and a reduction in the associated AP-5 µ5 protein. Using ultrastructural analysis, we show that these patient-derived lines consistently exhibit abundant multilamellar structures that are positive for markers of endolysosomes and are filled with aberrant storage material organized as exaggerated multilamellar whorls, striated belts and ‘fingerprint bodies’. This phenotype can be replicated in a HeLa cell culture model by siRNA knockdown of AP-5 ζ. The cellular phenotype bears striking resemblance to features described in a number of lysosomal storage diseases (LSDs). Collectively, these findings reveal an emerging picture of the role of AP-5 in endosomal and lysosomal homeostasis, illuminates a potential pathomechanism that is relevant to the role of AP-5 in neurons and expands the understanding of recessive HSPs. Moreover, the resulting accumulation of storage material in endolysosomes leads us to propose that AP-5 deficiency represents a new type of LSDs. PMID:26085577

Relationship of occupational therapy inpatient rehabilitation interventions and patient characteristics to outcomes following spinal cord injury: The SCIRehab Project

PubMed Central

Ozelie, Rebecca; Gassaway, Julie; Buchman, Emily; Thimmaiah, Deepa; Heisler, Lauren; Cantoni, Kara; Foy, Teresa; Hsieh, Ching-Hui (Jean); Smout, Randall J.; Kreider, Scott E. D.; Whiteneck, Gale

2012-01-01

Background/objective Describe associations of occupational therapy (OT) interventions delivered during inpatient spinal cord injury (SCI) rehabilitation and patient characteristics with outcomes at the time of discharge and 1-year post-injury. Methods Occupational therapists at six inpatient rehabilitation centers documented detailed information about treatment provided. Least squares regression modeling was used to predict outcomes at discharge and 1-year injury anniversary for a 75% subset; models were validated with the remaining 25%. Functional outcomes for injury subgroups (motor complete low tetraplegia and motor complete paraplegia) also were examined. Results OT treatment variables explain a small amount of variation in Functional Independence Measure (FIM) outcomes for the full sample and significantly more in two functionally homogeneous subgroups. For patients with motor complete paraplegia, more time spent in clothing management and hygiene related to toileting was a strong predictor of higher scores on the lower body items of the self-care component of the discharge motor FIM. Among patients with motor complete low tetraplegia, higher scores for the FIM lower body self-care items were associated with more time spent on lower body dressing, manual wheelchair mobility training, and bathing training. Active patient participation during OT treatment sessions also was predictive of FIM and other outcomes. Conclusion OT treatments add to explained variance (in addition to patient characteristics) for multiple outcomes. The impact of OT treatment on functional outcomes is more evident when examining more homogeneous patient groupings and outcomes specific to the groupings. Note This is the third of nine articles in the SCIRehab series. PMID:23318035

The risks of polypharmacy following spinal cord injury

PubMed Central

Kitzman, Patrick; Cecil, Darrin; Kolpek, Jimmi Hatton

2017-01-01

Objective The purpose of this study was to examine the overall prevalence of polypharmacy within the spinal cord injury (SCI) population, the level of polypharmacy with respect to seven classes of high-risk drugs commonly used to treat secondary conditions in the SCI population, and the overall risks for drug-related problems (DRP) related to polypharmacy. Design A retrospective case–control design. Setting A commercially available claims dataset that included patient cases from 4800 hospitals in the USA between 2007 and 2009. Participants Individuals with tetraplegia, paraplegia, and those with SCI but not specified as either tetraplegia or paraplegia as well as a control population of randomly selected, age- and sex-matched individuals without a diagnosis of SCI. Outcome measures The overall prevalence of polypharmacy, the prevalence of commonly prescribed high-risk medications, and the prevalence of reported DRPs. Results Overall, the patients in the SCI population were prescribed significantly more medications than their control counterparts. There was a higher rate of individuals being prescribed medications from multiple high-risk classes (e.g. analgesic-narcotics, anticonvulsant, antidepressant, and skeletal muscle relaxer), as well as multiple medications within each class (e.g. multiple analgesic-narcotics). The SCI group had a higher incidence of DRPs. Conclusion Our results are some of the first to demonstrate the extent of polypharmacy in individuals with SCI, including commonly prescribed high-risk medications, leading to a higher rate of DPRs. The higher rate of polypharmacy and DRPs can impact rehabilitation goals and community integration following neurologic injury. PMID:24970339

Mammalian knock out cells reveal prominent roles for atlastin GTPases in ER network morphology.

PubMed

Zhao, Guohua; Zhu, Peng-Peng; Renvoisé, Benoît; Maldonado-Báez, Lymarie; Park, Seong Hee; Blackstone, Craig

2016-11-15

Atlastins are large, membrane-bound GTPases that participate in the fusion of endoplasmic reticulum (ER) tubules to generate the polygonal ER network in eukaryotes. They also regulate lipid droplet size and inhibit bone morphogenetic protein (BMP) signaling, though mechanisms remain unclear. Humans have three atlastins (ATL1, ATL2, and ATL3), and ATL1 and ATL3 are mutated in autosomal dominant hereditary spastic paraplegia and hereditary sensory neuropathies. Cellular investigations of atlastin orthologs in most yeast, plants, flies and worms are facilitated by the presence of a single or predominant isoform, but loss-of-function studies in mammalian cells are complicated by multiple, broadly-expressed paralogs. We have generated mouse NIH-3T3 cells lacking all three mammalian atlastins (Atl1/2/3) using CRISPR/Cas9-mediated gene knockout (KO). ER morphology is markedly disrupted in these triple KO cells, with prominent impairment in formation of three-way ER tubule junctions. This phenotype can be rescued by expression of distant orthologs from Saccharomyces cerevisiae (Sey1p) and Arabidopsis (ROOT HAIR DEFECTIVE3) as well as any one of the three human atlastins. Minimal, if any, changes are observed in the morphology of mitochondria and the Golgi apparatus. Alterations in BMP signaling and increased sensitivity to ER stress are also noted, though effects appear more modest. Finally, atlastins appear required for the proper differentiation of NIH-3T3 cells into an adipocyte-like phenotype. These findings have important implications for the pathogenesis of hereditary spastic paraplegias and sensory neuropathies associated with atlastin mutations. Published by Elsevier Inc.

Virtual reality system in conjunction with neurorobotics and neuroprosthetics for rehabilitation of motor disorders.

PubMed

De Mauro, Alessandro; Carrasco, Eduardo; Oyarzun, David; Ardanza, Aitor; Frizera Neto, Anselmo; Torricelli, Diego; Pons, José Luis; Gil, Angel; Florez, Julian

2011-01-01

Cerebrovascular accidents (CVA) and spinal cord injuries (SCI) are the most common causes of paralysis and paresis with reported prevalence of 12,000 cases per million and 800 cases per million, respectively. Disabilities that follow CVA (hemiplegia) or SCI (paraplegia, tetraplegia) severely impair motor functions (e.g., standing, walking, reaching and grasping) and prevent the affected individuals from healthy-like, full and autonomous participation in daily activities. Our research focuses on the development of a new virtual reality (VR) system combined with wearable neurorobotics (NR), motor-neuroprosthetics (MNP) and brain neuro-machine interface (BNMI) to overcome the major limitations of current rehabilitation solutions.

Telangiectatic osteosarcoma of the spine: a case report.

PubMed

Amritanand, R; Venkatesh, K; Cherian, R; Shah, A; Sundararaj, G D

2008-09-01

Telangiectatic osteosarcoma (TOS) of the spine is rare accounting for only 0.08% of all primary osteosarcomas. Though a well described radio-pathological entity it is not often thought of as a cause of paraplegia. We describe the clinical, radiological and pathological features and discuss the treatment options of telangiectatic osteosarcoma of the dorsal spine presenting in a young man. The diagnostic pitfalls are discussed emphasising the fact that the diagnosis of TOS of the spine requires not only a multi modal approach of appropriate radiological and pathological tests but also an awareness of this condition.

Telangiectatic osteosarcoma of the spine: a case report

PubMed Central

Venkatesh, K.; Cherian, R.; Shah, A.; Sundararaj, G. D.

2008-01-01

Telangiectatic osteosarcoma (TOS) of the spine is rare accounting for only 0.08% of all primary osteosarcomas. Though a well described radio-pathological entity it is not often thought of as a cause of paraplegia. We describe the clinical, radiological and pathological features and discuss the treatment options of telangiectatic osteosarcoma of the dorsal spine presenting in a young man. The diagnostic pitfalls are discussed emphasising the fact that the diagnosis of TOS of the spine requires not only a multi modal approach of appropriate radiological and pathological tests but also an awareness of this condition. PMID:18421481

The relationship between the First World War and neurology: 100 years of "Shell Shock".

PubMed

Pedroso, José Luiz; Linden, Stefanie C; Barsottini, Orlando G; Maranhão, Péricles; Lees, Andrew J

2017-05-01

The First World War was a global war, beginning on 28 July 1914, until 11 November 1918. Soon after the beginning of the war, there was an "epidemic" of neurological conversion symptoms. Soldiers on both sides started to present in large numbers with neurological symptoms, such as dizziness, tremor, paraplegia, tinnitus, amnesia, weakness, headache and mutism of psychosomatic origin. This condition was known as shell shock, or "war neurosis". Because medically unexplained symptoms remain a major challenge, and considering the close relationship of symptoms described in shell shock with clinical neurology, we should study their history in order to improve future care.

Intensive Care Management of Thoracic Aortic Surgical Patients, Including Thoracic and Infradiaphragmatic Endovascular Repair (EVAR/TEVAR).

PubMed

Cole, Sheela Pai

2015-12-01

The patient with thoracic aortic disease can present for open or endovascular repair. Thoracic endovascular aortic repair (TEVAR) has emerged as a minimally invasive option for a multitude of aortic pathology, including dissections, aneurysms, traumatic injuries, and ulcers. Postoperative management of these patients depends on the extent of procedure, whether it was open or endovascular, and, finally, on the preoperative comorbidities present. While procedural success has catapulted TEVAR to popularity, midterm results have been mixed. Additionally, periprocedural complications such as paraplegia and renal failure remain a significant morbidity in these patients. © The Author(s) 2015.

Development of Functional Electrical Stimulation Rowing: The Rowstim Series.

PubMed

Andrews, Brian; Gibbons, Robin; Wheeler, Garry

2017-11-01

Potentially, functional electrical stimulation (FES)-assisted exercise may have an important therapeutic role in reducing comorbidities associated with spinal cord injury (SCI). Here, we present an overview of these secondary life-threatening conditions, discuss the rationale behind the development of a hybrid exercise called FES rowing, and describe our experience in developing FES rowing technology. FES rowing and sculling are unique forms of adaptive rowing for those with SCI. The paralyzed leg musculature is activated by multiple channels of electrical pulses delivered via self-adhesive electrodes attached to the skin. The stimulated muscle contractions are synchronized with voluntary rowing movements of the upper limbs. A range of steady-state FES rowing exercise intensities have been demonstrated from 15.2 ± 1.8 mL/kg/min in tetraplegia to 22.9 ±7.1 mL/kg/min in paraplegia. We expect that such high levels may help some to achieve significant reductions in the risks to their health, particularly where a dose-response relationship exists as is the case for cardiovascular disease and Type II diabetes. Furthermore, preliminary results suggest that cyclical forces more than 1.5 times body weight are imposed on the leg long bones which may help to reduce the risk of fragility fractures. We have demonstrated the feasibility of FES rowing on land and water using adapted rowing technology that includes; a fixed stretcher indoor ergometer (adapted Concept 2, Model E), a floating stretcher indoor ergometer (adapted Concept 2 Dynamic), a turbine powered water rowing tank, a custom hydraulic sculling simulator and a single scull (adapted Alden 16). This has involved volunteers with paraplegia and tetraplegia with SCI ranging from C4 to T12 AIS A using at least 4-channels of surface electrical stimulation. FES rowers, with SCI, have competed alongside non-SCI rowers over the Olympic distance of 2000 m at the British Indoor Rowing Championships in 2004, 2005, and 2006

Paraplegia in a Bornean orangutan (Pongo pygmaeus pygmaeus) due to multiple myeloma.

PubMed

Mauel, Susanne; Fritsch, Guido; Ochs, Andreas; Koch, Martin; Kershaw, Olivia; Gruber, Achim D

2009-10-01

A 38-year-old male Bornean orangutan (Pongo pygmaeus pygmaeus) developed progressive hind leg paresis. A computed tomography scan of the vertebral column revealed soft tissue type densities within vertebral bones. At necropsy infiltrating tumor masses were found in the vertebral bodies, protruding into the spinal canal and compressing the spinal cord. Microscopically neoplastic plasma cells infiltrated the vertebral bodies and adjacent soft tissues. Immunohistochemically, tumor cells tested positive for B cell markers (CD38, CD79alpha), kappa, and lambda light chains, while vimentin, GFAP, S100, and CD138 were not expressed. The tumor was classified as multiple myeloma on the basis of radiographic, pathological, and immunohistochemical findings. This first systematic case description on multiple myeloma in a non-human primate revealed many similarities with the disease in humans and the immunohistochemical tools proved suitable for their use in the orangutan.

Effects of Cooling During Exercise on Thermoregulatory Responses of Men With Paraplegia.

PubMed

Bongers, Coen C W G; Eijsvogels, Thijs M H; van Nes, Ilse J W; Hopman, Maria T E; Thijssen, Dick H J

2016-05-01

People with spinal cord injury (SCI) have an altered afferent input to the thermoregulatory center, resulting in a reduced efferent response (vasomotor control and sweating capacity) below the level of the lesion. Consequently, core body temperature rises more rapidly during exercise in individuals with SCI compared with people who are able-bodied. Cooling strategies may reduce the thermophysiological strain in SCI. The aim of this study was to examine the effects of a cooling vest on the core body temperature response of people with a thoracic SCI during submaximal exercise. Ten men (mean age=44 years, SD=11) with a thoracic lesion (T4-T5 or below) participated in this randomized crossover study. Participants performed two 45-minute exercise bouts at 50% maximal workload (ambient temperature 25°C), with participants randomized to a group wearing a cooling vest or a group wearing no vest (separate days). Core body temperature and skin temperature were continuously measured, and thermal sensation was assessed every 3 minutes. Exercise resulted in an increased core body temperature, skin temperature, and thermal sensation, whereas cooling did not affect core body temperature. The cooling vest effectively decreased skin temperature, increased the core-to-trunk skin temperature gradient, and tended to lower thermal sensation compared with the control condition. The lack of differences in core body temperature among conditions may be a result of the relative moderate ambient temperature in which the exercise was performed. Despite effectively lowering skin temperature and increasing the core-to-trunk skin temperature gradient, there was no impact of the cooling vest on the exercise-induced increase in core body temperature in men with low thoracic SCI. © 2016 American Physical Therapy Association.

Major complications of central neuraxial block: report on the Third National Audit Project of the Royal College of Anaesthetists.

PubMed

Cook, T M; Counsell, D; Wildsmith, J A W

2009-02-01

Serious complications of central neuraxial block (CNB) are rare. Limited information on their incidence and impact impedes clinical decision-making and patient consent. The Royal College of Anaesthetists Third National Audit Project was designed to inform this situation. A 2 week national census estimated the number of CNB procedures performed annually in the UK National Health Service. All major complications of CNBs performed over 1 yr (vertebral canal abscess or haematoma, meningitis, nerve injury, spinal cord ischaemia, fatal cardiovascular collapse, and wrong route errors) were reported. Each case was reviewed by an expert panel to assess causation, severity, and outcome. 'Permanent' injury was defined as symptoms persisting for more than 6 months. Efforts were made to validate denominator (procedures performed) and numerator (complications) data through national databases. The census phase produced a denominator of 707,455 CNB. Eighty-four major complications were reported, of which 52 met the inclusion criteria at the time they were reported. Data were interpreted 'pessimistically' and 'optimistically'. 'Pessimistically' there were 30 permanent injuries and 'optimistically' 14. The incidence of permanent injury due to CNB (expressed per 100,000 cases) was 'pessimistically' 4.2 (95% confidence interval 2.9-6.1) and 'optimistically' 2.0 (1.1-3.3). 'Pessimistically' there were 13 deaths or paraplegias, 'optimistically' five. The incidence of paraplegia or death was 'pessimistically' 1.8 per 100,000 (1.0-3.1) and 'optimistically' 0.7 (0-1.6). Two-thirds of initially disabling injuries resolved fully. The data are reassuring and suggest that CNB has a low incidence of major complications, many of which resolve within 6 months.

Physiological responses to exergaming after spinal cord injury.

PubMed

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

2012-01-01

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. 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). 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). 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.

Treatment of giant intradural (perimedullary) arteriovenous fistulas.

PubMed

Halbach, V V; Higashida, R T; Dowd, C F; Fraser, K W; Edwards, M S; Barnwell, S L

1993-12-01

Ten patients with giant intradural spinal arteriovenous fistulas (perimedullary Types II and III) were treated with embolization alone (three patients) or in combination with surgery (seven patients). Their ages at the time of treatment ranged from 2 to 40 years, with a mean of 19.5 years. The indications for treatment included progressive myelopathy in five patients, spinal subarachnoid hemorrhage in four, and acute paraplegia in one. Associated conditions included Rendu-Osler-Weber syndrome in two patients, and Cobb's syndrome in two patients. In one patient, the cause of the fistula may have been related to epidural anesthesia traumatizing a low tethered cord. Angiographically, the fistulas were subclassified in three groups: a single-hole fistula supplied by a single feeding medullary artery (three patients); a single-hole fistula supplied by multiple medullary arteries (three patients); and multiple separate fistulas supplied by multiple medullary arteries (four patients). Eight patients were classified as perimedullary Type III and two as perimedullary Type II. Embolic agents were delivered from transarterial routes in 14 procedures and transvenous routes in 2 procedures. A total of 16 embolizations and 8 operations were performed in 10 patients. Seven patients were cured of their fistula (as demonstrated by angiography), two patients had 5% residual filling and are scheduled for future therapy. One refused a follow-up angiographic examination. Complications related to embolization included rupture of the anterior spinal artery by a detachable balloon, resulting in transient worsening of paraplegia with recovery to baseline. Transient worsening of symptoms after surgery was common, but all patients returned to baseline or better. Dramatic improvement was observed in four patients.(ABSTRACT TRUNCATED AT 250 WORDS)

The Impact Of Sports Activities On Quality Of Life Of Persons With A Spinal Cord Injury

PubMed Central

Eminović, Fadilj; Dopsaj, Milivoj; Pavlović, Dragan; Arsić, Sladjana; Otašević, Jadranka

2016-01-01

Abstract Objectives Studying the quality of life of people with a spinal cord injury is of great importance as it allows the monitoring of both functioning and adaptation to disability. The aim of this study was to determine the difference between persons with a spinal cord injury involved in sports activities and those not involved in sports activities in relation to their quality of life and the presence of secondary health conditions (pressure ulcers, urinary infections, muscle spasms, osteoporosis, pain, kidney problems-infections, calculosis and poor circulation). Methods The study included a total of 44 participants with spinal cord injury-paraplegia of both genders; 26 of them were athletes and 18 were not athletes. The athletes were training actively for the last two years, minimally 2-3 times per week. A specially designed questionnaire, medical documentation and the Spinal Cord Injury Quality of Life Questionnaire (SCI QL-23) were used for research purposes. Chi-square test was used to analyze the differences between the groups, while multiple analysis of variance (MANOVA) was used to determine the differences between the sets of variables. Results Among the participants, the athletes perceived higher quality of life than the non-athletes (male gender p<0.001 and female gender p<0.05). Regarding secondary health conditions, the athletes reported the presence of less pain (p=0.034) and a subjective feeling of better circulation (p=0.023). Conclusion The implementation of sports activities significantly improves quality of life in the population of people with spinal cord injury-paraplegia. However, sports activities only partially affect secondary health conditions. PMID:27284378

Growth factors and cytokines in patients with long bone fractures and associated spinal cord injury.

PubMed

Khallaf, Fathy G; Kehinde, Elijah O; Mostafa, Ahmed

2016-06-01

The aim of the study was to test the effect of acute traumatic spinal cord injury of quadriplegia or paraplegia on bone healing in patients with associated long bone fractures and to investigate the molecular and cellular events of the underlying mechanism for a possible acceleration. Healing indicators of long bone fractures and growth factors, IGF-II, platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), Activin-A, and cytokine I-L-1, in the patients' blood were calculated and measured for 21 patients with spinal cord injuries and associated long bone fractures in prospective controlled study and compared to 20 patients with only spinal cord injuries, 30 patients with only long bone fractures, and 30 healthy volunteers. The study results showed that long bone fractures in patients with associated acute traumatic spinal cord injury of quadriplegia or paraplegia heal more expectedly, faster, and with exuberant florid union callus (P > 0.001) and show statistically significant higher levels of growth factors like PDGF, VEGF, Activin-A, and cytokine I-L-1, along the 3 weeks of follow-up (P > 0.005). I-IGF-II showed statistically significant subnormal level along the whole follow-up period in the same patients (P > 0.005). We concluded that long bone fractures in spinal cord injury patients heal more expectedly, faster, and with exuberant and florid callus formation; growth factors like IGF-II, PDGF, VEGF, Activin-A, and cytokine I-L-I have roles as mediators, in molecular events and as byproducts of the subtle mechanism of accelerated osteogenesis in these patients and may represent therapeutic potentials to serve as agents to enhance bone repair.

The often overlooked digital tuft: clues to diagnosis and pathophysiology of neuropathic disease and spondyloarthropathy

PubMed Central

Rothschild, B; Behnam, S

2005-01-01

Objective: To assess diagnostic implications of abnormalities of the pedal digital tufts and to identify features to facilitate distinguishing of spondyloarthropathy and leprosy. Background: Better criteria for distinguishing between these disorders are necessary if their character, natural history, and evolution are to be understood. Methods: Pedal x rays of 91 consecutive patients with diabetes, 21 alcoholic patients, 100 with spondyloarthropathy, 8 with scleroderma, and 137 with leprosy, and 188 defleshed skeletons of individuals with alcoholism, syphilis, cerebrovascular disease, and paraplegia from the Terry and Hamman-Todd collections were examined for evidence of osseous and articular pathologies. Digital tuft abnormalities were divided into irregularity, divot, flattening, resorption, whittling, and fragmentation. Results: Tuft divots were more common in alcoholics than in diabetic, and were more common in both than in the other groups studied. Tuft flattening was limited to alcoholic and neurosyphilis groups. Tuft whittling was especially prominent among individuals with spondyloarthropathy, contrasted with leprosy and diabetes. Aligned fractures were more common in diabetics than individuals with leprosy. Misaligned fractures were limited to individuals with leprosy and neurosyphilis. Leprosy and spondyloarthropathy were complicated by phalangeal and metatarsal whittling more commonly than other diseases studied. Background pedal abnormalities, derived from individuals with cardiovascular syphilis, cerebrovascular accidents, and paraplegia, was limited to abnormal divots only. Conclusions: Pedal digital tufts undergo a variety of pathological alterations useful in the recognition of disorders traditionally considered neuropathic in aetiology and in distinguishing differential considerations. Tuft flattening appears specific for alcoholism and neurosyphilis, and misaligned fractures seem specific for neurosyphilis and leprosy, providing differential

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

PubMed Central

Trbovich, Michelle

2014-01-01

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

Effect of a cooling vest on core temperature in athletes with and without spinal cord injury.

PubMed

Trbovich, Michelle; Ortega, Catherine; Schroeder, James; Fredrickson, Mark

2014-01-01

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. 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). 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). 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. 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.

Recovery of supraspinal control of leg movement in a chronic complete flaccid paraplegic man after continuous low-frequency pelvic nerve stimulation and FES-assisted training

PubMed Central

Possover, Marc; Forman, Axel

2017-01-01

Introduction: More than 30 years ago, functional electrical stimulation (FES) was developed as an orthotic system to be used for rehabilitation for SCI patients. In the present case report, FES-assisted training was combined with continuous low-frequency stimulation of the pelvic somatic nerves in a SCI patient. Case Presentation: We report on unexpected findings in a 41-year-old man with chronic complete flaccid paraplegia, since he was 18 years old, who underwent spinal stem cell therapy and a laparoscopic implantation of neuroprosthesis (LION procedure) in the pelvic lumbosacral nerves. The patient had complete flaccid sensomotoric paraplegia T12 as a result of a motor vehicle accident in 1998. In June 2011, he underwent a laparoscopic implantation of stimulation electrodes to the sciatic and femoral nerves for continuous low-frequency electrical stimulation and functional electrical stimulation of the pelvic nerves. Neither intraoperative direct stimulation of the pelvic nerves nor postoperative stimulation induced any sensation or muscle reactions. After 2 years of passive continuous low-frequency stimulation, the patient developed progressive recovery of electrically assisted voluntary motor functions below the lesions: he was first able to extend the right knee and 6 months later, the left. He is currently capable of voluntary weight-bearing standing and walking (with voluntary knee movements) about 50 m with open cuff crutches and drop foot braces. Discussion: Our findings suggest that continuous low-frequency pelvic nerve stimulation in combination with FES-assisted training might induce changes that affect both the upper and the lower motor neuron and allow supra- and infra-spinal inputs to engage residual spinal and peripheral pathways. PMID:28503316

Minocycline Effectively Protects the Rabbit's Spinal Cord From Aortic Occlusion-Related Ischemia.

PubMed

Drenger, Benjamin; Fellig, Yakov; Ben-David, Dror; Mintz, Bella; Idrees, Suhel; Or, Omer; Kaplan, Leon; Ginosar, Yehuda; Barzilay, Yair

2016-04-01

To identify the minocycline anti-inflammatory and antiapoptotic mechanisms through which it is believed to exert spinal cord protection during aortic occlusion in the rabbit model. An animal model of aortic occlusion-related spinal cord ischemia. Randomized study with a control group and pre-ischemia and post-ischemia escalating doses of minocycline to high-dose minocycline in the presence of either hyperglycemia, a pro-apoptotic maneuver, or wortmannin, a specific phosphatidylinositol 3-kinase antagonist. Tertiary medical center and school of medicine laboratory. Laboratory animals-rabbits. Balloon obstruction of infrarenal aorta introduced via femoral artery incision. Severe hindlimb paralysis (mean Tarlov score 0.36±0.81 out of 3) was observed in all the control group animals (9 of 11 with paraplegia and 2 of 11 with paraparesis) compared with 11 of 12 neurologically intact animals (mean Tarlov score 2.58±0.90 [p = 0.001 compared with control]) in the high-dose minocycline group. This protective effect was observed partially during a state of hyperglycemia and was completely abrogated by wortmannin. Minocycline administration resulted in higher neurologic scores (p = 0.003) and a shift to viable neurons and more apoptotic-stained nuclei resulting from reduced necrosis (p = 0.001). In a rabbit model of infrarenal aortic occlusion, minocycline effectively reduced paraplegia by increasing the number of viable neurons in a dose-dependent manner. Its action was completely abrogated by inhibiting the phosphatidylinositol 3-kinase pathway and was inhibited partially by the pro-apoptotic hyperglycemia maneuver, indicating that the activation of cell salvage pathways and mitochondrial sites are possible targets of minocycline action in an ischemic spinal cord. Copyright © 2016. Published by Elsevier Inc.

A cross-sectional study on self-management of pressure ulcer prevention in paraplegic patients.

PubMed

de Laat, H E W; de Munter, A C; van der Burg, M J; Ulrich, D J O; Kloeters, O

2017-02-01

Little is known about health activation and self-management behavior in preventing pressure ulcers (PU) in paraplegic patients. Therefore this study aimed to describe the extent of health activation and self-management behavior in paraplegics to prevent PU's and associations between this behavior and patient characteristics. Furthermore, we aimed to find differences in health activation in paraplegics who never had a PU compared to paraplegics with a previous history of PU's or a new-onset PU's. A cross-sectional survey on health activation and self-management behavior was conducted among adult paraplegics recruited from two rehabilitation centers in the Netherlands. The Patient Activation Measure (PAM-score) was used to measure the extent of health activation. Patient statements on their level of self management behavior to prevent PU were evaluated. The mean PAM-score (0-100) was 54 (±8.1; n = 162) indicating a low level of health activation. Two indicators turned out to be statistically significant associated with health activation: level of education (OR = 2.2, p = 0.017) and degree of paraplegia (OR = 2.8, p = 0.036). Evaluation of health activation levels amongst paraplegics with or without a PU- history showed no significant difference. Analysis of patients statements demonstrated a large discrepancy between intended and actual behavior to prevent pressure ulcers. Level of education and level of paraplegia are significantly associated with health activation. A positive PU-history is not associated with future responsible behavior nor for compliant behavior in terms of health management. Copyright © 2016 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.

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

PubMed Central

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

2013-01-01

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

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

NASA Astrophysics Data System (ADS)

Santos, Silvana; Bizzo, Nelio

2005-07-01

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.

Invasive histiocytic sarcoma of the lumbar spine in a ferret (Mustela putorius furo).

PubMed

Warschau, M; Hoffmann, M; Dziallas, P; Hansmann, F; Baumgärtner, W; Mischke, R; Cichowski, S; Fehr, M

2017-02-01

This report describes the history, clinical examination and histopathology of a histiocytic sarcoma in a domestic ferret. Clinical signs were acute paraplegia and dysuria. Physical examination revealed a firm, smooth, touch-sensitive mass in and around the lumbar vertebral column. Neurologic examination was consistent with a lesion between spinal cord segments T3 and L3. Magnetic resonance images revealed bone lesions of L2 and L3 combined with compression of the spinal cord due to a homogenous, isointense mass that was diagnosed as a malignant round cell tumour and the ferret was euthanased. Histopathology confirmed the diagnosis of an infiltrative histiocytic sarcoma. © 2017 British Small Animal Veterinary Association.

TWIICE - A lightweight lower-limb exoskeleton for complete paraplegics.

PubMed

Vouga, Tristan; Baud, Romain; Fasola, Jemina; Bouri, Mohamed; Bleuler, Hannes

2017-07-01

This paper introduces TWIICE, a lower-limb exoskeleton that enables people suffering from complete paraplegia to stand up and walk again. TWIICE provides complete mobilization of the lower-limbs, which is a first step toward enabling the user to regain independence in activities of the daily living. The tasks it can perform include level and inclined walking (up to 20° slope), stairs ascent and descent, sitting on a seat, and standing up. Participation in the world's first Cybathlon (Zurich, 2016) demonstrated good performance at these demanding tasks. In this paper, we describe the implementation details of the device and comment on preliminary results from a single user case study.

Detection and genetic characterization of a novel parvovirus distantly related to human bufavirus in domestic pigs.

PubMed

Hargitai, Renáta; Pankovics, Péter; Kertész, Attila Mihály; Bíró, Hunor; Boros, Ákos; Phan, Tung Gia; Delwart, Eric; Reuter, Gábor

2016-04-01

In this study, a novel parvovirus (strain swine/Zsana3/2013/HUN, KT965075) was detected in domestic pigs and genetically characterized by viral metagenomics and PCR methods. The novel parvovirus was distantly related to the human bufaviruses and was detected in 19 (90.5 %) of the 21 and five (33.3 %) of the 15 faecal samples collected from animals with and without cases of posterior paraplegia of unknown etiology from five affected farms and one control farm in Hungary, respectively. Swine/Zsana3/2013/HUN is highly prevalent in domestic pigs and potentially represents a novel parvovirus species in the subfamily Parvovirinae.

Self-rated health among persons with spinal cord injury: What is the role of physical ability?

PubMed Central

Machacova, Katerina; Lysack, Cathy; Neufeld, Stewart

2011-01-01

Objectives Self-rated health (SRH) is a powerful concept that has greatly advanced our understanding of health and health outcomes. The SRH measure has become increasingly common in health research. Yet, puzzles remain about what shapes SRH ratings. The absence of knowledge is particularly acute in the context of disability. The aim of this study was to examine the relationship between SRH and self-rated physical ability in a sample of individuals with spinal cord injury (SCI). Methods Data from 140 eligible participants drawn from a study of life in the community after SCI were analyzed. The study, cross-sectional in design, was conducted in a large urban city in the mid-western United States. Basic statistics such as ANOVA and chi-square tests were performed as appropriate, and a multiple linear regression analysis modeled the relationship between SRH and physical ability adjusting for potential confounding variables. Results Self-rated physical ability was significantly associated with SRH after controlling for relevant covariates (P < 0.001). An analysis of the interaction between physical ability and level of injury revealed that the relationship was significant for persons with paraplegia but not for persons with tetraplegia. Conclusions This study provides evidence that self-rated physical ability is an important factor associated with SRH for persons with SCI, but that the strength of the relationship depends on level of injury (paraplegia vs. tetraplegia). The challenge for future research is to replicate the study using a more comprehensive measure of physical ability and to ask how beliefs in one's ability to do those activities that are most meaningful and desired shape SRH. Only in this way will our understanding of the physical ability–SRH relationship be clarified. PMID:21756564

Five-Year Longitudinal Bone Evaluations in Individuals With Chronic Complete Spinal Cord Injury

PubMed Central

Garland, Douglas E; Adkins, Rodney H; Stewart, Charles A

2008-01-01

Background/Objectives: Knowledge of spinal cord injury (SCI) bone changes has been derived primarily through cross-sectional studies, many of which are controvertible. Longitudinal studies are sparse, and long-term longitudinal chronic studies are unavailable. The objective of this study was to provide a clearer perception of chronic longitudinal bone variations in people with complete SCI. Methods: Bone status of 31 individuals with chronic, complete SCI was assessed twice using dual-energy x-ray absorptiometry at an average interval of 5.06 ± 0.9 years. Because the sample of women was small (4), the primary analyses of change and comparisons of those with paraplegia vs tetraplegia were confined to the male participants. Results: Spine Z-scores showed a significant increase (P < 0.0001). The average Z-scores, initial and follow-up, were within the normal range. Hip Z-scores also showed a significant increase (P < 0.0001), and hip bone mineral density (BMD) increased in 48% of the participants. Knee BMD and lower extremity total bone mineral showed significant decreases (P < 0.003 and P < 0.02, respectively), but increases were seen in 33% and 26% at the respective sites. Individuals with tetraplegia had significantly lower values across all regions (P < 0.0001), and changes were significantly different compared with paraplegia (P < 0.0001). Bone values and changes in men vs women, despite the small sample of women, showed highly significant differences (P < 0.003–0.002). Conclusion: Chronic effects of complete SCI do not exclusively result in continued loss of BMD or a static state of lowered BMD; gain in BMD may occur. The nature and magnitude of the effects of complete SCI on BMD vary by site, with sex and level of injury, which has implications for treatment and its assessment. PMID:19086712

Exploring Spinal Cord Protection by Remote Ischemic Preconditioning: An Experimental Study.

PubMed

Herajärvi, Johanna; Anttila, Tuomas; Sarja, Henna; Mustonen, Caius; Haapanen, Henri; Mäkelä, Tuomas; Yannopoulos, Fredrik; Starck, Tuomo; Kallio, Mika; Tuominen, Hannu; Puistola, Ulla; Karihtala, Peeter; Kiviluoma, Kai; Anttila, Vesa; Juvonen, Tatu

2017-03-01

Paraplegia is one of the most severe complications occurring after the repair of thoracic and thoracoabdominal aortic aneurysms. Remote ischemic preconditioning (RIPC) has been shown to mitigate neurologic damage, and this study assessed its efficacy in preventing spinal cord ischemia. The study randomized 16 female pigs into an RIPC group (n = 8) and a control group (n = 8). The RIPC group underwent four cycles of 5-minute ischemia-reperfusion episodes by intermittent occlusion of the left iliac artery. All animals underwent systematic closure of the left subclavian artery and segmental arteries of the descending thoracic aorta to the level of diaphragm. Motor-evoked potential monitoring was performed in both hind limbs. Continuous electrocardiogram and hemodynamics were monitored, and pulmonary artery blood samples were collected. A neurologic assessment was performed 6 hours after the procedure. The thoracic and lumbar portions of the spinal cord were collected for histologic and immunohistochemical analysis. The bilateral motor-evoked potential amplitude responses were higher in the RIPC group (p < 0.05) than in the control group; the difference was detected already before spinal cord ischemia. Paraplegia occurred in 1 control animal. Immunohistochemical total scores of antioxidant response regulator nuclear factor erythroid 2-related factor 2 were better in the RIPC group (11.0; range, 8.5 to 14.0) than in the control group (5.2; range, 1.0 to 9.0; p = 0.023). RIPC induces electrophysiologic changes in the central nervous system that may confer spinal cord protection extending the resistance to ischemia. The significantly higher nuclear factor erythroid 2-related factor 2 scores suggest better neuronal cell protection against oxidative stress in the RIPC group. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Exercise and sports science Australia (ESSA) position statement on exercise and spinal cord injury.

PubMed

Tweedy, Sean M; Beckman, Emma M; Geraghty, Timothy J; Theisen, Daniel; Perret, Claudio; Harvey, Lisa A; Vanlandewijck, Yves C

2017-02-01

Traumatic spinal cord injury (SCI) may result in tetraplegia (motor and/or sensory nervous system impairment of the arms, trunk and legs) or paraplegia (motor and/or sensory impairment of the trunk and/or legs only). The adverse effects of SCI on health, fitness and functioning are frequently compounded by profoundly sedentary behaviour. People with paraplegia (PP) and tetraplegia (TP) have reduced exercise capacity due to paralysis/paresis and reduced exercising stroke volume. TP often further reduces exercise capacity due to lower maximum heart-rate and respiratory function. There is strong, consistent evidence that exercise can improve cardiorespiratory fitness and muscular strength in people with SCI. There is emerging evidence for a range of other exercise benefits, including reduced risk of cardio-metabolic disease, depression and shoulder pain, as well as improved respiratory function, quality-of-life and functional independence. Exercise recommendations for people with SCI are: ≥30min of moderate aerobic exercise on ≥5d/week or ≥20min of vigorous aerobic ≥3d/week; strength training on ≥2d/week, including scapula stabilisers and posterior shoulder girdle; and ≥2d/week flexibility training, including shoulder internal and external rotators. These recommendations may be aspirational for profoundly inactive clients and stratification into "beginning", "intermediate" and "advanced" will assist application of the recommendations in clinical practice. Flexibility exercise is recommended to preserve upper limb function but may not prevent contracture. For people with TP, Rating of Perceived Exertion may provide a more valid indication of exercise intensity than heart rate. The safety and effectiveness of exercise interventions can be enhanced by initial screening for autonomic dysreflexia, orthostatic hypotension, exercise-induced hypotension, thermoregulatory dysfunction, pressure sores, spasticity and pain. Copyright © 2016 Sports Medicine Australia

A retrospective study: Multivariate logistic regression analysis of the outcomes after pressure sores reconstruction with fasciocutaneous, myocutaneous, and perforator flaps.

PubMed

Chiu, Yu-Jen; Liao, Wen-Chieh; Wang, Tien-Hsiang; Shih, Yu-Chung; Ma, Hsu; Lin, Chih-Hsun; Wu, Szu-Hsien; Perng, Cherng-Kang

2017-08-01

Despite significant advances in medical care and surgical techniques, pressure sore reconstruction is still prone to elevated rates of complication and recurrence. We conducted a retrospective study to investigate not only complication and recurrence rates following pressure sore reconstruction but also preoperative risk stratification. This study included 181 ulcers underwent flap operations between January 2002 and December 2013 were included in the study. We performed a multivariable logistic regression model, which offers a regression-based method accounting for the within-patient correlation of the success or failure of each flap. The overall complication and recurrence rates for all flaps were 46.4% and 16.0%, respectively, with a mean follow-up period of 55.4 ± 38.0 months. No statistically significant differences of complication and recurrence rates were observed among three different reconstruction methods. In subsequent analysis, albumin ≤3.0 g/dl and paraplegia were significantly associated with higher postoperative complication. The anatomic factor, ischial wound location, significantly trended toward the development of ulcer recurrence. In the fasciocutaneous group, paraplegia had significant correlation to higher complication and recurrence rates. In the musculocutaneous flap group, variables had no significant correlation to complication and recurrence rates. In the free-style perforator group, ischial wound location and malnourished status correlated with significantly higher complication rates; ischial wound location also correlated with significantly higher recurrence rate. Ultimately, our review of a noteworthy cohort with lengthy follow-up helped identify and confirm certain risk factors that can facilitate a more informed and thoughtful pre- and postoperative decision-making process for patients with pressure ulcers. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All

Preventive Effect of Intrathecal Paracetamol on Spinal Cord Injury in Rats

PubMed Central

Sahin, Murat; Sayar, Ilyas; Peker, Kemal; Gullu, Huriye; Yildiz, Huseyin

2014-01-01

Background: Ischemic injury of the spinal cord during the surgical repair of thoracoabdominal aortic aneurysms might lead to paraplegia. Although a number of different mechanisms have been proposed, the exact cause of paraplegia has remained unknown, hampering the development of effective pharmacologic or other strategies for prevention of this condition. A number of studies suggested that cyclooxygenases (COX) contribute to neural breakdown; thus, COX inhibitors might reduce injury. Objectives: We aimed to assess the preventive effect of intrathecal (IT) pretreatment with paracetamol on spinal cord injury in a rat model. Materials and Methods: This experimental study was performed in Ataturk University Animal Research Laboratory Center, Erzurum, Turkey. Adult male Wistar rats were randomly allocated to three experimental groups (n = 6) to receive IT physiologic saline (controls), 50 µg of paracetamol, or 100 µg paracetamol one hour before induction of spinal cord ischemia. Six other rats were considered as the sham group. For the assessment of ischemic injury, motor functions of the hind limbs and histopathologic changes of the lumbar spinal cord were evaluated. Additional 20 rats were divided into two equal groups for the second part of the study where the survival rates were recorded in controls and in animals receiving 100 µg of paracetamol during the 28-day observation period. Results: Pretreatment with 100 µg of paracetamol resulted in a significant improvement in motor functions and histopathologic findings (P < 0.05). Despite a higher rate of survival in 100 µg of paracetamol group (70%) at day 28, the difference was not statistically significant in comparison with controls. Conclusions: Our results suggest a protective effect of pretreatment with IT paracetamol on ischemic spinal cord injury during thoracolumbar aortic aneurysm surgery. PMID:25763224

Control of paraplegic ankle joint stiffness using FES while standing.

PubMed

Hunt, K J; Gollee, H; Jaime, R P

2001-10-01

The goal of this work was to investigate the feasibility of ankle stiffness control using functional electrical stimulation (FES) while standing, as relevant to the development of feedback systems for balance control in paraplegia. The work was carried out using apparatus in which the subject stands with all joints above the ankles braced, and where ankle moment is provided via FES of the ankle flexor and extensor muscles. A feedback control strategy for ankle stiffness control is proposed in which the ankle moment is controlled to a reference value equal to the product of the desired stiffness and the measured ankle angle. Two subjects participated in the study: one neurologically-intact person, and one paraplegic person with a complete thoracic spinal cord lesion. The results show that during forward-leaning postures, when the plantarflexor muscles are stimulated, relatively high ankle moments of up to 60 Nm can be generated and accurate moment tracking is achieved. As a consequence, ankle stiffness is close to the desired value. During backward lean, on the other hand, the dorsiflexor muscles are stimulated. These muscles are relatively weak and only modest ankle moments of up to around 15 Nm can be produced. As a result, dorsiflexor stimulation readily saturates giving poor stiffness control. It was further observed that when the desired stiffness is higher more external force has to be applied to perturb the body away from the neutral (upright) position. We conclude that: (i) accurate ankle stiffness control, up to the fundamental strength limits of the muscles, can be achieved with controlled FES; (ii) ankle stiffness control using FES in paraplegia has the potential to ease the task of stabilising upright posture by application of additional upper-body forces.

Aortic aneurysm surgery: long-term patency of the reimplanted intercostal arteries.

PubMed

David, Nathalie; Roux, Nicolas; Douvrin, Françoise; Clavier, Erick; Bessou, Jean Paul; Plissonnier, Didier

2012-08-01

During aortic surgery, the long-term patency of reimplanted intercostal arteries is unknown, limiting the relevance to preserve spinal cord vascularization. Between January 2001 and January 2007, 40 patients were operated for either thoracic aortic aneurysm (TAA) or thoracoabdominal aortic aneurysm (TAAA). Twenty cases of aneurysms limited to the proximal descending thoracic aorta were treated using endovascular repair, without preoperative spinal cord artery identification. Twenty patients--seven with extensive TAA, seven with type I TAAA, two with type II TAAA, and four with type III TAAA--underwent open surgery. Before open surgery, preoperative angiography was performed to identify spinal cord vascularization; in one case, the angiography failed to identify it. The segmental artery destined to the spinal cord artery was identified as originating from outside the aneurysm in 7 patients and inside the aneurysm in 12 patients: T6 R (1), T8 L (2), T9 L (3), T10 L (3), T11 L (3), L1 L (1). During the surgery, normothermic and femorofemoral bypass was used for visceral protection. All segmental arteries identified as critical before surgery were reattached in the graft. Twenty-four months later, computed tomography scans were performed to assess the patency of the reattached segmental arteries. Three patients died, including one with paraplegia (T9 L). No other cases of paraplegia were reported. Computed tomography scans were performed in 10 patients. Segmental artery reattachment was patent in nine patients. Our experience indicates the long-term patency of reimplanted segmental artery, without any convincing evidence of its utility in preventing neurologic events during TAA and TAAA direct repair. Copyright © 2012 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.

Intramedullary dermoid cyst infection mimicking holocord tumor: should radical resection be mandatory?-a case report.

PubMed

Karaaslan, Burak; Ülkü, Göktuğ; Ucar, Murat; Demirdağ, Tuğba Bedir; İnan, Arda; Börcek, Alp Özgün

2016-11-01

Dermoid cysts are benign lesions which contain epidermal and dermal elements. Dermoid cysts usually contain a dermal sinus tract but this is not mandatory. Dermoid cysts can manifest by spinal cord infection without a dermal sinus tract. An infected spinal dermoid cyst associated with a holocord spinal abscess poses diagnostic and surgical challenges. Although radical surgical drainage is considered as the main treatment modality for spinal abscess, less extensive surgery for microbiological sampling and appropriate antibiotic treatment can be another alternative modality. A 1-year-old boy patient was admitted to our hospital with progressive paraplegia, bladder dysfunction, and neck rigidity. Medical history of the patient included recurrent urinary tract infection and cephalosporin treatments several times. Initial neurological examination revealed confusion, fever, neck rigidity, paraplegia (also, the motor power of the right upper extremity was three fifths that of the upper extremities). He had urinary and gastrointestinal retention. Conservative surgery was performed to take pathological and microbiological samples. With appropriate antibiotic regimen, the nuchal rigidity and fever improved dramatically. Infectious parameters in blood biochemistry significantly decreased after the antibiotic regimen. Holocord spinal abscesses are a rare entity. The source of the disease can be hemopoietic spread or contagious spread. The dermal sinus tract is major risk factor for contagious spread. The major hemopoietic sources are urogenital infection, endocarditis, and infective lung diseases. The hemopoietic spread is a more common source for pediatric patients. The thoracolumbar region is the most common site of involvement. Spinal infection has a tendency to extend longitudinally throughout spinal fibers. The pathogenesis of the holocord edema or syrinx is uncertain. The underlying etiology may be inflammation, infection, and associated venous congestion within the

An aggressive vertebral hemangioma in pregnancy: a case report.

PubMed

Slimani, Ouafae; Jayi, Sofia; Fdili Alaoui, Fatimazahra; Bouguern, Hakima; Chaara, Hekmat; Fikri, Ghizlane; Alaoui Rachidi, Siham; Sqalli Houssaini, Nadia; Himmich, Mariam; Abdelilah Melhouf, Moulay

2014-06-18

Pregnancy-related compressive myelopathy secondary to vertebral hemangioma is a rare occurrence and its treatment antepartum is rare. 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. At any term of pregnancy, extensive neurological involvement which is rapidly progressive due to compression should be considered for immediate decompression.

Spinal cord protection in descending thoracic and thoracoabdominal aortic aneurysm repair.

PubMed

Safi, H J; Campbell, M P; Ferreira, M L; Azizzadeh, A; Miller, C C

1998-01-01

During aneurysm repair of the descending thoracic or thoracoabdominal aorta, the likelihood of neurological complications increases greatly after only 30 minutes of spinal cord ischemia. However, the manifestation of paraplegia or paraparesis relates not only to aortic cross-clamping time, but to multiple factors that may include aortic dissection, previous aortic surgery, advanced age, preoperative renal insufficiency, rupture, and most significantly, aneurysm extent. At greatest risk is the patient with type II thoracoabdominal aortic aneurysm. For this patient the simple cross-clamp technique, which uses no protective surgical adjuncts, heightens the threat of neurological deficit. With the surgical adjuncts of cerebrospinal fluid drainage and distal aortic perfusion, the probability of neurological deficit is appreciably lowered.

Rupture of the retrocorporeal artery: a rare cause of spontaneous spinal epidural haematoma.

PubMed

Guédon, Alexis; Clarençon, Frédéric; Law-Ye, Bruno; Sourour, Nader; Gabrieli, Joseph; Rojas, Patricia; Chiras, Jacques; Peyre, Matthieu; Di Maria, Federico

2016-06-01

A 22-year-old man presented with a sudden backache and paraplegia (ASIA = B). Magnetic resonance imaging showed an anterior pan-spinal epidural haematoma. Digital subtraction angiography was performed and ruled out an underlying vascular malformation but showed an active contrast media leakage into the T-4 ventral epidural space with a pattern of pseudo-aneurysm. A rupture of a T-4 retrocorporeal artery was considered as the aetiology, possibly caused by a haemorrhagic sub-adventitial dissection. Treatment consisted in the embolisation of both the pseudo-aneurysm and the parent artery with liquid acrylic glue, followed by neurosurgical decompression in emergency. The patient had totally recovered (ASIA = E) by the 10-month clinical follow-up.

Continuous lumbar hemilaminectomy for intervertebral disc disease in an Amur tiger (Panthera tigris altaica).

PubMed

Flegel, Thomas; Böttcher, Peter; Alef, Michaele; Kiefer, Ingmar; Ludewig, Eberhard; Thielebein, Jens; Grevel, Vera

2008-09-01

A 13-yr-old Amur tiger (Panthera tigris altaica) was presented for an acute onset of paraplegia. Spinal imaging that included plain radiographs, myelography, and computed tomography performed under general anesthesia revealed lateralized spinal cord compression at the intervertebral disc space L4-5 caused by intervertebral disc extrusion. This extrusion was accompanied by an extensive epidural hemorrhage from L3 to L6. Therefore, a continuous hemilaminectomy from L3 to L6 was performed, resulting in complete decompression of the spinal cord. The tiger was ambulatory again 10 days after the surgery. This case suggests that the potential benefit of complete spinal cord decompression may outweigh the risk of causing clinically significant spinal instability after extensive decompression.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rousseau, Herve, E-mail: rousseau.h@chu-toulouse.fr; Elaassar, Omar; Marcheix, Bertrand

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 willmore » help to clarify the role of TEVAR compared with open repair of TAI.« less

Nontraumatic spinal subdural hematoma complicating direct factor Xa inhibitor treatment (rivaroxaban): a challenging management.

PubMed

Dargazanli, Cyril; Lonjon, Nicolas; Gras-Combe, Guillaume

2016-05-01

We report on a 72-year-old male patient who developed a nontraumatic spinal subdural hematoma (SSDH) during rivaroxaban therapy, a relatively new orally administered direct factor Xa inhibitor. The patient sustained a sudden onset of interscapular pain, followed by gait impairment and paraplegia. Magnetic resonance imaging (MRI) of the spine demonstrated SSDH from T6 to T8. Laboratory tests revealed a high rivaroxaban level, associated with a major hemorrhagic risk. Surgery was, therefore, performed the following morning, after normalization of coagulation parameters. Determining the time of safe surgery remains challenging when hemorrhagic complications happen with direct factor Xa inhibitor, especially when neurological prognosis is engaged. Spinal subdural hematoma has not previously been reported following rivaroxaban therapy.

Development of hydronephrosis secondary to poorly managed neurogenic bowel requiring surgical disimpaction in a patient with spinal cord injury: A case report

PubMed Central

Downs, Jairon; Wolfe, Tracy; Walker, Heather

2014-01-01

Context Case of an adult patient with paraplegia managing neurogenic bladder with intermittent catheterization who was not performing a standard bowel program for management of neurogenic bowel. Findings Patient presented with increasing spasticity, fecal incontinence, and abdominal pain and ultimately was hospitalized for management. Imaging revealed massive fecal impaction, resulting in ureteral obstruction and hydronephrosis. Despite repeated aggressive bowel regimens, serial abdominal X-rays showed continued large stool burden. Ultimately surgical intervention was required to evacuate the colon and subsequently the hydronephrosis resolved. Conclusion/Clinical relevance This case illustrates the importance of proper management of neurogenic bowel, as significant medical complications, such as hydronephrosis can occur with poorly managed neurogenic bowel. PMID:24617444

Hydrocephalus: a rare initial manifestation of sporadic intramedullary hemangioblastoma : Intramedullary hemangioblastoma presenting as hydrocephalus.

PubMed

Morais, Barbara Albuquerque; Cardeal, Daniel Dante; Ribeiro E Ribeiro, Renan; Frassetto, Fernando Pereira; Andrade, Fernanda Goncalves; Matushita, Hamilton; Teixeira, Manoel Jacobsen

2017-08-01

Intramedullary hemangioblastomas are rare benign vascular tumors, infrequent in pediatric patients. Clinical symptoms vary according to the age of presentation, tumor size, location, and concomitant syringomyelia. This is the second reported case of hemangioblastoma presenting with acute hydrocephalus. A 3-month-old infant with acute hydrocephalus was asymptomatic after a ventriculoperitoneal shunt was placed. She returned 3 months later with irritability, acute paraplegia, and respiratory distress. Magnetic resonance imaging (MRI) showed an intramedullary T8-T9 tumor with syringomyelia. She underwent surgical resection with good results during the 6-month follow-up. Intramedullary tumors may present as hydrocephalus and other nonspecific symptoms, with invariably delayed diagnosis in children, but must be considered in suspicious cases.

SPG11 Presenting with Tremor

PubMed Central

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

2012-01-01

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

Multiple Myeloma and Epidural Spinal Cord Compression : Case Presentation and a Spine Surgeon's Perspective

PubMed Central

Ha, Kee-Yong; Kim, Hyun-Woo

2013-01-01

Multiple myeloma, a multicentric hematological malignancy, is the most common primary tumor of the spine. As epidural myeloma causing spinal cord compression is a rare condition, its therapeutic approach and clinical results have been reported to be diverse, and no clear guidelines for therapeutic decision have been established. Three patients presented with progressive paraplegia and sensory disturbance. Image and serological studies revealed multiple myeloma and spinal cord compression caused by epidural myeloma. Emergency radiotherapy and steroid therapy were performed in all three cases. However, their clinical courses and results were distinctly different. Following review of our cases and the related literature, we suggest a systematic therapeutic approach for these patients to achieve better clinical results. PMID:24175035

Comorbidity and physical activity in people with paraplegia: a descriptive cross-sectional study.

PubMed

Montesinos-Magraner, L; Serra-Añó, P; García-Massó, X; Ramírez-Garcerán, L; González, L-M; González-Viejo, M Á

2018-01-01

Descriptive cross-sectional study. The study was conducted in the Spinal Cord Injury Unit of the University Vall d'Hebron Hospital and in the Physical Education and Sports Department of the University of Valencia. The aim of this study was to quantify the presence of comorbidities in spinal cord injury (SCI) subjects who did or did not perform regular physical activity (PA) and to identify the relationship between PA and the level of comorbidity. The sample consisted of patients with complete motor SCI (T2-T12), who were fitted with an accelerometer attached to the non-dominant wrist for a period of 1 week. The clinical and blood analytic variables were selected by an expert panel. In the exploratory analysis, we have found differences in the total number of pathologies between active and inactive patients, with fewer total pathologies in the active patient group. An association was found between the PA level and diabetes mellitus (; P=0.047; φ=0.25). We also observed an association between the cardioprotector level of high-density lipoprotein (HDL)-cholesterol and PA level (; P=0.057; Φ0.24). Our results suggest that patients considered active showed lower total comorbidity than inactive patients and higher protection levels against developing cardiovascular comorbidity.

Physical Activity and Quality of Life among Adults with Paraplegia in Odisha, India

PubMed Central

Ganesh, Shankar; Mishra, Chittaranjan

2016-01-01

Objectives: The complete rehabilitation of patients with spinal cord injuries (SCI) comprises both physical and psychosocial factors. This study therefore aimed to assess physical activity and quality of life (QOL) among paraplegic patients with SCI in Odisha, India. Methods: This cross-sectional prospective study was conducted between March 2010 and December 2013. All paraplegic patients treated at the Swami Vivekanand National Institute of Rehabilitation Training & Research in Odisha, India, during the study period who met the inclusion criteria were invited to participate in the study (n = 364). Structured face-to-face interviews were held with participants and QOL and physical activity were assessed using the abbreviated World Health Organization QOL instrument and the Physical Activity Scale for Individuals with Physical Disabilities, respectively. Results: A total of 84 people participated in the study (response rate: 23.1%). The mean age was 32.54 ± 10.75 years and 90.5% of the participants were male. Participants had a low mean metabolic equivalent score (18.18 ± 10.68 hours/day). Additionally, low mean scores were noted for the physical health, psychological well-being, social relationships and environment QOL domains (49.76 ± 18.74, 48.57 ± 17.04, 57.88 ± 17.04 and 49.85 ± 17.77, respectively). There was a strong positive association between levels of physical activity and all QOL domains (P <0.050). Physical activity and employment status were significant predictors of all QOL domains (P <0.001). Conclusion: Low physical activity levels and QOL were noted among the paraplegic subjects. Interventions promoting physical activity and employment may help to improve QOL among this patient group. PMID:26909214

[Robot-aided training in rehabilitation].

PubMed

Hachisuka, Kenji

2010-02-01

Recently, new training techniques that involve the use of robots have been used in the rehabilitation of patients with hemiplegia and paraplegia. Robots used for training the arm include the MIT-MANUS, Arm Trainer, mirror-image motion enabler (MIME) robot, and the assisted rehabilitation and measurement (ARM) Guide. Robots that are used for lower-limb training are the Rehabot, Gait Trainer, Lokomat, LOPES Exoskeleton Robot, and Gait Assist Robot. Robot-aided therapy has enabled the functional training of the arm and the lower limbs in an effective, easy, and comfortable manner. Therefore, with this type of therapy, the patients can repeatedly undergo sufficient and accurate training for a prolonged period. However, evidence of the benefits of robot-aided training has not yet been established.

Langerhans’ cell histiocytosis involving posterior elements of the dorsal spine: An unusual cause of extradural spinal mass in an adult

PubMed Central

Tyagi, Devendra K.; Balasubramaniam, Srikant; Savant, Hemant V.

2011-01-01

Langerhans cell histiocytosis (LCH) is a clonal proliferation of Langerhans cells occurring as an isolated lesion or as part of a systemic proliferation. It is commoner in children younger than 10 years of age with sparing of the posterior elements in more than 95% of cases. We describe a case of LCH in an adult female presenting with paraplegia. MRI revealed a well-defined extradural contrast enhancing mass at D2-D4 vertebral level involving the posterior elements of spine. D2-5 laminectomy with excision of lesion was performed which lead to marked improvement of patients neurological status. Histopathology was suggestive of eosinophilic granuloma. We describe the case, discuss its uniqueness and review the literature on this rare tumor presentation. PMID:23125497

Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders.

PubMed

Novarino, Gaia; Fenstermaker, Ali G; Zaki, Maha S; Hofree, Matan; Silhavy, Jennifer L; Heiberg, Andrew D; Abdellateef, Mostafa; Rosti, Basak; Scott, Eric; Mansour, Lobna; Masri, Amira; Kayserili, Hulya; Al-Aama, Jumana Y; Abdel-Salam, Ghada M H; Karminejad, Ariana; Kara, Majdi; Kara, Bulent; Bozorgmehri, Bita; Ben-Omran, Tawfeg; Mojahedi, Faezeh; El Din Mahmoud, Iman Gamal; Bouslam, Naima; Bouhouche, Ahmed; Benomar, Ali; Hanein, Sylvain; Raymond, Laure; Forlani, Sylvie; Mascaro, Massimo; Selim, Laila; Shehata, Nabil; Al-Allawi, Nasir; Bindu, P S; Azam, Matloob; Gunel, Murat; Caglayan, Ahmet; Bilguvar, Kaya; Tolun, Aslihan; Issa, Mahmoud Y; Schroth, Jana; Spencer, Emily G; Rosti, Rasim O; Akizu, Naiara; Vaux, Keith K; Johansen, Anide; Koh, Alice A; Megahed, Hisham; Durr, Alexandra; Brice, Alexis; Stevanin, Giovanni; Gabriel, Stacy B; Ideker, Trey; Gleeson, Joseph G

2014-01-31

Hereditary spastic paraplegias (HSPs) are neurodegenerative motor neuron diseases characterized by progressive age-dependent loss of corticospinal motor tract function. Although the genetic basis is partly understood, only a fraction of cases can receive a genetic diagnosis, and a global view of HSP is lacking. By using whole-exome sequencing in combination with network analysis, we identified 18 previously unknown putative HSP genes and validated nearly all of these genes functionally or genetically. The pathways highlighted by these mutations link HSP to cellular transport, nucleotide metabolism, and synapse and axon development. Network analysis revealed a host of further candidate genes, of which three were mutated in our cohort. Our analysis links HSP to other neurodegenerative disorders and can facilitate gene discovery and mechanistic understanding of disease.

An aggressive vertebral hemangioma in pregnancy: a case report

PubMed Central

2014-01-01

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

[Tumour lysis syndrome in small-cell lung cancer].

PubMed

Boshuizen, R C; Smit, A A J; Moons-Pasic, A; Bresser, P

2016-01-01

Small-cell lung cancer (SCLC) is a rapidly proliferating malignancy. Dramatic response to chemotherapy can therefore be expected. Unfortunately, tumour lysis prophylaxis is not mentioned in the current Dutch guidelines on SCLC treatment. A 64-year-old female was diagnosed with extensive SCLC and metastases. Shortly after diagnosis, chemotherapy was initiated. Based on Dutch guidelines, no tumour lysis prophylaxis was given. In addition to paraplegia, the patient also developed a clinical tumour lysis syndrome (TLS), and she passed away 5 days after start of treatment. Although tumour lysis prophylaxis is not mentioned in SCLC guidelines, tumour lysis in SCLC can occur as reported previously. Retrospectively, based on parameters applied to haematological malignancies, our patient was assessed as being at high risk of developing TLS.

[Neuraxial anesthesia after local anesthesia for management of percutaneous vertebroplasty complication during vertebroplasty].

PubMed

Balkarlı, Hüseyin; Kılıç, Mesut; Öztürk, İbrahim

Percutaneous vertebroplasty is a relatively safe, simple and commonly performed interventional procedure for the management of vertebral compression fractures. However, serious complications are rarely reported in the procedure. Those are pulmonary embolism, severe infection, paraplegia and an occurrence of a new fracture in an adjacent vertebra after vertebroplasty. Acute complications are generally associated with the procedure. We present the case of neuraxial anesthesia, developed after local anesthesia with 8mL of 2% prilocaine, in a 68-year-old woman who underwent percutaneous vertebroplasty after an osteoporotic collapsed fracture in the L 1 vertebra due to trauma. To our knowledge, this is the first case in the literature. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Neuraxial anesthesia after local anesthesia for management of percutaneous vertebroplasty complication during vertebroplasty.

PubMed

Balkarlı, Hüseyin; Kılıç, Mesut; Öztürk, İbrahim

Percutaneous vertebroplasty is a relatively safe, simple and commonly performed interventional procedure for the management of vertebral compression fractures. However, serious complications are rarely reported in the procedure. Those are pulmonary embolism, severe infection, paraplegia and an occurrence of a new fracture in an adjacent vertebra after vertebroplasty. Acute complications are generally associated with the procedure. We present the case of neuraxial anesthesia, developed after local anesthesia with 8mL of 2% prilocaine, in a 68-year-old woman who underwent percutaneous vertebroplasty after an osteoporotic collapsed fracture in the L 1 vertebra due to trauma. To our knowledge, this is the first case in the literature. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

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

PubMed Central

Renvoisé, Benoît; Blackstone, Craig

2010-01-01

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, Young-Min, E-mail: ymhan@chonbuk.ac.kr; Kwak, Ho-Sung; Jin, Gong-Young

2006-06-15

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 casemore » of a spinal epidural hematoma after thrombolysis in a case of DVT with a pulmonary thromboembolism.« less

A follow-up program in India for patients with spinal cord injury: paraplegia safari.

PubMed

Prabhaka, M M; Thakker, Tejas H

2004-01-01

Once patients with spinal cord injury (SCI) were discharged from the hospital, it was very difficult for them to return for follow-up, particularly during the first year, due to problems regarding finances and social issues, as well as extreme physical barriers. Because of these barriers, a large number of patients were presenting for re-admission for reasons that might have been prevented if they had come for routine follow-up. Therefore, it was felt that an attempt to visit the patient's residence to conduct a follow-up would be of great help. To evaluate and improve the status of rehabilitation of community-dwelling SCI patients in their homes and attempt to decrease the rate of re-admissions. In this program, the home visit team consisted of an orthopedic surgeon, physiotherapist, occupational therapist, prosthetist and orthotist engineer, medical social worker, and a nurse. Rehabilitated discharged patients received needed medical treatment, orthotics, and vocational guidance at their residences. Patients who required re-admission were assisted back to the hospital. The home visit program decreased the number of re-admissions by improving the status of rehabilitation, which raised the quality of care for patients with SCI.

Levodopa in Treatment of Decompression Sickness and of Air Embolism Induced Paraplegia in Rats.

DTIC Science & Technology

1981-08-28

nitrosoureas (BCNU, CCNU) made additional progress in the treatment of brain tumors. A lipid soluble agent , 1,3-bis (2-Chloroethyl)-l- Nitrosourea (BCNU...mechanisms of levodopa and some other agents in the prevention and in the recovery of rats from decompression sickness. For better clarity the...brain occurring in decompression sickness. B. Decompression Sickness Studies. We have shown that gelatin, an agent that protects platelets during freezing

Performance Evaluation of a Lower Limb Exoskeleton for Stair Ascent and Descent with Paraplegia*

PubMed Central

Farris, Ryan J.; Quintero, Hugo A.; Goldfarb, Michael

2013-01-01

This paper describes the application of a powered lower limb exoskeleton to aid paraplegic individuals in stair ascent and descent. A brief description of the exoskeleton hardware is provided along with an explanation of the control methodology implemented to allow stair ascent and descent. Tests were performed with a paraplegic individual (T10 complete injury level) and data is presented from multiple trials, including the hip and knee joint torque and power required to perform this functionality. Joint torque and power requirements are summarized, including peak hip and knee joint torque requirements of 0.75 Nm/kg and 0.87 Nm/kg, respectively, and peak hip and knee joint power requirements of approximately 0.65 W/kg and 0.85 W/kg, respectively. PMID:23366287

Aculaser therapy for the treatment of cerebral palsy

NASA Astrophysics Data System (ADS)

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

2012-03-01

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

Treating cerebral palsy with aculaser therapy

NASA Astrophysics Data System (ADS)

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

2008-03-01

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

Role of motor-evoked potential monitoring in conjunction with temporary clipping of spinal nerve roots in posterior thoracic spine tumor surgery.

PubMed

Eleraky, Mohammed A; Setzer, Matthias; Papanastassiou, Ioannis D; Baaj, Ali A; Tran, Nam D; Katsares, Kiesha M; Vrionis, Frank D

2010-05-01

The vascular supply of the thoracic spinal cord depends on the thoracolumbar segmental arteries. Because of the small size and ventral course of these arteries in relation to the dorsal root ganglion and ventral root, they cannot be reliably identified during surgery by anatomic or morphologic criteria. Sacrificing them will most likely result in paraplegia. The goal of this study was to evaluate a novel method of intraoperative testing of a nerve root's contribution to the blood supply of the thoracic spinal cord. This is a clinical retrospective study of 49 patients diagnosed with thoracic spine tumors. Temporary nerve root clipping combined with motor-evoked potential (MEP) and somatosensory-evoked potential (SSEP) monitoring was performed; additionally, postoperative clinical evaluation was done and reported in all cases. All cases were monitored by SSEP and MEPs. The nerve root to be sacrificed was temporarily clipped using standard aneurysm clips, and SSEP/MEP were assessed before and after clipping. Four nerve roots were sacrificed in four cases, three nerve roots in eight cases, and two nerve roots in 22 cases. Nerve roots were sacrificed bilaterally in 12 cases. Most patients (47/49) had no changes in MEP/SSEP and had no neurological deficit postoperatively. One case of a spinal sarcoma demonstrated changes in MEP after temporary clipping of the left T11 nerve root. The nerve was not sacrificed, and the patient was neurologically intact after surgery. In another case of a sarcoma, MEPs changed in the lower limbs after ligation of left T9 nerve root. It was felt that it was a global event because of anesthesia. Postoperatively, the patient had complete paraplegia but recovered almost completely after 6 months. Temporary nerve root clipping combined with MEP and SSEP monitoring may enhance the impact of neuromonitoring in the intraoperative management of patients with thoracic spine tumors and favorably influence neurological outcome. Copyright 2010 Elsevier

When and how should we manage thoracic aortic injuries in the modern era?

PubMed

Bottet, Benjamin; Bouchard, François; Peillon, Christophe; Baste, Jean-Marc

2016-12-01

A best evidence topic in cardiovascular surgery was written according to a structured protocol. The question addressed was what are the optimum treatment modality and timing of intervention for blunt thoracic aortic injury (BTAI) in the modern era? Of the 697 papers found using the reported search, 14 (5 meta-analyses, 2 prospective and 7 retrospective studies) represented the best evidence to answer the clinical question. The author, journal, country, date of publication, patient group studied, study type, relevant outcomes, results and weakness of these papers are tabulated. All five meta-analyses reported a reduction in mortality with thoracic endovascular aortic repair (TEVAR) compared with open repair (OR), but only four found the same benefit on paraplegia rate. Similarly, the two prospective and four retrospective studies showed significantly lower mortality with TEVAR than with OR. Only one study (a meta-analysis) reported a significantly lower stroke rate with TEVAR than with OR, whereas the 13 others reported a similar or even higher stroke rate. Other complication rates were identical. Four studies demonstrated that non-operative management (NOM) as a treatment option for BTAI was associated with increased mortality, even if it has declined in recent years. One study emphasized that some cases with minimal aortic injuries (Grade I and II on CT scan) could benefit from NOM. Regarding the timing of repair, only three studies analysed outcomes of delayed repair and reported significantly lower mortality than for early repair. We conclude that with lower mortality and similar overall complications including paraplegia but higher stroke rate, TEVAR is the most suitable treatment for BTAI in the modern era, where expertise exists, especially for cases of multiple associated injuries and in the older age group. Delayed aortic repair can be proposed based on CT scan analysis, but emergent repair should still be advocated for imminent free aortic rupture. NOM

Mammalian knock out cells reveal prominent roles for atlastin GTPases in ER network morphology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Guohua; Zhu, Peng-Peng; Renvoisé, Benoît

Atlastins are large, membrane-bound GTPases that participate in the fusion of endoplasmic reticulum (ER) tubules to generate the polygonal ER network in eukaryotes. They also regulate lipid droplet size and inhibit bone morphogenetic protein (BMP) signaling, though mechanisms remain unclear. Humans have three atlastins (ATL1, ATL2, and ATL3), and ATL1 and ATL3 are mutated in autosomal dominant hereditary spastic paraplegia and hereditary sensory neuropathies. Cellular investigations of atlastin orthologs in most yeast, plants, flies and worms are facilitated by the presence of a single or predominant isoform, but loss-of-function studies in mammalian cells are complicated by multiple, broadly-expressed paralogs. Wemore » have generated mouse NIH-3T3 cells lacking all three mammalian atlastins (Atl1/2/3) using CRISPR/Cas9-mediated gene knockout (KO). ER morphology is markedly disrupted in these triple KO cells, with prominent impairment in formation of three-way ER tubule junctions. This phenotype can be rescued by expression of distant orthologs from Saccharomyces cerevisiae (Sey1p) and Arabidopsis (ROOT HAIR DEFECTIVE3) as well as any one of the three human atlastins. Minimal, if any, changes are observed in the morphology of mitochondria and the Golgi apparatus. Alterations in BMP signaling and increased sensitivity to ER stress are also noted, though effects appear more modest. Finally, atlastins appear required for the proper differentiation of NIH-3T3 cells into an adipocyte-like phenotype. These findings have important implications for the pathogenesis of hereditary spastic paraplegias and sensory neuropathies associated with atlastin mutations. - Highlights: • NIH-3T3 cells lacking all three atlastin paralogs were generated using CRISPR/Cas9. • Cells lacking all atlastin GTPases exhibit far fewer 3-way ER tubule junctions. • ER morphology defects in atlastin knockout cells are rescued by distant plant and yeast orthologs. • Atlastin knock out cells

Aerobic capacity, orthostatic tolerance, and exercise perceptions at discharge from inpatient spinal cord injury rehabilitation.

PubMed

Pelletier, Chelsea A; Jones, Graham; Latimer-Cheung, Amy E; Warburton, Darren E; Hicks, Audrey L

2013-10-01

To describe physical capacity, autonomic function, and perceptions of exercise among adults with subacute spinal cord injury (SCI). Cross-sectional. Two inpatient SCI rehabilitation programs in Canada. Participants (N=41; mean age ± SD, 38.9 ± 13.7y) with tetraplegia (TP; n=19), high paraplegia (HP; n=8), or low paraplegia (LP; n=14) completing inpatient SCI rehabilitation (mean ± SD, 112.9 ± 52.5d postinjury). Not applicable. Peak exercise capacity was determined by an arm ergometry test. As a measure of autonomic function, orthostatic tolerance was assessed by a passive sit-up test. Self-efficacy for exercise postdischarge was evaluated by a questionnaire. There was a significant difference in peak oxygen consumption and heart rate between participants with TP (11.2 ± 3.4;mL·kg(-1)·min(-1) 113.9 ± 19.7 beats/min) and LP (17.1 ± 7.5 mL·kg(-1)·min(-1); 142.8 ± 22.7 beats/min). Peak power output was also significantly lower in the TP group (30.0 ± 6.9W) compared with the HP (55.5 ± 7.56W) and LP groups (62.5 ± 12.2W). Systolic blood pressure responses to the postural challenge varied significantly between groups (-3.0 ± 33.5 mmHg in TP, 17.8 ± 14.7 mmHg in HP, 21.6 ± 18.7 mmHg in LP). Orthostatic hypotension was most prevalent among participants with motor complete TP (73%). Results from the questionnaire revealed that although participants value exercise and see benefits to regular participation, they have low confidence in their abilities to perform the task of either aerobic or strengthening exercise. Exercise is well tolerated in adults with subacute SCI. Exercise interventions at this stage should focus on improving task-specific self-efficacy, and attention should be made to blood pressure regulation, particularly in individuals with motor complete TP. Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Sarcopenic Obesity in Adults With Spinal Cord Injury: A Cross-Sectional Study.

PubMed

Pelletier, Chelsea A; Miyatani, Masae; Giangregorio, Lora; Craven, B Catharine

2016-11-01

To describe (1) the frequency and utility of clinically relevant spinal cord injury (SCI)-specific and general population thresholds for obesity and sarcopenic obesity; and (2) the fat and lean soft tissue distributions based on the neurologic level of injury and the American Spinal Injury Association Impairment Scale. Cross-sectional. Tertiary SCI rehabilitation hospital. Persons (N=136; men, n=100; women, n=36) with chronic (mean ± SD: 15.6±11.3y postinjury) tetraplegia (n=66) or paraplegia (n=70). Not applicable. Body composition was assessed with anthropometrics and whole-body dual-energy x-ray absorptiometry. Muscle atrophy was quantified using a sarcopenia threshold of appendicular lean mass index (ALMI) (men, ≤7.26kg/m 2 ; women, ≤5.5kg/m 2 ). Obesity was defined by percentage body fat (men, ≥25%; women, ≥35%), visceral adipose tissue (≥130cm 2 ), and SCI-specific obesity thresholds (body mass index [BMI] ≥22kg/m 2 ; waist circumference ≥94cm). Sarcopenic obesity was defined as the presence of both sarcopenia and obesity. Groups were compared based on impairment characteristics using an analysis of covariance. Sarcopenic obesity was prevalent in 41.9% of the sample. ALMI was lower among participants with motor-complete (6.2±1.3kg/m 2 ) versus motor-incomplete (7.5±1.6kg/m 2 ) injuries (P<.01). Whole-body fat was greater among participants with tetraplegia (28.8±11.2kg) versus paraplegia (24.1±8.7kg; P<.05). Compared with general population guidelines (20.6%), SCI-specific BMI thresholds identified all the participants with obesity (77.9%) based on percentage body fat (72.1%). The observed frequency of sarcopenic obesity in this sample of individuals with chronic SCI is very high, and identification of obesity is dissimilar when using SCI-specific versus general population criteria. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Quantification of trunk and android lean mass using dual energy x-ray absorptiometry compared to magnetic resonance imaging after spinal cord injury.

PubMed

Rankin, Kathleen C; O'Brien, Laura C; Gorgey, Ashraf S

2018-02-20

To determine whether dual energy x-ray absorptiometry (DXA) compared to magnetic resonance imaging (MRI) may accurately quantify trunk lean mass (LM) after chronic spinal cord injury (SCI) and to investigate the relationships between trunk LM, visceral adiposity, trunk fat mass and basal metabolic rate (BMR). Cross-sectional design and correlational analysis. Research setting in a medical center. Twenty-two men with motor complete paraplegia (n = 14; T4-T11) and tetraplegia (n = 8; C5-C7) were recruited as part of a clinical trial. Not applicable. Trunk and android LM were measured using DXA. The volume of six trunk muscle groups were then measured using MRI to quantify trunk LM-MRI. Subcutaneous and visceral adipose tissue (VAT) cross-sectional areas were also measured using MRI. After overnight fast, BMR was evaluated using indirect calorimetry. Trunk LM-DXA (24 ± 3.3 kg) and android LM-DXA (3.6 ± 0.7 kg) overestimated (P < 0.0001) trunk LM-MRI (1.7 ± 0.5 kg). Trunk LM-MRI = 0.088* log (trunk LM-DXA)-0.415; r 2 =0.29, SEE= 0.44 kg, P = 0.007. Trunk LM-MRI = 1.53* android LM-DXA + 0.126; r 2 =0.26, SEE= 0.21 kg, P = 0.018. Percentage trunk LM-MRI was inversely related to VAT (r=-0.79, P < 0.0001) and trunk fat mass (r=-0.83, P < 0.001). Only trunk LM-DXA was related to BMR (r = 0.61, P = 0.002). Persons with tetraplegia have 13% smaller trunk muscle cross-sectional areas (P = 0.036) compared to those with paraplegia. Trunk LM-DXA and android LM-DXA overestimated trunk LM-MRI. Percentage trunk LM-MRI, but not LM-DXA, was inversely related to trunk central adiposity. The findings highlight the importance of exercising trunk LM to attenuate cardio-metabolic disorders after SCI.

[Polyradiculomeningoencephalitis caused by Epstein-Barr virus infection--description of a case with fatal outcome].

PubMed

Ringelstein, E B; Sobczak, H; Pfeifer, B; Hacke, W

1984-03-01

A 21 years old high school student, who, since early childhood, suffered from complete spinal paraplegia of unknown cause at D 10, suddenly, after a three week period with influenca -like prodromal symptoms, presented with acute polyradiculomeningoencephalitis . Positive reactions following Paul-Bunnell- Davidsohn -test and tests for specific antivirus IgG as well as specific IgM revealed acute Epstein-Barr-Virus infection, although no glandular signs could be found. The clinical findings consisted of peripheral sensory-motor tetraparesis, ataxia, nystagmus and disturbances of the caudal cranial nerves. Initially, the diagnosis of Fisher's syndrome was made. The orbicularis oculi reflex, however, indicated a circumscribed brainstem lesion in the medial reticular formation. This finding lead to the additional clinical diagnosis of encephalitis. Shortly after admission, a heart-arrest occurred, and, after successful reanimation, the patient presented with a "locked-in syndrome". On the 12th day after admission, he succumbed during a sudden drop of blood-pressure. Necropsy revealed septic shock as the cause of death, due to perforation of a duodenal ulcer. In the lower thoracic spinal cord a neurocytoma was found, which once lead to the paraplegia. Additionally, moderate inflammatory infiltrations were found in the basal leptomeninges, in the walls of several subcortical vessels and in the hypoglossal nerve. The infiltrations, at some sites, contained a large number of atypical lymphoid cells in the inflammatory meningeal exsudate . Microglial proliferation with satellitosis was found in the inferior olives, thus confirming the clinical diagnosis of polyradiculomeningoencephalitis . This case report should emphasize special features of EBV-infection with neurological complications: (1) in inflammatory diseases of the peripheral and central nervous system, infectious mononucleosis should always be drawn into the diagnostic considerations, even if heterophil antibodies

Surgical treatment of aspergillus spondylodiscitis.

PubMed

van Ooij, A; Beckers, J M; Herpers, M J; Walenkamp, G H

2000-02-01

Four cases of aspergillus spondylodiscitis were treated with operative debridement and fusion. In this rarely encountered mycotic infection of the spine in immunocompromised patients rapid destruction of the intervertebral disc and vertebral bodies can occur. In advanced cases antimycotic drug therapy is thought to be ineffective and a forcing indication for surgery exists when the destruction is progressive and spinal cord compression is imminent or manifest. Spinal instrumentation can be of help in maintaining or restoring spinal stability and maintaining spinal alignment. In our four patients the aspergillus spondylodiscitis was successfully eradicated and fusion achieved. In two of three patients with a neurologic deficit, this deficit disappeared. Two patients died within 6 months after the operative treatment, due to complications related to the underlying illness. One patient was left with a subtotal paraplegia.

X-linked adrenoleukodystrophy in heterozygous female patients: women are not just carriers.

PubMed

Lourenço, Charles Marques; Simão, Gustavo Novelino; Santos, Antonio Carlos; Marques, Wilson

2012-07-01

X-linked adrenoleukodystrophy (X-ALD) is a recessive X-linked disorder associated with marked phenotypic variability. Female carriers are commonly thought to be normal or only mildly affected, but their disease still needs to be better described and systematized. To review and systematize the clinical features of heterozygous women followed in a Neurogenetics Clinic. We reviewed the clinical, biochemical, and neuroradiological data of all women known to have X-ADL. The nine women identified were classified into three groups: with severe and aggressive diseases; with slowly progressive, spastic paraplegia; and with mildly decreased vibratory sensation, brisk reflexes, and no complaints. Many of these women did not have a known family history of X-ALD. Heterozygous women with X-ADL have a wide spectrum of clinical manifestations, ranging from mild to severe phenotypes.

Murmur from a bullet: Old lesion, new treatment.

PubMed

Neves, David; Bettencourt, Nuno; Braga, Pedro; Gama, Vasco

2015-06-01

Aortic disease can be highly variable in terms of lesion morphology, clinical presentation and etiology. We present the case of a young man who suffered a gunshot injury at the age of 12, resulting in paraplegia. Later a murmur was detected and at age 25 a pseudoaneurysm was diagnosed, with fistulization to the left pulmonary artery. Given his good functional status, he was initially managed by a conservative strategy, with regular follow-up. At age 35 left ventricular dilatation was observed with tachycardia and systolic dysfunction, and he was referred for transcatheter aortic valve replacement. Currently, at age 41, he is well in cardiovascular terms, with a good procedural result and professionally active. Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Fatal Septicaemia Following Suprapubic Cystostomy in a Paraplegic Patient: Never Do a Cystostomy without Prior Urine Culture and Appropriate Antibiogram!

PubMed Central

Vaidyanathan, Subramanian; Soni, Bakul M.; Oo, Tun; Hughes, Peter L.; Singh, Gurpreet

2010-01-01

Neuropathic urinary bladder is often colonised by multidrug-resistant bacteria. We report a 64-year-old male spinal cord injury patient with paraplegia, who received gentamicin on empirical basis before undergoing suprapubic cystostomy, as antibiotic sensitivity report of urine was not available. This patient developed fulminate septicaemia. Although appropriate antibiotic therapy (meropenem) was started when this patient manifested features of sepsis, acute renal failure occurred and he expired. Inappropriate initial antimicrobial therapy was the major contributory factor for this patient's mortality. Learning points from this case are (1) never do a cystostomy without prior urine culture and appropriate antibiogram; (2) in a chronic spinal cord injury patient, full blood count, liver function tests, albumin level, and albumin to globulin ratio should be performed before any surgical procedure. PMID:20589219

Quantifying the magnitude of torque physiotherapists apply when stretching the hamstring muscles of people with spinal cord injury.

PubMed

Harvey, Lisa A; McQuade, Lea; Hawthorne, Scott; Byak, Adrian

2003-07-01

To quantify the magnitude of stretch that physiotherapists apply to the hamstring muscles of people with spinal cord injury (SCI). Repeated-measures design. SCI unit in Australia. Fifteen individuals with motor complete paraplegia or tetraplegia. Twelve physiotherapists manually administered a stretch to the hamstring muscles of each subject. The stretch was applied by flexing the hip with the knee extended. Applied hip flexor torque. Therapists applied median hip flexor torques of between 30 and 68Nm, although some torques were as large as 121Nm. The stretch applied by different therapists to any 1 subject varied as much as 40-fold. There is a large range of stretch torques provided by physiotherapists to patients with SCI. Some therapists provide stretch torques well in excess of those tolerated by individuals with intact sensation.

Animal Models of Human Disease: Severe and Mild Lead Encephalopathy in the Neonatal Rat*

PubMed Central

Michaelson, I. Arthur; Sauerhoff, Mitchell W.

1974-01-01

Inorganic lead produces cerebral dysfunction and clinically definable encephalopathies in man. To date there have been few studies on the biochemical changes in brain following exposure to inorganic lead. Studies correlating toxicity with behavioral and brain neurochemical changes following lead exposure have been hindered because adult laboratory animals are resistant to the central nervous system effects of lead poisoning. Such studies have been impeded by lack of suitable experimental models until Pentschew and Garro showed that brain lesions develop in neonatal rats when a pregnant rat newly delivered of her litter is placed on a 4% lead carbonate containing diet. Lead passes into the developing sucklings via maternal milk. Lead-poisoned new-borns have pronounced retardation of growth and during the fourth week of ilfe develop the severe signs of lead encephalopathy, namely, extensive histological lesions of the cerebellum, brain edema, and paraplegia. There is an approximate 85-fold increase in the lead concentration of both the cerebellum and cerebral cortex relative to controls, but edema and gross vascular changes are confined to the cerebellum. Ingested lead had little effect on RNA, DNA, and protein concentrations of developing rat cerebellum and cerebral cortex. However, there was a reduction of between 10 and 20% in the DNA content of the cerebellum around 3 weeks of age in the lead-exposed sucklings. This suggests a failure of cell multiplication in this part of the brain. A critical evaluation of this experimental approach indicated that under similar dietary conditions experimental lactating rats eat 30% less food than controls resulting in: (a) sustained loss in body weight of nursing mothers and that (b) offsprings who develop paraplegia and cerebellar damage do so after gaining access to lead containing diet. We have studied mothers' food consumption and body weight changes and blood, milk, and brain lead content; and newborns' body and brain

Reproducable Paraplegia by Thoracic Aortic Occlusion in a Murine Model of Spinal Cord Ischemia-reperfusion

PubMed Central

Bell, Marshall T.; Reece, T. Brett; Smith, Phillip D.; Mares, Joshua; Weyant, Michael J.; Cleveland, Joseph C.; Freeman, Kirsten A.; Fullerton, David A.; Puskas, Ferenc

2014-01-01

Background Lower extremity paralysis continues to complicate aortic interventions. The lack of understanding of the underlying pathology has hindered advancements to decrease the occurrence this injury. The current model demonstrates reproducible lower extremity paralysis following thoracic aortic occlusion. Methods Adult male C57BL6 mice were anesthetized with isoflurane. Through a cervicosternal incision the aorta was exposed. The descending thoracic aorta and left subclavian arteries were identified without entrance into pleural space. Skeletonization of these arteries was followed by immediate closure (Sham) or occlusion for 4 min (moderate ischemia) or 8 min (prolonged ischemia). The sternotomy and skin were closed and the mouse was transferred to warming bed for recovery.  Following recovery, functional analysis was obtained at 12 hr intervals until 48 hr. Results Mice that underwent sham surgery showed no observable hind limb deficit. Mice subjected to moderate ischemia for 4 min had minimal functional deficit at 12 hr followed by progression to complete paralysis at 48 hr. Mice subjected to prolonged ischemia had an immediate paralysis with no observable hind-limb movement at any point in the postoperative period. There was no observed intraoperative or post operative mortality. Conclusion Reproducible lower extremity paralysis whether immediate or delayed can be achieved in a murine model. Additionally, by using a median sternotomy and careful dissection, high survival rates, and reproducibility can be achieved. PMID:24637534

Reproducable paraplegia by thoracic aortic occlusion in a murine model of spinal cord ischemia-reperfusion.

PubMed

Bell, Marshall T; Reece, T Brett; Smith, Phillip D; Mares, Joshua; Weyant, Michael J; Cleveland, Joseph C; Freeman, Kirsten A; Fullerton, David A; Puskas, Ferenc

2014-03-03

Lower extremity paralysis continues to complicate aortic interventions. The lack of understanding of the underlying pathology has hindered advancements to decrease the occurrence this injury. The current model demonstrates reproducible lower extremity paralysis following thoracic aortic occlusion. Adult male C57BL6 mice were anesthetized with isoflurane. Through a cervicosternal incision the aorta was exposed. The descending thoracic aorta and left subclavian arteries were identified without entrance into pleural space. Skeletonization of these arteries was followed by immediate closure (Sham) or occlusion for 4 min (moderate ischemia) or 8 min (prolonged ischemia). The sternotomy and skin were closed and the mouse was transferred to warming bed for recovery. Following recovery, functional analysis was obtained at 12 hr intervals until 48 hr. Mice that underwent sham surgery showed no observable hind limb deficit. Mice subjected to moderate ischemia for 4 min had minimal functional deficit at 12 hr followed by progression to complete paralysis at 48 hr. Mice subjected to prolonged ischemia had an immediate paralysis with no observable hind-limb movement at any point in the postoperative period. There was no observed intraoperative or post operative mortality. Reproducible lower extremity paralysis whether immediate or delayed can be achieved in a murine model. Additionally, by using a median sternotomy and careful dissection, high survival rates, and reproducibility can be achieved.

A novel microwave sensor to detect specific biomarkers in human cerebrospinal fluid and their relationship to cellular ischemia during thoracoabdominal aortic aneurysm repair.

PubMed

Fok, M; Bashir, M; Fraser, H; Strouther, N; Mason, A

2015-04-01

Thoraco-abdominal aneurysms (TAAA) represents a particularly lethal vascular disease that without surgical repair carries a dismal prognosis. However, there is an inherent risk from surgical repair of spinal cord ischaemia that can result in paraplegia. One method of reducing this risk is cerebrospinal fluid (CSF) drainage. We believe that the CSF contains clinically significant biomarkers that can indicate impending spinal cord ischaemia. This work therefore presents a novel measurement method for proteins, namely albumin, as a precursor to further work in this area. The work uses an interdigitated electrode (IDE) sensor and shows that it is capable of detecting various concentrations of albumin (from 0 to 100 g/L) with a high degree of repeatability at 200 MHz (R(2) = 0.991) and 4 GHz (R(2) = 0.975).

Anterior decompression and fusion for Aspergillus osteomyelitis of the lumbar spine associated with paraparesis.

PubMed

Korovessis, P; Repanti, M; Katsardis, T; Stamatakis, M

1994-12-01

A very rare case of Aspergillus fumigatus osteomyelitis of the spine is described. The differential diagnosis, medical and operative treatment, and follow-up evaluation are reported. To increase knowledge about the pathogenesis and treatment of vertebral osteomyelitis resulting from Aspergillus and to emphasize that such cases still exist. Vertebral osteomyelitis from Aspergillus species is an infrequently described disease in Europe and only few cases have been previously reported. A 48-year-old woman with Aspergillus fumigatus spondylitis in the lumbar spine and tuberculosis-lung infection and concomitant debilitating systemic disease was afflicted with incomplete paraplegia and underwent successful combined operative and medical treatment. Early anterior decompression with spinal fusion, combined with Amphotericin B therapy, was crucial in bringing about complete neurologic recovery and maintaining the sagittal lumbar profile. Excellent clinical and radiologic results were shown in the 42-month follow-up period.

Aggressive hemangioma of the spine in a pregnant female: a case report and literature review.

PubMed

Demirkale, İsmail; De Iure, Federico; Terzi, Silvia; Gasbarrini, Alessandro

2016-01-01

Type and timing of treatment for symptomatic hemangiomas in pregnant females are challenging due to fetus survival and conflicts in neurological recovery. In this article, we report a 40-year-old female patient at pregnancy week 23 with a complicated hemangioma at T1 level. Physical examination revealed an incomplete spastic paraplegia. Patient did not accept any surgery due to child's death risk. Patient was started corticoid treatment and no more weight bearing was allowed. At the 28th week of pregnancy, the patient underwent cesarean section immediately followed by selective arterial embolization, decompression, fixation, and radiotherapy. At two-year follow-up, the patient was pain free, without any signs of local recurrence and with complete neurological recovery. A multidisciplinary approach is mandatory to save the life of the fetus without damaging the spinal cord functions of the mother.

Components of quality of life for persons with a quadriplegic and paraplegic spinal cord injury.

PubMed

Manns, P J; Chad, K E

2001-11-01

This investigation determined the themes that represented quality of life for persons with a spinal cord injury. Fifteen people (6 females, 9 males; 7 persons with quadriplegia, 8 with paraplegia) participated in this study, which used naturalistic inquiry methodologies. Results showed that quality of life for this population, regardless of severity of impairment, consisted of nine themes: (a) physical function and independence, (b) accessibility, (c) emotional well-being, (d) stigma, (e) spontaneity, (f) relationships and social function, (g) occupation, (h) finances, and (i) physical well-being. The themes of life quality were similar for quadriplegics and paraplegics; however, physical function and independence and physical well-being affected the quality of life of persons with a quadriplegic injury to a greater extent. These findings may provide health professionals with information necessary to assist in the development of programs to enhance quality of life.

Carcinomatous myelitis and meningitis after a squamous cell carcinoma of the lip.

PubMed

Pougnet, Isabelle; Murati, Anne; Sarran, Anthony; Viens, Patrice; Sabatier, Renaud

2014-01-01

Nervous central system metastases from head and neck squamous cell carcinoma (SCC) are rare. We report an exceptional case of isolated leptomeningeal and spinal cord involvement few years after the diagnosis of invasive SCC of the lip. A 33-year-old man with a history of infracentimetric carcinoma of the lip developed back pain associated with progressive neurological disorders leading to paraplegia. This atypical presentation led to initial misdiagnosis, but radiological and cytological explorations finally confirmed the diagnosis of leptomeningeal and intramedullar secondary spinal cord lesions from his previously treated head and neck SCC. Systemic targeted therapy with epidermal growth factor receptor inhibitor and intrathecal chemotherapy led to prolonged disease stabilization. To our knowledge, this is the first case of isolated neurological metastases from a head and neck SCC. Combination of systemic targeted therapy and intrathecal chemotherapy may be effective in such cases.

Do overhead sports increase risk for rotator cuff tears in wheelchair users?

PubMed

Akbar, Michael; Brunner, Manuela; Ewerbeck, Volker; Wiedenhöfer, Bernd; Grieser, Thomas; Bruckner, Thomas; Loew, Markus; Raiss, Patric

2015-03-01

for the no-sports group (95% confidence interval, 1.7-2.6; P<.001). Similar results were found for the neurological level of lesion (T2-7/paraplegia. A high frequency of sports activity shows physiological benefits as well as improves the psychological status and quality of life in patients with SCI. The dilemma is how to increase physical activity to gain physiological and psychological health benefits without further increasing overuse of the upper extremities, particularly the shoulder, in patients with paraplegia. The data from this study may be helpful in elucidating the etiology of rotator cuff tear in athletes with paraplegia and in counseling patients with SCI regarding shoulder and upper extremity activity level and provide support for developing preventive strategies. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

[Efficacy of 3D print guide technique in one stage posterior approach for the treatment of cervical and thoracic tuberculosis with kyphosis].

PubMed

Shaxika, Nazierhan; Sun, Z G; Yuan, H; Wang, H

2017-11-21

Objective: To investigate the application of 3D printing technology in the treatment of patients with cervical kyphosis and paraplegia in different segments of the cervical spine after one-stage debridement, bone graft fusion and pedicle screw fixation. Methods: From January 2008 to January 2017, a total of 31 patients with thoracolumbar tuberculosis were treated in the Department of Orthopaedics, the Xinjiang Uygur Autonomous Region people's Hospital.Lesions of the thoracic spine (T1-T4) in 8 cases, (C5-C7) in 10 cases, cervical and thoracic segment in 13 cases, involving a total of 2 cases of vertebral body in 7 cases, 3 cases of vertebral body in 14 cases, 4 cases of vertebral body. 3D printing group (group A) 12 cases, non 3D printing group (group B) of 19 cases.All cases were treated with a posterior approach to the treatment of the cervical spinal cord around the spinal cord.After taking regular anti tuberculosis drugs in 6-12 months, follow-up observation of correction of kyphosis and paraplegia recovery, blood sedimentation rate (ESR), C-reactive protein (CRP) changes. Results: All cases were followed up for at least 6 months. Twelve patients were treated with 3D printing technique before operation, and the operation was performed according to the preoperative plan.The diameter and length of pedicle screws, the direction of insertion, and the distance between the insertion point and the posterior midline of the pedicle screw were similar to those in the 3D.Three days after the operation, the effect of fracture reduction was satisfactory, and the position of pedicle screws was good.After 6 months of follow-up, the X-ray showed that the pedicle screws were in good position, and there was no loosening and fracture.All the patients were healed, and there was no segmental instability.3D printing group during surgery bleeding, operation time, postoperative drainage volume, compared with the non 3D print group of surgical results, 3D printing group significantly

Transesophageal versus transcranial motor evoked potentials to monitor spinal cord ischemia.

PubMed

Tsuda, Kazumasa; Shiiya, Norihiko; Takahashi, Daisuke; Ohkura, Kazuhiro; Yamashita, Katsushi; Kando, Yumi; Arai, Yoshifumi

2016-02-01

We have previously reported that transesophageal motor evoked potential is feasible and more stable than transcranial motor evoked potential. This study aimed to investigate the efficacy of transesophageal motor evoked potential to monitor spinal cord ischemia. Transesophageal and transcranial motor evoked potentials were recorded in 13 anesthetized dogs at the bilateral forelimbs, anal sphincters, and hindlimbs. Spinal cord ischemia was induced by aortic balloon occlusion at the 8th to 10th thoracic vertebra level. In the 12 animals with motor evoked potential disappearance, occlusion was maintained for 10 minutes (n = 6) or 40 minutes (n = 6) after motor evoked potential disappearance. Neurologic function was evaluated by Tarlov score at 24 and 48 hours postoperatively. Time to disappearance of bilateral motor evoked potentials was quicker in transesophageal motor evoked potentials than in transcranial motor evoked potentials at anal sphincters (6.9 ± 3.1 minutes vs 8.3 ± 3.4 minutes, P = .02) and hindlimbs (5.7 ± 1.9 minutes vs 7.1 ± 2.7 minutes, P = .008). Hindlimb function was normal in all dogs in the 10-minute occlusion group, and motor evoked potentials recovery (>75% on both sides) after reperfusion was quicker in transesophageal motor evoked potentials than transcranial motor evoked potentials at hindlimbs (14.8 ± 5.6 minutes vs 24.7 ± 8.2 minutes, P = .001). At anal sphincters, transesophageal motor evoked potentials always reappeared (>25%), but transcranial motor evoked potentials did not in 3 of 6 dogs. In the 40-minute occlusion group, hindlimb motor evoked potentials did not reappear in 4 dogs with paraplegia. Among the 2 remaining dogs, 1 with paraparesis (Tarlov 3) showed delayed recovery (>75%) of hindlimb motor evoked potentials without reappearance of anal sphincter motor evoked potentials. In another dog with spastic paraplegia, transesophageal motor evoked potentials from the hindlimbs remained less than 20%, whereas transcranial motor

Spinal Cord Injury After Extremity Surgery in Children With Thoracic Kyphosis.

PubMed

Pruszczynski, Blazej; Mackenzie, William G; Rogers, Kenneth; White, Klane K

2015-10-01

Spinal cord injury is a rare complication after lower extremity surgery in children with skeletal dysplasia and thoracic kyphosis. We encountered two patients who had this complication, from among 51 (39 from Nemours/Alfred I. duPont Hospital for Children and 12 from Seattle Children's Hospital) who underwent lower extremity surgery during an 8.5-year period (June 2004 to December 2012). Because spinal cord injury is a devastating complication likely not known to most physicians treating patients with skeletal dysplasias, we sought to examine factors that may contribute to this rare complication. We performed a retrospective review of two patients with skeletal dysplasia who had paraplegia develop after extremity surgery. Outcome measures included operative time, vital signs, and postsurgery recovery of neurologic deficit. MR images were reviewed. Two patients were found-an 8.5-year-old boy with spondyloepiphyseal dysplasia congenita with a 76°-thoracic kyphosis apex at T4 and a 6.5-year-old boy with mucopolysaccharidosis type 1-H with an 80°-thoracic kyphosis apex at T2. Bilateral proximal femoral osteotomies or bilateral innominate and proximal femoral osteotomies had been performed. The spinal cord injuries occurred at the apex of the kyphosis as determined by clinical examination and MRI assessment. In both patients, the mean arterial blood pressure decreased below 50 mm Hg and might be a factor in the etiology of the paralysis. The first patient recovered motor function in 5 months; the second had no recovery. Paraplegia is extremely rare after nonspine operations. Many factors contribute to the risk for a spinal cord event: low mean arterial pressure, duration of the surgery, position on the operating table, the kyphotic spine deformity, or unappreciated vascular disease. Motor-evoked potentials and somatosensory-evoked potentials together potentially provide high sensitivity and specificity for predicting a postoperative neurologic deficit. Based on our

Tuberculous spondylitis diagnosed through Xpert MTB/RIF assay in urine: a case report.

PubMed

Sikalengo, George; Ramirez, Adria; Faini, Diana; Mwamelo, Kim; Battegay, Manuel; Jugheli, Levan; Hatz, Christoph; Reither, Klaus; Letang, Emilio

2016-09-26

Extrapulmonary tuberculosis (EPTB) is associated with high rates of morbidity and mortality. Diagnosis of EPTB is challenging in resource-limited settings due to difficulties in obtaining samples, as well as the paucibacillarity of the specimens. Skeletal tuberculosis accounts for 10-35 % of EPTB cases, with vertebral osteomyelitis (Pott's disease) representing 50 % of the cases. We present two cases of suspected Pott's disease, diagnosed through GeneXpert MTB/RIF assay in urine at a rural Tanzanian hospital. Case I A 49-year old male, HIV-1 positive, on co-formulated tenofovir disoproxil fumarate/lamivudine/efavirenz since 2009 and CD4 counts of 205 cells/μL (13 %). He presented with lower back pain and progressive lower limb weakness for two weeks prior to admission. The physical examination revealed bilateral flaccid paraplegia with reduced reflexes, but otherwise unremarkable findings. A lateral lumbar X-ray showed noticeable reduction of intervertebral space between L4 and L5, and a small calcification in the anterior longitudinal ligament between L4 and L5, being compatible with focal spondylosis deformans but inconclusive with regard to tuberculous spondylitis. An abdominal ultrasound showed normal kidneys, bladder and prostate gland. The urinalysis and complete blood counts (CBC) were normal. M. Tuberculosis was detected through GeneXpert MTB/RIF in centrifuged urine, with no resistance to rifampicin. Case II A 76-year old female, HIV-1 negative, presented with lower back pain and progressive weakness and numbness of the lower limbs for two months prior to admission. The physical examination revealed paraplegia, but otherwise unremarkable findings. The lumbosacral X-ray findings were compatible with spondylosis deformans of the lumbar spine and possible tuberculous spondylitis in L3-L4. The abdominal and renal ultrasound showed normal kidneys and bladder. The urinalysis and CBC were normal. M. Tuberculosis was detected through GeneXpert MTB/RIF in

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

PubMed Central

2010-01-01

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 (α-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 α-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); α-TOL control group (CE) which received intramuscular (i.m.) α-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 α-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). α-TOL administration in IRIE group significantly improved all the previously measured parameters compared with

Spinal cord blood flow and ischemic injury after experimental sacrifice of thoracic and abdominal segmental arteries.

PubMed

Etz, Christian D; Homann, Tobias M; Luehr, Maximilian; Kari, Fabian A; Weisz, Donald J; Kleinman, George; Plestis, Konstadinos A; Griepp, Randall B

2008-06-01

Spinal cord blood flow (SCBF) after sacrifice of thoracoabdominal aortic segmental arteries (TAASA) during thoracoabdominal aortic aneurysm (TAAA) repair remains poorly understood. This study explored SCBF for 72 h after sacrifice of all TAASA. Fourteen juvenile Yorkshire pigs underwent complete serial TAASA sacrifice (T4-L5). Six control pigs underwent anesthesia and cooling to 32 degrees C with no TAASA sacrifice. In the experimental animals, spinal cord function was continuously monitored using motor evoked potentials (MEPs) until 1h after clamping the last TAASA. Fluorescent microspheres enabled segmental measurement of SCBF along the entire spinal cord before, and 5 min, 1 h, 5 h, 24 h and 72 h after complete TAASA sacrifice. A modified Tarlov score was obtained for 3 days after surgery. All the pigs with complete TAASA sacrifice retained normal cord function (MEP) until 1h after TAASA ligation. Seven pigs (50%) with complete TAASA sacrifice recovered after 72 h; seven pigs suffered paraparesis or paraplegia. Intraoperatively, and until 1h postoperatively, SCBF was similar among the three groups along the entire cord. Postoperatively, SCBF did not decrease in any group, but significant hyperemia occurred at 5h in controls and recovery animals, but did not occur in pigs that developed paraparesis or paraplegia in the T8-L2 segments (p=0.0002) and L3-S segments (p=0.0007). At 24h, SCBF remained marginally lower from T8 caudally; at 72h, SCBF was similar among all groups along the entire cord. SCBF in the segments T8-L2 at 5h predicted functional recovery (p=0.003). This study suggests that critical spinal cord ischemia after complete TAASA sacrifice does not occur immediately (intraoperatively), but is delayed 1-5h or longer after clamping, and represents failure to mount a hyperemic response to rewarming and awakening. The short duration of low SCBF associated with spinal cord injury suggests that hemodynamic and metabolic manipulation lasting only 24-72 h may

Exoskeletons' design and usefulness evidence according to a systematic review of lower limb exoskeletons used for functional mobility by people with spinal cord injury.

PubMed

Lajeunesse, Veronique; Vincent, Claude; Routhier, François; Careau, Emmanuelle; Michaud, François

2016-10-01

Rehabilitation professionals have little information concerning lower limb exoskeletons for people with paraplegia. This study has four objectives: (1) Outline the characteristics of the exoskeletons' design and their usefulness evidence as assistive mobility devices in the community for the Rewalk™, Mina, Indego®, Ekso™ (previously known as the eLEGS™) and Rex®; (2) document functional mobility outcomes of using these exoskeletons; (3) document secondary skills and benefits achieved with these exoskeletons, safety, user satisfaction and applicability in the community; and (4) establish level of scientific evidence of the selected studies. A systematic review of the literature (January 2004 to April 2014) was done using the databases PubMed, CINAHL and Embase and groups of keywords associated with "exoskeleton", "lower limb" and "paraplegia". Seven articles were selected. Exoskeleton use is effective for walking in a laboratory but there are no training protocols to modify identified outcomes over the term usage (ReWalk™: 3 months, Mina: 2 months and Indego®: 1 session). Levels of evidence of selected papers are low. The applicability and effectiveness of lower limb exoskeletons as assistive devices in the community have not been demonstrated. More research is needed on walking performance with these exoskeletons compared to other mobility devices and other training contexts in the community. Implications for rehabilitation Characteristics of the exoskeletons' design and their usefulness evidence as assistive mobility devices in the community are addressed for the Rewalk™, Mina, Indego®, Ekso™ and Rex® ReWalk™, Indego® and Mina lower limb exoskeletons are effective for walking in a laboratory for individuals with complete lower-level SCI. The ReWalk™ has the best results for walking, with a maximum speed of 0.51 m/s after 45 sessions lasting 60 to 120 min; it is comparable to the average speed per day or per week in a manual wheelchair. The

Spinal cord compression in pseudohypoparathyroidism.

PubMed

Roberts, Timothy T; Khasnavis, Siddharth; Papaliodis, Dean N; Citone, Isabella; Carl, Allen L

2013-12-01

Spinal cord compression associated with pseudohypoparathyroidism (PHP) is an increasingly reported sequelae of the underlying metabolic syndrome. The association of neurologic dysfunction with PHP is not well appreciated. We believe this to be secondary to a combination of underlying congenital stenosis, manifest by short pedicles secondary to premature physeal closure, and hypertrophic ossification of the vertebral bony and ligamentous complexes. The purpose of this case report is to review the case of spinal stenosis in a child with PHP Type Ia. We are aware of only eight published reports of patients with PHP Type Ia and spinal stenosis-there are only two previously known cases of pediatric spinal stenosis secondary to PHP. This is a case report detailing the symptoms, diagnosis, interventions, complications, and ultimate outcomes of a pediatric patient undergoing spinal decompression and fusion for symptomatic stenosis secondary to PHP Type Ia. Literature search was reviewed regarding the reports of spinal stenosis and PHP, and the results are culminated and discussed. We report on a 14-year-old obese male with PHP and progressive lower extremity weakness secondary to congenital spinal stenosis. Examination revealed functional upper extremities with spastic paraplegia of bilateral lower extremities. The patient's neurologic function was cautiously monitored, but he deteriorated to a bed-bound state, preoperatively. The patient's chart was reviewed, summarized, and presented. Literature was searched using cross-reference of PHP and the terms "spinal stenosis," "myelopathy", "myelopathic," and "spinal cord compression." All relevant case reports were reviewed, and the results are discussed herein. The patient underwent decompression and instrumented fusion of T2-T11. He improved significantly with regard to lower extremity function, achieving unassisted ambulation function after extensive rehabilitation. Results from surgical decompression in previously reported

Rapid Progressive Disease After Nivolumab Therapy in Three Patients with Metastatic Renal Cell Carcinoma

PubMed Central

KOBARI, YUKI; KONDO, TSUNENORI; TAKAGI, TOSHIO; OMAE, KENJI; NAKAZAWA, HAYAKAZU; TANABE, KAZUNARI

2017-01-01

Background/Aim: Rapid progressive disease (RPD), accelerated tumour growth immediate after the initiation of immune checkpoint inhibitor therapy, has been reported in melanoma and lung cancer. Herein, we describe 3 cases of RPD during the initial phase of nivolumab treatment for metastatic renal cell carcinoma. Patients and Methods: The first and second patients received nivolumab in the fourth-line setting. The third patient received nivolumab therapy as third-line treatment. Results: The first patient developed severe respiratory failure due to carcinomatous lymphangiosis 14 days after initiation of nivolumab therapy. The second patient developed leg paraplegia due to rapid growth of the metastatic tumour at the sixth thoracic vertebrae 5 days later. The third patient developed grade 4 hypercalcemia due to RPD on day 3. Conclusion: Clinicians should be aware of RPD during the initial phase of nivolumab therapy, especially in patients with critical lesions in the late-line setting. PMID:28652455

Primary Vaginal Calculus in a Woman with Disability: Case Report and Literature Review.

PubMed

Castellan, Pietro; Nicolai, Michele; De Francesco, Piergustavo; Di Tizio, Luciano; Castellucci, Roberto; Bada, Maida; Marchioni, Michele; Cindolo, Luca; Schips, Luigi

2017-01-01

Background: Vaginal stones are rare and often unknown entities. Most urologists may never see a case in their careers. Case Presentation: We present the case of a 34-year-old bedridden Caucasian woman with mental and physical disabilities who presented with a large primary vaginal calculus, which, surprisingly, had remained undiagnosed until the patient suffered a right renal colic caused by a ureteral stone. The vagina was completely filled and a digital examination was not possible. For this reason, the stone was removed using surgical pliers with some maneuvering. A vesicovaginal fistula was excluded, as well as foreign bodies or other nidi of infection. After, urethral lithotripsy was performed as planned. The postoperative course and follow-up were uneventful. Conclusion: Although vaginal calculi are extremely rare in literature, their differential diagnosis should be considered in women with incontinence and associated disabilities, paraplegia, or prolonged immobilization in recumbent position.

The Crossroads of Synaptic Growth Signaling, Membrane Traffic and Neurological Disease: Insights from Drosophila.

PubMed

Deshpande, Mugdha; Rodal, Avital A

2016-02-01

Neurons require target-derived autocrine and paracrine growth factors to maintain proper identity, innervation, homeostasis and survival. Neuronal growth factor signaling is highly dependent on membrane traffic, both for the packaging and release of the growth factors themselves, and for regulation of intracellular signaling by their transmembrane receptors. Here, we review recent findings from the Drosophila larval neuromuscular junction (NMJ) that illustrate how specific steps of intracellular traffic and inter-organelle interactions impinge on signaling, particularly in the bone morphogenic protein, Wingless and c-Jun-activated kinase pathways, regulating elaboration and stability of NMJ arbors, construction of synapses and synaptic transmission and homeostasis. These membrane trafficking and signaling pathways have been implicated in human motor neuron diseases including amyotrophic lateral sclerosis and hereditary spastic paraplegia, highlighting their importance for neuronal health and survival. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

New domains of neural cell-adhesion molecule L1 implicated in X-linked hydrocephalus and MASA syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jouet, M.; Kenwick, S.; Moncla, A.

1995-06-01

The neural cell-adhesion molecule L1 is involved in intercellular recognition and neuronal migration in the CNS. Recently, we have shown that mutations in the gene encoding L1 are responsible for three related disorders; X-linked hydrocephalus, MASA (mental retardation, aphasia, shuffling gait, and adducted thumbs) syndrome, and spastic paraplegia type I (SPG1). These three disorders represent a clinical spectrum that varies not only between families but sometimes also within families. To date, 14 independent L1 mutations have been reported and shown to be disease causing. Here we report nine novel L1 mutations in X-linked hydrocephalus and MASA-syndrome families, including the firstmore » examples of mutations affecting the fibronectin type III domains of the molecule. They are discussed in relation both to phenotypes and to the insights that they provide into L1 function. 39 refs., 5 figs., 3 tabs.« less

Troyer Syndrome Protein Spartin Is Mono-Ubiquitinated and Functions in EGF Receptor Trafficking

PubMed Central

Jupille, Henri; Fatheddin, Parvin; Puertollano, Rosa

2007-01-01

Troyer syndrome is an autosomal recessive hereditary spastic paraplegia caused by mutation in the spartin (SPG20) gene, which encodes a widely expressed protein of unknown function. This mutation results in premature protein truncation and thus might signify a loss-of-function disease mechanism. In this study, we have found that spartin is mono-ubiquitinated and functions in degradation of the epidermal growth factor receptor (EGFR). Upon EGF stimulation, spartin translocates from the cytoplasm to the plasma membrane and colocalizes with internalized EGF-Alexa. Knockdown of spartin by small interfering RNA decreases the rate of EGFR degradation and also affects EGFR internalization, recycling, or both. Furthermore, overexpression of spartin results in a prominent decrease in EGFR degradation. Taken together, our data suggest that spartin is involved in the intracellular trafficking of EGFR and that impaired endocytosis may underlie the pathogenesis of Troyer syndrome. PMID:17332501

Vertebral osteomyelitis and epidural abscess caused by gas gangrene presenting with complete paraplegia: a case report.

PubMed

Akagawa, Manabu; Kobayashi, Takashi; Miyakoshi, Naohisa; Abe, Eiji; Abe, Toshiki; Kikuchi, Kazuma; Shimada, Yoichi

2015-04-11

Gas gangrene is most often caused by Clostridium perfringens infection. Gas gangrene is a medical emergency that develops suddenly. The mortality rate is higher with trunk involvement than with involvement of the extremities, which carries a better prognosis. With respect to vertebral involvement, there are few reports in the literature. The purpose of this paper is to report a very rare case of vertebral osteomyelitis caused by gas gangrene. A 78-year-old Japanese woman with diabetes mellitus was admitted to our hospital with the chief complaints of back pain, dysuria, and complete paralysis of both legs. A computed tomography scan showed soft tissue swelling anterolaterally at intervertebral disc level T11/12 and a gas-containing epidural abscess that compressed her spinal cord. Cultures later grew Clostridium perfringens and Escherichia coli. Hemilaminectomy was done from T10 to T12, and an epidural abscess was removed. She went on to have fusion surgery 6 weeks after the initial operation and subsequently experienced complete pain relief. She was discharged 2 months later, at which time she was able to walk with a cane. Examination 18 months after surgery showed normal gait without a cane. Discitis caused by gas gangrene infection was successfully treated by immediate debridement and subsequent fusion surgery.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nordon, Ian M., E-mail: inordon@sgul.ac.uk; Hinchliffe, Robert J.; Loftus, Ian M.

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%.more » 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.« less

Nontraumatic Myelopathy Associated With Surfing

PubMed Central

Avilés-Hernández, Israel; García-Zozaya, Inigo; DeVillasante, Jorge M

2007-01-01

Background/Objective: Ischemic nontraumatic spinal cord injury associated with surfing is a novel diagnosis believed to be related to prolonged spine hyperextension while lying prone on the surfboard. Only 9 cases have been documented. This report features possible risk factors, etiology, diagnostic imaging, and outcomes of surfer's myelopathy. Design: Case report. Results: A 37-year-old man developed T11 American Spinal Injury Association (ASIA) A paraplegia shortly after surfing. The clinical history and magnetic resonance imaging findings were compatible with an ischemic insult to the distal thoracic spinal cord. Our patient did not have any of the proposed risk factors associated with this condition, and, contrary to most reports, he sustained a complete spinal cord lesion without neurological recovery by 8 weeks post injury. Conclusions: Surfer's myelopathy, because of its proposed mechanism of injury, is amenable to medical intervention. Increased awareness of this condition may lead to early recognition and treatment, which should contribute to improved neurological outcomes. PMID:17684897

Atraumatic Spinal Cord Injury in the Novice Surfer: A Comprehensive Review and Update

PubMed Central

Flick, David; Cheng, Moses

2017-01-01

Novice surfers are at risk for a rare but potentially devastating form of atraumatic myelopathy. There are 16 published studies on this condition, including 66 cases. The most common suggested mechanism of injury is static hyperextension. However, active mechanisms, in contrast to static, have also been proposed and may be contributory. First time surfers, defined as those who have never been on a surfboard prior to the day of injury, are at particular risk. These individuals make up 89.5%–100% of the reported novice surfers found in the various reports. Multiple neurologic deficits occur and often include paraparesis, paraplegia, urinary retention, and hyperesthesia. While these deficits resolve in some cases, there are reports of multiple instances of permanent injury. Increased awareness of this condition is arguably the most effective preventative measure, as it may lead to avoidance of the predisposing postures. It may also lead to earlier diagnosis in the acute setting, which will become relevant as treatment modalities continue to be refined. PMID:28210528

Lipid Involvement in Neurodegenerative Diseases of the Motor System: Insights from Lysosomal Storage Diseases.

PubMed

Dodge, James C

2017-01-01

Lysosomal storage diseases (LSDs) are a heterogeneous group of rare inherited metabolic diseases that are frequently triggered by the accumulation of lipids inside organelles of the endosomal-autophagic-lysosomal system (EALS). There is now a growing realization that disrupted lysosomal homeostasis (i.e., lysosomal cacostasis) also contributes to more common neurodegenerative disorders such as Parkinson disease (PD). Lipid deposition within the EALS may also participate in the pathogenesis of some additional neurodegenerative diseases of the motor system. Here, I will highlight the lipid abnormalities and clinical manifestations that are common to LSDs and several diseases of the motor system, including amyotrophic lateral sclerosis (ALS), atypical forms of spinal muscular atrophy, Charcot-Marie-Tooth disease (CMT), hereditary spastic paraplegia (HSP), multiple system atrophy (MSA), PD and spinocerebellar ataxia (SCA). Elucidating the underlying basis of intracellular lipid mislocalization as well as its consequences in each of these disorders will likely provide innovative targets for therapeutic research.

Complications and total care of a child with acute leukemia.

PubMed

Vietti, T J; Ragab, A H

1975-03-01

The complications which occur in a child with acute leukemia depend on the stage of the disease and the therapeutic regiman. Most children will present with some manifestation of marrow failure. An occasional child will have marked leukocytosis and disturbance of organ function due to massive leukemic infiltrates. Metabolic disturbances such as hyperuricemia and hyperphosphatemia-hypocalcemia may develop, expecially after therapy is initiated. The myelosuppression and immunosuppression due to drug toxicity may result in opportunistic infections. Other toxicities which can occur with a chemotherapeutic regimen are numerois and varied, and the physician must be cognizant of them in order to minimize damage. Therapy to the central nervous system, either for subclinical or clinical disease, has been associated with a variety of symptoms ranging from meningismus to paraplegia and death. To prevent the development of these complications, and to manage them effectively if they occur, the physician must be knowlegeable about their etiology, clinical and laboratory manifestations, and treatment.

Inhibition of Lysosome Membrane Recycling Causes Accumulation of Gangliosides that Contribute to Neurodegeneration.

PubMed

Boutry, Maxime; Branchu, Julien; Lustremant, Céline; Pujol, Claire; Pernelle, Julie; Matusiak, Raphaël; Seyer, Alexandre; Poirel, Marion; Chu-Van, Emeline; Pierga, Alexandre; Dobrenis, Kostantin; Puech, Jean-Philippe; Caillaud, Catherine; Durr, Alexandra; Brice, Alexis; Colsch, Benoit; Mochel, Fanny; El Hachimi, Khalid Hamid; Stevanin, Giovanni; Darios, Frédéric

2018-06-26

Lysosome membrane recycling occurs at the end of the autophagic pathway and requires proteins that are mostly encoded by genes mutated in neurodegenerative diseases. However, its implication in neuronal death is still unclear. Here, we show that spatacsin, which is required for lysosome recycling and whose loss of function leads to hereditary spastic paraplegia 11 (SPG11), promotes clearance of gangliosides from lysosomes in mouse and human SPG11 models. We demonstrate that spatacsin acts downstream of clathrin and recruits dynamin to allow lysosome membrane recycling and clearance of gangliosides from lysosomes. Gangliosides contributed to the accumulation of autophagy markers in lysosomes and to neuronal death. In contrast, decreasing ganglioside synthesis prevented neurodegeneration and improved motor phenotype in a SPG11 zebrafish model. Our work reveals how inhibition of lysosome membrane recycling leads to the deleterious accumulation of gangliosides, linking lysosome recycling to neurodegeneration. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

A method for paraplegic upper-body posture estimation during standing: a pilot study for rehabilitation purposes.

PubMed

Pages, Gaël; Ramdani, Nacim; Fraisse, Philippe; Guiraud, David

2009-06-01

This paper presents a contribution for restoring standing in paraplegia while using functional electrical stimulation (FES). Movement generation induced by FES remains mostly open looped and stimulus intensities are tuned empirically. To design an efficient closed-loop control, a preliminary study has been carried out to investigate the relationship between body posture and voluntary upper body movements. A methodology is proposed to estimate body posture in the sagittal plane using force measurements exerted on supporting handles during standing. This is done by setting up constraints related to the geometric equations of a two-dimensional closed chain model and the hand-handle interactions. All measured quantities are subject to an uncertainty assumed unknown but bounded. The set membership estimation problem is solved via interval analysis. Guaranteed uncertainty bounds are computed for the estimated postures. In order to test the feasibility of our methodology, experiments were carried out with complete spinal cord injured patients.

Three cases with L1 syndrome and two novel mutations in the L1CAM gene.

PubMed

Marín, Rosario; Ley-Martos, Miriam; Gutiérrez, Gema; Rodríguez-Sánchez, Felicidad; Arroyo, Diego; Mora-López, Francisco

2015-11-01

Mutations in the L1CAM gene have been identified in the following various X-linked neurological disorders: congenital hydrocephalus; mental retardation, aphasia, shuffling gait, and adducted thumbs (MASA) syndrome; spastic paraplegia; and agenesis of the corpus callosum. These conditions are currently considered different phenotypes of a single entity known as L1 syndrome. We present three families with L1 syndrome. Sequencing of the L1CAM gene allowed the identification of the following mutations involved: a known splicing mutation (c.3531-12G>A) and two novel ones: a missense mutation (c.1754A>C; p.Asp585Ala) and a nonsense mutation (c.3478C>T; p.Gln1160Stop). The number of affected males and carrier females identified in a relatively small population suggests that L1 syndrome may be under-diagnosed. L1 syndrome should be considered in the differential diagnosis of intellectual disability or mental retardation in children, especially when other signs such as hydrocephalus or adducted thumbs are present.

Mutations in PNPLA6 are linked to photoreceptor degeneration and various forms of childhood blindness

PubMed Central

Kmoch, S.; Majewski, J.; Ramamurthy, V.; Cao, S.; Fahiminiya, S.; Ren, H.; MacDonald, I.M.; Lopez, I.; Sun, V.; Keser, V.; Khan, A.; Stránecký, V.; Hartmannová, H.; Přistoupilová, A.; Hodaňová, K.; Piherová, L.; Kuchař, L.; Baxová, A.; Chen, R.; Barsottini, O.G.P.; Pyle, A.; Griffin, H.; Splitt, M.; Sallum, J.; Tolmie, J.L.; Sampson, J.R.; Chinnery, P.; Canada, Care4Rare; Banin, E.; Sharon, D.; Dutta, S.; Grebler, R.; Helfrich-Foerster, C.; Pedroso, J.L.; Kretzschmar, D.; Cayouette, M.; Koenekoop, R.K.

2015-01-01

Blindness due to retinal degeneration affects millions of people worldwide, but many disease-causing mutations remain unknown. PNPLA6 encodes the patatin-like phospholipase domain containing protein 6, also known as neuropathy target esterase (NTE), which is the target of toxic organophosphates that induce human paralysis due to severe axonopathy of large neurons. Mutations in PNPLA6 also cause human spastic paraplegia characterized by motor neuron degeneration. Here we identify PNPLA6 mutations in childhood blindness in seven families with retinal degeneration, including Leber congenital amaurosis and Oliver McFarlane syndrome. PNPLA6 localizes mostly at the inner segment plasma membrane in photo-receptors and mutations in Drosophila PNPLA6 lead to photoreceptor cell death. We also report that lysophosphatidylcholine and lysophosphatidic acid levels are elevated in mutant Drosophila. These findings show a role for PNPLA6 in photoreceptor survival and identify phospholipid metabolism as a potential therapeutic target for some forms of blindness. PMID:25574898

The effects of neck and trunk stabilization exercises on cerebral palsy children’s static and dynamic trunk balance: case series

PubMed Central

Shin, Ji-won; Song, Gui-bin; Ko, Jooyeon

2017-01-01

[Purpose] The purpose of this case series was to examination the effects of trunk and neck stabilization exercise on the static, dynamic trunk balance abilities of children with cerebral palsy. [Subjects and Methods] The study included 11 school aged children diagnosed with paraplegia due to a premature birth. Each child engaged in exercise treatments twice per week for eight weeks; each treatment lasted for 45 minutes. After conducting a preliminary assessment, exercise treatments were designed based on each child’s level of functioning. Another assessment was conducted after the eight weeks of treatment. [Results] The Trunk Control Measurement Scale evaluation showed that the exercise treatments had a significant effect on static sitting balance, selective movement control, dynamic reaching, and total Trunk Control Measurement Scale scores. [Conclusion] The results indicate that neck and trunk stabilization exercises that require children’s active participation are helpful for improving static and dynamic balance ability among children diagnosed with cerebral palsy. PMID:28533628

Exercise effect with the wheelchair aerobic fitness trainer on conditioning and metabolic function in disabled persons: a pilot study.

PubMed

Midha, M; Schmitt, J K; Sclater, M

1999-03-01

To determine the effect of exercise with the wheelchair aerobic fitness trainer (WAFT) on anthropometric indices, conditioning, and endocrine and metabolic parameters in persons with lower extremity disability. Exercise sessions with the WAFT lasted 20 to 30 minutes for two to three sessions. Tertiary-care Veterans Administration medical center. Twelve subjects (3 with quadriplegia, 7 with paraplegia, 1 with cerebrovascular accident, 1 with bilateral above-knee amputation). Anthropometric indices (heart rate, blood pressure, weight, oxygen utilization, body mass index, upper arm and abdominal circumference, arm power) and endocrine and metabolic parameters (fasting serum glucose, lipids, and thyroid function) were determined before and after 10 weeks of exercise with the WAFT. All patients noted improved feelings of well-being after training. Mean resting heart rate, upper arm fat area, and fasting serum cholesterol level decreased significantly. Peak oxygen consumption, midarm circumference, and free thyroxine index increased significantly with training. WAFT improves quality of life, conditioning, and endocrine-metabolic parameters in disabled persons.

Artificial gait in complete spinal cord injured subjects: how to assess clinical performance.

PubMed

Pithon, Karla Rocha; Abreu, Daniela Cristina Carvalho de; Vasconcelos-Neto, Renata; Martins, Luiz Eduardo Barreto; Cliquet, Alberto

2015-02-01

Adapt the 6 minutes walking test (6MWT) to artificial gait in complete spinal cord injured (SCI) patients aided by neuromuscular electrical stimulation. Nine male individuals with paraplegia (AIS A) participated in this study. Lesion levels varied between T4 and T12 and time post injured from 4 to 13 years. Patients performed 6MWT 1 and 6MWT 2. They used neuromuscular electrical stimulation, and were aided by a walker. The differences between two 6MWT were assessed by using a paired t test. Multiple r-squared was also calculated. The 6MWT 1 and 6MWT 2 were not statistically different for heart rate, distance, mean speed and blood pressure. Multiple r-squared (r2 = 0.96) explained 96% of the variation in the distance walked. The use of 6MWT in artificial gait towards assessing exercise walking capacity is reproducible and easy to apply. It can be used to assess SCI artificial gait clinical performance.

[Genetics of tremor].

PubMed

Kuhlenbäumer, G; Hopfner, F

2018-04-01

Tremor is a symptom of many diseases and can constitute a disease of its own: essential tremor. The genetics of essential tremor and differential diagnosis of monogenic diseases with the symptom tremor. Literature search and search of clinical genetics databases, e.g. OMIM, GeneReviews, MDSGene and the German Neurological Society (DGN) guidelines. The genetics of essential tremor remain unresolved in spite of large, adequately powered studies. Tremor is a symptom of differential diagnostic value in many movement disorders. A slight tremor might have been missed or not reported in many descriptions of movement disorders. Progress in the genetics of essential tremor probably requires a more detailed phenotyping allowing stratification into phenotypically defined subgroups. Tremor should always be included in the examination and description of movement disorders even if tremor is not a cardinal symptom. Tremor might be helpful in the differential diagnosis of hereditary dystonia, hereditary ataxia, spastic paraplegia and other movement disorders.

Advanced Technical Considerations for Implanting the t-Branch Off-the-Shelf Multibranched Stent-Graft to Treat Thoracoabdominal Aneurysms.

PubMed

Ferreira, Marcelo; Ferreira, Diego; Cunha, Rodrigo; Bicalho, Guilherme; Rodrigues, Eduardo

2018-06-01

To demonstrate different techniques and device modifications that can expand the anatomic suitability of the off-the-shelf multibranched t-Branch for treatment of thoracoabdominal aortic aneurysm. The t-Branch device is not customized for specific patient anatomy, and the most frequent limitations to its use are an inadequate sealing zone and renal artery anatomy. Experience with this device has prompted the development of several techniques that can be employed to maximize the suitability of this stent-graft. Advice is offered on modification of the device to minimize the risk of paraplegia or better match patient anatomy. Maneuvers are explained to ease delivery through tortuous anatomy or existing stent-grafts, catheterize visceral target vessels, select a bridging stent, reduce ischemia time in the limbs, and alter the configuration of the branches. Employing adjunctive maneuvers can increase the anatomic suitability of the t-Branch; in our experience, these techniques have increased the applicability to more than 80% of all elective and urgent thoracoabdominal aortic aneurysm cases.

Worklife After Traumatic Spinal Cord Injury

PubMed Central

Pflaum, Christopher; McCollister, George; Strauss, David J; Shavelle, Robert M; DeVivo, Michael J

2006-01-01

Objective: To develop predictive models to estimate worklife expectancy after spinal cord injury (SCI). Design: Inception cohort study. Setting: Model SCI Care Systems throughout the United States. Participants: 20,143 persons enrolled in the National Spinal Cord Injury Statistical Center database since 1973. Intervention: Not applicable. Main Outcome Measure: Postinjury employment rates and worklife expectancy. Results: Using logistic regression, we found a greater likelihood of being employed in any given year to be significantly associated with younger age, white race, higher education level, being married, having a nonviolent cause of injury, paraplegia, ASIA D injury, longer time postinjury, being employed at injury and during the previous postinjury year, higher general population employment rate, lower level of Social Security Disability Insurance benefits, and calendar years after the passage of the Americans with Disabilities Act. Conclusions: The likelihood of postinjury employment varies substantially among persons with SCI. Given favorable patient characteristics, worklife should be considerably higher than previous estimates. PMID:17044388

Outbreaks of Neuroinvasive Astrovirus Associated with Encephalomyelitis, Weakness, and Paralysis among Weaned Pigs, Hungary

PubMed Central

Boros, Ákos; Albert, Mihály; Pankovics, Péter; Bíró, Hunor; Pesavento, Patricia A.; Phan, Tung Gia; Delwart, Eric

2017-01-01

A large, highly prolific swine farm in Hungary had a 2-year history of neurologic disease among newly weaned (25- to 35-day-old) pigs, with clinical signs of posterior paraplegia and a high mortality rate. Affected pigs that were necropsied had encephalomyelitis and neural necrosis. Porcine astrovirus type 3 was identified by reverse transcription PCR and in situ hybridization in brain and spinal cord samples in 6 animals from this farm. Among tissues tested by quantitative RT-PCR, the highest viral loads were detected in brain stem and spinal cord. Similar porcine astrovirus type 3 was also detected in archived brain and spinal cord samples from another 2 geographically distant farms. Viral RNA was predominantly restricted to neurons, particularly in the brain stem, cerebellum (Purkinje cells), and cervical spinal cord. Astrovirus was generally undetectable in feces but present in respiratory samples, indicating a possible respiratory infection. Astrovirus could cause common, neuroinvasive epidemic disease. PMID:29148391

Outbreaks of Neuroinvasive Astrovirus Associated with Encephalomyelitis, Weakness, and Paralysis among Weaned Pigs, Hungary.

PubMed

Boros, Ákos; Albert, Mihály; Pankovics, Péter; Bíró, Hunor; Pesavento, Patricia A; Phan, Tung Gia; Delwart, Eric; Reuter, Gábor

2017-12-01

A large, highly prolific swine farm in Hungary had a 2-year history of neurologic disease among newly weaned (25- to 35-day-old) pigs, with clinical signs of posterior paraplegia and a high mortality rate. Affected pigs that were necropsied had encephalomyelitis and neural necrosis. Porcine astrovirus type 3 was identified by reverse transcription PCR and in situ hybridization in brain and spinal cord samples in 6 animals from this farm. Among tissues tested by quantitative RT-PCR, the highest viral loads were detected in brain stem and spinal cord. Similar porcine astrovirus type 3 was also detected in archived brain and spinal cord samples from another 2 geographically distant farms. Viral RNA was predominantly restricted to neurons, particularly in the brain stem, cerebellum (Purkinje cells), and cervical spinal cord. Astrovirus was generally undetectable in feces but present in respiratory samples, indicating a possible respiratory infection. Astrovirus could cause common, neuroinvasive epidemic disease.

Chymodiactin in patients with herniated lumbar intervertebral disc(s). An open-label, multicenter study.

PubMed

McDermott, D J; Agre, K; Brim, M; Demma, F J; Nelson, J; Wilson, R R; Thisted, R A

1985-04-01

To extent the safety information for Chymodiactin (chymopapain for injection), 37 neurologic and orthopedic surgeons conducted an open-label, multicenter, phase 3 clinical study. A total of 1,498 patients with one or two herniated lumbar intervertebral discs were enrolled. Therapeutic results were generally favorable, with the percentages of patients achieving either excellent or good (or successful) results ranging from 79.6% to 88.9%, depending on criteria employed in the tabulation. There were 13 cases of anaphylaxis, and 2 of these patients died of complications of anaphylaxis. Two additional patients experienced serious neurologic problems. The first of these two patients developed transverse myelitis and paraplegia approximately 3 weeks following chemonucleolysis. Transdural discograms at three levels had been done approximately 2 days prior to chemonucleolysis, in violation of the protocol. The second patient developed acute cauda equina syndrome, and, despite emergency laminectomy, had permanent neurologic sequelae. Back spasm and stiffness/soreness were the most frequently encountered adverse experiences.

Ultrasound-Guided Steroid Injection of the Pisotriquetral Joint: A Multidisciplinary Effort.

PubMed

Brose, Steven W; Montfort, Janel; Gustafson, Kenneth J; Mittebrun, Ionica; Gauriloff, Samantha; Mosher, Mary; Bourbeau, Dennis J

2017-12-01

From the perspective of a multidisciplinary team, the authors describe the first reported use of ultrasound guidance for steroid injection into the pisotriquetral joint to relieve wrist pain of a person with spinal cord injury undergoing acute inpatient rehabilitation. Musculoskeletal ultrasound guidance was used to improve the accuracy of a corticosteroid injection of the pisotriquetral joint and the basal thumb in a 70-year-old man with paraplegia experiencing multifocal degenerative wrist pain. There was no bleeding or bruising after the injections, and the patient reported complete pain resolution 1 wk after the injections, which continued for over 1 yr. A multidisciplinary team was key in diagnosis, selection of treatment, and evaluation of treatment effect. Corticosteroid injection of the pisotriquetral joint under ultrasound guidance can be used as a treatment modality for managing wrist pain stemming from that joint. Further investigation and studies evaluating the use of ultrasound versus other imaging modalities for injection of the wrist are indicated.

Simultaneously diagnosed pulmonary thromboembolism and hemopericardium in a man with thoracic spinal cord injury.

PubMed

Han, Jae-Young; Seon, Hyo-Jeong; Choi, In-Sung; Ahn, Youngkeun; Jeong, Myung-Ho; Lee, Sam-Gyu

2012-05-01

Simultaneous pulmonary thromboembolism (PTE) and hemopericardium is a rare but life-threatening condition. As hemopericardium is a contraindication to anticoagulation treatment, it is challenging to handle both conditions together. The objective of the study was to report a rare case of a man with thoracic spinal cord injury presenting with simultaneous PTE and hemopericardium. Case report. A 43-year-old man with incomplete T9 paraplegia (American Spinal Injury Association Impairment Scale D) complained of fever one and a half months after spinal cord injury sustained in a fall. During evaluation of fever origin, chest computed tomography and transthoracic echocardiogram revealed simultaneous PTE and hemopericardium. After serial echocardiograms over 2 days demonstrated stability, intravenous heparin, and oral warfarin were administered and his medical status was observed closely. Ultimately, both conditions improved without significant complications. We report successful treatment of man with acute spinal cord injury who presented with simultaneously diagnosed PTE and hemopericardium, a rare complication involving two distinct and opposing pathological mechanisms and conflicting treatments.

Experiencing Functional Electrical Stimulation Roots on Education, and Clinical Developments in Paraplegia and Tetraplegia With Technological Innovation.

PubMed

Varoto, Renato; Cliquet, Alberto

2015-10-01

Cybernetics-based concepts can allow for complete independence for paralyzed individuals, including sensory motor recovery. Spinal cord injuries are responsible for a huge stress on health and a financial burden to society. This article focuses on novel procedures such as functional diagnosis for paraplegics and tetraplegics, cybertherapies toward lessening comorbidities such as cardiovascular diseases, osteoporosis, etc., and the production of new technology for upper and lower limb control. Functional electrical stimulation reflects a unique opportunity for bipedal gait to be achieved by paraplegics and tetraplegics. Education and training of undergraduates and postgraduates in engineering and life sciences have also been a major aim of this work. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Prediction of limb lean tissue mass from bioimpedance spectroscopy in persons with chronic spinal cord injury

PubMed Central

Cirnigliaro, Christopher M.; La Fountaine, Michael F.; Emmons, Racine; Kirshblum, Steven C.; Asselin, Pierre; Spungen, Ann M.; Bauman, William A.

2013-01-01

Background Bioimpedance spectroscopy (BIS) is a non-invasive, simple, and inexpensive modality that uses 256 frequencies to determine the extracellular volume impedance (ECVRe) and intracellular volume impedance (ICVRi) in the total body and regional compartments. As such, it may have utility as a surrogate measure to assess lean tissue mass (LTM). Objective To compare the relationship between LTM from dual-energy X-ray absorptiometry (DXA) and BIS impedance values in spinal cord injury (SCI) and able-bodied (AB) control subjects using a cross-sectional research design. Methods In 60 subjects (30 AB and 30 SCI), a total body DXA scan was used to obtain total body and leg LTM. BIS was performed to measure the impedance quotient of the ECVRe and ICVRi in the total body and limbs. Results BIS-derived ECVRe yielded a model for LTM in paraplegia, tetraplegia, and control for the right leg (RL) (R2 = 0.75, standard errors of estimation (SEE) = 1.02 kg, P < 0.0001; R2 = 0.65, SEE = 0.91 kg, P = 0.0006; and R2 = 0.54, SEE = 1.31 kg, P < 0.0001, respectively) and left leg (LL) (R2 = 0.76, SEE = 1.06 kg, P < 0.0001; R2 = 0.64, SEE = 0.83 kg, P = 0.0006; and R2 = 0.54, SEE = 1.34 kg, P < 0.0001, respectively). The ICVRi was similarly predictive of LTM in paraplegia, tetraplegia, and AB controls for the RL (R2 = 0.85, SEE = 1.31 kg, P < 0.0001; R2 = 0.52, SEE = 0.95 kg, P = 0.003; and R2 = 0.398, SEE = 1.46 kg, P = 0.0003, respectively) and LL (R2 = 0.62, SEE = 1.32 kg, P = 0.0003; R2 = 0.57, SEE = 0.91 kg, P = 0.002; and R2 = 0.42, SEE = 1.31 kg, P = 0.0001, respectively). Conclusion Findings demonstrate that the BIS-derived impedance quotients for ECVRe and ICVRi may be used as surrogate markers to track changes in leg LTM in persons with SCI. PMID:23941792

Total aortic arch replacement with the elephant trunk technique: single-centre 30-year results.

PubMed

Shrestha, Malakh; Martens, Andreas; Krüger, Heike; Maeding, Illona; Ius, Fabio; Fleissner, Felix; Haverich, Axel

2014-02-01

The combined disease of the aortic arch and the descending aorta (aneurysms and dissection) remains a surgical challenge. Various approaches have been used to treat this complex pathology. In the two-stage operation, at the first-stage operation, the aortic arch is replaced through a median sternotomy. Later, at the second-stage operation, the descending thoracic aorta is replaced through a lateral thoracotomy. The elephant trunk (ET) technique was introduced by H.G. Borst at our centre in March 1982, greatly simplifying the second-phase operation. We present our 30-year experience. From March 1982 to March 2012, 179 patients (112 males, age 56.4±12.6 years) received an ET procedure for the combined disease of the aortic arch and the descending aorta (91 aneurysms, 88 dissections (47 acute)). Fifty-six of these patients had undergone previous cardiac operations. Concomitant procedures were performed if necessary. The cerebral protection was done either by deep (till 1999) or moderate hypothermic circulatory arrest and selective antegrade cerebral perfusion (SACP, after 1999). Cardiopulmonary bypass (CPB) and X-clamp times were 208.5±76.5 min and 123.7±54.8 min, respectively. The intraoperative mortality and 30-day mortality during the first-stage operation were 1.7% (3/179) and 17.3% (31/179, 15 with AADA), respectively. Perioperative stroke was 7.9% (n=14/176). Postoperative recurrent nerve palsy was present in 18.2% (32/176) and paraplegia in 5.6% (10/176). The second-stage completion operation was performed as early as possible. Fifty-seven second-stage completion procedures were performed, either surgically (n=50) or through interventional techniques (n=7). The intraoperative and 30-day mortality after the second-stage completion procedures were 5.2% (3/57) and 7.0% (4/57), respectively. The stroke, recurrent nerve palsy and paraplegia rates were 0, 0 and 7% (4/54), respectively. The ET technique has greatly facilitated the two-stage approach to the surgical

Operation of a brain-computer interface walking simulator for individuals with spinal cord injury

PubMed Central

2013-01-01

Background Spinal cord injury (SCI) can leave the affected individuals with paraparesis or paraplegia, thus rendering them unable to ambulate. Since there are currently no restorative treatments for this population, novel approaches such as brain-controlled prostheses have been sought. Our recent studies show that a brain-computer interface (BCI) can be used to control ambulation within a virtual reality environment (VRE), suggesting that a BCI-controlled lower extremity prosthesis for ambulation may be feasible. However, the operability of our BCI has not yet been tested in a SCI population. Methods Five participants with paraplegia or tetraplegia due to SCI underwent a 10-min training session in which they alternated between kinesthetic motor imagery (KMI) of idling and walking while their electroencephalogram (EEG) were recorded. Participants then performed a goal-oriented online task, where they utilized KMI to control the linear ambulation of an avatar while making 10 sequential stops at designated points within the VRE. Multiple online trials were performed in a single day, and this procedure was repeated across 5 experimental days. Results Classification accuracy of idling and walking was estimated offline and ranged from 60.5% (p = 0.0176) to 92.3% (p = 1.36×10−20) across participants and days. Offline analysis revealed that the activation of mid-frontal areas mostly in the μ and low β bands was the most consistent feature for differentiating between idling and walking KMI. In the online task, participants achieved an average performance of 7.4±2.3 successful stops in 273±51 sec. These performances were purposeful, i.e. significantly different from the random walk Monte Carlo simulations (p<0.01), and all but one participant achieved purposeful control within the first day of the experiments. Finally, all participants were able to maintain purposeful control throughout the study, and their online performances improved over time. Conclusions

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

ERIC Educational Resources Information Center

Davis, Kay

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…

Weight Bearing Over-ground Stepping in an Exoskeleton with Non-invasive Spinal Cord Neuromodulation after Motor Complete Paraplegia.

PubMed

Gad, Parag; Gerasimenko, Yury; Zdunowski, Sharon; Turner, Amanda; Sayenko, Dimitry; Lu, Daniel C; Edgerton, V Reggie

2017-01-01

We asked whether coordinated voluntary movement of the lower limbs could be regained in an individual having been completely paralyzed (>4 year) and completely absent of vision (>15 year) using two novel strategies-transcutaneous electrical spinal cord stimulation at selected sites over the spine as well as pharmacological neuromodulation by buspirone. We also asked whether these neuromodulatory strategies could facilitate stepping assisted by an exoskeleton (EKSO, EKSO Bionics, CA) that is designed so that the subject can voluntarily complement the work being performed by the exoskeleton. We found that spinal cord stimulation and drug enhanced the level of effort that the subject could generate while stepping in the exoskeleton. In addition, stimulation improved the coordination patterns of the lower limb muscles resulting in a more continuous, smooth stepping motion in the exoskeleton along with changes in autonomic functions including cardiovascular and thermoregulation. Based on these data from this case study it appears that there is considerable potential for positive synergistic effects after complete paralysis by combining the over-ground step training in an exoskeleton, combined with transcutaneous electrical spinal cord stimulation either without or with pharmacological modulation.

[Ancient disease, but not a thing of the past: Pott's paraplegia in an HIV-positive health-care worker].

PubMed

Jurado, Leonardo F

2017-04-01

Centro de Investigación UNINAVARRA-CINA, Fundación Universitaria Navarra, Neiva, ColombiaGrupo de Investigación MICOBAC-UN, Departamento de Microbiología, Facultad de Medicina, Universidad Nacional de Colombia, Bogotá, D.C., Colombia.

Quality of life and self-esteem in patients with paraplegia and pressure ulcers: a controlled cross-sectional study.

PubMed

Lourenco, L; Blanes, L; Salomé, G M; Ferreira, L M

2014-06-01

To evaluate health-related quality of life (HRQoL) and self-esteem in patients with traumatic spinal cord injury (SCI) and pressure ulcers. This study was a controlled cross-sectional study. HRQoL was assessed using the generic Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) questionnaire and the Rosenberg Self-Esteem/UNIFESP-EPM Scale. A total of 120 patients with traumatic SCI were included in the sample, of which 60 had pressure ulcers and were assigned to the study group, and 60 had no pressure ulcers and were assigned to the control group. Statistical analysis was performed using the chi-square test, Fisher's exact test, and Student's t-test. Of the 60 patients in the study group, 83.3% were men and the mean age was 38.17 years (SD = 9.08 years). When compared with controls, patients in the study group reported significantly lower scores (worse health status) on all SF-36 subscales (p less than or equal to 0.0013) except for general health (p=0.109). The RSE/UNIFESP-EMP scale total score indicated that patients with pressure ulcers had significantly lower self-esteem than controls (p<0.001). Pressure ulcers had an adverse impact on the HRQoL and self-esteem of patients with SCI. There were no external sources of funding for this study. The authors have no conflicts of interest to declare.

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

PubMed Central

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

The import of acetyl-CoA into the ER lumen by AT-1/SLC33A1 is essential for the Nε-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

Toward Multimodal Human-Robot Interaction to Enhance Active Participation of Users in Gait Rehabilitation.

PubMed

Gui, Kai; Liu, Honghai; Zhang, Dingguo

2017-11-01

Robotic exoskeletons for physical rehabilitation have been utilized for retraining patients suffering from paraplegia and enhancing motor recovery in recent years. However, users are not voluntarily involved in most systems. This paper aims to develop a locomotion trainer with multiple gait patterns, which can be controlled by the active motion intention of users. A multimodal human-robot interaction (HRI) system is established to enhance subject's active participation during gait rehabilitation, which includes cognitive HRI (cHRI) and physical HRI (pHRI). The cHRI adopts brain-computer interface based on steady-state visual evoked potential. The pHRI is realized via admittance control based on electromyography. A central pattern generator is utilized to produce rhythmic and continuous lower joint trajectories, and its state variables are regulated by cHRI and pHRI. A custom-made leg exoskeleton prototype with the proposed multimodal HRI is tested on healthy subjects and stroke patients. The results show that voluntary and active participation can be effectively involved to achieve various assistive gait patterns.

Total vertebrectomy and spine shortening for the treatment of T12-L1 spine dislocation: Management with suboptimal resources.

PubMed

Lorente, Alejandro; Palacios, Pablo; Burgos, Jesús; Barrios, Carlos; Lorente, Rafael

2018-04-21

Total vertebrectomy with spine shortening has been reported for the treatment of difficult cases of traumatic spine dislocation, both in acute and chronic phase. We report an exceptional case of a five-week-old T12-L1 spine dislocation in a 25-year-old female with complete paraplegia as a result of trauma in Ciudad de León (Nicaragua). In view of the time since the dislocation, we performed a complete L1 vertebrectomy in order to reduce the dorsolumbar hinge. For osteosynthesis material we had only eight screws and two Steffee plates. We therefore introduced pedicle screws at levels T11, T12, L2 and L3 on the right side and T11, T12, L3 and L4 on the left, and performed manual reduction of the spine. Steffee plates were placed and we added sublaminar wires to reinforce the osteosynthesis. Fifteen months after surgery, there has been no neurological improvement. Copyright © 2018 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

A network of genetic repression and derepression specifies projection fates in the developing neocortex.

PubMed

Srinivasan, Karpagam; Leone, Dino P; Bateson, Rosalie K; Dobreva, Gergana; Kohwi, Yoshinori; Kohwi-Shigematsu, Terumi; Grosschedl, Rudolf; McConnell, Susan K

2012-11-20

Neurons within each layer in the mammalian cortex have stereotypic projections. Four genes-Fezf2, Ctip2, Tbr1, and Satb2-regulate these projection identities. These genes also interact with each other, and it is unclear how these interactions shape the final projection identity. Here we show, by generating double mutants of Fezf2, Ctip2, and Satb2, that cortical neurons deploy a complex genetic switch that uses mutual repression to produce subcortical or callosal projections. We discovered that Tbr1, EphA4, and Unc5H3 are critical downstream targets of Satb2 in callosal fate specification. This represents a unique role for Tbr1, implicated previously in specifying corticothalamic projections. We further show that Tbr1 expression is dually regulated by Satb2 and Ctip2 in layers 2-5. Finally, we show that Satb2 and Fezf2 regulate two disease-related genes, Auts2 (Autistic Susceptibility Gene2) and Bhlhb5 (mutated in Hereditary Spastic Paraplegia), providing a molecular handle to investigate circuit disorders in neurodevelopmental diseases.

Retrograde Ascending Dissection After Thoracic Endovascular Aortic Repair Combined With the Chimney Technique and Successful Open Repair Using the Frozen Elephant Trunk Technique.

PubMed

Hirano, Koji; Tokui, Toshiya; Nakamura, Bun; Inoue, Ryosai; Inagaki, Masahiro; Maze, Yasumi; Kato, Noriyuki

2018-01-01

The chimney technique can be combined with thoracic endovascular aortic repair (TEVAR) to both obtain an appropriate landing zone and maintain blood flow of the arch vessels. However, surgical repair becomes more complicated if retrograde type A aortic dissection occurs after TEVAR with the chimney technique. We herein report a case involving a 73-year-old woman who developed a retrograde ascending dissection 3 months after TEVAR for acute type B aortic dissection. To ensure an adequate proximal sealing distance, the proximal edge of the stent graft was located at the zone 2 level and an additional bare stent was placed at the left subclavian artery (the chimney technique) at the time of TEVAR. Enhanced computed tomography revealed an aortic dissection involving the ascending aorta and aortic arch. Surgical aortic repair using the frozen elephant trunk technique was urgently performed. The patient survived without stroke, paraplegia, renal failure, or other major complications. Retrograde ascending dissection can occur after TEVAR combined with the chimney technique. The frozen elephant trunk technique is useful for surgical repair in such complicated cases.

The Vocational Training FacilityAn Interactive Learning Program to Return Persons With Physical Disabilities to Employment.

PubMed

Hammel, J M; Van Der Loos, H F; Lepage, P; Burgar, C; Perkash, I; Shafer, D; Topp, E; Lees, D

1994-01-01

This paper describes the results of the program-development phase of the Vocational Training Facility (VTF) taking place at the Palo Alto Veterans Affairs Medical Center Rehabilitation Research and Development Center. The VTF staff has developed a self-paced, multimedia curriculum comprised of adapted training packages, interactive videos, and additional training and testing materials designed to teach entry-level desktop publishing and reasonable accommodation skills to individuals with spinal cord injuries. The curriculum is taught via the Macintosh™ computer to allow independent, "hands-off" access to training materials. Each student is given an integrated workstation that is equipped with the Desktop Vocational Assistant Robot (De VAR); a set of low-and high-technology assistive hardware, software, and devices; and ergonomic furniture and adaptations customized to fit individual learning and access needs. Each student completes a 12-week, full-time training program followed by a 3-month internship with a local corporate sponsor. This paper summarizes the evaluation results of the VTF program by the first nine students, with spinal cord injuries ranging paraplegia to high-level quadriplegia, who have completed the program.

Data supporting mitochondrial morphological changes by SPG13-associated HSPD1 mutants.

PubMed

Miyamoto, Yuki; Megumi, Funakoshi-Tago; Hasegawa, Nanami; Eguchi, Takahiro; Tanoue, Akito; Tamura, Hiroomi; Yamauchi, Junji

2016-03-01

The data is related to the research article entitled "Hypomyelinating leukodystrophy-associated missense mutation in HSPD1 blunts mitochondrial dynamics" [1]. In addition to hypomyelinating leukodystrophy (HLD) 4 (OMIM no. 612233), it is known that spastic paraplegia (SPG) 13 (OMIM no. 605280) is caused by HSPD1's amino acid mutation. Two amino acid mutations Val-98-to-Ile (V98I) and Gln-461-to-Glu (Q461E) are associated with SPG13 [2]. In order to investigate the effects of HSPD1's V98I or Q461E mutant on mitochondrial morphological changes, we transfected each of the respective mutant-encoding genes into Cos-7 cells. Either of V98I or Q461E mutant exhibited increased number of mitochondria and short length mitochondrial morphologies. Using MitoTracker dye-incorporating assay, decreased mitochondrial membrane potential was also observed in both cases. The data described here supports that SPG13-associated HSPD1 mutant participates in causing aberrant mitochondrial morphological changes with decreased activities.

Neuroprotective effect of curcumin on spinal cord in rabbit model with ischemia/reperfusion.

PubMed

Liu, Zhi-Qiang; Xing, Shan-Shan; Zhang, Wei

2013-03-01

Ischemic/reperfusion (I/R) injury of the spinal cord is a serious complication that can result from thoracoabdominal aortic surgery. To investigate the neuroprotective effect of curcumin against I/R injury in a rabbit model. A total of 36 rabbits were randomly divided into three groups: sham, I/R, and curcumin-treated group. Rabbits were subject to 30-min aortic occlusion to induce transient spinal cord ischemia. Neurological function was observed after reperfusion and spinal cord segment (L3-L5) was collected for histopathological evaluation. Malondialdehyde (MDA) and total superoxide dismutase (SOD) activity were also assayed. Rabbits in I/R group were induced to paraplegia. While after 48-hour treatment, compared with I/R group, curcumin significantly improved neurological function, reduced cell apoptosis and MDA levels as well as increased SOD activity (P < 0.05). The results suggest that curcumin, at least in an animal model, can attenuate transient spinal cord ischemic injury potentially via reducing oxidative damage, which may provide a novel approach in the treatment of spinal cord ischemic injury.

Als2 mRNA splicing variants detected in KO mice rescue severe motor dysfunction phenotype in Als2 knock-down zebrafish.

PubMed

Gros-Louis, Francois; Kriz, Jasna; Kabashi, Edor; McDearmid, Jonathan; Millecamps, Stéphanie; Urushitani, Makoto; Lin, Li; Dion, Patrick; Zhu, Qinzhang; Drapeau, Pierre; Julien, Jean-Pierre; Rouleau, Guy A

2008-09-01

Recessive ALS2 mutations are linked to three related but slightly different neurodegenerative disorders: amyotrophic lateral sclerosis, hereditary spastic paraplegia and primary lateral sclerosis. To investigate the function of the ALS2 encoded protein, we generated Als2 knock-out (KO) mice and zAls2 knock-down zebrafish. The Als2(-/-) mice lacking exon 2 and part of exon 3 developed mild signs of neurodegeneration compatible with axonal transport deficiency. In contrast, zAls2 knock-down zebrafish had severe developmental abnormalities, swimming deficits and motor neuron perturbation. We identified, by RT-PCR, northern and western blotting novel Als2 transcripts in mouse central nervous system. These Als2 transcripts were present in Als2 null mice as well as in wild-type littermates and some rescued the zebrafish phenotype. Thus, we speculate that the newly identified Als2 mRNA species prevent the Als2 KO mice from developing severe neurodegenerative disease and might also regulate the severity of the motor neurons phenotype observed in ALS2 patients.

The evolutionary saga of circumcision from a religious perspective.

PubMed

Raveenthiran, Venkatachalam

2018-03-08

Circumcision is the oldest surgical operation known to mankind. It probably originated as a less radical form of genital mutilation inflicted on prisoners of war. Over time it was adopted by the Egyptian priesthood and nobility, perhaps inspired by the mythology of Osiris. In turn, circumcision became part of the Jewish and Muslim religious cultures. In contrast, ancient Greeks valued an intact prepuce, as evident from the nude figures of Renaissance art. In the 19th century, circumcision was touted as a treatment for excessive masturbation, seizures, epilepsy, and paraplegia. Adoption of the procedure by medical science was almost akin to a religious belief. By the mid-20th century, it was widely performed on male infants on the pretext of phimosis when the prepuce was not retractable. In 1949, Gairdner documented that the tight prepuce of infants gradually becomes retractile as childhood progresses. Thus, childhood circumcision solely for non-retractile prepuce is unnecessary, which is the foundation for modern anti-circumcision movements. Copyright © 2018 Elsevier Inc. All rights reserved.

Aortic rupture complicating a fracture of an ankylosed thoracic spine. A case report.

PubMed

Savolaine, E R; Ebraheim, N A; Stitgen, S; Jackson, W T

1991-11-01

A 34-year-old man was injured in a motorcycle accident and suffered both aortic rupture and thoracic spinal fracture, complicated by an underlying undetected ankylosing spondylitis. The latter disease can affect the integrity of vascular and spinal structure. Aortography is recommended as a high priority for the patient in an unstable cardiovascular condition requiring a definitive diagnosis. Aortic rupture and thoracic spine fracture may occur from high energy deceleration trauma. Motor vehicle passenger and pedestrian injuries are most commonly involved, although airline accidents and high falls also generate some cases. Mediastinal widening, displacement of esophagus and trachea, apical dissection of blood, and, especially, paravertebral pleural space widening are common to both injuries. Whereas most mediastinal hematomas are nonaortic in origin, a combined injury must be considered because clinical features may also overlap. These include hypotension (hypovolemic or spinal shock), paraplegia, and severe back pain. In light of the high mortality and time constraints associated with aortic rupture, immediate diagnostic resolution is necessary for appropriate management and priority of investigation.

Phenotypic Evolution of UNC80 Loss of Function

PubMed Central

Valkanas, Elise; Schaffer, Katherine; Dunham, Christopher; Maduro, Valerie; du Souich, Christèle; Rupps, Rosemarie; Adams, David R.; Baradaran-Heravi, Alireza; Flynn, Elise; Malicdan, May C.; Gahl, William A.; Toro, Camilo; Boerkoel, Cornelius F.

2017-01-01

Failure to thrive arises as a complication of a heterogeneous group of disorders. We describe two female siblings with spastic paraplegia and global developmental delay but also, atypically for the HSPs, poor weight gain classified as failure to thrive. After extensive clinical and biochemical investigations failed to identify the etiology, we used exome sequencing to identify biallelic UNC80 mutations (NM_032504.1:c.[3983-3_3994delinsA];[2431C>T]. The paternally inherited NM_032504.1:c.3983-3_3994delinsA is predicted to encode p.Ser1328Argfs*19 and the maternally inherited NM_032504.1:c.2431C>T is predicted to encode p.Arg811*. No UNC80 mRNA was detectable in patient cultured skin fibroblasts, suggesting UNC80 loss of function by nonsense mediated mRNA decay. Further supporting the UNC80 mutations as causative of these siblings disorder, biallelic mutations in UNC80 have recently been described among individuals with an overlapping phenotype. This report expands the disease spectrum associated with UNC80 mutations. PMID:27513830

Endovascular repair of traumatic thoracic aortic tears.

PubMed

Mansour, M Ashraf; Kirk, Jeffrey S; Cuff, Robert F; Banegas, Shonda L; Ambrosi, Gavin M; Liao, Timothy H; Chambers, Christopher M; Wong, Peter Y; Heiser, John C

2012-03-01

Patients with thoracic aorta injuries (TAI) present a unique challenge. The purpose of this study was to review the outcomes of thoracic endovascular aortic repair (TEVAR) in patients with TAI. A retrospective chart review of all patients admitted for TEVAR for trauma was performed. In a 5-year period, 19 patients (6 women and 13 men; average age, 42 y) were admitted to our trauma center with TAI. Mechanism of injury was a motor vehicle crash in 12 patients, motorcycle crash in 2 patients, automobile-pedestrian accident in 2 patients, 1 fall, 1 crush injury, and 1 stab wound to the back. A thoracic endograft was used in 6 patients and proximal aortic cuffs were used in 13 patients (68%). One patient (5%) died. There were no strokes, myocardial infarctions, paraplegia, or renal failure. TEVAR for TAI appears to be a safe option for patients with multiple injuries. TEVAR in young patients is still controversial because long-term endograft behavior is unknown. Copyright © 2012 Elsevier Inc. All rights reserved.

The m-AAA Protease Associated with Neurodegeneration Limits MCU Activity in Mitochondria.

PubMed

König, Tim; Tröder, Simon E; Bakka, Kavya; Korwitz, Anne; Richter-Dennerlein, Ricarda; Lampe, Philipp A; Patron, Maria; Mühlmeister, Mareike; Guerrero-Castillo, Sergio; Brandt, Ulrich; Decker, Thorsten; Lauria, Ines; Paggio, Angela; Rizzuto, Rosario; Rugarli, Elena I; De Stefani, Diego; Langer, Thomas

2016-10-06

Mutations in subunits of mitochondrial m-AAA proteases in the inner membrane cause neurodegeneration in spinocerebellar ataxia (SCA28) and hereditary spastic paraplegia (HSP7). m-AAA proteases preserve mitochondrial proteostasis, mitochondrial morphology, and efficient OXPHOS activity, but the cause for neuronal loss in disease is unknown. We have determined the neuronal interactome of m-AAA proteases in mice and identified a complex with C2ORF47 (termed MAIP1), which counteracts cell death by regulating the assembly of the mitochondrial Ca 2+ uniporter MCU. While MAIP1 assists biogenesis of the MCU subunit EMRE, the m-AAA protease degrades non-assembled EMRE and ensures efficient assembly of gatekeeper subunits with MCU. Loss of the m-AAA protease results in accumulation of constitutively active MCU-EMRE channels lacking gatekeeper subunits in neuronal mitochondria and facilitates mitochondrial Ca 2+ overload, mitochondrial permeability transition pore opening, and neuronal death. Together, our results explain neuronal loss in m-AAA protease deficiency by deregulated mitochondrial Ca 2+ homeostasis. Copyright © 2016 Elsevier Inc. All rights reserved.

Interaction of the SPG21 protein ACP33/maspardin with the aldehyde dehydrogenase ALDH16A1

PubMed Central

2017-01-01

Mast syndrome (SPG21) is an autosomal-recessive complicated form of hereditary spastic paraplegia characterized by dementia, thin corpus callosum, white matter abnormalities, and cerebellar and extrapyramidal signs in addition to spastic paraparesis. A nucleotide insertion resulting in premature truncation of the SPG21 gene product acidic cluster protein 33 (ACP33)/maspardin underlies this disorder, likely causing loss of protein function. However, little is known about the function of maspardin. Here, we report that maspardin localizes prominently to cytoplasm as well as to membranes, possibly at trans-Golgi network/late endosomal compartments. Immunoprecipitation of maspardin with identification of coprecipitating proteins by mass spectrometry revealed the aldehyde dehydrogenase ALDH16A1 as an interacting protein. This interaction was confirmed using overexpressed proteins as well as by fusion protein pull down experiments, and these proteins colocalized in cells. Further studies of the function of ALDH16A1 and the role of the maspardin–ALDH16A1 interaction in neuronal cells may clarify the cellular pathogenesis of Mast syndrome. PMID:19184135

Combination of icotinib, surgery, and internal-radiotherapy of a patient with lung cancer severely metastasized to the vertebrae bones with EGFR mutation: a case report.

PubMed

Qu, Li-Li; Qin, Hai-Feng; Gao, Hong-Jun; Liu, Xiao-Qing

2015-01-01

A 48-year-old Chinese female was referred to us regarding EGFR-mutated advanced non-small cell lung cancer, and metastasis to left scapula and vertebrae bones which caused pathological fracture at T8 and T10 thoracic vertebrae. An aggressive combined therapy with icotinib, vertebrae operation, and radioactive particle implantation and immunotherapy was proposed to prevent paraplegia, relieve pain, and control the overall and local tumor lesions. No postoperative symptoms were seen after surgery, and the pain was significantly relieved. Icotinib merited a 31-month partial response with grade 1 diarrhea as its drug-related adverse event. High dose of icotinib was administered after pelvis lesion progression for 3 months with good tolerance. Combination therapy of icotinib, surgery, and internal radiation for metastases of the vertebrae bones from non-small cell lung cancer seems to be a very promising technique both for sufficient pain relief and for local control of the tumor, vertebrae operation can be an encouraging option for patients with EFGR positive mutation and good prognosis indicator.

A class of dynamin-like GTPases involved in the generation of the tubular ER network

PubMed Central

Hu, Junjie; Shibata, Yoko; Zhu, Peng-Peng; Voss, Christiane; Rismanchi, Neggy; Prinz, William A.; Rapoport, Tom A.; Blackstone, Craig

2009-01-01

The endoplasmic reticulum (ER) consists of tubules that are shaped by the reticulons and DP1/Yop1p, but how the tubules form an interconnected network is unknown. Here, we show that mammalian atlastins, which are dynamin-like, integral membrane GTPases, interact with the tubule-shaping proteins. The atlastins localize to the tubular ER and are required for proper network formation in vivo and in vitro. Depletion of the atlastins or overexpression of dominant-negative forms inhibits tubule interconnections. The Sey1p GTPase in S. cerevisiae is likely a functional ortholog of the atlastins; it shares the same signature motifs and membrane topology and interacts genetically and physically with the tubule-shaping proteins. Cells simultaneously lacking Sey1p and a tubule-shaping protein have ER morphology defects. These results indicate that formation of the tubular ER network depends on conserved dynamin-like GTPases. Since atlastin-1 mutations cause a common form of hereditary spastic paraplegia, we suggest ER shaping defects as a novel neuropathogenic mechanism. PMID:19665976

Anaesthesia for vascular emergencies.

PubMed

Ellard, L; Djaiani, G

2013-01-01

Patients presenting with vascular emergencies including acute aortic syndrome, ruptured thoracic or abdominal aortic aneurysms, thoracic aortic trauma and acute lower limb ischaemia have a high risk of peri-operative morbidity and mortality. Although anatomical suitability is not universal, endovascular surgery may improve mortality and the results of ongoing randomised controlled trials are awaited. Permissive hypotension pre-operatively should be the standard of care with the systolic blood pressure kept to 50-100 mmHg as long as consciousness is maintained. The benefit of local anaesthesia over general anaesthesia is not definitive and this decision should be tailored for a given patient and circumstance. Cerebrospinal fluid drainage for prevention of paraplegia is often impractical in the emergency setting and is not backed by strong evidence; however, it should be considered postoperatively if symptoms develop. We discuss the pertinent anaesthetic issues when a patient presents with a vascular emergency and the impact that endovascular repair has on anaesthetic management. Anaesthesia © 2012 The Association of Anaesthetists of Great Britain and Ireland.

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene.

PubMed

Nicolas, Aude; Kenna, Kevin P; Renton, Alan E; Ticozzi, Nicola; Faghri, Faraz; Chia, Ruth; Dominov, Janice A; Kenna, Brendan J; Nalls, Mike A; Keagle, Pamela; Rivera, Alberto M; van Rheenen, Wouter; Murphy, Natalie A; van Vugt, Joke J F A; Geiger, Joshua T; Van der Spek, Rick A; Pliner, Hannah A; Shankaracharya; Smith, Bradley N; Marangi, Giuseppe; Topp, Simon D; Abramzon, Yevgeniya; Gkazi, Athina Soragia; Eicher, John D; Kenna, Aoife; Mora, Gabriele; Calvo, Andrea; Mazzini, Letizia; Riva, Nilo; Mandrioli, Jessica; Caponnetto, Claudia; Battistini, Stefania; Volanti, Paolo; La Bella, Vincenzo; Conforti, Francesca L; Borghero, Giuseppe; Messina, Sonia; Simone, Isabella L; Trojsi, Francesca; Salvi, Fabrizio; Logullo, Francesco O; D'Alfonso, Sandra; Corrado, Lucia; Capasso, Margherita; Ferrucci, Luigi; Moreno, Cristiane de Araujo Martins; Kamalakaran, Sitharthan; Goldstein, David B; Gitler, Aaron D; Harris, Tim; Myers, Richard M; Phatnani, Hemali; Musunuri, Rajeeva Lochan; Evani, Uday Shankar; Abhyankar, Avinash; Zody, Michael C; Kaye, Julia; Finkbeiner, Steven; Wyman, Stacia K; LeNail, Alex; Lima, Leandro; Fraenkel, Ernest; Svendsen, Clive N; Thompson, Leslie M; Van Eyk, Jennifer E; Berry, James D; Miller, Timothy M; Kolb, Stephen J; Cudkowicz, Merit; Baxi, Emily; Benatar, Michael; Taylor, J Paul; Rampersaud, Evadnie; Wu, Gang; Wuu, Joanne; Lauria, Giuseppe; Verde, Federico; Fogh, Isabella; Tiloca, Cinzia; Comi, Giacomo P; Sorarù, Gianni; Cereda, Cristina; Corcia, Philippe; Laaksovirta, Hannu; Myllykangas, Liisa; Jansson, Lilja; Valori, Miko; Ealing, John; Hamdalla, Hisham; Rollinson, Sara; Pickering-Brown, Stuart; Orrell, Richard W; Sidle, Katie C; Malaspina, Andrea; Hardy, John; Singleton, Andrew B; Johnson, Janel O; Arepalli, Sampath; Sapp, Peter C; McKenna-Yasek, Diane; Polak, Meraida; Asress, Seneshaw; Al-Sarraj, Safa; King, Andrew; Troakes, Claire; Vance, Caroline; de Belleroche, Jacqueline; Baas, Frank; Ten Asbroek, Anneloor L M A; Muñoz-Blanco, José Luis; Hernandez, Dena G; Ding, Jinhui; Gibbs, J Raphael; Scholz, Sonja W; Floeter, Mary Kay; Campbell, Roy H; Landi, Francesco; Bowser, Robert; Pulst, Stefan M; Ravits, John M; MacGowan, Daniel J L; Kirby, Janine; Pioro, Erik P; Pamphlett, Roger; Broach, James; Gerhard, Glenn; Dunckley, Travis L; Brady, Christopher B; Kowall, Neil W; Troncoso, Juan C; Le Ber, Isabelle; Mouzat, Kevin; Lumbroso, Serge; Heiman-Patterson, Terry D; Kamel, Freya; Van Den Bosch, Ludo; Baloh, Robert H; Strom, Tim M; Meitinger, Thomas; Shatunov, Aleksey; Van Eijk, Kristel R; de Carvalho, Mamede; Kooyman, Maarten; Middelkoop, Bas; Moisse, Matthieu; McLaughlin, Russell L; Van Es, Michael A; Weber, Markus; Boylan, Kevin B; Van Blitterswijk, Marka; Rademakers, Rosa; Morrison, Karen E; Basak, A Nazli; Mora, Jesús S; Drory, Vivian E; Shaw, Pamela J; Turner, Martin R; Talbot, Kevin; Hardiman, Orla; Williams, Kelly L; Fifita, Jennifer A; Nicholson, Garth A; Blair, Ian P; Rouleau, Guy A; Esteban-Pérez, Jesús; García-Redondo, Alberto; Al-Chalabi, Ammar; Rogaeva, Ekaterina; Zinman, Lorne; Ostrow, Lyle W; Maragakis, Nicholas J; Rothstein, Jeffrey D; Simmons, Zachary; Cooper-Knock, Johnathan; Brice, Alexis; Goutman, Stephen A; Feldman, Eva L; Gibson, Summer B; Taroni, Franco; Ratti, Antonia; Gellera, Cinzia; Van Damme, Philip; Robberecht, Wim; Fratta, Pietro; Sabatelli, Mario; Lunetta, Christian; Ludolph, Albert C; Andersen, Peter M; Weishaupt, Jochen H; Camu, William; Trojanowski, John Q; Van Deerlin, Vivianna M; Brown, Robert H; van den Berg, Leonard H; Veldink, Jan H; Harms, Matthew B; Glass, Jonathan D; Stone, David J; Tienari, Pentti; Silani, Vincenzo; Chiò, Adriano; Shaw, Christopher E; Traynor, Bryan J; Landers, John E

2018-03-21

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS. Copyright © 2018 Elsevier Inc. All rights reserved.

Custom-made versus off-the-shelf multibranched endografts for endovascular repair of thoracoabdominal aortic aneurysms.

PubMed

Bisdas, Theodosios; Donas, Konstantinos P; Bosiers, Michel J; Torsello, Giovanni; Austermann, Martin

2014-11-01

This study compared early outcomes between the custom-made and the new off-the-shelf multibranched endograft (mbEVAR, t-branch; Cook Medical, Bloomington, Ind) for the endovascular repair of thoracoabdominal aortic aneurysms (TAAAs). Between January 2010 and January 2013, 46 consecutive patients with TAAAs underwent endovascular aortic repair with mbEVARs. A custom-made device was used in 24 patients (group A, 52%), with Crawford classification type I, 2 (8%); type II, 4 (17%); type III, 9 (38%); and type IV/V, 9 (38%), and the a t-branch endograft was used in 22 patients (group B, 47%), with type II, 9 (41%); type III, 12 (55%); and type IV/V, 1 (4%). The main outcome measure was technical success, defined as successful target revascularization without occlusion of the bridging endografts or type I or III endoleak at the completion angiography. Secondary end points were mortality, unplanned reinterventions, branch occlusion, paraplegia, and persistent (after discharge) paraparesis. Technical success was 100% in both groups. The 30-day mortality was 8% in group A (n = 2) and 0% in group B (P = .51). Survival rates at 6 months were 71% in group A (mean follow-up, 13 ± 11 months) and 94% in group B (mean follow-up, 6 ± 3 months; (P = .04). There was only one procedure-related death caused by cerebral bleeding and herniation in group A. The freedom-from-reintervention rate at 6 months was 100% in group A (mean follow-up, 12 ± 11.5 months) and 90% in group B (mean follow-up, 6 ± 3.9 months; P = .07). No branch occlusions were observed in group A, whereas a branch occlusion occurred in three patients in group B (in all cases the bridging endograft for the renal artery). In two patients, the possible reason for branch occlusion was a thrombophilic disorder, whereas in one patient, the reason remains unknown. Paraplegia was observed in one patient in each group (group A: 4%; group B: 5%; P = .51) and persistent paraparesis in two patients in group A (8

Interference of different types of seats on postural control system during a forward-reaching task in individuals with paraplegia.

PubMed

de Abreu, Daniela Cristina Carvalho; Takara, Kelly; Metring, Nathália Lopes; Reis, Júlia Guimarães; Cliquet, Alberto

2012-09-01

We aimed to evaluate the influence of different types of wheelchair seats on paraplegic individuals' postural control using a maximum anterior reaching test. Balance evaluations during 50, 75, and 90% of each individual's maximum reach in the forward direction using two different cushions on seat (one foam and one gel) and a no-cushion condition were carried out on 11 individuals with a spinal cord injury (SCI) and six individuals without SCI. Trunk anterior displacement and the time spent to perform the test were assessed. No differences were found for the three types of seats in terms of trunk anterior displacement and the time spent to perform the test when intragroup comparisons were made in both groups (P>0.05). The intergroup comparison showed that body displacement was less prominent and the time spent to perform the test was more prolonged for individuals with SCI (P<0.05), which suggests a postural control deficit. The seat type did not affect the ability of the postural control system to maintain balance during the forward-reaching task.

Effects of resistance-guided high intensity interval functional electrical stimulation cycling on an individual with paraplegia: A case report.

PubMed

Dolbow, David R; Credeur, Daniel P

2018-03-01

Individuals with spinal cord injury (SCI) are more than twice as likely to develop and die from cardio-metabolic diseases as compared to able-bodied. This increased risk is thought to be in part due to accelerated muscle atrophy and reduced blood flow through sublesional arteries. Thus, strategies to recondition paralyzed skeletal muscles may help reduce cardio-metabolic disease risk. The purpose of this case report was to examine the impact of a novel, resistance-guided, high intensity interval training functional electrical stimulation (RG-HIIT-FES) cycling program on cardio-metabolic health in people with chronic SCI. One adult female with chronic T10 SCI. A novel RG-HIIT-FES cycling program three times per week for 10 weeks. Measures of body composition and cardio-metabolic health (vascular endothelial function of the brachial artery via flow-mediated dilation) and HbA1c blood values were performed at baseline and following completion of the RG-HIIT-FES program. Total body lean mass and legs lean mass increased 2.8% and 5.3% respectively while vastus lateralis thickness increased by 59.5%. Reactive hyperemia and flow mediated dilation change in brachial artery diameter increased by 11.1% and 147.7% following the program, respectively. HbA1c level changed minimally (5 to 4.9%). This case report suggests that RG-HIIT-FES cycling was an effective strategy to improve lean mass, and systemic vascular endothelial health in an individual with chronic SCI.

Interference of Different Types of Seats on Postural Control System during a Forward-Reaching Task in Individuals with Paraplegia

ERIC Educational Resources Information Center

de Abreu, Daniela Cristina Carvalho; Takara, Kelly; Metring, Nathalia Lopes; Reis, Julia Guimaraes; Cliquet, Alberto, Jr.

2012-01-01

We aimed to evaluate the influence of different types of wheelchair seats on paraplegic individuals' postural control using a maximum anterior reaching test. Balance evaluations during 50, 75, and 90% of each individual's maximum reach in the forward direction using two different cushions on seat (one foam and one gel) and a no-cushion condition…

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

PubMed

Bhuyan, Ashok Krishna; Sarma, Dipti; Kaimal Saikia, Uma; Choudhury, Bipul Kumar

2014-01-01

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.

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

PubMed Central

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

2014-01-01

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

Effects of co-administration of clenbuterol and testosterone propionate on skeletal muscle in paraplegic mice.

PubMed

Ung, Roth-Visal; Rouleau, Pascal; Guertin, Pierre A

2010-06-01

Spinal cord injury (SCI) is generally associated with a rapid and significant decrease in muscle mass and corresponding changes in skeletal muscle properties. Although beta(2)-adrenergic and androgen receptor agonists are anabolic substances clearly shown to prevent or reverse muscle wasting in some pathological conditions, their effects in SCI patients remain largely unknown. Here we studied the effects of clenbuterol and testosterone propionate administered separately or in combination on skeletal muscle properties and adipose tissue in adult CD1 mice spinal-cord-transected (Tx) at the low-thoracic level (i.e., induced complete paraplegia). Administered shortly post-Tx, these substances were found to differentially reduce loss in body weight, muscle mass, and muscle fiber cross-sectional area (CSA) values. Although all three treatments induced significant effects, testosterone-treated animals were generally less protected against Tx-related changes. However, none of the treatments prevented fat tissue loss or muscle fiber type conversion and functional loss generally found in Tx animals. These results provide evidence suggesting that clenbuterol alone or combined with testosterone may constitute better clinically-relevant treatments than testosterone alone to decrease muscle atrophy (mass and fiber CSA) in SCI subjects.

[Disseminated cryptococcosis in an immunocompetent patient].

PubMed

Elkhihal, B; Hasnaoui, A; Ghfir, I; Moustachi, A; Aoufi, S; Lyagoubi, M

2015-09-01

Disseminated cryptococcosis is a serious opportunistic fungal infection caused by a yeast-encapsulated fungus of the genus Cryptococcus neoformans. It occurs most often in patients with a significant deficit of cellular immunity and preferentially affects the central nervous system. The skin and the lungs are the most commonly affected sites outside the neuro-subarachnoid location. We report the case of a patient apparently immunocompetent who had a disseminated cryptococcosis. The disease started with the multiple purplish skin lesions, large umbilicated on the face, groin, forearm and leg with progressively increasing volume. This symptomatology had evolved in the context of weight loss and poor general condition. The diagnosis was established by the presence of cryptococcal at the skin biopsy and cerebrospinal fluid. Research of immunosuppression common pathologies were negative. Treatment was initiated based on amphotericin B for 40 days. The patient's condition deteriorates onset of paraplegia and swallowing disorders causing death in an array of cachexia. This observation points out that disseminated cryptococcosis can occur in an immunocompetent patient. The skin lesions may be the first sign of the disease. Copyright © 2015. Published by Elsevier Masson SAS.

Drosophila Atlastin in motor neurons is required for locomotion and presynaptic function.

PubMed

De Gregorio, Cristian; Delgado, Ricardo; Ibacache, Andrés; Sierralta, Jimena; Couve, Andrés

2017-10-15

Hereditary spastic paraplegias (HSPs) are characterized by spasticity and weakness of the lower limbs, resulting from length-dependent axonopathy of the corticospinal tracts. In humans, the HSP-related atlastin genes ATL1 - ATL3 catalyze homotypic membrane fusion of endoplasmic reticulum (ER) tubules. How defects in neuronal Atlastin contribute to axonal degeneration has not been explained satisfactorily. Using Drosophila , we demonstrate that downregulation or overexpression of Atlastin in motor neurons results in decreased crawling speed and contraction frequency in larvae, while adult flies show progressive decline in climbing ability. Broad expression in the nervous system is required to rescue the atlastin -null Drosophila mutant ( atl 2 ) phenotype. Importantly, both spontaneous release and the reserve pool of synaptic vesicles are affected. Additionally, axonal secretory organelles are abnormally distributed, whereas presynaptic proteins diminish at terminals and accumulate in distal axons, possibly in lysosomes. Our findings suggest that trafficking defects produced by Atlastin dysfunction in motor neurons result in redistribution of presynaptic components and aberrant mobilization of synaptic vesicles, stressing the importance of ER-shaping proteins and the susceptibility of motor neurons to their mutations or depletion. © 2017. Published by The Company of Biologists Ltd.

Pseudoclavibacter otitis media in a 3-year-old boy with pulmonary and spinal tuberculosis.

PubMed

Ayuthaya, Satja Issaranggoon na; Leelaporn, Amornrut; Kiratisin, Pattarachai; Oberdorfer, Peninnah

2015-05-01

Pseudoclavibacter has rarely been documented as an etiologic agent of infection in humans. We presented the first case report of Pseudoclavibacter otitis media in a boy with pulmonary and spinal tuberculosis.A 3-year-old boy was referred to our hospital due to prolonged fever and progressive paraplegia for 3 months. He had yellowish discharge from both ear canals. The pleural fluid culture was positive for Mycobacterium tuberculosis. The discharge from both ears culture yielded yellow colonies of gram-positive bacilli with branching. This organism was positive for modified acid-fast bacilli stain but negative for acid-fast bacilli stain. Biochemical characteristics of this isolate were positive for catalase test but negative for oxidase, nitrate, esculin, and sugar utilization tests. The organism was further subjected to be identified by 16S ribosomal deoxyribonucleic acid gene sequencing. The result yielded Pseudoclavibacter species (99.4% identical), which could be most likely a potential pathogen in immunocompromised host like this patient. He responded well with intravenous trimetroprim-sulfamethoxazole for 6 weeks.This is the first case report of Pseudoclavibacter otitis media in children, and this case could emphasize Pseudoclavibacter species as a potential pathogen in immunocompromised host.

Pseudoclavibacter Otitis Media in a 3-Year-Old Boy With Pulmonary and Spinal Tuberculosis

PubMed Central

Ayuthaya, Satja Issaranggoon na; Leelaporn, Amornrut; Kiratisin, Pattarachai; Oberdorfer, Peninnah

2015-01-01

Abstract Pseudoclavibacter has rarely been documented as an etiologic agent of infection in humans. We presented the first case report of Pseudoclavibacter otitis media in a boy with pulmonary and spinal tuberculosis. A 3-year-old boy was referred to our hospital due to prolonged fever and progressive paraplegia for 3 months. He had yellowish discharge from both ear canals. The pleural fluid culture was positive for Mycobacterium tuberculosis. The discharge from both ears culture yielded yellow colonies of gram-positive bacilli with branching. This organism was positive for modified acid-fast bacilli stain but negative for acid-fast bacilli stain. Biochemical characteristics of this isolate were positive for catalase test but negative for oxidase, nitrate, esculin, and sugar utilization tests. The organism was further subjected to be identified by 16S ribosomal deoxyribonucleic acid gene sequencing. The result yielded Pseudoclavibacter species (99.4% identical), which could be most likely a potential pathogen in immunocompromised host like this patient. He responded well with intravenous trimetroprim-sulfamethoxazole for 6 weeks. This is the first case report of Pseudoclavibacter otitis media in children, and this case could emphasize Pseudoclavibacter species as a potential pathogen in immunocompromised host. PMID:25929901

Delayed Induction of Human NTE (PNPLA6) Rescues Neurodegeneration and Mobility Defects of Drosophila swiss cheese (sws) Mutants.

PubMed

Sujkowski, Alyson; Rainier, Shirley; Fink, John K; Wessells, Robert J

2015-01-01

Human PNPLA6 gene encodes Neuropathy Target Esterase protein (NTE). PNPLA6 gene mutations cause hereditary spastic paraplegia (SPG39 HSP), Gordon-Holmes syndrome, Boucher-Neuhäuser syndromes, Laurence-Moon syndrome, and Oliver-McFarlane syndrome. Mutations in the Drosophila NTE homolog swiss cheese (sws) cause early-onset, progressive behavioral defects and neurodegeneration characterized by vacuole formation. We investigated sws5 flies and show for the first time that this allele causes progressive vacuolar formation in the brain and progressive deterioration of negative geotaxis speed and endurance. We demonstrate that inducible, neuron-specific expression of full-length human wildtype NTE reduces vacuole formation and substantially rescues mobility. Indeed, neuron-specific expression of wildtype human NTE is capable of rescuing mobility defects after 10 days of adult life at 29°C, when significant degeneration has already occurred, and significantly extends longevity of mutants at 25°C. These results raise the exciting possibility that late induction of NTE function may reduce or ameliorate neurodegeneration in humans even after symptoms begin. In addition, these results highlight the utility of negative geotaxis endurance as a new assay for longitudinal tracking of degenerative phenotypes in Drosophila.

WASH and WAVE actin regulators of the Wiskott-Aldrich syndrome protein (WASP) family are controlled by analogous structurally related complexes.

PubMed

Jia, Da; Gomez, Timothy S; Metlagel, Zoltan; Umetani, Junko; Otwinowski, Zbyszek; Rosen, Michael K; Billadeau, Daniel D

2010-06-08

We recently showed that the Wiskott-Aldrich syndrome protein (WASP) family member, WASH, localizes to endosomal subdomains and regulates endocytic vesicle scission in an Arp2/3-dependent manner. Mechanisms regulating WASH activity are unknown. Here we show that WASH functions in cells within a 500 kDa core complex containing Strumpellin, FAM21, KIAA1033 (SWIP), and CCDC53. Although recombinant WASH is constitutively active toward the Arp2/3 complex, the reconstituted core assembly is inhibited, suggesting that it functions in cells to regulate actin dynamics through WASH. FAM21 interacts directly with CAPZ and inhibits its actin-capping activity. Four of the five core components show distant (approximately 15% amino acid sequence identify) but significant structural homology to components of a complex that negatively regulates the WASP family member, WAVE. Moreover, biochemical and electron microscopic analyses show that the WASH and WAVE complexes are structurally similar. Thus, these two distantly related WASP family members are controlled by analogous structurally related mechanisms. Strumpellin is mutated in the human disease hereditary spastic paraplegia, and its link to WASH suggests that misregulation of actin dynamics on endosomes may play a role in this disorder.

Technique of spinal cord compression induced by inflation of epidural balloon catheter in rabbits (Oryctologus cuniculus): efficient and easy to use model.

PubMed

Fonseca, Antonio F B DA; Scheffer, Jussara P; Coelho, Barbara P; Aiello, Graciane; Guimarães, Arthur G; Gama, Carlos R B; Vescovini, Victor; Cabral, Paula G A; Oliveira, André L A

2016-09-01

The most common cause of spinal cord injury are high impact trauma, which often result in some motor impairment, sensory or autonomic a greater or lesser extent in the distal areas the level of trauma. In terms of survival and complications due to sequelae, veterinary patients have a poor prognosis unfavorable. Therefore justified the study of experimental models of spinal cord injury production that could provide more support to research potential treatments for spinal cord injuries in medicine and veterinary medicine. Preclinical studies of acute spinal cord injury require an experimental animal model easily reproducible. The most common experimental animal model is the rat, and several techniques for producing a spinal cord injury. The objective of this study was to describe and evaluate the effectiveness of acute spinal cord injury production technique through inflation of Fogarty(r) catheter using rabbits as an experimental model because it is a species that has fewer conclusive publications and contemplating. The main requirements of a model as low cost, handling convenience, reproducibility and uniformity. The technique was adequate for performing preclinical studies in neuro-traumatology area, effectively leading to degeneration and necrosis of the nervous tissue fostering the emergence of acute paraplegia.

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

PubMed Central

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

2010-01-01

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

Transcranial magnetic stimulation--may be useful as a preoperative screen of motor tract function.

PubMed

Galloway, Gloria M; Dias, Brennan R; Brown, Judy L; Henry, Christina M; Brooks, David A; Buggie, Ed W

2013-08-01

Transcranial motor stimulation with noninvasive cortical surface stimulation, using a high-intensity magnetic field referred to as transcranial magnetic stimulation generally, is considered a nonpainful technique. In contrast, transcranial electric stimulation of the motor tracts typically cannot be done in unanesthesized patients. Intraoperative monitoring of motor tract function with transcranial electric stimulation is considered a standard practice in many institutions for patients during surgical procedures in which there is potential risk of motor tract impairment so that the risk of paraplegia or paraparesis can be reduced. Because transcranial electric stimulation cannot be typically done in the outpatient setting, transcranial magnetic stimulation may be able to provide a well-tolerated method for evaluation of the corticospinal motor tracts before surgery. One hundred fifty-five patients aged 5 to 20 years were evaluated preoperatively with single-stimulation nonrepetitive transcranial magnetic stimulation for preoperative assessment. The presence of responses to transcranial magnetic stimulation reliably predicted the presence of responses to transcranial electric stimulation intraoperatively. No complications occurred during the testing, and findings were correlated to the clinical history and used in the setup of the surgical monitoring.

Effect of high-frequency repetitive transcranial magnetic stimulation on motor cortical excitability and sensory nerve conduction velocity in subacute-stage incomplete spinal cord injury patients.

PubMed

Cha, Hyun Gyu; Ji, Sang-Goo; Kim, Myoung-Kwon

2016-07-01

[Purpose] The aim of the present study was to determine whether repetitive transcranial magnetic stimulation can improve sensory recovery of the lower extremities in subacute-stage spinal cord injury patients. [Subjects and Methods] This study was conducted on 20 subjects with diagnosed paraplegia due to spinal cord injury. These 20 subjects were allocated to an experimental group of 10 subjects that underwent active repetitive transcranial magnetic stimulation or to a control group of 10 subjects that underwent sham repetitive transcranial magnetic stimulation. The SCI patients in the experimental group underwent active repetitive transcranial magnetic stimulation and conventional rehabilitation therapy, whereas the spinal cord injury patients in the control group underwent sham repetitive transcranial magnetic stimulation and conventional rehabilitation therapy. Participants in both groups received therapy five days per week for six-weeks. Latency, amplitude, and sensory nerve conduction velocity were assessed before and after the six week therapy period. [Results] A significant intergroup difference was observed for posttreatment velocity gains, but no significant intergroup difference was observed for amplitude or latency. [Conclusion] repetitive transcranial magnetic stimulation may be improve sensory recovery of the lower extremities in subacute-stage spinal cord injury patients.

Seat-belt injuries of the spine in young children.

PubMed

Rumball, K; Jarvis, J

1992-07-01

Seat-belt fractures of the lumbar spine in adolescents and adults are well recognised but there are few reports of these injuries in young children. We reviewed all seat-belt injuries in skeletally immature patients (Risser 0), seen at a tertiary referral centre between 1974 and 1991. There were ten cases, eight girls and two boys, with an average age of 7.5 years (3 to 13). Four distinct patterns of injury were observed, most commonly at the L2 to L4 level. Paraplegia, which is thought to be uncommon, occurred in three of our ten cases. Four children had intra-abdominal injuries requiring laparotomy. There was a delay in diagnosis either of the spinal or of the intra-abdominal injury in five cases, although all had contusion of the abdominal wall, the 'seat-belt sign'. Treatment of the fractures was conservative, by bed rest and then hyperextension casts. The incidence of this potentially devastating injury can be reduced by the optimal use of restraints, but there is often a delay in diagnosis. Our classification system may aid in the early detection and evaluation of this injury.

Field hospital treatment of blast wounds of the musculoskeletal system during the Yugoslav civil war.

PubMed

Covey, D C; Lurate, R B; Hatton, C T

2000-05-01

The spectrum of wounding and treatment of forty-one patients with musculoskeletal blast injuries at a U.S. military field hospital in the former Yugoslavia was reviewed. Patients underwent wound exploration, irrigation, debridement, broad-spectrum antibiotic therapy, early fracture stabilization, and appropriate reconstructive surgery. Four patients developed wound infections. Two patients died as a result of their injuries (overall mortality 5 percent). There were three below-knee amputations and five other amputations (above-knee, ankle, midtarsal, partial forefoot, and finger). Three patients sustained lumbar burst fractures from mines that exploded under their vehicles, resulting in paraplegia in one case. Our patients underwent 112 surgical procedures, an average of 2.1 per patient. Twenty-two patients (54 percent) had other injuries or conditions in addition to their orthopaedic wounds. There were wide variations in the bone and soft tissue injuries caused by detonating ordnance, and the tissue damage was qualitatively different from that caused by gunshot wounds. Early debridement, leaving wounds open, and treatment with broad-spectrum antibiotics were important factors in wound healing to allow subsequent successful reconstructive surgery in an austere field setting.

Work-related traumatic spinal cord lesions in Chile, a 20-year epidemiological analysis.

PubMed

Correa, G I; Finkelstein, J M; Burnier, L A; Danilla, S E; Tapia, L Z; Torres, V N; Castillo, J C

2011-02-01

Retrospective cohort study. To describe the characteristics of patients with work-related traumatic spinal cord injuries (TSCI) in Chile. Hospital del Trabajador in Santiago, Santiago, Chile. Patients suffering from TSCI incurred at the workplace from 1986 to 2005 were identified through records of the Asociación Chilena de Seguridad (ACHS, Chilean Safety Association). The medical records of 173 patients, 172 men and 1 woman, were analyzed. The yearly average incidence was 7.8 per million workers. Age at TSCI onset was 38.2 ± 12.1 years. The principal external causes for TSCI incurred at the workplace were falls from a height in 86 cases (49.7%) and trauma blows to the vertebral spine in 61 cases (35.3 %). More falls occurred in the field construction, and other traumas occurred as a result of traumatic blows caused by tree trunks and stones in forestry and mining sectors. Mortality in this series was 8.7%, and the worst prognosis was for older patients with complete tetraplegia. The paraplegia:tetraplegia ratio was 3.2:1. The characteristics of workplace TSCI are specific to this population. It is important therefore to develop prevention programs for specific work-related TSCI.

A case study on the application of International Classification of Functioning, Disability and Health (ICF)-based tools for vocational rehabilitation in spinal cord injury.

PubMed

Glässel, Andrea; Rauch, Alexandra; Selb, Melissa; Emmenegger, Karl; Lückenkemper, Miriam; Escorpizo, Reuben

2012-01-01

Vocational rehabilitation (VR) plays a key role in bringing persons with acquired disabilities back to work, while encouraging employment participation. The purpose of this case study is to illustrate the systematic application of International Classification of Functioning, Disability, and Health (ICF)-based documentation tools by using ICF Core Sets in VR shown with a case example of a client with traumatic spinal cord injury (SCI). The client was a 26-year-old male with paraplegia (7th thoracic level), working in the past as a mover. This case study describes the integration of the ICF Core Sets for VR into an interdisciplinary rehabilitation program by using ICF-based documentation tools. Improvements in the client's impairments, activity limitations, and participation restrictions were observed following rehabilitation. Goals in different areas of functioning were achieved. The use of the ICF Core Sets in VR allows a comprehensive assessment of the client's level of functioning and intervention planning. Specifically, the Brief ICF Core Set in VR can provide domains for intervention relevant to each member of an interdisciplinary team and hence, can facilitate the VR management process in a SCI center in Switzerland.

Endovascular Management of Thoracic Aortic Aneurysms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fattori, Rossella, E-mail: rossella.fattori@unibo.it; Russo, Vincenzo; Lovato, Luigi

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 themore » 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.« less

Lack of Spartin Protein in Troyer Syndrome

PubMed Central

Bakowska, Joanna C.; Wang, Heng; Xin, Baozhong; Sumner, Charlotte J.; Blackstone, Craig

2017-01-01

Background Hereditary spastic paraplegias (SPG1-SPG33) are characterized by progressive spastic weakness of the lower limbs. A nucleotide deletion (1110delA) in the (SPG20; OMIM 275900) spartin gene is the origin of autosomal recessive Troyer syndrome. This mutation is predicted to cause premature termination of the spartin protein. However, it remains unknown whether this truncated spartin protein is absent or is present and partially functional in patients. Objective To determine whether the truncated spartin protein is present or absent in cells derived from patients with Troyer syndrome. Design Case report. Setting Academic research. Patients We describe a new family with Troyer syndrome due to the 1110delA mutation. Main Outcome Measures We cultured primary fibroblasts and generated lymphoblasts from affected individuals, carriers, and control subjects and subjected these cells to immunoblot analyses. Results Spartin protein is undetectable in several cell lines derived from patients with Troyer syndrome. Conclusions Our data suggest that Troyer syndrome results from complete loss of spartin protein rather than from the predicted partly functional fragment. This may reflect increased protein degradation or impaired translation. PMID:18413476

Transient paraplegia due to accidental intrathecal bupivacaine infiltration following pre-emptive analgesia in a patient with missed sacral dural ectasia.

PubMed

Kanna, P Rishimugesh; Sekar, Chelliah; Shetty, Ajoy Prasad; Rajasekaran, Shanmughanathan

2010-11-15

A case report with review of the literature. To highlight the need for careful magnetic resonance imaging evaluation for the presence of incidental lumbosacral dural anomalies before attempting caudal epidural interventions. Pre-emptive analgesia through the caudal epidural route provides good postoperative pain relief in spine surgeries. Several precautions have been advised in the literature. Presence of sacral-dural ectasia should be considered a relative contraindication for this procedure. A 50-year old woman underwent posterior instrumented spinal fusion for L4-L5 spondylolisthesis under general anesthesia. She received single shot caudal epidural analgesia at the start of the procedure. After complete emergence from anesthesia, she had complete motor and sensory loss below the T12 spinal level, which reversed to normal neurology in 6 hours. Retrospective evaluation of the patient's magnetic resonance imaging showed an ectatic, low lying lumbosacral dural sac which had been overlooked in the initial evaluation. The drugs given by the caudal route have been accidentally administered into the thecal sac causing a brief period of neurologic deficit. This unexpected complication has been reported only in the pediatric literature before. It is important to look for the presence of lumbosacral dural anomalies before planning caudal epidural injections in adults also. Sacral dural ectasia and other lumbosacral anomalies must be recognized as contraindications for caudal epidural pre-emptive analgesia for spine surgery. Other modes of postoperative pain relief should be tried in these patients.

Experience with the conventional and frozen elephant trunk techniques: a single-centre study.

PubMed

Leontyev, Sergey; Borger, Michael A; Etz, Christian D; Moz, Monica; Seeburger, Joerg; Bakhtiary, Farhard; Misfeld, Martin; Mohr, Friedrich W

2013-12-01

The treatment of patients with extensive thoracic aortic disease involving the arch and descending/thoracoabdominal aorta is often performed using an elephant trunk procedure. We retrospectively analysed our results comparing two different techniques: the conventional elephant trunk (cET) and the frozen elephant trunk (FET) operation. Between January 2003 and December 2011, 171 consecutive patients underwent total aortic arch replacement with either a cET (n = 125) or FET (n = 46) technique. The mean age was 64 ± 13 years and was significantly higher in the FET group (P < 0.01). Acute Type A aortic dissection was the indication for surgery in 53.6% of cET and 17.4% of FET patients, and degenerative or atherosclerotic aneurysm accounted for 33.6% of cET and 58.7% of FET patients. The remaining patients were operated on for chronic Type A or acute or chronic Type B dissections with arch involvement. In-hospital mortality was 21.6 vs 8.7% for cET and FET patients, respectively (P = 0.1). Logistic regression analysis revealed Type A aortic dissection (odds ratio (OR) 3.1, P = 0.01) as the only independent predictor of hospital mortality. Stroke occurred in 16 vs 13% of cET vs FET patients (P = 0.4). Type A aortic dissection was an independent predictor of stroke by multivariable analysis (OR 2.6, P = 0.03), and axillary arterial cannulation was protective against stroke (OR 0.4, P = 0.04). The occurrence of new-onset paraplegia was significantly higher in the FET group (21.7 vs 4.0%, P < 0.001), and aortic repair with the FET technique was an independent predictor for paraplegia (OR 6.6, P = 0.001). Among patients receiving FET, a body core temperature during circulatory arrest of ≥ 28 °C in combination with a prolonged circulatory arrest time of >40 min was an independent predictor for permanent spinal cord injury (OR 5.0, 95% CI 1.1-20, P = 0.038). The estimated 1-, 3- and 5-year survival were 70 ± 4, 70 ± 4 and 68 ± 4% (cET) and 4 ± 7 and 60 ± 9, 40 ± 1

Attenuation of spinal cord ischemia-reperfusion injury by specific α-2a receptor activation with dexmedetomidine.

PubMed

Bell, Marshall T; Puskas, Ferenc; Smith, Phillip D; Agoston, Viktor A; Fullerton, David A; Meng, Xianzhong; Weyant, Michael J; Reece, T Brett

2012-11-01

the administration of the α-2a receptor antagonist atipamezole. Dexmedetomidine appears to attenuate spinal cord ischemia-reperfusion injury via α-2a receptor-mediated agonism. There remains a significant risk of paraplegia after thoracoabdominal aortic interventions. This complication is devastating to the patient and the health care system. Pharmacologic adjuncts to further decrease this complication have been studied; however, few viable options exist. The α-2a agonists have been shown to improve outcomes after strokes but have not been studied in spinal cord ischemia. We show that dexmedetomidine, a commonly used α-2a agonist in the operating room, can preserve neurologic function in mice after aortic cross-clamping. Although the protective mechanism of dexmedetomidine remains unknown, it might prove to be beneficial in reducing the incidence of paraplegia after aortic interventions. Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Real-Time Strap Pressure Sensor System for Powered Exoskeletons

PubMed Central

Tamez-Duque, Jesús; Cobian-Ugalde, Rebeca; Kilicarslan, Atilla; Venkatakrishnan, Anusha; Soto, Rogelio; Contreras-Vidal, Jose Luis

2015-01-01

Assistive and rehabilitative powered exoskeletons for spinal cord injury (SCI) and stroke subjects have recently reached the clinic. Proper tension and joint alignment are critical to ensuring safety. Challenges still exist in adjustment and fitting, with most current systems depending on personnel experience for appropriate individual fastening. Paraplegia and tetraplegia patients using these devices have impaired sensation and cannot signal if straps are uncomfortable or painful. Excessive pressure and blood-flow restriction can lead to skin ulcers, necrotic tissue and infections. Tension must be just enough to prevent slipping and maintain posture. Research in pressure dynamics is extensive for wheelchairs and mattresses, but little research has been done on exoskeleton straps. We present a system to monitor pressure exerted by physical human-machine interfaces and provide data about levels of skin/body pressure in fastening straps. The system consists of sensing arrays, signal processing hardware with wireless transmission, and an interactive GUI. For validation, a lower-body powered exoskeleton carrying the full weight of users was used. Experimental trials were conducted with one SCI and one able-bodied subject. The system can help prevent skin injuries related to excessive pressure in mobility-impaired patients using powered exoskeletons, supporting functionality, independence and better overall quality of life. PMID:25690551

Physical activity is related to lower levels of pain, fatigue and depression in individuals with spinal-cord injury: a correlational study.

PubMed

Tawashy, A E; Eng, J J; Lin, K H; Tang, P F; Hung, C

2009-04-01

This was a prospective cross-sectional study for people with chronic spinal cord injury (SCI). To (1) evaluate the intensity level and nature of physical activity in community-dwelling individuals living with SCI, and (2) explore the relation between descriptive individual variables (for example, lesion level), secondary complications and participation in physical activity. Urban community setting. A total of 49 subjects with SCI who used a manual wheelchair for primary mode of mobility (mean years since injury, 11.8; mean age, 43.7 years; 67% paraplegia) completed the physical activity recall assessment for people with SCI (PARA-SCI). Approximately 50% of reported physical activity among individuals with SCI is due to activities of daily living. The amount of physical activity was not related to lesion level, age, body mass index or waistline size. Greater heavy-intensity activity was related to lower levels of pain and fatigue and higher levels of self-efficacy, whereas higher amounts of mild-intensity activity and total activity were related to less depressive symptoms. Activities of daily living are a large component for physical activity among individuals with SCI. It appears that greater physical activity is associated with less secondary complications (pain, fatigue and depression) in individuals with SCI.

Musculoskeletal Deterioration and Hemicorporectomy After Spinal Cord Injury

PubMed Central

Dudley-Javoroski, Shauna

2014-01-01

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

Analysis of Genetic Mutations in a Cohort of Hereditary Optic Neuropathy in Shanghai, China.

PubMed

Gan, Dekang; Li, Mengwei; Wu, Jihong; Sun, Xinghuai; Tian, Guohong

2017-01-01

To evaluate the clinical classification and characteristics of hereditary optic neuropathy patients in a single center in China. Retrospective case study. Patients diagnosed with hereditary optic neuropathy between January 2014 and December 2015 in the neuro-ophthalmology division in Shanghai Eye and ENT Hospital of Fudan University were recruited. Clinical features as well as visual field, brain/orbital MRI, and spectrum domain optical coherence tomography (SD-OCT) were analyzed. Eighty-two patients diagnosed by gene test were evaluated, including 66 males and 16 females. The mean age of the patients was 19.4 years (range, 5-46 years). A total of 158 eyes were analyzed, including 6 unilateral, 61 bilateral, and 15 sequential. The median duration of the disease was 0.5 year (range, 0.1-20 years). Genetic test identified 68 patients with Leber hereditary optic neuropathy, 9 with dominant optic neuropathy, and 2 with a Wolfram gene mutation. There was also one case of hereditary spastic paraplegia, spinocerebellar ataxia, and polymicrogyria with optic nerve atrophy, respectively. Leber hereditary optic neuropathy is the most common detected type of hereditary optic neuropathy in Shanghai, China. The detection of other autosomal mutations in hereditary optic neuropathy is limited by the currently available technique.

Development of an evidence-informed leisure time physical activity resource for adults with spinal cord injury: the SCI Get Fit Toolkit.

PubMed

Arbour-Nicitopoulos, K P; Martin Ginis, K A; Latimer-Cheung, A E; Bourne, C; Campbell, D; Cappe, S; Ginis, S; Hicks, A L; Pomerleau, P; Smith, K

2013-06-01

To systematically develop an evidence-informed leisure time physical activity (LTPA) resource for adults with spinal cord injury (SCI). Canada. The Appraisal of Guidelines, Research and Evaluation (AGREE) II protocol was used to develop a toolkit to teach and encourage adults with SCI how to make smart and informed choices about being physically active. A multidisciplinary expert panel appraised the evidence and generated specific recommendations for the content of the toolkit. Pilot testing was conducted to refine the toolkit's presentation. Recommendations emanating from the consultation process were that the toolkit be a brief, evidence-based resource that contains images of adults with tetraplegia and paraplegia, and links to more detailed online information. The content of the toolkit should include the physical activity guidelines (PAGs) for adults with SCI, activities tailored to manual and power chair users, the benefits of LTPA, and strategies to overcome common LTPA barriers for adults with SCI. The inclusion of action plans and safety tips was also recommended. These recommendations have resulted in the development of an evidence-informed LTPA resource to assist adults with SCI in meeting the PAGs. This toolkit will have important implications for consumers, health care professionals and policy makers for encouraging LTPA in the SCI community.

Spontaneous cord transection due to invasive aspergillus spondylitis in an immunocompetent child.

PubMed

Karthik, K; Shetty, Ajoy Prasad; Rajasekaran, S

2011-07-01

Invasive spinal aspergillosis in an immunocompetent child is rare and often there is a considerable delay in diagnosis. A 13-year-old male child treated medically as tuberculosis of spine elsewhere for 1 year, came with complete paraplegia, dorsolumbar kyphosis and intermittently discharging sinus in the back. The child was taken up for surgical decompression and stabilization. Intraoperatively black granulomatous material was noted inside the canal extending anteriorly towards the vertebral body. There was complete cord transection with severe vertebral destruction and osteoporosis. The pathology and microbiology confirmed aspergillosis and the child was started on antifungal treatment. At further follow up, the infection was found to spread to the lung and caused further vertebral destruction. A change in the antifungal medication controlled further spread but failed to eradicate the infection at 2-year follow-up. In this patient, the delay led to extensive vertebral destruction with spine deformity and spontaneous cord transection. Retrospective review of the clinical and radiological findings suggests that this complication could have been prevented if these findings were carefully interpreted. In this era of transplantation and increase in use of immunosuppressive drugs the authors suggests having fungal infection as a differential diagnosis for infections of the spine.

Clinical Guideline for Treatment of Symptomatic Thoracic Spinal Stenosis.

PubMed

Chen, Zhong-qiang; Sun, Chui-guo

2015-08-01

Thoracic spinal stenosis is a relatively common disorder causing paraplegia in the population of China. Until nowadays, the clinical management of thoracic spinal stenosis is still demanding and challenging with lots of questions remaining to be answered. A clinical guideline for the treatment of symptomatic thoracic spinal stenosis has been created by reaching the consensus of Chinese specialists using the best available evidence as a tool to aid practitioners involved with the care of this disease. In this guideline, many fundamental questions about thoracic spinal stenosis which were controversial have been explained clearly, including the definition of thoracic spinal stenosis, the standard procedure for diagnosing symptomatic thoracic spinal stenosis, indications for surgery, and so on. According to the consensus on the definition of thoracic spinal stenosis, the soft herniation of thoracic discs has been excluded from the pathological factors causing thoracic spinal stenosis. The procedure for diagnosing thoracic spinal stenosis has been quite mature, while the principles for selecting operative procedures remain to be improved. This guideline will be updated on a timely schedule and adhering to its recommendations should not be mandatory because it does not have the force of law. © 2015 Chinese Orthopaedic Association and Wiley Publishing Asia Pty Ltd.

Targeted high-throughput sequencing identifies mutations in atlastin-1 as a cause of hereditary sensory neuropathy type I.

PubMed

Guelly, Christian; Zhu, Peng-Peng; Leonardis, Lea; Papić, Lea; Zidar, Janez; Schabhüttl, Maria; Strohmaier, Heimo; Weis, Joachim; Strom, Tim M; Baets, Jonathan; Willems, Jan; De Jonghe, Peter; Reilly, Mary M; Fröhlich, Eleonore; Hatz, Martina; Trajanoski, Slave; Pieber, Thomas R; Janecke, Andreas R; Blackstone, Craig; Auer-Grumbach, Michaela

2011-01-07

Hereditary sensory neuropathy type I (HSN I) is an axonal form of autosomal-dominant hereditary motor and sensory neuropathy distinguished by prominent sensory loss that leads to painless injuries. Unrecognized, these can result in delayed wound healing and osteomyelitis, necessitating distal amputations. To elucidate the genetic basis of an HSN I subtype in a family in which mutations in the few known HSN I genes had been excluded, we employed massive parallel exon sequencing of the 14.3 Mb disease interval on chromosome 14q. We detected a missense mutation (c.1065C>A, p.Asn355Lys) in atlastin-1 (ATL1), a gene that is known to be mutated in early-onset hereditary spastic paraplegia SPG3A and that encodes the large dynamin-related GTPase atlastin-1. The mutant protein exhibited reduced GTPase activity and prominently disrupted ER network morphology when expressed in COS7 cells, strongly supporting pathogenicity. An expanded screen in 115 additional HSN I patients identified two further dominant ATL1 mutations (c.196G>C [p.Glu66Gln] and c.976 delG [p.Val326TrpfsX8]). This study highlights an unexpected major role for atlastin-1 in the function of sensory neurons and identifies HSN I and SPG3A as allelic disorders.

The clinical maze of mitochondrial neurology

PubMed Central

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

2014-01-01

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

[A nurse's experience using the super-link system theory to help a T6 spinal cord injury patient return to school].

PubMed

Li, Pei-Yeh; Wu, Tzu-Jung; Sung, Shi-Hui; Chen, Hsiao-Yu

2010-04-01

The subject of this article is a 20 year-old female with thoracic spinal cord injury with paraplegia suffered during a car accident. The article reports on the nursing experience in helping the patient manage her autonomic dysreflexia (AD), training the patient in self-catheterization, and using relevant social resources in order to achieve a successful return to her studies at school. The authors collected data using interviews, observations, and physical assessments between November 20 and December 30, 2008. The two nursing diagnoses of AD and inadequate preparation for a successful return to school during rehabilitation hospitalization were made during caring procedures. Holistic nursing assessment was employed and the Super-Link System Theory was applied to establish a link between the hospital and school. Individual nursing interventions used included understanding the inducement and treatment of AD, performing self-catheterization, and enhancing the support system by introducing successful clients and relevant social resources in order to transition the patient successfully to her new post-injury life. The patient consequently transitioned smoothly from rehabilitation hospital to school. The authors hope this case report will provide a useful reference for nurses charged with caring for patients with spinal cord injuries while still enrolled at school.

Histopathologic correlation of magnetic resonance imaging signal patterns in a spinal cord injury model.

PubMed

Weirich, S D; Cotler, H B; Narayana, P A; Hazle, J D; Jackson, E F; Coupe, K J; McDonald, C L; Langford, L A; Harris, J H

1990-07-01

Magnetic resonance imaging (MRI) provides a noninvasive method of monitoring the pathologic response to spinal cord injury. Specific MR signal intensity patterns appear to correlate with degrees of improvement in the neurologic status in spinal cord injury patients. Histologic correlation of two types of MR signal intensity patterns are confirmed in the current study using a rat animal model. Adult male Sprague-Dawley rats underwent spinal cord trauma at the midthoracic level using a weight-dropping technique. After laminectomy, 5- and 10-gm brass weights were dropped from designated heights onto a 0.1-gm impounder placed on the exposed dura. Animals allowed to regain consciousness demonstrated variable recovery of hind limb paraplegia. Magnetic resonance images were obtained from 2 hours to 1 week after injury using a 2-tesla MRI/spectrometer. Sacrifice under anesthesia was performed by perfusive fixation; spinal columns were excised en bloc, embedded, sectioned, and observed with the compound light microscope. Magnetic resonance axial images obtained during the time sequence after injury demonstrate a distinct correlation between MR signal intensity patterns and the histologic appearance of the spinal cord. Magnetic resonance imaging delineates the pathologic processes resulting from acute spinal cord injury and can be used to differentiate the type of injury and prognosis.

Percutaneous tracheostomy in patients with cervical spine fractures--feasible and safe.

PubMed

Ben Nun, Alon; Orlovsky, Michael; Best, Lael Anson

2006-08-01

The aim of this study is to evaluate the short and long-term results of percutaneous tracheostomy in patients with documented cervical spine fracture. Between June 2000 and September 2005, 38 consecutive percutaneous tracheostomy procedures were performed on multi-trauma patients with cervical spine fracture. Modified Griggs technique was employed at the bedside in the general intensive care department. Staff thoracic surgeons and anesthesiologists performed all procedures. Demographics, anatomical conditions, presence of co-morbidities and complication rates were recorded. The average operative time was 10 min (6-15). Two patients had minor complications. One patients had minor bleeding (50 cc) and one had mild cellulitis. Nine patients had severe paraparesis or paraplegia prior to the PCT procedure and 29 were without neurological damage. There was no PCT related neurological deterioration. Twenty-eight patients were discharged from the hospital, 21 were decannulated. The average follow-up period was 18 months (1-48). There was no delayed, procedure related, complication. These results demonstrate that percutaneous tracheostomy is feasible and safe in patients with cervical spine fracture with minimal short and long-term morbidity. We believe that percutaneous tracheostomy is the procedure of choice for patients with cervical spine fracture who need prolonged ventilatory support.

Comparison of energy efficiency between Wearable Power-Assist Locomotor (WPAL) and two types of knee-ankle-foot orthoses with a medial single hip joint (MSH-KAFO).

PubMed

Yatsuya, Kanan; Hirano, Satoshi; Saitoh, Eiichi; Tanabe, Shigeo; Tanaka, Hirotaka; Eguchi, Masayuki; Katoh, Masaki; Shimizu, Yasuhiro; Uno, Akito; Kagaya, Hitoshi

2018-01-01

To compare the energy efficiency of Wearable Power-Assist Locomotor (WPAL) with conventional knee-ankle-foot orthoses (MSH-KAFO) such as Hip and Ankle Linked Orthosis (HALO) or Primewalk. Cross over case-series. Chubu Rosai Hospital, Aichi, Japan, which is affiliated with the Japan Organization of Occupational Health and Safety. Six patients were trained with MSH-KAFO (either HALO or Primewalk) and WPAL. They underwent 6-minute walk tests with each orthosis. Energy efficiency was estimated using physiological cost index (PCI) as well as heart rate (HR) and modified Borg score. Trial energy efficiency with MSH-KAFO was compared with WPAL to assess if differences in PCI became greater between MSH-KAFO and WPAL as time goes on during the 6-minute walk. Spearman correlation coefficient of time (range: 0.5-6.0 minutes) with the difference was calculated. The same statistical procedures were repeated for HR and modified Borg score. Greater energy efficiency, representing a lower gait demand, was observed in trials with WPAL compared with MSH-KAFO (Spearman correlation coefficients for PCI, HR and modified Borg were 0.93, 0.90 and 0.97, respectively, all P < 0.0001). WPAL is a practical and energy efficient type of robotics that may be used by patients with paraplegia.

Fishing for causes and cures of motor neuron disorders

PubMed Central

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

2014-01-01

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

Fishing for causes and cures of motor neuron disorders.

PubMed

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

2014-07-01

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. © 2014. Published by The Company of Biologists Ltd.

Spastin, atlastin, and ER relocalization are involved in axon but not dendrite regeneration

PubMed Central

Rao, Kavitha; Stone, Michelle C.; Weiner, Alexis T.; Gheres, Kyle W.; Zhou, Chaoming; Deitcher, David L.; Levitan, Edwin S.; Rolls, Melissa M.

2016-01-01

Mutations in >50 genes, including spastin and atlastin, lead to hereditary spastic paraplegia (HSP). We previously demonstrated that reduction of spastin leads to a deficit in axon regeneration in a Drosophila model. Axon regeneration was similarly impaired in neurons when HSP proteins atlastin, seipin, and spichthyin were reduced. Impaired regeneration was dependent on genetic background and was observed when partial reduction of HSP proteins was combined with expression of dominant-negative microtubule regulators, suggesting that HSP proteins work with microtubules to promote regeneration. Microtubule rearrangements triggered by axon injury were, however, normal in all genotypes. We examined other markers to identify additional changes associated with regeneration. Whereas mitochondria, endosomes, and ribosomes did not exhibit dramatic repatterning during regeneration, the endoplasmic reticulum (ER) was frequently concentrated near the tip of the growing axon. In atlastin RNAi and spastin mutant animals, ER accumulation near single growing axon tips was impaired. ER tip concentration was observed only during axon regeneration and not during dendrite regeneration. In addition, dendrite regeneration was unaffected by reduction of spastin or atlastin. We propose that the HSP proteins spastin and atlastin promote axon regeneration by coordinating concentration of the ER and microtubules at the growing axon tip. PMID:27605706

A valuable animal model of spinal cord injury to study motor dysfunctions, comorbid conditions, and aging associated diseases.

PubMed

Rouleau, Pascal; Guertin, Pierre A

2013-01-01

Most animal models of contused, compressed or transected spinal cord injury (SCI) require a laminectomy to be performed. However, despite advantages and disadvantages associated with each of these models, the laminectomy itself is generally associated with significant problems including longer surgery and anaesthesia (related post-operative complications), neuropathic pain, spinal instabilities, deformities, lordosis, and biomechanical problems, etc. This review provides an overview of findings obtained mainly from our laboratory that are associated with the development and characterization of a novel murine model of spinal cord transection that does not require a laminectomy. A number of studies successfully conducted with this model provided strong evidence that it constitutes a simple, reliable and reproducible transection model of complete paraplegia which is particularly useful for studies on large cohorts of wild-type or mutant animals - e.g., drug screening studies in vivo or studies aimed at characterizing neuronal and non-neuronal adaptive changes post-trauma. It is highly suitable also for studies aimed at identifying and developing new pharmacological treatments against aging associated comorbid problems and specific SCI-related dysfunctions (e.g., stereotyped motor behaviours such as locomotion, sexual response, defecation and micturition) largely related with 'command centers' located in lumbosacral areas of the spinal cord.

Loss of lower limb motor evoked potentials and spinal cord injury during the initial exposure in scoliosis surgery.

PubMed

Legatt, Alan D; Fried, Stephen J; Amaral, Terry D; Sarwahi, Vishal; Moguilevitch, Marina

2014-04-01

To report a case of motor evoked potential changes and spinal cord injury during the initial dissection in scoliosis surgery. Motor evoked potentials to transcranial electrical stimulation were recorded from multiple muscles. Somatosensory evoked potentials to limb nerve stimulation were recorded from the scalp. Clear motor evoked potentials were initially present in all monitored muscles. The patient was then pharmacologically paralyzed for the initial dissection. More than usual bleeding was encountered during that dissection, prompting transfusion. As the neuromuscular blockade subsided, motor evoked potentials persisted in the hand muscles but disappeared and remained absent in all monitored leg muscles. The spine had not been instrumented. A wake-up test demonstrated paraplegia; the surgery was aborted. There were no adverse somatosensory evoked potential changes. MRI showed an anterior spinal cord infarct. Copious soft tissue bleeding during the initial dissection might have lowered pressures in critical segmental arteries enough to cause spinal cord infarction through a steal phenomenon. The lack of somatosensory evoked potential changes reflected sparing of the dorsal columns. When neuromuscular blockade is used during the initial soft tissue dissection, motor evoked potentials should be assessed after this, but before spinal instrumentation, to determine whether there had been any spinal cord compromise during the initial dissection.

Traumatic spinal cord injuries in southeast Turkey: an epidemiological study.

PubMed

Karamehmetoğlu, S S; Nas, K; Karacan, I; Sarac, A J; Koyuncu, H; Ataoğlu, S; Erdoğan, F

1997-08-01

In 1994, a retrospective study of new cases of traumatic Spinal Cord Injury (SCI) was conducted in all the hospitals in Southeast Turkey: 75 new traumatic SCI were identified. The estimated annual incidence was 16.9 per million population. The male/female ratio was 5.8/1. The mean age was 31.3, being 31.25 for male patients and 31.36 for female patients. 70.7% of all patients were under the age of 40. The major causes of SCI were falls (37.3%) and gunshot wounds (29.3%), followed by car accidents (25.3%), and stab wounds (1.3%). Thirty one patients (41.3%) were tetraplegic and 44 (58.7%) paraplegic. In tetraplegic patients the commonest level was C5, in those with paraplegia L1. The commonest associated injury was head trauma followed by fractures of the extremity(ies). Severe head trauma, being a major cause of death, may have obscured the actual incidence of SCI. Most of gunshot injured SCI patients were young soldiers fighting against the rebels. As there was no available data for the rebels with SCI, the actual incidence of SCI in Southeast (SE) Turkey should be higher than that found in this study.

Clinical mitochondrial genetics

PubMed Central

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

1999-01-01

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

Cisplatin-induced hypokalemic paralysis.

PubMed

Mohammadianpanah, Mohammad; Omidvari, Shapour; Mosalaei, Ahmad; Ahmadloo, Niloofar

2004-08-01

Profound hypokalemic conditions resulting from cisplatin therapy have been known to produce hypokalemic paralysis in rare cases. We describe such a case of cisplatin-induced hypokalemic paralysis. A 15-year-old Persian girl with ovarian dysgerminoma presented with severe generalized weakness and paraplegia 1 week after the fourth course of cisplatin-based chemotherapy. On physical examination, there was symmetric flaccid paralysis and areflexia in all of the extremities and particularly in the lower limbs. Her serum potassium concentration was 1.7 mmol/L. Metastatic disease was excluded by a comprehensive systemic evaluation. Complete clinical and paraclinical recovery was achieved after short-term administration of potassium supplement. Adverse drug reactions are common with cisplatin, but the drug is only rarely associated with hypokalemic paralysis. Based on the Naranjo causality algorithm, an objective assessment revealed cisplatin to be a probable cause of hypokalemic paralysis in this case. This adverse drug event--whether isolated or secondary to hypomagnesemia--may be deceptive, leading to a fatal mistake in the oncology setting, and should therefore be precisely differentiated from cancer-related complications. This case suggests that cisplatin should be added to the list of agents causing hypokalemic paralysis. Regular serum electrolyte measurement, the early detection of cation deficiency, and appropriate replacement of cations are all recommended.

Inbreeding levels in Northeast Brazil: Strategies for the prospecting of new genetic disorders.

PubMed

Santos, Silvana; Kok, Fernando; Weller, Mathias; de Paiva, Francisco Rennan Lopes; Otto, Paulo A

2010-04-01

A new autosomal recessive genetic condition, the SPOAN syndrome (an acronym for spastic paraplegia, optic atrophy and neuropathy syndrome), was recently discovered in an isolated region of the State of Rio Grande do Norte in Northeast Brazil, in a population that was identified by the IBGE (Brazilian Institute of Geography and Statistics) as belonging to the Brazilian communities with the highest rates of "deficiencies" (Neri, 2003), a term used to describe diseases, malformations, and handicaps in general. This prompted us to conduct a study of consanguinity levels in five of its municipal districts by directly interviewing their inhabitants. Information on 7,639 couples (corresponding to about 40% of the whole population of the studied districts) was obtained. The research disclosed the existence of very high frequencies of consanguineous marriages, which varied from about 9% to 32%, suggesting the presence of a direct association between genetic diseases such as the SPOAN syndrome, genetic drift and inbreeding levels. This fact calls for the introduction of educational programs for the local populations, as well as for further studies aiming to identify and characterize other genetic conditions. Epidemiological strategies developed to collect inbreeding data, with the collaboration of health systems available in the region, might be very successful in the prospecting of genetic disorders.

The effects of exercise on human articular cartilage

PubMed Central

Eckstein, F; Hudelmaier, M; Putz, R

2006-01-01

The effects of exercise on articular hyaline articular cartilage have traditionally been examined in animal models, but until recently little information has been available on human cartilage. Magnetic resonance imaging now permits cartilage morphology and composition to be analysed quantitatively in vivo. This review briefly describes the methodological background of quantitative cartilage imaging and summarizes work on short-term (deformational behaviour) and long-term (functional adaptation) effects of exercise on human articular cartilage. Current findings suggest that human cartilage deforms very little in vivo during physiological activities and recovers from deformation within 90 min after loading. Whereas cartilage deformation appears to become less with increasing age, sex and physical training status do not seem to affect in vivo deformational behaviour. There is now good evidence that cartilage undergoes some type of atrophy (thinning) under reduced loading conditions, such as with postoperative immobilization and paraplegia. However, increased loading (as encountered by elite athletes) does not appear to be associated with increased average cartilage thickness. Findings in twins, however, suggest a strong genetic contribution to cartilage morphology. Potential reasons for the inability of cartilage to adapt to mechanical stimuli include a lack of evolutionary pressure and a decoupling of mechanical competence and tissue mass. PMID:16637874

Long-Term Training with a Brain-Machine Interface-Based Gait Protocol Induces Partial Neurological Recovery in Paraplegic Patients.

PubMed

Donati, Ana R C; Shokur, Solaiman; Morya, Edgard; Campos, Debora S F; Moioli, Renan C; Gitti, Claudia M; Augusto, Patricia B; Tripodi, Sandra; Pires, Cristhiane G; Pereira, Gislaine A; Brasil, Fabricio L; Gallo, Simone; Lin, Anthony A; Takigami, Angelo K; Aratanha, Maria A; Joshi, Sanjay; Bleuler, Hannes; Cheng, Gordon; Rudolph, Alan; Nicolelis, Miguel A L

2016-08-11

Brain-machine interfaces (BMIs) provide a new assistive strategy aimed at restoring mobility in severely paralyzed patients. Yet, no study in animals or in human subjects has indicated that long-term BMI training could induce any type of clinical recovery. Eight chronic (3-13 years) spinal cord injury (SCI) paraplegics were subjected to long-term training (12 months) with a multi-stage BMI-based gait neurorehabilitation paradigm aimed at restoring locomotion. This paradigm combined intense immersive virtual reality training, enriched visual-tactile feedback, and walking with two EEG-controlled robotic actuators, including a custom-designed lower limb exoskeleton capable of delivering tactile feedback to subjects. Following 12 months of training with this paradigm, all eight patients experienced neurological improvements in somatic sensation (pain localization, fine/crude touch, and proprioceptive sensing) in multiple dermatomes. Patients also regained voluntary motor control in key muscles below the SCI level, as measured by EMGs, resulting in marked improvement in their walking index. As a result, 50% of these patients were upgraded to an incomplete paraplegia classification. Neurological recovery was paralleled by the reemergence of lower limb motor imagery at cortical level. We hypothesize that this unprecedented neurological recovery results from both cortical and spinal cord plasticity triggered by long-term BMI usage.

Long-Term Training with a Brain-Machine Interface-Based Gait Protocol Induces Partial Neurological Recovery in Paraplegic Patients

PubMed Central

Donati, Ana R. C.; Shokur, Solaiman; Morya, Edgard; Campos, Debora S. F.; Moioli, Renan C.; Gitti, Claudia M.; Augusto, Patricia B.; Tripodi, Sandra; Pires, Cristhiane G.; Pereira, Gislaine A.; Brasil, Fabricio L.; Gallo, Simone; Lin, Anthony A.; Takigami, Angelo K.; Aratanha, Maria A.; Joshi, Sanjay; Bleuler, Hannes; Cheng, Gordon; Rudolph, Alan; Nicolelis, Miguel A. L.

2016-01-01

Brain-machine interfaces (BMIs) provide a new assistive strategy aimed at restoring mobility in severely paralyzed patients. Yet, no study in animals or in human subjects has indicated that long-term BMI training could induce any type of clinical recovery. Eight chronic (3–13 years) spinal cord injury (SCI) paraplegics were subjected to long-term training (12 months) with a multi-stage BMI-based gait neurorehabilitation paradigm aimed at restoring locomotion. This paradigm combined intense immersive virtual reality training, enriched visual-tactile feedback, and walking with two EEG-controlled robotic actuators, including a custom-designed lower limb exoskeleton capable of delivering tactile feedback to subjects. Following 12 months of training with this paradigm, all eight patients experienced neurological improvements in somatic sensation (pain localization, fine/crude touch, and proprioceptive sensing) in multiple dermatomes. Patients also regained voluntary motor control in key muscles below the SCI level, as measured by EMGs, resulting in marked improvement in their walking index. As a result, 50% of these patients were upgraded to an incomplete paraplegia classification. Neurological recovery was paralleled by the reemergence of lower limb motor imagery at cortical level. We hypothesize that this unprecedented neurological recovery results from both cortical and spinal cord plasticity triggered by long-term BMI usage. PMID:27513629

Acute, Nontraumatic Spontaneous Spinal Subdural Hematoma: A Case Report and Systematic Review of the Literature

PubMed Central

Abel, Taylor J.

2017-01-01

Spontaneous spinal subdural hematoma (sSDH) is a rare condition outright. Moreover, cases that occur spontaneously in the absence of an identifiable etiology are considerably less common and remain poorly understood. Here, we present the case of a 43-year-old man with spontaneous sSDH presenting with acute onset low back pain and paraplegia. Urgent magnetic resonance imaging identified a dorsal SDH from T8 to T11 with compression of the spinal cord. Emergent T8–T10 laminectomies with intradural exploration and hematoma evacuation were performed. However, despite prompt identification and appropriate action, the patient's recovery was modest and significant disability remained at discharge. This unique and unusual case demonstrates that spontaneous sSDH requires prompt surgical treatment to minimize associated morbidity and supports the association between the presence of severe neurological deficits upon initial presentation with less favorable outcomes. We performed a comprehensive systematic review of spontaneous sSDH of unknown etiology, which demonstrates that emergent surgical intervention is indicated for patients presenting with severe neurological deficits and the presence of these deficits is predictive of poor neurological outcome. Furthermore, conservative management should be considered in patients presenting with mild neurological deficits as spontaneous resolution followed by favorable neurological outcomes is often observed in these patients. PMID:29441210

Paralyzed by desire: a new type of body integrity identity disorder.

PubMed

Giummarra, Melita J; Bradshaw, John L; Hilti, Leonie M; Nicholls, Michael E R; Brugger, Peter

2012-03-01

Body incongruity in body integrity identity disorder (BIID) manifests in the desire to have a healthy limb amputated. We describe a variant of the disorder: the desire to become paralyzed (paralysis-BIID). Sixteen otherwise healthy participants, recruited through Internet-based forums, websites, or word of mouth, completed questionnaires about details of their desire and accompanying symptoms. Onset of the desire for paralysis typically preceded puberty. All participants indicated a specific level for desired spinal cord injury. All participants simulated paralysis through mental imagery or physical pretending, and 9 (56%) reported erotic interest in paraplegia and/or disability. Our key new finding was that 37.5% of paralysis-BIID participants were women, compared with 4.4% women in a sample of 68 individuals with amputation-BIID. BIID reflects a disunity between self and body, usually with a prominent sexual component. Sex-related differences are emerging: unlike men, a higher proportion of women desire paralysis than desire amputation, and, while men typically seek unilateral amputation, women typically seek bilateral amputation. We propose that these sex-related differences in BIID manifestation may relate to sex differences in cerebral lateralization, or to disruption of representation and/or processing of body-related information in right-hemisphere frontoparietal networks.

Body integrity identity disorder: the persistent desire to acquire a physical disability.

PubMed

First, Michael B; Fisher, Carl E

2012-01-01

Body integrity identity disorder (BIID) is a rare and unusual psychiatric condition characterized by a persistent desire to acquire a physical disability (e.g., amputation, paraplegia) since childhood that to date has not been formally described in the psychiatric nosology. Most BIID sufferers experience a chronic and dysphoric sense of inappropriateness regarding their being able-bodied, and many have been driven to actualize their desired disability through surreptitious surgical or other more dangerous methods. This review aims to characterize the history and phenomenology of this condition, to present its differential diagnosis, and to consider possible etiologies, treatment options, and ethical considerations. Review of the psychiatric and neurological literature. A growing body of data suggests the existence of a discrete entity with onset by early adolescence and a negative impact on functioning. Parallel neurological conditions and preliminary experimental investigations suggest a possible neurobiological component in at least a portion of cases. While attempts at treatment have been described, no systematic evidence for efficacy has emerged. BIID is a unique nosological entity with significant consequences for its sufferers and as such may warrant inclusion in some form in the forthcoming DSM-5 and ICD-11. Copyright © 2011 S. Karger AG, Basel.

Proteolipid Protein Is Required for Transport of Sirtuin 2 into CNS Myelin

PubMed Central

Werner, Hauke B.; Kuhlmann, Katja; Shen, Siming; Uecker, Marina; Schardt, Anke; Dimova, Kalina; Orfaniotou, Foteini; Dhaunchak, Ajit; Brinkmann, Bastian G.; Möbius, Wiebke; Guarente, Lenny; Casaccia-Bonnefil, Patrizia; Jahn, Olaf; Nave, Klaus-Armin

2009-01-01

Mice lacking the expression of proteolipid protein (PLP)/DM20 in oligodendrocytes provide a genuine model for spastic paraplegia (SPG-2). Their axons are well myelinated but exhibit impaired axonal transport and progressive degeneration, which is difficult to attribute to the absence of a single myelin protein. We hypothesized that secondary molecular changes in PLPnull myelin contribute to the loss of PLP/DM20-dependent neuroprotection and provide more insight into glia-axonal interactions in this disease model. By gel-based proteome analysis, we identified >160 proteins in purified myelin membranes, which allowed us to systematically monitor the CNS myelin proteome of adult PLPnull mice, before the onset of disease. We identified three proteins of the septin family to be reduced in abundance, but the nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase sirtuin 2 (SIRT2) was virtually absent. SIRT2 is expressed throughout the oligodendrocyte lineage, and immunoelectron microscopy revealed its association with myelin. Loss of SIRT2 in PLPnull was posttranscriptional, suggesting that PLP/DM20 is required for its transport into the myelin compartment. Because normal SIRT2 activity is controlled by the NAD+/NADH ratio, its function may be coupled to the axo-glial metabolism and the long-term support of axons by oligodendrocytes. PMID:17634366

Spinal cord lesions shrink peripersonal space around the feet, passive mobilization of paraplegic limbs restores it.

PubMed

Scandola, Michele; Aglioti, Salvatore Maria; Bonente, Claudio; Avesani, Renato; Moro, Valentina

2016-04-06

Peripersonal space (PPS) is the space surrounding us within which we interact with objects. PPS may be modulated by actions (e.g. when using tools) or sense of ownership (e.g. over a rubber hand). Indeed, intense and/or prolonged use of a tool may induce a sense of ownership over it. Conversely, inducing ownership over a rubber hand may activate brain regions involved in motor control. However, the extent to which PPS is modulated by action-dependent or ownership-dependent mechanisms remains unclear. Here, we explored the PPS around the feet and the sense of ownership over lower limbs in people with Paraplegia following Complete spinal cord Lesions (PCL) and in healthy subjects. PCL people can move their upper body but have lost all sensory-motor functions in their lower body (e.g. lower limbs). We tested whether PPS alterations reflect the topographical representations of various body parts. We found that the PPS around the feet was impaired in PCL who however had a normal representation of the PPS around the hands. Significantly, passive mobilization of paraplegic limbs restored the PPS around the feet suggesting that activating action representations in PCL brings about short-term changes of PPS that may thus be more plastic than previously believed.

[Physiotherapy for spasticity].

PubMed

Albert, T; Yelnik, A

2003-05-01

The aims of physiotherapy techniques used for the treatment of spasticity are to favor sensorimotor recovery and gesture relearning and to lead to an optimal independence in daily life activities. For stroke and head injury patients, there are several techniques sometimes based on opposing principles. The concept of Bobath tries to inhibit the spastic paralysis and the associated reactions to improve the voluntary motricity of limbs with the ultimate goal of enabling exercises in a functional situation, sometimes after a very long period of therapy. On the contrary, according to the concept of Brunnstom, the goal of exercise is to strengthen the spastic paralysis and the associated reactions to enable the upright position and walking as soon as possible. This technique is especially used in very severe deficiencies where the aim is to avoid the bedridden situation. Three active principles can be identified for neurological rehabilitation. Electrical stimulation is not used routinely by rehabilitation teams. It allows to reduce the spasticity of antagonist muscles working against stimulated muscles. It participates in improving the strength of contraction of weak muscles notably in subjects with incomplete paraplegia. Finally, it can be used to improve or replace a functional command (lifting the foot during walking, for example). Nevertheless, electrical stimulation cannot replace basic rehabilitation exercises.

PROGNOSTIC FACTORS IN PATIENTS WITH PRESSURE SORES IN A UNIVERSITY HOSPITAL IN SOUTHERN BRAZIL

PubMed Central

WALTER, GUSTAVO PALMEIRO; SEIDEL, WILLIAM; GIUSTINA, RENATA DELLA; BINS-ELY, JORGE; MAURICI, ROSEMERI; NARCISO-SCHIAVON, JANAÍNA LUZ

2017-01-01

ABSTRACT Objective: Despite advances in medical care, patients who are hospitalized or have spinal cord injuries often develop pressure sores. The objective of this study was to describe the epidemiological characteristics of pressure sores and evaluate factors associated with recurrence and cure. Methods: In this historical cohort study, clinical and laboratory data were collected from medical records between 1997 and 2016. Results: Sixty individuals with pressure ulcers were included; mean patient age was 38.1±16.5 (37.0) years, 83.3% were men, and 86.8% identified as white. Most patients (85.1%) had paraplegia, amputation, or trauma of the lower limbs with motor sequelae; the remainder (14.9%) were quadriplegic. Most (78.3%) underwent surgery, and the mean follow-up time was 1.8±2.5 years. The lesions were cured in 25 patients; they recurred in 25% of the patients, and recurrence was seen to be associated with the location of the lesions. Patients with recurrent lesions had more medical consultations and a longer treatment time. Individuals whose ulcers had healed had fewer lesions, higher body mass index (BMI), and a higher proportion of these patients underwent surgery. Conclusions: BMI and location and number of lesions are prognostic factors. Level of Evidence IV, Case Series. PMID:29375252

[Pedicled superior gluteal artery perforator bilateral quadrilobed flaps for repair of large sacrococcygeal pressure sores].

PubMed

Hai, Henglin; Li, Huatao; Chen, Yang; Li, Qiang; Wu, Shenggang; Lili, Wang; Yan, Lei; Xiaoying, Zhou

2013-03-01

To investigate the effectiveness of pedicled superior gluteal artery perforator bilateral quadrilobed flaps for repairing large sacrococcygeal pressure sores. Between June 2003 and August 2011, 6 paraplegia patients with large sacrococcygeal pressure sores were repaired with the pedicled superior gluteal artery perforator bilateral quadrilobed flaps. There were 2 males and 4 females with an average age of 45.6 years (range, 37-62 years). The mean disease duration was 8.4 months (range, 3-26 months). According to National Pressure Ulcer Advisory Panel (NPUAP) standard, 6 cases rated as degree IV. The size of pressure sores ranged from 15 cm x 13 cm to 18 cm x 16 cm. The size of flaps ranged from 18 cm x 14 cm to 21 cm x 15 cm. After operation, all flaps survived successfully. The wounds healed by first intention in 5 cases; partial dehiscence of incision occurred in 1 case, which was cured after dressing change for 26 days. Six patients were followed up 6-24 months (mean, 12.5 months). The appearance and texture of the flaps were smooth and soft with good elasticity and no ulceration. Pedicled superior gluteal artery perforator bilateral quadrilobed flaps can repair large sacrococcygeal pressure sores. The appearance of flaps is smooth and has good compression-resistance effect.

PROGNOSTIC FACTORS IN PATIENTS WITH PRESSURE SORES IN A UNIVERSITY HOSPITAL IN SOUTHERN BRAZIL.

PubMed

Walter, Gustavo Palmeiro; Seidel, William; Giustina, Renata Della; Bins-Ely, Jorge; Maurici, Rosemeri; Narciso-Schiavon, Janaína Luz

2017-01-01

Despite advances in medical care, patients who are hospitalized or have spinal cord injuries often develop pressure sores. The objective of this study was to describe the epidemiological characteristics of pressure sores and evaluate factors associated with recurrence and cure. In this historical cohort study, clinical and laboratory data were collected from medical records between 1997 and 2016. Sixty individuals with pressure ulcers were included; mean patient age was 38.1±16.5 (37.0) years, 83.3% were men, and 86.8% identified as white. Most patients (85.1%) had paraplegia, amputation, or trauma of the lower limbs with motor sequelae; the remainder (14.9%) were quadriplegic. Most (78.3%) underwent surgery, and the mean follow-up time was 1.8±2.5 years. The lesions were cured in 25 patients; they recurred in 25% of the patients, and recurrence was seen to be associated with the location of the lesions. Patients with recurrent lesions had more medical consultations and a longer treatment time. Individuals whose ulcers had healed had fewer lesions, higher body mass index (BMI), and a higher proportion of these patients underwent surgery. BMI and location and number of lesions are prognostic factors. Level of Evidence IV, Case Series.

[Results of selective posterior radiculetomy at the lumbar and cervical level].

PubMed

Vlahovitch, B; Fuentes, J M

1975-01-01

At the light of authors' present experience, radicletomy appears as an excellent antalgic operative procedure in the case of roots with high functional risk (brachial plexus and lumbar plexus). In the absence of any motor deficiency or ataxia, it appears that radicletomy is of help in the cure of severe hypertonies of the extremities (sequelae of cerebral stem contusions). Conversely, in the spastic sequelae of hemi- or paraparesias, lumbar-sacral posterior selective radicotomy is a sure procedure that procures results nearly super-imposable to radicletomy with an appreciable gain in time. At last, for what concerns the motor involvements of the upper extremity ending in spasticity, selective radicletomy recovers its rights and has to be preferred to S.P.R. The indications may be summarized as follows: -- At the level of the lower extremities: in the case of paraparetic sequelae or of sequelae due to spastic paraplegia, a S.P.R. has to be performed; for what concerns antalgic surgery, in the absence of motor deficiency, the best indication is radicletomy. -- At the level of the upper extremities: in the case of dystonic sequeale of the cerebral stem, spastic pain bound with hemiplegia or with carcinoma etc. (herpes zoster..), radicletomy constitutes the ideal surgical procedure.

The effects of exercise on human articular cartilage.

PubMed

Eckstein, F; Hudelmaier, M; Putz, R

2006-04-01

The effects of exercise on articular hyaline articular cartilage have traditionally been examined in animal models, but until recently little information has been available on human cartilage. Magnetic resonance imaging now permits cartilage morphology and composition to be analysed quantitatively in vivo. This review briefly describes the methodological background of quantitative cartilage imaging and summarizes work on short-term (deformational behaviour) and long-term (functional adaptation) effects of exercise on human articular cartilage. Current findings suggest that human cartilage deforms very little in vivo during physiological activities and recovers from deformation within 90 min after loading. Whereas cartilage deformation appears to become less with increasing age, sex and physical training status do not seem to affect in vivo deformational behaviour. There is now good evidence that cartilage undergoes some type of atrophy (thinning) under reduced loading conditions, such as with postoperative immobilization and paraplegia. However, increased loading (as encountered by elite athletes) does not appear to be associated with increased average cartilage thickness. Findings in twins, however, suggest a strong genetic contribution to cartilage morphology. Potential reasons for the inability of cartilage to adapt to mechanical stimuli include a lack of evolutionary pressure and a decoupling of mechanical competence and tissue mass.

Spinal cord lesions shrink peripersonal space around the feet, passive mobilization of paraplegic limbs restores it

PubMed Central

Scandola, Michele; Aglioti, Salvatore Maria; Bonente, Claudio; Avesani, Renato; Moro, Valentina

2016-01-01

Peripersonal space (PPS) is the space surrounding us within which we interact with objects. PPS may be modulated by actions (e.g. when using tools) or sense of ownership (e.g. over a rubber hand). Indeed, intense and/or prolonged use of a tool may induce a sense of ownership over it. Conversely, inducing ownership over a rubber hand may activate brain regions involved in motor control. However, the extent to which PPS is modulated by action-dependent or ownership-dependent mechanisms remains unclear. Here, we explored the PPS around the feet and the sense of ownership over lower limbs in people with Paraplegia following Complete spinal cord Lesions (PCL) and in healthy subjects. PCL people can move their upper body but have lost all sensory-motor functions in their lower body (e.g. lower limbs). We tested whether PPS alterations reflect the topographical representations of various body parts. We found that the PPS around the feet was impaired in PCL who however had a normal representation of the PPS around the hands. Significantly, passive mobilization of paraplegic limbs restored the PPS around the feet suggesting that activating action representations in PCL brings about short-term changes of PPS that may thus be more plastic than previously believed. PMID:27049439

Real-time strap pressure sensor system for powered exoskeletons.

PubMed

Tamez-Duque, Jesús; Cobian-Ugalde, Rebeca; Kilicarslan, Atilla; Venkatakrishnan, Anusha; Soto, Rogelio; Contreras-Vidal, Jose Luis

2015-02-16

Assistive and rehabilitative powered exoskeletons for spinal cord injury (SCI) and stroke subjects have recently reached the clinic. Proper tension and joint alignment are critical to ensuring safety. Challenges still exist in adjustment and fitting, with most current systems depending on personnel experience for appropriate individual fastening. Paraplegia and tetraplegia patients using these devices have impaired sensation and cannot signal if straps are uncomfortable or painful. Excessive pressure and blood-flow restriction can lead to skin ulcers, necrotic tissue and infections. Tension must be just enough to prevent slipping and maintain posture. Research in pressure dynamics is extensive for wheelchairs and mattresses, but little research has been done on exoskeleton straps. We present a system to monitor pressure exerted by physical human-machine interfaces and provide data about levels of skin/body pressure in fastening straps. The system consists of sensing arrays, signal processing hardware with wireless transmission, and an interactive GUI. For validation, a lower-body powered exoskeleton carrying the full weight of users was used. Experimental trials were conducted with one SCI and one able-bodied subject. The system can help prevent skin injuries related to excessive pressure in mobility-impaired patients using powered exoskeletons, supporting functionality, independence and better overall quality of life.

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

PubMed Central

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

2014-01-01

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

[Surgical coverage technics of pressure sores and their outcomes].

PubMed

Bilkay, Ufuk; Helvaci, Evren; Tokat, Cenk; Ozek, Cüneyt; Akin, Yalçin

2006-04-01

We reviewed the outcome of 66 patients with 100 pressure sores between 1984 and 2002. In the current study, 100 pressure sores in 66 patients (45 male, 21 female; mean age 39.4; range 13 to 80 years) who underwent surgical repair of pressure sores reconstructed using myocutaneous or fasciocutaneous flaps, skin grafts, excision and closure. The risk factors for pressure sores included acute trauma-induced spinal cord injury in 40 (61%) patients with paraplegia and in 5 (7%) patients with quadriplegia; congenital spina bifida and multiple sclerosis in 7 (11%) patients and prolonged immobilization in 14 (21 patients) patients. We achieved an overall pressure sore recurrence rate of 22% and overall patient recurrence of 24% in a-3-year follow-up. The recurrence rates according to anatomic sites; 23% (10 of 43) for the ischial pressure sore, sacral 21% (8 of 37), and trochanteric 20% (4 of 20). Fasciocutaneous and myocutaneous flap reconstructions were the most durable, as they were associated with 17% (6 of 34) and 12% recurrence rates (5 of 39). To reduce the recurrence rates the authors advocate the use of myocutaneous and fasciocutaneous flaps instead of skin grafts or direct closure for the coverage of pressure sores.

A comparison of hydrostatic weighing and air displacement plethysmography in adults with spinal cord injury.

PubMed

Clasey, Jody L; Gater, David R

2005-11-01

To compare (1) total body volume (V(b)) and density (D(b)) measurements obtained by hydrostatic weighing (HW) and air displacement plethysmography (ADP) in adults with spinal cord injury (SCI); (2) measured and predicted thoracic gas volume (V(TG)); and (3) differences in percentage of fat measurements using ADP-obtained D(b) and HW-obtained D(b) measures that were interchanged in a 4-compartment body composition model (4-comp %fat). Twenty adults with SCI underwent ADP and V(TG), and HW testing. In a subgroup (n=13) of subjects, 4-comp %fat procedures were computed. Research laboratories in a university setting. Twenty adults with SCI below the T3 vertebrae and motor complete paraplegia. Not applicable. Statistical analyses, including determination of group mean differences, shared variance, total error, and 95% confidence intervals. The 2 methods yielded small yet significantly different V(b) and D(b). The groups' mean V(TG) did not differ significantly, but the large relative differences indicated an unacceptable amount of individual error. When the 4-comp %fat measurements were compared, there was a trend toward significant differences (P=.08). ADP is a valid alternative method of determining the V(b) and D(b) in adults with SCI; however, the predicted V(TG) should be used with caution.

Comparative shoulder kinematics during free standing, standing depression lifts and daily functional activities in persons with paraplegia: considerations for shoulder health.

PubMed

Riek, L M; Ludewig, P M; Nawoczenski, D A

2008-05-01

Case series; nonparametric repeated-measures analysis of variance. To compare and contrast three-dimensional shoulder kinematics during frequently utilized upper extremity weight-bearing activities (standing depression lifts used in brace walking, weight-relief raises, transfers) and postures (sitting rest, standing in a frame) in spinal cord injury (SCI). Movement Analysis Laboratory, Department of Physical Therapy, Ithaca College, Rochester, NY, USA. Three female and two male subjects (39.2+/-6.1 years old) at least 12 months post-SCI (14.6+/-6.7 years old), SCI distal to T2 and with an ASIA score of A. The Flock of Birds magnetic tracking device was used to measure three-dimensional positions of the scapula, humerus and thorax during various activities. Standing in a frame resulted in significantly less scapular anterior tilt (AT) and greater glenohumeral external rotation (GHER) than standing depression lifts and weight-relief raises. Standing frame posture offers the most favorable shoulder joint positions (less scapular AT and greater GHER) when compared to sitting rest posture, weight-relief raises, transfers and standing depression lifts. Knowledge of kinematic patterns associated with each activity is an essential first step to understanding the potential impact on shoulder health. Choosing specific activities or modifying techniques within functional activities that promote favorable shoulder positions may preserve long-term shoulder health.

ALS5/SPG11/KIAA1840 mutations cause autosomal recessive axonal Charcot-Marie-Tooth disease.

PubMed

Montecchiani, Celeste; Pedace, Lucia; Lo Giudice, Temistocle; Casella, Antonella; Mearini, Marzia; Gaudiello, Fabrizio; Pedroso, José L; Terracciano, Chiara; Caltagirone, Carlo; Massa, Roberto; St George-Hyslop, Peter H; Barsottini, Orlando G P; Kawarai, Toshitaka; Orlacchio, Antonio

2016-01-01

Charcot-Marie-Tooth disease is a group of hereditary peripheral neuropathies that share clinical characteristics of progressive distal muscle weakness and atrophy, foot deformities, distal sensory loss, as well as diminished tendon reflexes. Hundreds of causative DNA changes have been found, but much of the genetic basis of the disease is still unexplained. Mutations in the ALS5/SPG11/KIAA1840 gene are a frequent cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum and peripheral axonal neuropathy, and account for ∼ 40% of autosomal recessive juvenile amyotrophic lateral sclerosis. The overlap of axonal Charcot-Marie-Tooth disease with both diseases, as well as the common autosomal recessive inheritance pattern of thin corpus callosum and axonal Charcot-Marie-Tooth disease in three related patients, prompted us to analyse the ALS5/SPG11/KIAA1840 gene in affected individuals with autosomal recessive axonal Charcot-Marie-Tooth disease. We investigated 28 unrelated families with autosomal recessive axonal Charcot-Marie-Tooth disease defined by clinical, electrophysiological, as well as pathological evaluation. Besides, we screened for all the known genes related to axonal autosomal recessive Charcot-Marie-Tooth disease (CMT2A2/HMSN2A2/MFN2, CMT2B1/LMNA, CMT2B2/MED25, CMT2B5/NEFL, ARCMT2F/dHMN2B/HSPB1, CMT2K/GDAP1, CMT2P/LRSAM1, CMT2R/TRIM2, CMT2S/IGHMBP2, CMT2T/HSJ1, CMTRID/COX6A1, ARAN-NM/HINT and GAN/GAN), for the genes related to autosomal recessive hereditary spastic paraplegia with thin corpus callosum and axonal peripheral neuropathy (SPG7/PGN, SPG15/ZFYVE26, SPG21/ACP33, SPG35/FA2H, SPG46/GBA2, SPG55/C12orf65 and SPG56/CYP2U1), as well as for the causative gene of peripheral neuropathy with or without agenesis of the corpus callosum (SLC12A6). Mitochondrial disorders related to Charcot-Marie-Tooth disease type 2 were also excluded by sequencing POLG and TYMP genes. An additional locus for autosomal recessive Charcot

ALS5/SPG11/ KIAA1840 mutations cause autosomal recessive axonal Charcot–Marie–Tooth disease

PubMed Central

Montecchiani, Celeste; Pedace, Lucia; Lo Giudice, Temistocle; Casella, Antonella; Mearini, Marzia; Gaudiello, Fabrizio; Pedroso, José L.; Terracciano, Chiara; Caltagirone, Carlo; Massa, Roberto; St George-Hyslop, Peter H.; Barsottini, Orlando G. P.; Kawarai, Toshitaka

2016-01-01

Abstract Charcot–Marie–Tooth disease is a group of hereditary peripheral neuropathies that share clinical characteristics of progressive distal muscle weakness and atrophy, foot deformities, distal sensory loss, as well as diminished tendon reflexes. Hundreds of causative DNA changes have been found, but much of the genetic basis of the disease is still unexplained. Mutations in the ALS5/SPG11/ KIAA1840 gene are a frequent cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum and peripheral axonal neuropathy, and account for ∼40% of autosomal recessive juvenile amyotrophic lateral sclerosis. The overlap of axonal Charcot–Marie–Tooth disease with both diseases, as well as the common autosomal recessive inheritance pattern of thin corpus callosum and axonal Charcot–Marie–Tooth disease in three related patients, prompted us to analyse the ALS5/SPG11/ KIAA1840 gene in affected individuals with autosomal recessive axonal Charcot–Marie–Tooth disease. We investigated 28 unrelated families with autosomal recessive axonal Charcot–Marie–Tooth disease defined by clinical, electrophysiological, as well as pathological evaluation. Besides, we screened for all the known genes related to axonal autosomal recessive Charcot–Marie-Tooth disease (CMT2A2/HMSN2A2/ MFN2 , CMT2B1/ LMNA , CMT2B2/ MED25 , CMT2B5/ NEFL , ARCMT2F/dHMN2B/ HSPB1 , CMT2K/ GDAP1 , CMT2P/ LRSAM1 , CMT2R/ TRIM2 , CMT2S/ IGHMBP2 , CMT2T/ HSJ1 , CMTRID/ COX6A1 , ARAN-NM/ HINT and GAN/ GAN ), for the genes related to autosomal recessive hereditary spastic paraplegia with thin corpus callosum and axonal peripheral neuropathy (SPG7/ PGN , SPG15/ ZFYVE26, SPG21/ ACP33 , SPG35/ FA2H , SPG46/ GBA2 , SPG55/ C12orf65 and SPG56/ CYP2U1 ), as well as for the causative gene of peripheral neuropathy with or without agenesis of the corpus callosum ( SLC12A6 ) . Mitochondrial disorders related to Charcot–Marie–Tooth disease type 2 were also excluded by sequencing POLG and

Identification of IFRD1 variant in a Han Chinese family with autosomal dominant hereditary spastic paraplegia associated with peripheral neuropathy and ataxia.

PubMed

Lin, Pengfei; Zhang, Dong; Xu, Guangrun; Yan, Chuanzhu

2018-04-01

Spinocerebellar ataxias (SCAs) are a group of autosomal dominant, clinically heterogeneous neurodegenerative disorders. SCA18 is a rare autosomal dominant sensory/motor neuropathy with ataxia (OMIM#607458) associated with a single missense variant c.514 A>G in the interferon related developmental regulator 1 (IFRD1) gene previously reported in a five-generation American family of Irish origin. However, to date, there have been no other reports of the IFRD1 mutation to confirm its role in SCA. Here, we report a Han Chinese family with SCA18; the family members presented with a slowly progressing gait ataxia, pyramidal tract signs, and peripheral neuropathy. We identified a missense variant (c.514 A>G, p.I172V) in IFRD1 gene in the family using targeted next-generation sequencing and Sanger direct sequencing with specific primers. Our results suggest that the IFRD1 gene may be the causative allele for SCA18.

The myelin proteolipid DMα in fishes.

PubMed

Brösamle, Christian

2010-05-01

Vertebrate myelin membranes are compacted and held in close apposition by three structural proteins of myelin, myelin basic protein, myelin protein zero (MPZ) and myelin proteolipid protein (PLP1/DMalpha). PLP1/DMalpha is considered to function as a scaffolding protein and play a role in intracellular trafficking in oligodendrocytes. In humans, point mutations, duplications or deletions of PLP1 are associated with Pelizaeus-Merzbacher disease and spastic paraplegia Type 2. PLP1 is highly conserved between mammals, but less so in lower vertebrates. This has led some researchers to question whether certain fish species express PLP1 orthologues at all, and to suggest that the function of PLP1/DMalpha in the central nervous system (CNS) may have been taken over by MPZ. Here, we review the evidence for the conservation of orthologues of PLP1/DMalpha in actinopterygian fishes and provide a comparison of currently available sequence data across 17 fish species. Our analysis demonstrates that orthologues of PLP1/DMalpha have been retained and are functionally expressed in many, if not all, extant species of bony fish. Many of the amino acids that, when mutated, are associated with severe CNS pathology are conserved in teleosts, demonstrating conservation of essential functions and justifying the development of novel disease models in species such as the zebrafish.

Intracellular and extracellular expression of the major inducible 70kDa heat shock protein in experimental ischemia-reperfusion injury of the spinal cord.

PubMed

Awad, Hamdy; Suntres, Zacharias; Heijmans, John; Smeak, Daniel; Bergdall-Costell, Valerie; Christofi, Fievos L; Magro, Cynthia; Oglesbee, Michael

2008-08-01

Inflammatory responses exacerbate ischemia-reperfusion (IR) injury of spinal cord, although understanding of mediators is incomplete. The major inducible 70kDa heat shock protein (hsp70) is induced by ischemia and extracellular hsp70 (e-hsp70) can modulate inflammatory responses, but there is no published information regarding e-hsp70 levels in the cerebrospinal fluid (CSF) or serum as part of any neurological disease state save trauma. The present work addresses this deficiency by examining e-hsp70 in serum and CSF of dogs in an experimental model of spinal cord IR injury. IR injury of spinal cord caused hind limb paraplegia within 2-3 h that was correlated to lumbosacral poliomalacia with T cell infiltrates at 3 d post-ischemia. In this context, we showed a 5.2-fold elevation of e-hsp70 in CSF that was induced by ischemia and was sustained for the following 3 d observation interval. Plasma e-hsp70 levels were unaffected by IR injury, indicating e-hsp70 release from within the central nervous system. A putative source of this e-hsp70 was ependymal cells in the ischemic penumbra, based upon elevated i-hsp70 levels detected within these cells. Results warrant further investigation of e-hsp70's potential to modulate spinal cord IR injury.

Assessment of passive knee stiffness and viscosity in individuals with spinal cord injury using pendulum test.

PubMed

Joghtaei, Mahmoud; Arab, Amir Massoud; Hashemi-Nasl, Hamed; Joghataei, Mohammad Taghi; Tokhi, Mohammad Osman

2015-03-01

Stiffness and viscosity represent passive resistances to joint motion related with the structural properties of the joint tissue and of the musculotendinous complex. Both parameters can be affected in patients with spinal cord injury (SCI). The purpose of this study was to measure passive knee stiffness and viscosity in patients with SCI with paraplegia and healthy subjects using Wartenberg pendulum test. Non-experimental, cross-sectional, case-control design. An outpatient physical therapy clinic, University of social welfare and Rehabilitation Science, Iran. A sample of convenience sample of 30 subjects participated in the study. Subjects were categorized into two groups: individuals with paraplegic SCI (n = 15, age: 34.60 ± 9.18 years) and 15 able-bodied individuals as control group (n = 15, age: 30.66 ± 11.13 years). Not applicable. Passive pendulum test of Wartenberg was used to measure passive viscous-elastic parameters of the knee (stiffness, viscosity) in all subjects. Statistical analysis (independent t-test) revealed significant difference in the joint stiffness between healthy subjects and those with paraplegic SCI (P = 0.01). However, no significant difference was found in the viscosity between two groups (P = 0.17). Except for first peak flexion angle, all other displacement kinematic parameters exhibited no statistically significant difference between normal subjects and subjects with SCI. Patients with SCI have significantly greater joint stiffness compared to able-bodied subjects.

Inverted Pendulum Standing Apparatus for Investigating Closed-Loop Control of Ankle Joint Muscle Contractions during Functional Electrical Stimulation.

PubMed

Tan, John F; Masani, Kei; Vette, Albert H; Zariffa, José; Robinson, Mark; Lynch, Cheryl; Popovic, Milos R

2014-01-01

The restoration of arm-free standing in individuals with paraplegia can be facilitated via functional electrical stimulation (FES). In developing adequate control strategies for FES systems, it remains challenging to test the performance of a particular control scheme on human subjects. In this study, we propose a testing platform for developing effective control strategies for a closed-loop FES system for standing. The Inverted Pendulum Standing Apparatus (IPSA) is a mechanical inverted pendulum, whose angular position is determined by the subject's ankle joint angle as controlled by the FES system while having the subject's body fixed in a standing frame. This approach provides a setup that is safe, prevents falling, and enables a research and design team to rigorously test various closed-loop controlled FES systems applied to the ankle joints. To demonstrate the feasibility of using the IPSA, we conducted a case series that employed the device for studying FES closed-loop controllers for regulating ankle joint kinematics during standing. The utilized FES system stimulated, in able-bodied volunteers, the plantarflexors as they prevent toppling during standing. Four different conditions were compared, and we were able to show unique performance of each condition using the IPSA. We concluded that the IPSA is a useful tool for developing and testing closed-loop controlled FES systems for regulating ankle joint position during standing.

Inverted Pendulum Standing Apparatus for Investigating Closed-Loop Control of Ankle Joint Muscle Contractions during Functional Electrical Stimulation

PubMed Central

Tan, John F.; Masani, Kei; Vette, Albert H.; Zariffa, José; Robinson, Mark; Lynch, Cheryl; Popovic, Milos R.

2014-01-01

The restoration of arm-free standing in individuals with paraplegia can be facilitated via functional electrical stimulation (FES). In developing adequate control strategies for FES systems, it remains challenging to test the performance of a particular control scheme on human subjects. In this study, we propose a testing platform for developing effective control strategies for a closed-loop FES system for standing. The Inverted Pendulum Standing Apparatus (IPSA) is a mechanical inverted pendulum, whose angular position is determined by the subject's ankle joint angle as controlled by the FES system while having the subject's body fixed in a standing frame. This approach provides a setup that is safe, prevents falling, and enables a research and design team to rigorously test various closed-loop controlled FES systems applied to the ankle joints. To demonstrate the feasibility of using the IPSA, we conducted a case series that employed the device for studying FES closed-loop controllers for regulating ankle joint kinematics during standing. The utilized FES system stimulated, in able-bodied volunteers, the plantarflexors as they prevent toppling during standing. Four different conditions were compared, and we were able to show unique performance of each condition using the IPSA. We concluded that the IPSA is a useful tool for developing and testing closed-loop controlled FES systems for regulating ankle joint position during standing. PMID:27350992

Early Experiences with the Endovascular Repair of Ruptured Descending Thoracic Aortic Aneurysm

PubMed Central

Choi, Jae-Sung; Oh, Se Jin; Sung, Yong Won; Moon, Hyun Jong; Lee, Jung Sang

2016-01-01

Background The aim of this study was to report our early experiences with the endovascular repair of ruptured descending thoracic aortic aneurysms (rDTAAs), which are a rare and life-threatening condition. Methods Among 42 patients who underwent thoracic endovascular aortic repair (TEVAR) between October 2010 and September 2015, five patients (11.9%) suffered an rDTAA. Results The mean age was 72.4±5.1 years, and all patients were male. Hemoptysis and hemothorax were present in three (60%) and two (40%) patients, respectively. Hypovolemic shock was noted in three patients who underwent emergency operations. A hybrid operation was performed in three patients. The mean operative time was 269.8±72.3 minutes. The mean total length of aortic coverage was 186.0±49.2 mm. No 30-day mortality occurred. Stroke, delirium, and atrial fibrillation were observed in one patient each. Paraplegia did not occur. Endoleak was found in two patients (40%), one of whom underwent an early and successful reintervention. During the mean follow-up period of 16.8±14.8 months, two patients died; one cause of death was a persistent type 1 endoleak and the other cause was unknown. Conclusion TEVAR for rDTAA was associated with favorable early mortality and morbidity outcomes. However, early reintervention should be considered if persistent endoleak occurs. PMID:27064672

Targeted High-Throughput Sequencing Identifies Mutations in atlastin-1 as a Cause of Hereditary Sensory Neuropathy Type I

PubMed Central

Guelly, Christian; Zhu, Peng-Peng; Leonardis, Lea; Papić, Lea; Zidar, Janez; Schabhüttl, Maria; Strohmaier, Heimo; Weis, Joachim; Strom, Tim M.; Baets, Jonathan; Willems, Jan; De Jonghe, Peter; Reilly, Mary M.; Fröhlich, Eleonore; Hatz, Martina; Trajanoski, Slave; Pieber, Thomas R.; Janecke, Andreas R.; Blackstone, Craig; Auer-Grumbach, Michaela

2011-01-01

Hereditary sensory neuropathy type I (HSN I) is an axonal form of autosomal-dominant hereditary motor and sensory neuropathy distinguished by prominent sensory loss that leads to painless injuries. Unrecognized, these can result in delayed wound healing and osteomyelitis, necessitating distal amputations. To elucidate the genetic basis of an HSN I subtype in a family in which mutations in the few known HSN I genes had been excluded, we employed massive parallel exon sequencing of the 14.3 Mb disease interval on chromosome 14q. We detected a missense mutation (c.1065C>A, p.Asn355Lys) in atlastin-1 (ATL1), a gene that is known to be mutated in early-onset hereditary spastic paraplegia SPG3A and that encodes the large dynamin-related GTPase atlastin-1. The mutant protein exhibited reduced GTPase activity and prominently disrupted ER network morphology when expressed in COS7 cells, strongly supporting pathogenicity. An expanded screen in 115 additional HSN I patients identified two further dominant ATL1 mutations (c.196G>C [p.Glu66Gln] and c.976 delG [p.Val326TrpfsX8]). This study highlights an unexpected major role for atlastin-1 in the function of sensory neurons and identifies HSN I and SPG3A as allelic disorders. PMID:21194679

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

PubMed Central

Chang, Jaerak; Blackstone, Craig

2014-01-01

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

Epidural steroid injections: update on efficacy, safety, and newer medications for injection.

PubMed

Kozlov, N; Benzon, H T; Malik, K

2015-08-01

The best evidence for epidural injection appears to be in the setting of radicular pain with epidural steroid and non-steroid injections more efficacious than non-epidural injections. Studies showed the efficacy of non-particulate steroid to approach the efficacy of particulate steroid and very limited comparisons demonstrated no significant difference between epidural steroid and epidural non-steroid (local anesthetic) injection. Preliminary studies evaluating epidural injection of disease modifying anti-rheumatic drugs such etanercept and tocilizumab showed conflicting results and had significant limitations. Randomized studies support better efficacy of transforaminal injection due to greater incidence of ventral epidural spread of injectate when compared to interlaminar injection. Thus, the transforaminal approach is recommended when unilateral radicular pain is limited to one nerve root. However, the transforaminal approach is associated with greater incidence of central nervous system injury, including paraplegia, attributed to embolization of the particulate steroid. Recent studies showed that non-particulate steroids potentially last as long as particulate steroids. Therefore non-particulate steroid should be used in initial transforaminal epidural injection. Future studies should look into the role of adjunct diagnostic aids, including digital subtraction angiography, in detecting intravascular injection and the ideal site of needle placement, whether it is the safe triangle or the triangle of Kambin. Finally, the role of epidural disease -modifying antirheumatic drugs in the management of back pain needs to be better elucidated.

Mutation analysis of genes within the dynactin complex in a cohort of hereditary peripheral neuropathies.

PubMed

Tey, S; Ahmad-Annuar, A; Drew, A P; Shahrizaila, N; Nicholson, G A; Kennerson, M L

2016-08-01

The cytoplasmic dynein-dynactin genes are attractive candidates for neurodegenerative disorders given their functional role in retrograde transport along neurons. The cytoplasmic dynein heavy chain (DYNC1H1) gene has been implicated in various neurodegenerative disorders, and dynactin 1 (DCTN1) genes have been implicated in a wide spectrum of disorders including motor neuron disease, Parkinson's disease, spinobulbar muscular atrophy and hereditary spastic paraplegia. However, the involvement of other dynactin genes with inherited peripheral neuropathies (IPN) namely, hereditary sensory neuropathy, hereditary motor neuropathy and Charcot-Marie-Tooth disease is under reported. We screened eight genes; DCTN1-6 and ACTR1A and ACTR1B in 136 IPN patients using whole-exome sequencing and high-resolution melt (HRM) analysis. Eight non-synonymous variants (including one novel variant) and three synonymous variants were identified. Four variants have been reported previously in other studies, however segregation analysis within family members excluded them from causing IPN in these families. No variants of disease significance were identified in this study suggesting the dynactin genes are unlikely to be a common cause of IPNs. However, with the ease of querying gene variants from exome data, these genes remain worthwhile candidates to assess unsolved IPN families for variants that may affect the function of the proteins. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Spatacsin and spastizin act in the same pathway required for proper spinal motor neuron axon outgrowth in zebrafish.

PubMed

Martin, Elodie; Yanicostas, Constantin; Rastetter, Agnès; Alavi Naini, Seyedeh Maryam; Maouedj, Alissia; Kabashi, Edor; Rivaud-Péchoux, Sophie; Brice, Alexis; Stevanin, Giovanni; Soussi-Yanicostas, Nadia

2012-12-01

Hereditary spastic paraplegias (HSPs) are rare neurological conditions caused by degeneration of the long axons of the cerebrospinal tracts, leading to locomotor impairment and additional neurological symptoms. There are more than 40 different causative genes, 24 of which have been identified, including SPG11 and SPG15 mutated in complex clinical forms. Since the vast majority of the causative mutations lead to loss of function of the corresponding proteins, we made use of morpholino-oligonucleotide (MO)-mediated gene knock-down to generate zebrafish models of both SPG11 and SPG15 and determine how invalidation of the causative genes (zspg11 and zspg15) during development might contribute to the disease. Micro-injection of MOs targeting each gene caused locomotor impairment and abnormal branching of spinal cord motor neurons at the neuromuscular junction. More severe phenotypes with abnormal tail developments were also seen. Moreover, partial depletion of both proteins at sub-phenotypic levels resulted in the same phenotypes, suggesting for the first time, in vivo, a genetic interaction between these genes. In conclusion, the zebrafish orthologues of the SPG11 and SPG15 genes are important for proper development of the axons of spinal motor neurons and likely act in a common pathway to promote their proper path finding towards the neuromuscular junction. Copyright © 2012 Elsevier Inc. All rights reserved.

Nonclassic presentation of pheochromocytoma: difficulties in diagnosis and management of the normotensive patient.

PubMed

Gonzalez-Pantaleon, Adalberto D; Simon, Barbara

2008-01-01

To report an unusual presentation of pheochromocytoma along with challenges in diagnosis and management. We report a clinical case history and describe diagnostic methods and pitfalls. The preoperative medical preparation in a normotensive patient is described. A 33-year-old man fell off a ladder, resulting in C6 paraplegia. After C7-T1 laminectomy, he was transferred to a rehabilitation center where he reported lightheadedness, shortness of breath, and chest pain during therapy sessions. A left adrenal mass was incidentally discovered during the workup to rule out a pulmonary embolism. He reported no history of hypertension, and no elevated blood pressure readings had been documented. Magnetic resonance imaging of the adrenal glands showed a well-defined left adrenal mass measuring 3.9 x 3.2 x 3.3 cm, which was hyperintense on T2-weighted images. Twenty-four hour urinary catecholamine concentrations were unremarkable; urinary metanephrines were markedly elevated. During hospital admission, blood pressure was in the low to normotensive range, requiring a cautious approach to alpha-adrenergic blockade and surgical preparation. He under-went uneventful laparoscopic left adrenalectomy; surgical pathology was consistent with pheochromocytoma. This case illustrates a nonclassic presentation of pheochromocytoma and demonstrates that urinary catecholamines alone are not sufficient for a biochemical diagnosis of large pheochromocytomas. Preoperative preparation in normotensive patients can be achieved with alpha-adrenergic blockade, hydration, and liberal salt intake.

Stigma of visible and invisible chronic conditions.

PubMed

Joachim, G; Acorn, S

2000-07-01

Nurses deliver care to people with various forms of chronic illnesses and conditions. Some chronic conditions, such as paraplegia, are visible while others, such as diabetes, are invisible. Still others, such as multiple sclerosis, are both visible and invisible. Having a chronic illness or condition and being different from the general population subjects a person to possible stigmatization by those who do not have the illness. Coping with stigma involves a variety of strategies including the decision about whether to disclose the condition and suffer further stigma, or attempt to conceal the condition or aspects of the condition and pass for normal. We present a beginning framework that describes the relationship between the elements of stigma and the decision to disclose or hide a chronic condition based on its visibility or invisibility. The specific aims were to combine the results from a meta-study on qualitative research with a review of the quantitative literature, then develop a theoretical framework. Although an understanding of how patients cope with stigmatizing conditions is essential for nurses who aim to deliver comprehensive individualized patient care, there is little current literature on this subject. The relationship between visibility and invisibility and disclosure and non-disclosure remains poorly understood. A framework to facilitate a deeper understanding of the dynamics of chronic illnesses and conditions may prove useful for practice.

Sexual Functioning in Men Living with a Spinal Cord Injury-A Narrative Literature Review.

PubMed

Sunilkumar, M M; Boston, Patricia; Rajagopal, M R

2015-01-01

Sexual dysfunction is a major concern for Indian men living with a spinal cord injury. To examine the literature related to sexuality traumatic cord injury and its impact on sexual functioning. Databases using Cumulative Index to Nursing and Allied Health Literature (CINAHL) 2000-2012, Medline 1989-2012, Applied Social Sciences Index and Abstracts (ASSIA) 1989-2012 and Google Scholar were the search engines used used for literature review. The search yielded a total of 457 articles and only 75 of them were found relevant. The minimum number of articles required to meet the inclusion criteria for this review was 25-30 articles. Out of the 75 articles, 33 were considered relevant or related to the topic of sexual functioning, spinal cord injury, and paraplegia. Six areas were identified: Sexual stigmatization, physiological barriers to sexual satisfaction, clinical aspects of sexual functioning, biomedical approaches to sexual dysfunction, partner satisfaction, and lack of accessibility to sexual education. Spinal cord injury and sexual functioning affects a large segment of the male Indian population, yet most current research focuses on quantitative measurement with the emphasis on ejaculatory dysfunction, orgasm impairment, incontinence, and other physiological dysfunction. Further research is needed to address the subjective accounts of patients themselves with respect to the emotional and social impact of sexual disability. This would help to identify the best possible outcomes for both treatment and rehabilitation.

Acute spontaneous thoracic epidural hematoma, triggered by weight-lifting training, in a retired sportsman: case report and literature review.

PubMed

Anghelescu, Aurelian; Rasina, Alin

2017-01-01

Spontaneous spinal epidural hematoma (SSEH) is a rare clinical entity, most often with acute symptomatic spinal cord compression and potentially permanent neurologic deficits. SSEH usually has surgical solutions and a good outcome after hematoma evacuation. A 61-year-old professional weight-lifting coach presented to the emergency department with sudden back pain, rapidly progressive paraparesis, and neurogenic bladder, after an intense training, 5 h previously. Magnetic resonance imaging revealed a ventral thoracic epidural hematoma with significant compression at Th3-Th6. Surgical procedure was performed within the first 12 h: decompressive laminectomy from Th3 to Th7 vertebral levels and near total epidural hematoma removal. The patient improved rapidly from Th5 AIS-C to Th7 AIS-D paraplegia with independent ambulation, after the intervention. The rehabilitation program led to further improvement of the neurologic deficits and a favorable outcome, to AIS-E. Weightlifting has been reported as SSEH precipitating factor in young athletes. Our case is unique however, because the athlete was older. The underlying pathophysiological mechanism is represented by intravenous pressure changes and bleeding of the epidural venous plexus during a prolonged Valsalva maneuver, induced by strenuous, repeated efforts. Spondylosis, hypertension, and low doses of aspirin were incriminated as risk factors for SSEH. Prompt diagnosis, emergent decompressive intervention, early rehabilitation, and secondary prophylaxis were essential for a good outcome.

Corticosteroid Treatment for Metastatic Spinal Cord Compression: A Review.

PubMed

Skeoch, Gordon D; Tobin, Matthew K; Khan, Sajeel; Linninger, Andreas A; Mehta, Ankit I

2017-05-01

Narrative review. Metastatic spinal cord compression (MSCC) is a very frequent complication among cancer patients. Presenting commonly as nocturnal back pain, MSCC typically progresses to lower extremity paresis, loss of ambulatory capabilities, and paraplegia. In addition to standard treatment modalities, corticosteroid administration has been utilized in preclinical and clinical settings as adjunctive therapy to reduce local spinal cord edema and improve clinical symptoms. This article serves as a review of existing literature regarding corticosteroid management of MSCC and seeks to provide potential avenues of research on the topic. A literature search was performed using PubMed in order to consolidate existing information regarding dexamethasone treatment of MSCC. Of all search results, 7 articles are reviewed, establishing the current understanding of metastatic spine disease and dexamethasone treatment in both animal models and in clinical trials. Treatment with high-dose corticosteroids is associated with an increased rate of potentially serious systemic side effects. For this reason, definitive guidelines for the use of dexamethasone in the management of MSCC are unavailable. It is still unclear what role dexamethasone plays in the treatment of MSCC. It is evident that new, more localizable therapies may provide more acceptable treatment strategies using corticosteroids. Looking forward, the potential for more targeted, localized application of the steroid through the use of nanotechnology would decrease the incidence of adverse effects while maintaining the drug's efficacy.

Visual perception and appraisal of persons with impairments: a randomised controlled field experiment using photo elicitation.

PubMed

Reinhardt, Jan Dietrich; Ballert, Carolina Saskia; Fellinghauer, Bernd; Lötscher, Alexander; Gradinger, Felix; Hilfiker, Roger; Graf, Sibylle; Stucki, Gerold

2011-01-01

Visual cues from persons with impairments may trigger stereotypical generalisations that lead to prejudice and discrimination. The main objective of this pilot study is to examine whether visual stimuli of impairment activate latent prejudice against disability and whether this connection can be counteracted with priming strategies. In a field experiment, participants were asked to rate photographs showing models with mental impairments, wheelchair users with paraplegia, and persons without any visible impairment. Participants should appraise the models with regard to several features (e.g. communicativeness, intelligence). One hundred participants rated 12 photo models yielding a total of 1183 observations. One group of participants was primed with a cover story introducing visual perception of impairment as the study's gist, while controls received neutral information. Photo models with mental impairments were rated lowest and models without visible impairment highest. In participants who did not have prior contacts with persons with impairments, priming led to a levelling of scores of models with and without impairment. Prior contacts with persons with impairments created similar effects as the priming. Unexpectedly, a pattern of converse double discrimination to the disadvantage of men with mental impairments was revealed. Signs of stereotypical processing of visual cues of impairment have been found in participants of the Swiss general population. Personal contact with persons with impairments as well as priming participants seems to reduce stereotyping.

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

NASA Astrophysics Data System (ADS)

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

2012-07-01

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 α/β-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.