Science.gov

Sample records for paraplegia

  1. [Paraplegia after acute thoracic pain].

    PubMed

    Kleinfeldt, T; Rehders, T C; Raab, U; Ince, H; Nienaber, C A

    2006-01-01

    Severe neurological complications such as spinal cord ischemia and paraplegia can occur with acute aortic dissection in 3%. This report describes the case of a 67-year old patient with delayed onset of paraplegia 8 h after acute chest pain. Contrast enhanced computed tomography documented Stanford type B dissection confined to a short segment of the aorta. Furthermore, magnetic resonance imaging revealed intraspinal intraaxial hematoma of the myelon, which can explain the neurological complication. This case shows that even in the scenario of acute aortic dissection other mechanisms for paraplegia may be operational than dissection itself. Paraplegia in this case results from intramyelon bleeding preceding aortic dissection. PMID:16341679

  2. Genetics Home Reference: Spastic paraplegia type 8

    MedlinePLUS

    ... interact with the structural framework inside cells (the cytoskeleton) and may attach (bind) to other proteins. KIAA0196 ... spastic paraplegia type 8? autosomal ; autosomal dominant ; cell ; cytoskeleton ; expressed ; gene ; hereditary ; inherited ; mutation ; nervous system ; paraplegia ; ...

  3. Genetics Home Reference: Spastic paraplegia type 11

    MedlinePLUS

    ... system ; neuropathy ; nystagmus ; paraplegia ; peripheral ; peripheral nervous system ; pes cavus ; prevalence ; protein ; recessive ; scoliosis ; sensory cells ; sensory neuropathy ; spasticity ; tissue ; ...

  4. Problems and perspectives in paraplegia

    NASA Technical Reports Server (NTRS)

    Nashold, B.

    1974-01-01

    Improved clinical treatment of the paraplegic, developed during World War II, has reduced the overall mortality rate from close to 100 percent to 30 percent. Despite major clinical improvements, mainly in treatment of the acute phase of paraplegia, and despite greater rehabilitation efforts, the spinal injured person is never rehabilitated in the sense that he reaches an optimum and stays there. He is always exposed to the constant threat of deterioration of his physiological, sociological, and psychological state.

  5. Genetics Home Reference: Spastic paraplegia type 4

    MedlinePLUS

    ... that make up the cell's structural framework (the cytoskeleton). Microtubules are also involved in transporting cell components ... type 4? autosomal ; autosomal dominant ; cell ; cell division ; cytoskeleton ; gene ; hereditary ; inherited ; microtubule ; mutation ; nervous system ; paraplegia ; ...

  6. Paraplegia following balloon assistance after cardiac surgery.

    PubMed

    Criado, A; Agosti, J; Horno, R; Jimenez, C

    1981-01-01

    Contrapulsation by means of an intra-aortic balloon is an effective and well-known therapeutic measure in the postoperative period after cardiac surgery, mainly when interrupting cardiopulmonary bypass in left ventricular failure situation (3, 4). We present the case of a patient who developed paraplegia 38 hours after surgery, which was attributed to contrapulsation. PMID:7268331

  7. Acute Aortic Occlusion Presenting as Flaccid Paraplegia

    PubMed Central

    Kilany, Ayman; Al-Hashel, Jasem Y.; Rady, Azza

    2015-01-01

    A 67-year-old male known to be hypertensive and diabetic had a sudden onset of severe low back pain and flaccid paraplegia with no sensory level or bladder affection and the distal pulsations were felt. Acute compressive myelopathy was excluded by MRI of the dorsal and lumbar spines. The nerve conduction study and CSF analysis was suggestive of acute demyelinating polyneuropathy. The patient developed ischemic changes of the lower limb and CT angiography revealed severe stenosis of the abdominal aorta and both common iliac arteries. We emphasize the importance of including acute aortic occlusion in the differential diagnosis of acute flaccid paraplegia especially in the presence of severe back pain even if the distal pulsations were felt. PMID:25866688

  8. Paraplegia with lumbar artery compression by the diaphragmatic crus.

    PubMed

    Batt, Michel; Rogopoulos, André; Benchimol, Daniel; Chapot, René; Jean-Baptiste, Elixène; Baque, Patrick

    2008-10-01

    The authors report three cases of transient and recurrent paraplegia due to compression of the second right lumbar artery by the diaphragmatic crus. Circumstances of appearance are suggestive when paraplegia occurs in dorsolumbar hyperlordosis and low cardiac output is an associated hemodynamic risk factor. Selective medullary arteriography is indispensable for diagnosis and can demonstrate three signs: an anterior spinal dorsolumbar artery (artery of Adamkiewicz) that does not descend to the conus medullaris; posterior spinal arteries arising from the second lumbar arteries that vascularize the conus medullaris; existence of a tight stenosis on the second right lumbar artery that is aggravated during dynamic maneuvers. Section of the right diaphragmatic crus and release of the second right lumbar artery from the aorta to the fibrous arcade of the psoas permits definitive cure of symptoms. PMID:18586436

  9. Rehabilitation for patients with paraplegia and lower extremity amputation

    PubMed Central

    Wang, Fangyong; Hong, Yi

    2015-01-01

    [Purpose] To study the characteristics and treatment strategy for patients with paraplegia and lower extremity amputation. [Subjects] Six cases were selected from among the patients admitted to the China Rehabilitation Research Center from 1991 to 2014. The criteria for the six cases were spinal cord injury with amputation immediately or in a short time (1 week) after the trauma. [Methods] General information, clinical diagnosis, treatment, rehabilitation and other data were analyzed. [Results] All the six cases were injured by high energy or complex energy accidents: two cases by falls after high voltage electric shock, one by an oil pipeline explosion, one by the impact of a falling tower crane and received high energy traffic accident injuries (one was hit by a train, and the other was hit by a truck at high speed). All the six cases had thoracic and lumbar vertebral injuries and complete paraplegia. Amputation stump infection occurred in four cases. After comprehensive rehabilitation treatment, patients’ functional independence measure (FIM) scores improved significantly, but American Spinal Injury Association (ASIA) scores and ASIA Impairment Scale (AIS) grades showed no significant improvement. [Conclusion] When formulating the clinical treatment and rehabilitation for spinal cord injury with amputation patients, simultaneous consideration of the characteristics of the spinal cord injury and amputation is needed to develop an individualized strategy. For spinal cord injury with limb amputation patients, prostheses should allow the improvement of patients’ self-care ability. PMID:26644641

  10. Implications of elbow arthrodesis for individuals with paraplegia.

    PubMed

    Young, J H

    1993-03-01

    A 38-year-old woman who had a recent injury resulting in T-3 Frankel Class C paraplegia and a comminuted fracture of the right elbow is described in this case report. The elbow required an arthrodesis, but the position in which the elbow should be fused was not initially known. To illustrate to the rehabilitation team and the patient the advantages and disadvantages of each of two elbow positions under consideration for the arthrodesis, the author recruited an individual with paraplegia to demonstrate some activities of daily living with two elbow splints that stimulated the two positions of fusion being considered. The patient and the rehabilitation team concluded that the 30-degree flexion fusion offered more functional mobility than the 90-degree flexion fusion. At the completion of her initial rehabilitation, the patient was a full-time manual wheelchair user. She was independent in all self-care and transfers, including uneven transfers to heights of 22.9 cm (9 in) over and 45.7 (18 in) lower than the wheelchair seat. She drives a four-wheel-drive vehicle and is independent in stowing her wheelchair. PMID:8438007

  11. Double Incontinence as a First Symptom of Saddle Embolism of the Aorta Leads to Sudden Paraplegia.

    PubMed

    Sabzi, Feridoun; Faraji, Reza

    2015-11-01

    An aortic saddle embolus causing cauda equine syndrome followed by paraplegia is an exceedingly rare phenomenon in post-operative period in coronary artery bypass grafting. In non-CABG cases, reported documentation of neurological recovery from this event is even rarer. A 57-year-old male 8 days after uneventful OPCAP presented with severe lower extremity pain and sudden fecal and urinary incontinence, followed by the absence of pulsations in the lower limbs and paraplegia, during 20-minute period. He underwent immediate bilateral transfemoral embolectomy. The postoperative period was uneventful. The paraplegia recovered immediately after embolectomy and recovery from anesthesia. An angiography has been made to verify that a high origin of the great radicular artery above T12 level may be responsible for better recovery of paraplegia when its ostium obstructed by a saddle embolus relieved using embolectomy. Early surgical intervention in restoring the blood flow into the great radicular artery may prevent severe histological changes hitherto responsible for non-recovery from paraplegia in the earlier reports. Three unique characteristics of this article are as follows: 1) Occurrence of this complication in the post-operative period in off-pump CABG surgery; 2) Commencing of emboli with bizarre symptoms of double incontinence; 3) Combination of cauda equine syndrome and complete paralysis. PMID:26497379

  12. Hereditary spastic paraplegia with recessive trait caused by mutation in KLC4 gene.

    PubMed

    Bayrakli, Fatih; Poyrazoglu, Hatice Gamze; Yuksel, Sirin; Yakicier, Cengiz; Erguner, Bekir; Sagiroglu, Mahmut Samil; Yuceturk, Betul; Ozer, Bugra; Doganay, Selim; Tanrikulu, Bahattin; Seker, Askin; Akbulut, Fatih; Ozen, Ali; Per, Huseyin; Kumandas, Sefer; Altuner Torun, Yasemin; Bayri, Yasar; Sakar, Mustafa; Dagcinar, Adnan; Ziyal, Ibrahim

    2015-12-01

    We report an association between a new causative gene and spastic paraplegia, which is a genetically heterogeneous disorder. Clinical phenotyping of one consanguineous family followed by combined homozygosity mapping and whole-exome sequencing analysis. Three patients from the same family shared common features of progressive complicated spastic paraplegia. They shared a single homozygous stretch area on chromosome 6. Whole-exome sequencing revealed a homozygous mutation (c.853_871del19) in the gene coding the kinesin light chain 4 protein (KLC4). Meanwhile, the unaffected parents and two siblings were heterozygous and one sibling was homozygous wild type. The 19 bp deletion in exon 6 generates a stop codon and thus a truncated messenger RNA and protein. The association of a KLC4 mutation with spastic paraplegia identifies a new locus for the disease. PMID:26423925

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

    SciTech Connect

    Kobayashi, H.; Hoffman, E.P.; Matise, T.C.

    1994-09-01

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

  14. 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"…

  15. Alteration of ornithine metabolism leads to dominant and recessive hereditary spastic paraplegia.

    PubMed

    Coutelier, Marie; Goizet, Cyril; Durr, Alexandra; Habarou, Florence; Morais, Sara; Dionne-Laporte, Alexandre; Tao, Feifei; Konop, Juliette; Stoll, Marion; Charles, Perrine; Jacoupy, Maxime; Matusiak, Raphaël; Alonso, Isabel; Tallaksen, Chantal; Mairey, Mathilde; Kennerson, Marina; Gaussen, Marion; Schule, Rebecca; Janin, Maxime; Morice-Picard, Fanny; Durand, Christelle M; Depienne, Christel; Calvas, Patrick; Coutinho, Paula; Saudubray, Jean-Marie; Rouleau, Guy; Brice, Alexis; Nicholson, Garth; Darios, Frédéric; Loureiro, José L; Zuchner, Stephan; Ottolenghi, Chris; Mochel, Fanny; Stevanin, Giovanni

    2015-08-01

    Hereditary spastic paraplegias are heterogeneous neurological disorders characterized by a pyramidal syndrome with symptoms predominantly affecting the lower limbs. Some limited pyramidal involvement also occurs in patients with an autosomal recessive neurocutaneous syndrome due to ALDH18A1 mutations. ALDH18A1 encodes delta-1-pyrroline-5-carboxylate synthase (P5CS), an enzyme that catalyses the first and common step of proline and ornithine biosynthesis from glutamate. Through exome sequencing and candidate gene screening, we report two families with autosomal recessive transmission of ALDH18A1 mutations, and predominant complex hereditary spastic paraplegia with marked cognitive impairment, without any cutaneous abnormality. More interestingly, we also identified monoallelic ALDH18A1 mutations segregating in three independent families with autosomal dominant pure or complex hereditary spastic paraplegia, as well as in two sporadic patients. Low levels of plasma ornithine, citrulline, arginine and proline in four individuals from two families suggested P5CS deficiency. Glutamine loading tests in two fibroblast cultures from two related affected subjects confirmed a metabolic block at the level of P5CS in vivo. Besides expanding the clinical spectrum of ALDH18A1-related pathology, we describe mutations segregating in an autosomal dominant pattern. The latter are associated with a potential trait biomarker; we therefore suggest including amino acid chromatography in the clinico-genetic work-up of hereditary spastic paraplegia, particularly in dominant cases, as the associated phenotype is not distinct from other causative genes. PMID:26026163

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

    PubMed Central

    2013-01-01

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

  17. Prevalence of Oxidative Stress and Metabolic Syndrome in Adults with Paraplegia and Tetraplegia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objectives: To investigate the extent of oxidative stress and metabolic syndrome (MetS) in people with spinal cord injuries (SCI) and to identify the major factors associated with oxidative stress and MetS in this population. Methods: 24 subjects with paraplegia (PARA), 26 subjects with tetraplegia ...

  18. Paraplegia Following Intercostal Nerve Neurolysis with Alcohol and Thoracic Epidural Injection in Lung Cancer Patient

    PubMed Central

    Kim, Byoung Ho; No, Min Young; Han, Sang Ju; Park, Cheol Hwan

    2015-01-01

    The goal of cancer treatment is generally pain reduction and function recovery. However, drug therapy does not treat pain adequately in approximately 43% of patients, and the latter may have to undergo a nerve block or neurolysis. In the case reported here, a 42-year-old female patient with lung cancer (adenocarcinoma) developed paraplegia after receiving T8-10 and 11th intercostal nerve neurolysis and T9-10 interlaminar epidural steroid injections. An MRI results revealed extensive swelling of the spinal cord between the T4 spinal cord and conus medullaris, and T5, 7-11, and L1 bone metastasis. Although steroid therapy was administered, the paraplegia did not improve. PMID:25852838

  19. [A case of SAPHO syndrome with paraplegia due to a thoracic kyphosis].

    PubMed

    Fujii, Tomoko; Matsudaira, Koh; Oda, Hiromi; Seichi, Atsushi; Nakamura, Kozo

    2002-08-01

    A 63-year-old man visited our hospital in January 1993 because of back pain, which had been present for a year and persisted. The patient was diagnosed compression fracture of thoracic spine by another hospital. Thoracic plain radiographs revealed destructive and sclerotic changes with reduction of height of T 8, T 9 vertebral body. He had kyphosis on this level. Radiographs of the chest revealed hyperostosis of bilateral proximal clavicle. We diagnosed SAPHO syndrome (synovitis, acne, pustlosis, hyperostosis, and osteomyelitis: SAPHO) with T 8, T 9 spondylodiscitis, however without any skin manifestations. Oral indomethacin was effective, however thoracic kyphosis progressed gradually. Spastic gait and paraplegia appeared from February 1998, at last on July he was unable to walk independently. MRI showed the compression of spinal cord on T 8, T 9 level. We performed circumferential decompression and fusion with instrumentation. His paraplegia improved after surgery. We describe a rare case of SAPHO syndrome with paraplegia due to a thoracic kyphosis. PMID:12355864

  20. Hereditary spastic paraplegia: clinical-genetic characteristics and evolving molecular mechanisms.

    PubMed

    Lo Giudice, Temistocle; Lombardi, Federica; Santorelli, Filippo Maria; Kawarai, Toshitaka; Orlacchio, Antonio

    2014-11-01

    Hereditary spastic paraplegia (HSP) is a group of clinically and genetically heterogeneous neurological disorders characterized by pathophysiologic hallmark of length-dependent distal axonal degeneration of the corticospinal tracts. The prominent features of this pathological condition are progressive spasticity and weakness of the lower limbs. To date, 72 spastic gait disease-loci and 55 spastic paraplegia genes (SPGs) have been identified. All modes of inheritance (autosomal dominant, autosomal recessive, and X-linked) have been described. Recently, a late onset spastic gait disorder with maternal trait of inheritance has been reported, as well as mutations in genes not yet classified as spastic gait disease. Several cellular processes are involved in its pathogenesis, such as membrane and axonal transport, endoplasmic reticulum membrane modeling and shaping, mitochondrial function, DNA repair, autophagy, and abnormalities in lipid metabolism and myelination processes. Moreover, recent evidences have been found about the impairment of endosome membrane trafficking in vesicle formation and about the involvement of oxidative stress and mtDNA polymorphisms in the onset of the disease. Interactome networks have been postulated by bioinformatics and biological analyses of spastic paraplegia genes, which would contribute to the development of new therapeutic approaches. PMID:24954637

  1. Spinocerebellar ataxia type 3/Machado-Joseph disease manifested as spastic paraplegia: A clinical and genetic study

    PubMed Central

    SONG, YANMIN; LIU, YUNHAI; ZHANG, NING; LONG, LILI

    2015-01-01

    The aim of the present study was to conduct a familial investigation and provide a genetic diagnosis to a family presenting with spastic paraplegia and clinically diagnosed with hereditary spastic paraplegia (HSP). Blood samples were obtained from the family, and mutations in the gene causing spinocerebellar ataxia type 3 (SCA3)/Machado-Joseph disease (MJD), known as MJD1, were analyzed using the polymerase chain reaction, 8% denaturing polyacrylamide gel electrophoresis, and T-vector ligation and sequencing. The trinucleotide repeat number of the mutant allele was 80, leading to a genetic diagnosis of SCA3/MJD. This suggests that patients with SCA3/MJD characteristically present with typical spastic paraplegia without evident manifestations of ataxia. For those families with HSP involving the nervous system and showing genetic anticipation, an MJD1 genetic diagnosis should be considered to assist in clinical diagnosis of HSP. PMID:25574208

  2. Dysfunction of spatacsin leads to axonal pathology in SPG11-linked hereditary spastic paraplegia.

    PubMed

    Pérez-Brangulí, Francesc; Mishra, Himanshu K; Prots, Iryna; Havlicek, Steven; Kohl, Zacharias; Saul, Domenica; Rummel, Christine; Dorca-Arevalo, Jonatan; Regensburger, Martin; Graef, Daniela; Sock, Elisabeth; Blasi, Juan; Groemer, Teja W; Schlötzer-Schrehardt, Ursula; Winkler, Jürgen; Winner, Beate

    2014-09-15

    Hereditary spastic paraplegias are a group of inherited motor neuron diseases characterized by progressive paraparesis and spasticity. Mutations in the spastic paraplegia gene SPG11, encoding spatacsin, cause an autosomal-recessive disease trait; however, the precise knowledge about the role of spatacsin in neurons is very limited. We for the first time analyzed the expression and function of spatacsin in human forebrain neurons derived from human pluripotent stem cells including lines from two SPG11 patients and two controls. SPG11 patients'-derived neurons exhibited downregulation of specific axonal-related genes, decreased neurite complexity and accumulation of membranous bodies within axonal processes. Altogether, these data point towards axonal pathologies in human neurons with SPG11 mutations. To further corroborate spatacsin function, we investigated human pluripotent stem cell-derived neurons and mouse cortical neurons. In these cells, spatacsin was located in axons and dendrites. It colocalized with cytoskeletal and synaptic vesicle (SV) markers and was present in synaptosomes. Knockdown of spatacsin in mouse cortical neurons evidenced that the loss of function of spatacsin leads to axonal instability by downregulation of acetylated tubulin. Finally, time-lapse assays performed in SPG11 patients'-derived neurons and spatacsin-silenced mouse neurons highlighted a reduction in the anterograde vesicle trafficking indicative of impaired axonal transport. By employing SPG11 patient-derived forebrain neurons and mouse cortical neurons, this study provides the first evidence that SPG11 is implicated in axonal maintenance and cargo trafficking. Understanding the cellular functions of spatacsin will allow deciphering mechanisms of motor cortex dysfunction in autosomal-recessive hereditary spastic paraplegia. PMID:24794856

  3. Dysfunction of spatacsin leads to axonal pathology in SPG11-linked hereditary spastic paraplegia

    PubMed Central

    Pérez-Brangulí, Francesc; Mishra, Himanshu K.; Prots, Iryna; Havlicek, Steven; Kohl, Zacharias; Saul, Domenica; Rummel, Christine; Dorca-Arevalo, Jonatan; Regensburger, Martin; Graef, Daniela; Sock, Elisabeth; Blasi, Juan; Groemer, Teja W.; Schlötzer-Schrehardt, Ursula; Winkler, Jürgen; Winner, Beate

    2014-01-01

    Hereditary spastic paraplegias are a group of inherited motor neuron diseases characterized by progressive paraparesis and spasticity. Mutations in the spastic paraplegia gene SPG11, encoding spatacsin, cause an autosomal-recessive disease trait; however, the precise knowledge about the role of spatacsin in neurons is very limited. We for the first time analyzed the expression and function of spatacsin in human forebrain neurons derived from human pluripotent stem cells including lines from two SPG11 patients and two controls. SPG11 patients'-derived neurons exhibited downregulation of specific axonal-related genes, decreased neurite complexity and accumulation of membranous bodies within axonal processes. Altogether, these data point towards axonal pathologies in human neurons with SPG11 mutations. To further corroborate spatacsin function, we investigated human pluripotent stem cell-derived neurons and mouse cortical neurons. In these cells, spatacsin was located in axons and dendrites. It colocalized with cytoskeletal and synaptic vesicle (SV) markers and was present in synaptosomes. Knockdown of spatacsin in mouse cortical neurons evidenced that the loss of function of spatacsin leads to axonal instability by downregulation of acetylated tubulin. Finally, time-lapse assays performed in SPG11 patients'-derived neurons and spatacsin-silenced mouse neurons highlighted a reduction in the anterograde vesicle trafficking indicative of impaired axonal transport. By employing SPG11 patient-derived forebrain neurons and mouse cortical neurons, this study provides the first evidence that SPG11 is implicated in axonal maintenance and cargo trafficking. Understanding the cellular functions of spatacsin will allow deciphering mechanisms of motor cortex dysfunction in autosomal-recessive hereditary spastic paraplegia. PMID:24794856

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

    PubMed

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

    2014-07-01

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

  5. Spastic paraplegia, optic atrophy, microcephaly with normal intelligence, and XY sex reversal: a new autosomal recessive syndrome?

    PubMed Central

    Teebi, A S; Miller, S; Ostrer, H; Eydoux, P; Colomb-Brockmann, C; Oudjhane, K; Watters, G

    1998-01-01

    Two female sibs of first cousin Iranian parents were found to have the syndrome of spastic paraplegia, optic atrophy with poor vision, microcephaly, and normal cognitive development. Karyotype analysis showed a normal female constitution in one and a male constitution (46,XY) in the other. The XY female showed normal female external genitalia, normal uterus and tubes, and streak gonads. SRY gene sequencing was normal. We conclude that the present family probably represents a new autosomal recessive trait of pleiotropic effects including XY sex reversal and adds further evidence for the heterogeneity of spastic paraplegia syndromes as well as sex reversal syndromes. Images PMID:9733035

  6. Mutations in phospholipase DDHD2 cause autosomal recessive hereditary spastic paraplegia (SPG54)

    PubMed Central

    Gonzalez, Michael; Nampoothiri, Sheela; Kornblum, Cornelia; Oteyza, Andrés Caballero; Walter, Jochen; Konidari, Ioanna; Hulme, William; Speziani, Fiorella; Schöls, Ludger; Züchner, Stephan; Schüle, Rebecca

    2013-01-01

    Hereditary spastic paraplegias (HSP) are a genetically heterogeneous group of disorders characterized by a distal axonopathy of the corticospinal tract motor neurons leading to progressive lower limb spasticity and weakness. Intracellular membrane trafficking, mitochondrial dysfunction and myelin formation are key functions involved in HSP pathogenesis. Only recently defects in metabolism of complex lipids have been implicated in a number of HSP subtypes. Mutations in the 23 known autosomal recessive HSP genes explain less than half of autosomal recessive HSP cases. To identify novel autosomal recessive HSP disease genes, exome sequencing was performed in 79 index cases with autosomal recessive forms of HSP. Resulting variants were filtered and intersected between families to allow identification of new disease genes. We identified two deleterious mutations in the phospholipase DDHD2 gene in two families with complicated HSP. The phenotype is characterized by early onset of spastic paraplegia, mental retardation, short stature and dysgenesis of the corpus callosum. Phospholipase DDHD2 is involved in intracellular membrane trafficking at the golgi/ endoplasmic reticulum interface and has been shown to possess phospholipase A1 activity in vitro. Discovery of DDHD2 mutations in HSP might therefore provide a link between two key pathogenic themes in HSP: membrane trafficking and lipid metabolism. PMID:23486545

  7. Exome sequencing released a case of X-linked adrenoleukodystrophy mimicking recessive hereditary spastic paraplegia.

    PubMed

    Zhan, Zi-Xiong; Liao, Xin-Xin; Du, Juan; Luo, Ying-Ying; Hu, Zhao-Ting; Wang, Jun-Ling; Yan, Xin-Xiang; Zhang, Jian-Guo; Dai, Mei-Zhi; Zhang, Peng; Xia, Kun; Tang, Bei-Sha; Shen, Lu

    2013-07-01

    Genetic heterogeneity is common in many Mendelian disorders such as hereditary spastic paraplegia (HSP), which makes the genetic diagnosis more complicated. The goal of this study was to investigate a Chinese family with recessive hereditary spastic paraplegia, of which causative mutations could not be identified using the conventional PCR-based direct sequencing. Next-generation sequencing of all the transcripts of whole genome exome, after on-array hybrid capture, was performed on two affected male subjects (the proband and his brother). A missense mutation (c.1661G>A, p.R554H) was identified in ABCD1. Subsequently, PCR-based direct sequencing of other family members revealed that the mutation was co-segregating with the disease, indicating that ABCD1 mutation was the pathogenic event for this family. Very long-chain fatty acids (VLCFA) assay in the two affected cases confirmed X-ALD. Our study suggests exome sequencing can be used not only to find a novel causative gene, but also to quickly identify mutations of known genes when the clinical elements are etiologically misleading. PMID:23664929

  8. 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…

  9. Disseminated mycobacteriosis manifesting as paraplegia in two Parma wallabies (Macropus parma) naturally exposed to Mycobacterium avium.

    PubMed

    Robveille, Cynthia; Albaric, Olivier; Gaide, Nicolas; Abadie, Jérome

    2015-11-01

    Two captive female Parma wallabies (Macropus parma) died after a history of flaccid paraplegia. On postmortem examination, granulomatous and suppurative osteomyelitis involving the left ischium and the lumbosacral region, with meningeal extension at the cauda equina, and caseonecrotic mastitis were the most significant changes. Multiple small nodules in the liver and spleen, and an enlargement of some lymph nodes with central caseous necrosis were also observed. Microscopically, a disseminated granulomatous inflammation with numerous multinucleate giant cells was seen. Numerous acid-fast bacilli were detected in macrophages, in multinucleated giant cells, and free in the central necrosis and suppurative exudate. After culture, polymerase chain reaction assays were carried out to detect the 65-kDa heat shock protein (Hsp65) and insertion sequences (IS)1245 and IS900. The causative agent was identified as Mycobacterium avium subsp. avium. PMID:26450834

  10. Hereditary ataxias and paraplegias in Cantabria, Spain. An epidemiological and clinical study.

    PubMed

    Polo, J M; Calleja, J; Combarros, O; Berciano, J

    1991-04-01

    A clinical, genetic and epidemiological study of hereditary ataxias and paraplegias was conducted within a defined area (Cantabria) in Northern Spain from 1974 to 1986. The series comprised 48 index cases and 65 affected relatives. On prevalence day, 103 patients were alive, giving a prevalence of 20.2 cases per 100,000. There were 24 patients (18 families) with Friedreich's ataxia (FA), 12 (6 families) with early onset cerebellar ataxia (EOCA) differing from FA, 6 (3 families) with dominantly transmitted late onset cerebellar ataxia (LOCA), 11 with 'idiopathic' LOCA, 49 (9 families) with 'pure' hereditary spastic paraplegia (HSP), and 1 patient with congenital cerebellar ataxia. The prevalence found here is comparable with the highest figures described in previous surveys. This may in part be due to the great number of secondary cases in our series. A high frequency of parental consanguinity occurred in FA patients, 'pseudodominant' inheritance being observed in 1 family. The clinical features were those of classical FA except for later onset and slower course in 1 family, and retained tendon reflexes in the lower limbs in 2 cases. Such data indicate the need for modification of the essential criteria for the disease. EOCA included 4 patients with normoreflexic ataxia and 1 patient with ataxia and luteinizing hormone-releasing hormone deficiency. In addition, there were 7 patients from 2 unrelated families with a homogeneous syndrome characterized by autosomal recessive inheritance, cerebellar ataxia, retinitis pigmentosa and sensory neuropathy. This syndrome is therefore a well defined nosological entity to be added to the list of autosomal recessive mendelian phenotypes. The clinical picture of patients with LOCA was either a 'pure' cerebellar or a 'cerebellar-plus' syndrome. Genetic subgroups of 'pure' HSP were autosomal dominant type I in 5 families and type II in 2, and autosomal recessive in 2 families. PMID:2043954

  11. Retinal nerve fibre layer loss in hereditary spastic paraplegias is restricted to complex phenotypes

    PubMed Central

    2012-01-01

    Background Reduction of retinal nerve fibre layer (RNFL) thickness was shown as part of the neurodegenerative process in a range of different neurodegenerative pathologies including Alzheimer?s disease (AD), idiopathic Parkinson’s disease (PD), spinocerebellar ataxia (SCA) and multiple system atrophy (MSA). To further clarify the specificity of RNFL thinning as a potential marker of neurodegenerative diseases we investigated RNFL thickness in Hereditary Spastic Paraplegia (HSP), an axonal, length-dependent neurodegenerative pathology of the upper motor neurons. Methods Spectral domain optical coherence tomography (OCT) was performed in 28 HSP patients (clinically: pure HSP = 22, complicated HSP = 6; genetic subtypes: SPG4 = 13, SPG5 = 1, SPG7 = 3, genetically unclassified: 11) to quantify peripapillary RNFL thickness. Standardized examination assessed duration of disease, dependency on assistive walking aids and severity of symptoms quantified with Spastic Paraplegia Rating Scale (SPRS). Results HSP patients demonstrated no significant thinning of global RNFL (pglobal = 0.61). Subgroup analysis revealed significant reduction in temporal and temporal inferior sectors for patients with complex (p<0.05) but not pure HSP phenotypes. Two of three SPG7-patients showed severe temporal and temporal inferior RNFL loss. Disease duration, age and severity of symptoms were not significantly correlated with global RNFL thickness. Conclusion Clinically pure HSP patients feature no significant reduction in RNFL, whereas complex phenotypes display an abnormal thinning of temporal and temporal inferior RNFL. Our data indicate that RNFL thinning does not occur unspecifically in all neurodegenerative diseases but is in HSP restricted to subtypes with multisystemic degeneration. PMID:23176075

  12. Protrudin Regulates Endoplasmic Reticulum Morphology and Function Associated with the Pathogenesis of Hereditary Spastic Paraplegia*

    PubMed Central

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

    2014-01-01

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

  13. 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

  14. Paraplegia after epidural-general anesthesia in a Morquio patient with moderate thoracic spinal stenosis

    PubMed Central

    Krane, Elliot J.; Tomatsu, Shunji; Theroux, Mary C.; Lee, Roland R.

    2014-01-01

    Purpose We describe an instance in which complete paraplegia was evident immediately postoperatively after apparently uneventful lumbar epidural-general anesthesia in a patient with Morquio Type A syndrome (Morquio A) with moderate thoracic spinal stenosis. Clinical features A 16-yr-old male with Morquio A received lumbar epidural-general anesthesia for bilateral distal femoral osteotomies. Preoperative imaging had revealed a stable cervical spine and moderate thoracic spinal stenosis with a mild degree of spinal cord compression. Systolic blood pressure (BP) was maintained within 20% of the pre-anesthetic baseline value. The patient sustained a severe thoracic spinal cord infarction. The epidural anesthetic contributed to considerable delay in the recognition of the diagnosis of paraplegia. Conclusion This experience leads us to suggest that, in patients with Morquio A, it may be prudent to avoid the use of epidural anesthesia without very firm indication, to support BP at or near baseline levels in the presence of even moderate spinal stenosis, and to avoid flexion or extension of the spinal column in intraoperative positioning. If the spinal cord/column status is unknown or if the patient is known to have any degree of spinal stenosis, we suggest that the same rigorous BP support practices that are typically applied in other patients with severe spinal stenosis, especially stenosis with myelomalacia, should apply to patients with Morquio A and that spinal cord neurophysiological monitoring should be employed. In the event that cord imaging is not available, e.g., emergency procedures, it would be prudent to assume the presence of spinal stenosis. PMID:25323122

  15. The Extended Posterior Circumferential Decompression Technique in the Management of Tubercular Spondylitis with and without Paraplegia

    PubMed Central

    Rathinavelu, Barani; Krishnan, Venkatesh; Amritanand, Rohit; Sundararaj, Gabriel David

    2014-01-01

    Study Design Retrospective clinical series. Purpose To study the clinical, functional and radiological results of patients with tuberculous spondylitis with and without paraplegia, treated surgically using the "Extended Posterior Circumferential Decompression (EPCD)" technique. Overview of Literature With the increasing possibility of addressing all three columns by a single approach, posterior and posterolateral approaches are gaining acceptance. A single exposure for cases with neurological deficit and kyphotic deformity requiring circumferential decompression, anterior column reconstruction and posterior instrumentation is helpful. Methods Forty-one patients with dorsal/dorsolumbar/lumbar tubercular spondylitis who were operated using the EPCD approach between 2006 to 2009 were included. Postoperatively, patients were started on nine-month anti-tuberculous treatment. They were serially followed up to thirty-six months and both clinical measures (including pain, neurological status and ambulatory status) and radiological measures (including kyphotic angle correction, loss of correction and healing status) were used for assessment. Results Disease-healing with bony fusion (interbody fusion) was seen in 97.5% of cases. Average deformity (kyphosis) correction was 54.6% in dorsal spine and 207.3% in lumbar spine. Corresponding loss of correction was 3.6 degrees in dorsal spine and 1.9 degrees in the lumbar spine. Neurological recovery in Frankel B and C paraplegia was 85.7% and 62.5%, respectively. Conclusions The EPCD approach permits all the advantages of a single or dual session anterior and posterior surgery, with significant benefits in terms of decreased operative time, reduced hospital stay and better kyphotic angle correction. PMID:25558312

  16. 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 limbs, suggesting that SPG7 mutations at the heterozygous state might predispose to late-onset neurodegenerative disorders, mimicking autosomal dominant inheritance. Finally, a novel missense SPG7 mutation at the heterozygous state (Asp411Ala) was identified as the cause of autosomal dominant optic neuropathy in a large family, indicating that some SPG7 mutations can occasionally be dominantly inherited and be an uncommon cause of isolated optic neuropathy. Altogether, these results emphasize the clinical variability associated with SPG7 mutations, ranging from optic neuropathy to spastic paraplegia, and support the view that SPG7 screening should be carried out in both conditions. PMID:23065789

  17. Autosomal recessive hereditary spastic paraplegia-clinical and genetic characteristics of a well-defined cohort.

    PubMed

    Yoon, G; Baskin, B; Tarnopolsky, M; Boycott, K M; Geraghty, M T; Sell, E; Goobie, S; Meschino, W; Banwell, B; Ray, P N

    2013-11-01

    We describe the clinical and genetic features of a well-characterized cohort of patients with autosomal recessive hereditary spastic paraplegia (ARHSP) in the province of Ontario. Patients with documented corticospinal tract abnormalities were screened by whole gene sequencing and multiplex ligation probe amplification for mutations in nine genes known to cause ARHSP. Of a cohort of 39 patients, a genetic diagnosis was established in 17 (44 %) and heterozygous mutations were detected in 8 (21 %). Mutations were most frequent in SPG7 (12 patients), followed by SPG11 (10 patients), PNPLA6 (SPG39, 2 patients), and ZFYVE26 (SPG15, 2 patients). Although there are associations between some clinical manifestations of ARHSP and specific genes, many patients are tested at an early stage of the disease when phenotype/genotype correlations are not obvious. Accurate molecular characterization of well-phenotyped cohorts of patients will be essential to establishing the natural history of these rare degenerative disorders to enable future clinical trials. PMID:23733235

  18. Rapidly deteriorating course in Dutch hereditary spastic paraplegia type 11 patients.

    PubMed

    de Bot, Susanne T; Burggraaff, Rogier C; Herkert, Johanna C; Schelhaas, Helenius J; Post, Bart; Diekstra, Adinda; van Vliet, Reinout O; van der Knaap, Marjo S; Kamsteeg, Erik-Jan; Scheffer, Hans; van de Warrenburg, Bart P; Verschuuren-Bemelmans, Corien C; Kremer, Hubertus P H

    2013-11-01

    Although SPG11 is the most common complicated hereditary spastic paraplegia, our knowledge of the long-term prognosis and life expectancy is limited. We therefore studied the disease course of all patients with a proven SPG11 mutation as tested in our laboratory, the single Dutch laboratory providing SPG11 mutation analysis, between 1 January 2009 and 1 January 2011. We identified nine different SPG11 mutations, four of which are novel, in nine index patients. Eighteen SPG11 patients from these nine families were studied by means of a retrospective chart analysis and additional interview/examination. Ages at onset were between 4 months and 14 years; 39% started with learning difficulties rather than gait impairment. Brain magnetic resonance imaging showed a thin corpus callosum and typical periventricular white matter changes in the frontal horn region (known as the 'ears-of the lynx'-sign) in all. Most patients became wheelchair bound after a disease duration of 1 to 2 decades. End-stage disease consisted of loss of spontaneous speech, severe dysphagia, spastic tetraplegia with peripheral nerve involvement and contractures. Several patients died of complications between ages 30 and 48 years, 3-4 decades after onset of gait impairment. Other relevant features during the disease were urinary and fecal incontinence, obesity and psychosis. Our study of 18 Dutch SPG11-patients shows the potential serious long-term consequences of SPG11 including a possibly restricted life span. PMID:23443022

  19. A Preliminary Assessment of Legged Mobility Provided by a Lower Limb Exoskeleton for Persons With Paraplegia

    PubMed Central

    Farris, Ryan J.; Quintero, Hugo A.; Murray, Spencer A.; Ha, Kevin H.; Hartigan, Clare; Goldfarb, Michael

    2015-01-01

    This paper presents an assessment of a lower limb exoskeleton for providing legged mobility to people with paraplegia. In particular, the paper presents a single-subject case study comparing legged locomotion using the exoskeleton to locomotion using knee–ankle–foot orthoses (KAFOs) on a subject with a T10 motor and sensory complete injury. The assessment utilizes three assessment instruments to characterize legged mobility, which are the timed up-and-go test, the Ten-Meter Walk Test (10 MWT), and the Six-Minute Walk Test (6 MWT), which collectively assess the subject’s ability to stand, walk, turn, and sit. The exertion associated with each assessment instrument was assessed using the Physiological Cost Index. Results indicate that the subject was able to perform the respective assessment instruments 25%, 70%, and 80% faster with the exoskeleton relative to the KAFOs for the timed up-and-go test, the 10 MWT, and the 6 MWT, respectively. Measurements of exertion indicate that the exoskeleton requires 1.6, 5.2, and 3.2 times less exertion than the KAFOs for each respective assessment instrument. The results indicate that the enhancement in speed and reduction in exertion are more significant during walking than during gait transitions. PMID:23797285

  20. 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

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

    SciTech Connect

    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 American 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.

  2. 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

  3. Loss of association of REEP2 with membranes leads to hereditary spastic paraplegia.

    PubMed

    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

    2014-02-01

    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

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

    PubMed Central

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

    2009-01-01

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

  5. Successful surgical treatment of descending aorta interruption in a 29-year-old woman with acute paraplegia and subarachnoid hemorrhage: a case report.

    PubMed

    Bai, Shutang; Wang, Zhiheng; Zhang, Liang; Fu, Hongdu; Zhuang, Huanwei; Cao, Xianjun; Liang, Liming; Yang, Yanqi

    2015-01-01

    Interruption of the descending aorta is an extremely rare great vessel malformation. In this report, we describe a very unusual case of a 29-year-old female with a 13-year history of hypertension who was found to have an interruption of the descending aorta when she was hospitalized with a subarachnoid hemorrhage and symptoms of acute paraplegia. We successfully surgically corrected the defect using a Gore-Tex® graft to bypass the aortic interruption. The patient's blood pressure postoperatively returned to normal, and the patient recovered completely from her paraplegia by the time of her 5-month follow-up visit. PMID:26045082

  6. 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. PMID:26403765

  7. Tau missorting and spastin-induced microtubule disruption in neurodegeneration: Alzheimer Disease and Hereditary Spastic Paraplegia.

    PubMed

    Zempel, Hans; Mandelkow, Eva-Maria

    2015-01-01

    In Alzheimer Disease (AD), the mechanistic connection of the two major pathological hallmarks, namely deposition of Amyloid-beta (A?) in the form of extracellular plaques, and the pathological changes of the intracellular protein Tau (such as phosphorylation, missorting, aggregation), is not well understood. Genetic evidence from AD and Down Syndrome (Trisomy 21), and animal models thereof, suggests that aberrant production of A? is upstream of Tau aggregation, but also points to Tau as a critical effector in the pathological process. Yet, the cascade of events leading from increased levels of A? to Tau-dependent toxicity remains a matter of debate.Using primary neurons exposed to oligomeric forms of A?, we have found that Tau becomes mislocalized (missorted) into the somatodendritic compartment. Missorting of Tau correlates with loss of microtubules and downstream consequences such as loss of mature spines, loss of synaptic activity, and mislocalization of mitochondria.In this cascade, missorting of Tau induces mislocalization of TTLL6 (Tubulin-Tyrosine-Ligase-Like 6) into the dendrites. TTLL6 induces polyglutamylation of microtubules, which acts as a trigger for spastin mediated severing of dendritic microtubules. Loss of microtubules makes cells unable to maintain transport of mitochondria, which in turn results in synaptic dysfunction and loss of mature spines. These pathological changes are absent in TauKO derived primary neurons. Thus, Tau mediated mislocalization of TTLL6 and spastin activation reveals a pathological gain of function for Tau and spastin in this cellular model system of AD.In contrast, in hereditary spastic paraplegia (HSP) caused by mutations of the gene encoding spastin (spg4 alias SPAST), spastin function in terms of microtubule severing is decreased at least for the gene product of the mutated allele, resulting in overstable microtubules in disease model systems. Whether total spastin severing activity or microtubule stability in human disease is also affected is not yet clear. No human disease has been associated so far with the long-chain polyglutamylation enzyme TTLL6, or the other TTLLs (1,5,11) possibly involved.Here we review the findings supporting a role for Tau, spastin and TTLL6 in AD and other tauopathies, HSP and neurodegeneration, and summarize possible therapeutic approaches for AD and HSP. PMID:26691836

  8. 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

  9. 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

  10. Lack of enzyme activity in GBA2 mutants associated with hereditary spastic paraplegia/cerebellar ataxia (SPG46).

    PubMed

    Sultana, Saki; Reichbauer, Jennifer; Schüle, Rebecca; Mochel, Fanny; Synofzik, Matthis; van der Spoel, Aarnoud C

    2015-09-11

    Glucosylceramide is a membrane glycolipid made up of the sphingolipid ceramide and glucose, and has a wide intracellular distribution. Glucosylceramide is degraded to ceramide and glucose by distinct, non-homologous enzymes, including glucocerebrosidase (GBA), localized in the endolysosomal pathway, and ?-glucosidase 2 (GBA2), which is associated with the plasma membrane and/or the endoplasmic reticulum. It is well established that mutations in the GBA gene result in endolysosomal glucosylceramide accumulation, which triggers Gaucher disease. In contrast, the biological significance of GBA2 is less well understood. GBA2-deficient mice present with male infertility, but humans carrying mutations in the GBA2 gene are affected with a combination of cerebellar ataxia and spastic paraplegia, as well as with thin corpus callosum and cognitive impairment (SPastic Gait locus #46, SPG46). To improve our understanding of the biochemical consequences of the GBA2 mutations, we have evaluated five nonsense and five missense GBA2 mutants for their enzyme activity. In transfected cells, the mutant forms of GBA2 were present in widely different amounts, ranging from overabundant to very minor, compared to the wild type enzyme. Nevertheless, none of the GBA2 mutant cDNAs raised the enzyme activity in transfected cells, in contrast to the wild-type enzyme. These results suggest that SPG46 patients have a severe deficit in GBA2 activity, because the GBA2 mutants are intrinsically inactive and/or reduced in amount. This assessment of the expression levels and enzyme activities of mutant forms of GBA2 offers a first insight in the biochemical basis of the complex pathologies seen in SPG46. PMID:26220345

  11. 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

  12. 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 ?-tubulin, a marker of stabilised microtubules, and to slower speed of peroxisome trafficking. Here we screened multiple concentrations of four tubulin-binding drugs for their ability to rescue levels of acetylated ?-tubulin in patient-derived ONS cells. Drug doses that restored acetylated ?-tubulin to levels in control-derived ONS cells were then selected for their ability to rescue peroxisome trafficking deficits. Automated microscopic screening identified very low doses of the four drugs (0.5?nM taxol, 0.5?nM vinblastine, 2?nM epothilone D, 10?µM noscapine) that rescued acetylated ?-tubulin in patient-derived ONS cells. These same doses rescued peroxisome trafficking deficits, restoring peroxisome speeds to untreated control cell levels. These results demonstrate a novel approach for drug screening based on high throughput automated microscopy for acetylated ?-tubulin followed by functional validation of microtubule-based peroxisome transport. From a clinical perspective, all the drugs tested are used clinically, but at much higher doses. Importantly, epothilone D and noscapine can enter the central nervous system, making them potential candidates for future clinical trials. PMID:24857849

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

    PubMed

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

    2014-01-01

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

  14. Microarray analysis unmasked two siblings with pure hereditary spastic paraplegia shared a run of homozygosity region on chromosome 3q28-q29.

    PubMed

    Yu, Wenqian; You, Xiangdong; Wang, Dong; Dong, Kai; Su, Jing; Li, Chuanfen; Liu, Jinxiu; Zhang, Qianqian; You, Feng; Wang, Xiangrong; Huang, Jing; Qiao, Bin; Duan, Wenyuan

    2015-12-15

    Hereditary spastic paraplegia (HSP) is a clinical and genetic heterogeneity group of neurodegenerative disorders which is characterized by progressive weakness and spasticity of the lower limbs. More than 70 genetic types of HSP have been described so far. Here we describe a Chinese non-consanguineous family with two affected siblings manifesting early-onset autosomal recessive HSP in pure forms. To identify genotype and characterize phenotype, CytoScan HD array analysis was performed on the two siblings. A run of homozygosity (ROH) shared by the two patients was detected on chromosome 3q28-q29. The ROH region, about 7.7Mb on the chromosome 3:190172058-197851260 partially overlapped with the ROH region of SPG14 previously reported. Subsequently, microsatellite analysis confirmed this ROH and whole-exome sequencing was carried out while no causative mutations were found in the exons of known HSP genes and 68 candidate genes in that region. In conclusion, our data suggest the ROH in this region may play a pivotal role in SPG14 pathogenesis. This is the first clinical description of a pure form spastic paraplegia in a non-consanguineous family associated with the SPG14 locus. PMID:26671141

  15. Abnormal Paraplegin Expression in Swollen Neurites, ?- and ?-Synuclein Pathology in a Case of Hereditary Spastic Paraplegia SPG7 with an Ala510Val Mutation

    PubMed Central

    Thal, Dietmar R.; Züchner, Stephan; Gierer, Stephan; Schulte, Claudia; Schöls, Ludger; Schüle, Rebecca; Synofzik, Matthis

    2015-01-01

    Mutations in the SPG7 gene are the most frequent cause of autosomal recessive hereditary spastic paraplegias and spastic ataxias. Ala510Val is the most common SPG7 mutation, with a frequency of up to 1% in the general population. Here we report the clinical, genetic, and neuropathological findings in a homozygous Ala510Val SPG7 case with spastic ataxia. Neuron loss with associated gliosis was found in the inferior olivary nucleus, the dentate nucleus of the cerebellum, the substantia nigra and the basal nucleus of Meynert. Neurofilament and/or paraplegin accumulation was observed in swollen neurites in the cerebellar and cerebral cortex. This case also showed subcortical ?-pathology in an unique distribution pattern largely restricted to the brainstem. ?-synuclein containing Lewy bodies (LBs) were observed in the brainstem and the cortex, compatible with a limbic pattern of Braak LB-Disease stage 4. Taken together, this case shows that the spectrum of pathologies in SPG7 can include neuron loss of the dentate nucleus and the inferior olivary nucleus as well as neuritic pathology. The progressive supranuclear palsy-like brainstem predominant pattern of ? pathology and ?-synuclein containing Lewy bodies in our SPG7 cases may be either coincidental or related to SPG7 in addition to neuron loss and neuritic pathology. PMID:26506339

  16. 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

    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

    2015-04-15

    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 ? 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

  17. Genetics Home Reference: Spastic paraplegia type 15

    MedlinePLUS

    ... protein interferes with normal cytokinesis and whether impaired cell division contributes to the signs and symptoms of spastic ... atrophy ; autophagy ; autosomal ; autosomal recessive ; bradykinesia ; breakdown ; cell ; cell division ; cerebellum ; cerebral cortex ; corpus callosum ; cytokinesis ; disability ; gene ; ...

  18. Genetics Home Reference: Spastic paraplegia type 31

    MedlinePLUS

    ... REEP1 protein is located within cell compartments called mitochondria, which are the energy-producing centers in cells, ... The function of the REEP1 protein in the mitochondria is unknown. REEP1 gene mutations that cause spastic ...

  19. Genetics Home Reference: Spastic paraplegia type 2

    MedlinePLUS

    ... proteolipid protein 1 and DM20 can cause a reduction in the formation of myelin (dysmyelination) which can ... January 4, 2016 Lister Hill National Center for Biomedical Communications U.S. National Library of Medicine , National Institutes ...

  20. Genetics Home Reference: Spastic paraplegia type 7

    MedlinePLUS

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

  1. Genetics Home Reference: Spastic paraplegia type 3A

    MedlinePLUS

    ... cord (central nervous system), particularly in nerve cells (neurons) that extend down the spinal cord (corticospinal tracts). These neurons send electrical signals that lead to voluntary muscle ...

  2. 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

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

    PubMed Central

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

    2013-01-01

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

  4. Original electronic design to perform epimysial and neural stimulation in paraplegia

    NASA Astrophysics Data System (ADS)

    Guiraud, David; Stieglitz, Thomas; Taroni, Gérard; Divoux, Jean-Louis

    2006-12-01

    This paper presents an original electronic architecture to manage epimysial and neural stimulation using the same implantable device. All the muscles needed to achieve lower limb movements such as standing and walking can thus be activated. Mainly for surgical reasons, some muscles need to be stimulated through different inputs: epimysium or motor nerve. We developed an electronic solution, including the design of an application-specific integrated circuit, to meet the requirements of both types of stimulation. Five years after the successful implantation of the system, we were able to evaluate the system's performance. The patient is still using the system at home and no failure occurred during this 5-year period. We conclude that the electronic design not only provides a unique investigative tool for research, but that it can also be used to restore the motor function of the lower limb. This technology has an advantage over external stimulation because the patient can safely use the system at home. However, improvements such as lower power consumption, and thus greater autonomy, are needed. We further conclude that the modelling of the electrical behaviour of the electrodes is reliable and the estimated parameter values are homogeneous and consistent for the same type of electrode. Thus, the three parameters of the first-order model can be identified from an acute animal experiment and provide a means to optimize the design of the output stage of implanted stimulators.

  5. Acute paraplegia due to spinal arteriovenous fistula in two patients with hereditary hemorrhagic telangiectasia.

    PubMed

    Poisson, Alice; Vasdev, Ashok; Brunelle, Francis; Plauchu, Henri; Dupuis-Girod, Sophie

    2009-02-01

    Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by recurrent epistaxis, cutaneous telangiectasia, and visceral arteriovenous malformations (AVM). Of these, spinal AVM is a rare manifestation that concerns mainly children. In this report, we describe two cases of spinal AVM revealed by acute paraparesis due to subarachnoid hemorrhage in children with HHT and reviewed the literature on spinal arteriovenous malformations in HHT. In most of the cases reported, the clinical presentation was acute in the pediatric population and insidious during adulthood. The prognosis of spinal AVM mainly depends on the presence or not of medullar signs and symptoms and on the delay before treatment. In conclusion, any child with a family history of HHT should be considered at risk for spinal AVM in order to improve management of such complications and to decrease the risk of neurological sequellae. PMID:19020899

  6. Diagnosis, investigation and management of hereditary spastic paraplegias in the era of next-generation sequencing

    E-print Network

    Hensiek, Anke; Kirker, Stephen; Reid, Evan

    2014-12-06

    , pseudobulbar palsy, joint contractures SPG19 AD %607152 P SPG20/ SPARTIN Spartin AR #275900 C Troyer syndrome: dysarthria, pseudobulbar palsy, intellectual disability, amyotrophy, short stature J Neurol 123 Table 1 continued Gene Protein Inherited OMIM Comment... ’-nucleotidase AR #613162 C Optic atrophy, thin corpus callosum, intellectual disability SPG46/GBA2 Non-lysosomal glucosylceramidase AR #614409 C Cerebellar signs, intellectual impairment, cerebral atrophy, cerebellar atrophy, thin corpus callosum, pseudobulbar...

  7. 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. PMID:25205000

  8. Feedback control of unsupported standing in paraplegia--part I: optimal control approach.

    PubMed

    Hunt, K J; Munih, M; de N Donaldson, N

    1997-12-01

    This is the first of a pair of papers which describe an investigation into the feasibility of providing artificial balance to paraplegics using electrical stimulation of the paralyzed muscles. By bracing the body above the shanks, only stimulation of the plantarflexors is necessary. This arrangement prevents any influence from the intact neuromuscular system above the spinal cord lesion. In this paper, we extend the design of the controllers to a nested-loop LQG (linear quadratic Gaussian) stimulation controller which has ankle moment feedback (inner loops) and inverted pendulum angle feedback (outer loop). Each control loop is tuned by two parameters, the control weighting and an observer rise-time, which together determine the behavior. The nested structure was chosen because it is robust, despite changes in the muscle properties (fatigue) and interference from spasticity. PMID:9422458

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

    PubMed Central

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

    2013-01-01

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

  10. 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…

  11. Effect of vibration stimulation on dysbasia of spastic paraplegia in neuromyelitis optica: a possible example of neuronal plasticity.

    PubMed

    Lin, Hsin-Ni; Nagaoka, Masanori; Hayashi, Yasuko; Hatori, Kozo

    2012-01-01

    We analysed the effect of vibration stimulation (VS) on dysbasia of neuromyelitis optica (NMO). The patient was a 36-year-old woman who was diagnosed with NMO and had difficulties in walking. VS was applied to the lower limb muscles on the left, more spastic, side with an ordinary vibrator. The performance of standing up and walking improved with VS. Even with improved performance after VS, the amount of surface EMG of the lower limbs did not increase as a whole, but the EMG patterns among the lower leg muscles changed remarkably. VS produced reciprocity within antagonistic muscles. Variability of EMG amplitudes decreased remarkably during the walking cycle, not only on the vibrated side, but also on the non-vibrated side. The effect lasted longer than several dozen minutes after the cessation of VS. We conjectured that central pattern generator (CPG) and neuronal plasticity were the result of VS. PMID:23045444

  12. 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. PMID:26437800

  13. 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…

  14. Abstract--A system to restore walking in the vicinity of a wheelchair for people with paraplegia resulting from spinal

    E-print Network

    Durfee, William K.

    and reinforced ankle foot orthosis (AFO). The trunk corset (Rolyan AquaForm Corset, Sammons Preston) was shipped flat and was then fitted over a person of 6 feet height and given as generic shape as possible. The hip is attached to ankle foot or

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

    E-print Network

    Sokolowski, Marla

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

  16. Late functioning adrenocortical carcinoma in a 5-year-old girl.

    PubMed Central

    Marsden, H B; Jones, P M; Lees, P D; Hann, I M

    1978-01-01

    A 5-year-old with adrenocortical carcinoma presented with acute paraplegia. The tumour was initially nonfunctioning but finally showed rapid dissemination and the patient then developed Cushingoid features and virilisation. PMID:646449

  17. Accommodation Information by Disability

    MedlinePLUS

    ... Migraine Headaches Multiple Chemical Sensitivity or Environmental Illness Multiple Sclerosis Muscular Dystrophy Myasthenia Gravis O Obesity One Hand Use P Paraplegia Parkinson's Disease Personality Disorders Phobias Photosensitivity Post-Polio Syndrome Post-Traumatic Stress ...

  18. 16 CFR 1116.2 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... including coma and spinal cord injuries; (v) Paraplegia, quadriplegia, or permanent paralysis or paresis, to... care in a rehabilitation facility; (5) Severe burns, including any third degree burn over ten...

  19. 5 CFR 831.1209 - Termination of disability annuity because of restoration to earning capacity.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...perform the duties of the occupation or business. Examples of such disabilities include blindness, paraplegia, multiple sclerosis, and cerebral hemorrhage. Claims involving transportation or equipment may be deducted only in the amount...

  20. 5 CFR 831.1209 - Termination of disability annuity because of restoration to earning capacity.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...perform the duties of the occupation or business. Examples of such disabilities include blindness, paraplegia, multiple sclerosis, and cerebral hemorrhage. Claims involving transportation or equipment may be deducted only in the amount...

  1. 5 CFR 831.1209 - Termination of disability annuity because of restoration to earning capacity.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...perform the duties of the occupation or business. Examples of such disabilities include blindness, paraplegia, multiple sclerosis, and cerebral hemorrhage. Claims involving transportation or equipment may be deducted only in the amount...

  2. Multimotor Transport in a System of Active and Inactive Kinesin-1 Motors Lara Scharrel,1,2

    E-print Network

    Jülicher, Frank

    - eases (4,5). In particular, two diseases, hereditary spastic paraplegia (HSP) and Charcot-Marie-Tooth. Defects in axonal transport have been linked to Alzheimer's and other neurodegenerative diseases. However

  3. 34 CFR 373.4 - What definitions apply?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...from amputation, arthritis, autism, blindness, burn injury, cancer, cerebral palsy, cystic fibrosis, deafness, head injury...paraplegia, quadriplegia and other spinal cord conditions, sickle-cell anemia, specific learning disabilities, end-stage...

  4. 34 CFR 350.5 - What definitions apply?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...from amputation, arthritis, autism, blindness, burn injury, cancer, cerebral palsy, cystic fibrosis, deafness, head injury...paraplegia, quadriplegia, other spinal cord impairments, sickle cell anemia, specific learning disability, end-stage...

  5. 34 CFR 385.4 - What definitions apply to these programs?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...amputation, arthritis, autism, blindness, burn injury, cancer, cerebral palsy, cystic fibrosis, deafness, head injury...paraplegia, quadriplegia and other spinal cord conditions, sickle-cell anemia, specific learning disabilities, end-stage...

  6. 34 CFR 385.4 - What definitions apply to these programs?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...amputation, arthritis, autism, blindness, burn injury, cancer, cerebral palsy, cystic fibrosis, deafness, head injury...paraplegia, quadriplegia and other spinal cord conditions, sickle-cell anemia, specific learning disabilities, end-stage...

  7. 34 CFR 350.5 - What definitions apply?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...from amputation, arthritis, autism, blindness, burn injury, cancer, cerebral palsy, cystic fibrosis, deafness, head injury...paraplegia, quadriplegia, other spinal cord impairments, sickle cell anemia, specific learning disability, end-stage...

  8. 34 CFR 373.4 - What definitions apply?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...from amputation, arthritis, autism, blindness, burn injury, cancer, cerebral palsy, cystic fibrosis, deafness, head injury...paraplegia, quadriplegia and other spinal cord conditions, sickle-cell anemia, specific learning disabilities, end-stage...

  9. 34 CFR 350.5 - What definitions apply?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...from amputation, arthritis, autism, blindness, burn injury, cancer, cerebral palsy, cystic fibrosis, deafness, head injury...paraplegia, quadriplegia, other spinal cord impairments, sickle cell anemia, specific learning disability, end-stage...

  10. 34 CFR 369.4 - What definitions apply to these programs?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...from amputation, arthritis, autism, blindness, burn injury, cancer, cerebral palsy, cystic fibrosis, deafness, head injury...paraplegia, quadriplegia and other spinal cord conditions, sickle-cell anemia, specific learning disabilities, end-stage...

  11. 34 CFR 361.5 - Applicable definitions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...amputation, arthritis, autism, blindness, burn injury, cancer, cerebral palsy, cystic fibrosis, deafness, head injury...conditions (including paraplegia and quadriplegia), sickle cell anemia, specific learning disability, end-stage...

  12. 34 CFR 377.5 - What definitions apply?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...from amputation, arthritis, autism, blindness, burn injury, cancer, cerebral palsy, cystic fibrosis, deafness, head injury...conditions (including paraplegia and quadriplegia), sickle cell anemia, specific learning disability, end-stage...

  13. 34 CFR 350.5 - What definitions apply?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...from amputation, arthritis, autism, blindness, burn injury, cancer, cerebral palsy, cystic fibrosis, deafness, head injury...paraplegia, quadriplegia, other spinal cord impairments, sickle cell anemia, specific learning disability, end-stage...

  14. 34 CFR 377.5 - What definitions apply?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...from amputation, arthritis, autism, blindness, burn injury, cancer, cerebral palsy, cystic fibrosis, deafness, head injury...conditions (including paraplegia and quadriplegia), sickle cell anemia, specific learning disability, end-stage...

  15. 34 CFR 361.5 - Applicable definitions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...amputation, arthritis, autism, blindness, burn injury, cancer, cerebral palsy, cystic fibrosis, deafness, head injury...conditions (including paraplegia and quadriplegia), sickle cell anemia, specific learning disability, end-stage...

  16. 34 CFR 373.4 - What definitions apply?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...from amputation, arthritis, autism, blindness, burn injury, cancer, cerebral palsy, cystic fibrosis, deafness, head injury...paraplegia, quadriplegia and other spinal cord conditions, sickle-cell anemia, specific learning disabilities, end-stage...

  17. 34 CFR 377.5 - What definitions apply?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...from amputation, arthritis, autism, blindness, burn injury, cancer, cerebral palsy, cystic fibrosis, deafness, head injury...conditions (including paraplegia and quadriplegia), sickle cell anemia, specific learning disability, end-stage...

  18. 34 CFR 377.5 - What definitions apply?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...from amputation, arthritis, autism, blindness, burn injury, cancer, cerebral palsy, cystic fibrosis, deafness, head injury...conditions (including paraplegia and quadriplegia), sickle cell anemia, specific learning disability, end-stage...

  19. 34 CFR 361.5 - Applicable definitions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...amputation, arthritis, autism, blindness, burn injury, cancer, cerebral palsy, cystic fibrosis, deafness, head injury...conditions (including paraplegia and quadriplegia), sickle cell anemia, specific learning disability, end-stage...

  20. 34 CFR 361.5 - Applicable definitions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...amputation, arthritis, autism, blindness, burn injury, cancer, cerebral palsy, cystic fibrosis, deafness, head injury...conditions (including paraplegia and quadriplegia), sickle cell anemia, specific learning disability, end-stage...

  1. 34 CFR 385.4 - What definitions apply to these programs?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...amputation, arthritis, autism, blindness, burn injury, cancer, cerebral palsy, cystic fibrosis, deafness, head injury...paraplegia, quadriplegia and other spinal cord conditions, sickle-cell anemia, specific learning disabilities, end-stage...

  2. 34 CFR 369.4 - What definitions apply to these programs?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...from amputation, arthritis, autism, blindness, burn injury, cancer, cerebral palsy, cystic fibrosis, deafness, head injury...paraplegia, quadriplegia and other spinal cord conditions, sickle-cell anemia, specific learning disabilities, end-stage...

  3. 34 CFR 369.4 - What definitions apply to these programs?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...from amputation, arthritis, autism, blindness, burn injury, cancer, cerebral palsy, cystic fibrosis, deafness, head injury...paraplegia, quadriplegia and other spinal cord conditions, sickle-cell anemia, specific learning disabilities, end-stage...

  4. 34 CFR 373.4 - What definitions apply?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...from amputation, arthritis, autism, blindness, burn injury, cancer, cerebral palsy, cystic fibrosis, deafness, head injury...paraplegia, quadriplegia and other spinal cord conditions, sickle-cell anemia, specific learning disabilities, end-stage...

  5. 34 CFR 350.5 - What definitions apply?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...from amputation, arthritis, autism, blindness, burn injury, cancer, cerebral palsy, cystic fibrosis, deafness, head injury...paraplegia, quadriplegia, other spinal cord impairments, sickle cell anemia, specific learning disability, end-stage...

  6. 34 CFR 369.4 - What definitions apply to these programs?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...from amputation, arthritis, autism, blindness, burn injury, cancer, cerebral palsy, cystic fibrosis, deafness, head injury...paraplegia, quadriplegia and other spinal cord conditions, sickle-cell anemia, specific learning disabilities, end-stage...

  7. 34 CFR 373.4 - What definitions apply?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...from amputation, arthritis, autism, blindness, burn injury, cancer, cerebral palsy, cystic fibrosis, deafness, head injury...paraplegia, quadriplegia and other spinal cord conditions, sickle-cell anemia, specific learning disabilities, end-stage...

  8. 34 CFR 377.5 - What definitions apply?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...from amputation, arthritis, autism, blindness, burn injury, cancer, cerebral palsy, cystic fibrosis, deafness, head injury...conditions (including paraplegia and quadriplegia), sickle cell anemia, specific learning disability, end-stage...

  9. 34 CFR 385.4 - What definitions apply to these programs?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...amputation, arthritis, autism, blindness, burn injury, cancer, cerebral palsy, cystic fibrosis, deafness, head injury...paraplegia, quadriplegia and other spinal cord conditions, sickle-cell anemia, specific learning disabilities, end-stage...

  10. 34 CFR 385.4 - What definitions apply to these programs?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...amputation, arthritis, autism, blindness, burn injury, cancer, cerebral palsy, cystic fibrosis, deafness, head injury...paraplegia, quadriplegia and other spinal cord conditions, sickle-cell anemia, specific learning disabilities, end-stage...

  11. 34 CFR 350.5 - What definitions apply?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... PROGRAM General § 350.5 What definitions apply? (a) The following definitions in 34 CFR part 77 apply to... epilepsy), paraplegia, quadriplegia, other spinal cord impairments, sickle cell anemia, specific...

  12. 34 CFR 350.5 - What definitions apply?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... PROGRAM General § 350.5 What definitions apply? (a) The following definitions in 34 CFR part 77 apply to... epilepsy), paraplegia, quadriplegia, other spinal cord impairments, sickle cell anemia, specific...

  13. Psychosocial outcomes among youth with spinal cord injury by neurological impairment.

    PubMed

    Riordan, Anne; Kelly, Erin H; Klaas, Sara J; Vogel, Lawrence C

    2015-01-01

    Objective Examine psychosocial outcomes of youth with spinal cord injury (SCI) as a function of neurological level (paraplegia/tetraplegia) and severity (American Spinal Injury Association (ASIA) Impairment Scale (AIS)). Design Survey research. Setting Three pediatric SCI specialty centers in the USA. Participants Youth with SCI ages 5-18 with neurological impairment classifications of: tetraplegia AIS ABC (tetraplegia ABC), paraplegia AIS ABC (paraplegia ABC), or AIS D. Outcome Measures Children's Assessment of Participation and Enjoyment, Pediatric Quality of Life Inventory, Revised Children's Manifest Anxiety Scale, and Children's Depression Inventory. Results Three hundred and forty youth participated; 57% were male; 60% were Caucasian, 21% Hispanic, 7% African-American, 2% Native American, and 3% reported "other". Their mean age was 8.15 years (standard deviation (SD) = 5.84) at injury and 13.18 years (SD = 3.87) at interview. Ninety-six youth (28%) had tetraplegia ABC injuries, 191 (56%) paraplegia ABC injuries, and 53 (16%) AIS D injuries. Neurological impairment was significantly related to participation and quality of life (QOL). Specifically, youth with paraplegia ABC and AIS D injuries participated in more activities than youth with tetraplegia ABC (P = 0.002; P = 0.018, respectively) and youth with paraplegia ABC participated more often than youth with tetraplegia ABC (P = 0.006). Youth with paraplegia ABC reported higher social QOL than youth with tetraplegia ABC (P = 0.001) and AIS D injuries (P = 0.002). Groups did not differ regarding mental health. Conclusion Interventions should target youth with tetraplegia ABC, as they may need support in terms of participation, and both youth with tetraplegia ABC and AIS D injuries in terms of social integration. PMID:24621027

  14. Neurological Complications Following Endoluminal Repair of Thoracic Aortic Disease

    SciTech Connect

    Morales, J. P.; Taylor, P. R.; Bell, R. E.; Chan, Y. C.; Sabharwal, T.; Carrell, T. W. G.; Reidy, J. F.

    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, general in 50, and local in 5 patients. Seven patients developed paraplegia (3.8%; two urgent and five elective). All occurred in-hospital apart from one associated with severe hypotension after a myocardial infarction at 3 weeks. Four of these recovered with cerebrospinal fluid (CSF) drainage. One patient with paraplegia died and two had permanent neurological deficit. The rate of permanent paraplegia and death was 1.6%. There were seven strokes (3.8%; four urgent and three elective). Three patients made a complete recovery, one had permanent expressive dysphasia, and three died. The rate of permanent stroke and death was 2.1%. Endoluminal treatment of thoracic aortic disease is an attractive alternative to open surgery; however, there is still a risk of paraplegia and stroke. Permanent neurological deficits and death occurred in 3.7% of the patients in this series. We conclude that prompt recognition of paraplegia and immediate insertion of a CSF drain can be an effective way of recovering spinal cord function and improving the prognosis.

  15. Mutations in the mitochondrial gene C12ORF65 lead to syndromic autosomal recessive intellectual disability and show genotype phenotype correlation.

    PubMed

    Buchert, Rebecca; Uebe, Steffen; Radwan, Farah; Tawamie, Hasan; Issa, Shaher; Shimazaki, Haruo; Henneke, Marco; Ekici, Arif B; Reis, André; Abou Jamra, Rami

    2013-11-01

    Homozygosity mapping and exome sequencing in two affected siblings of a consanguineous family with mild intellectual disability, spastic paraplegia, and strabismus revealed a homozygous premature stop mutation at codon 139 of C12ORF65. Two previous studies reported truncating mutations at positions 84 and 132 of the protein. However, symptoms of the referred patients were only partially overlapping. Considering our findings, we now conclude that truncating mutations in C12ORF65 lead to a variable phenotype with intellectual disability, spastic paraplegia, and ophthalmoplegia as common symptoms. Further, we confirm a genotype-phenotype correlation between increasing length of the truncated protein and decreasing severity of symptoms. PMID:24080142

  16. Pelizaeus-Merzbacher Disease

    MedlinePLUS

    ... disease (PMD) is a rare, progressive, degenerative central nervous system disorder in which coordination, motor abilities, and intellectual function ... Spastic Paraplegia Type 2 (SPG2). The PLP1-related disorders span a ... nervous system involvement (PMD) to progressive weakness and stiffness of ...

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

    E-print Network

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

  18. [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. PMID:1225017

  19. Safety Belt Education Using Visual Crash Images and Low-Cost Incentives.

    ERIC Educational Resources Information Center

    Bross, Michael H.; Spellicy, Martin J.

    1994-01-01

    Describes a community-based safety belt promotional program held at 10 public high schools. Safety belt assemblies, which created vivid crash images, were conducted using police officers, ambulance personnel, people with paraplegia, and athletes. Incentives were awarded to buckled students over 10 weeks. The program resulted in increased safety…

  20. 34 CFR 373.4 - What definitions apply?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... defined in 34 CFR 361.5. (Authority: 29 U.S.C. 711(c)) Individual with a disability is defined as follows... injury, cancer, cerebral palsy, cystic fibrosis, deafness, head injury, heart disease, hemiplegia...), paraplegia, quadriplegia and other spinal cord conditions, sickle-cell anemia, specific learning...

  1. 34 CFR 373.4 - What definitions apply?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... defined in 34 CFR 361.5. (Authority: 29 U.S.C. 711(c)) Individual with a disability is defined as follows... injury, cancer, cerebral palsy, cystic fibrosis, deafness, head injury, heart disease, hemiplegia...), paraplegia, quadriplegia and other spinal cord conditions, sickle-cell anemia, specific learning...

  2. 34 CFR 350.5 - What definitions apply?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... PROGRAM General § 350.5 What definitions apply? (a) The following definitions in 34 CFR part 77 apply to..., blindness, burn injury, cancer, cerebral palsy, cystic fibrosis, deafness, head injury, heart disease... epilepsy), paraplegia, quadriplegia, other spinal cord impairments, sickle cell anemia, specific...

  3. 34 CFR 350.5 - What definitions apply?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... PROGRAM General § 350.5 What definitions apply? (a) The following definitions in 34 CFR part 77 apply to..., blindness, burn injury, cancer, cerebral palsy, cystic fibrosis, deafness, head injury, heart disease... epilepsy), paraplegia, quadriplegia, other spinal cord impairments, sickle cell anemia, specific...

  4. TRAVEL ACCIDENT INSURANCE The maximum benefit (Principal Sum) is $100,000 of Accidental Death and Dismemberment (Age

    E-print Network

    of combination of any two: Hand, Foot, Sight of One Eye Quadriplegia The Principal Sum Paraplegia 75 to seven days Aggregate Limit of Insurance: $1,000,000 per Accident Coverage y 24-Hour Business Travel y Trust Member employer and have an accident while traveling for college- approved business, this Travel

  5. Novel Cyclovirus in Human Cerebrospinal Fluid, Malawi, 2010–2011

    PubMed Central

    Zijlstra, Ed E; van Hellemond, Jaap J.; Schapendonk, Claudia M.E.; Bodewes, Rogier; Schürch, Anita C.; Haagmans, Bart L.; Osterhaus, Albert D.M.E.

    2013-01-01

    To identify unknown human viruses, we analyzed serum and cerebrospinal fluid samples from patients with unexplained paraplegia from Malawi by using viral metagenomics. A novel cyclovirus species was identified and subsequently found in 15% and 10% of serum and cerebrospinal fluid samples, respectively. These data expand our knowledge of cyclovirus diversity and tropism. PMID:23968557

  6. 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,…

  7. This two day symposium highlights progress in the rehabilitation and treatment of spinal cord injury and honours the contributions of more than $700,000 for spinal cord research in Winnipeg.

    E-print Network

    Manitoba, University of

    This two day symposium highlights progress in the rehabilitation and treatment of spinal cord injury and honours the contributions of more than $700,000 for spinal cord research in Winnipeg. We Cord Research Centre The Spinal Cord Research Centre and the Manitoba Paraplegia Foundation cordially

  8. 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).…

  9. 34 CFR 369.4 - What definitions apply to these programs?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... PROJECTS General § 369.4 What definitions apply to these programs? (a) The following definitions in 34 CFR... for vocational rehabilitation services. (34 CFR part 361) (Authority: Sec. 12(c) of the Act; 29 U.S.C... disorders, neurological disorders (including stroke and epilepsy), paraplegia, quadriplegia and other...

  10. 34 CFR 385.4 - What definitions apply to these programs?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... § 385.4 What definitions apply to these programs? (a) The following definitions in 34 CFR part 77 apply... services means the same as the term is defined in 34 CFR 369.4(b). (Authority: Secs. 7, 12(c), and 101(a)(7... disorders, neurological disorders (including stroke and epilepsy), paraplegia, quadriplegia and other...

  11. 34 CFR 377.5 - What definitions apply?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... this part are defined in 34 CFR 77.1: Applicant Application Award Budget period Department EDGAR... 34 CFR 74.3: Grant Grantee (c) Other definitions. The following definitions also apply to this part... stroke and epilepsy), spinal cord conditions (including paraplegia and quadriplegia), sickle cell...

  12. 34 CFR 377.5 - What definitions apply?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... this part are defined in 34 CFR 77.1: Applicant Application Award Budget period Department EDGAR... 34 CFR 74.3: Grant Grantee (c) Other definitions. The following definitions also apply to this part... stroke and epilepsy), spinal cord conditions (including paraplegia and quadriplegia), sickle cell...

  13. 34 CFR 377.5 - What definitions apply?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... this part are defined in 34 CFR 77.1: Applicant Application Award Budget period Department EDGAR... 34 CFR 74.3: Grant Grantee (c) Other definitions. The following definitions also apply to this part... stroke and epilepsy), spinal cord conditions (including paraplegia and quadriplegia), sickle cell...

  14. 34 CFR 385.4 - What definitions apply to these programs?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... § 385.4 What definitions apply to these programs? (a) The following definitions in 34 CFR part 77 apply... services means the same as the term is defined in 34 CFR 369.4(b). (Authority: Secs. 7, 12(c), and 101(a)(7... disorders, neurological disorders (including stroke and epilepsy), paraplegia, quadriplegia and other...

  15. 34 CFR 377.5 - What definitions apply?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... this part are defined in 34 CFR 77.1: Applicant Application Award Budget period Department EDGAR... 34 CFR 74.3: Grant Grantee (c) Other definitions. The following definitions also apply to this part... stroke and epilepsy), spinal cord conditions (including paraplegia and quadriplegia), sickle cell...

  16. 34 CFR 369.4 - What definitions apply to these programs?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... PROJECTS General § 369.4 What definitions apply to these programs? (a) The following definitions in 34 CFR... for vocational rehabilitation services. (34 CFR part 361) (Authority: Sec. 12(c) of the Act; 29 U.S.C... disorders, neurological disorders (including stroke and epilepsy), paraplegia, quadriplegia and other...

  17. Economic Impacts of Treatment for Type II or III Thoracoabdominal Aortic Aneurysm in the United States

    PubMed Central

    Vaislic, Mickael; Vaislic, Claude; Alsac, Jean-Marc; Benjelloun, Amira; Chocron, Sidney; Unterseeh, Thierry; Fabiani, Jean-Noel

    2014-01-01

    Background: Current treatment for extensive thoracoabdominal aortic aneurysms (TAAAs) involves high-risk surgical and endovascular repairs, with a hospital mortality exceeding 20%, and a postoperative paraplegia rate beyond 10.5%. Objectives: The aim of this study was to present an estimation of the economic impacts of surgical and endovascular treatments of types II and III TAAAs in the US as well as the economic consequences of the elimination of spinal cord injury and mortality via an endovascular repair of extensive TAAAs (1). Materials and Methods: We compared the current hospital charges of endovascular and surgical repair of extensive TAAAs, also provided a cost analysis of health care charges resulting from paraplegia in the United States, and determined the prevalence of extensive TAAAs found yearly during autopsies in the U.S. Based on the figures gathered and the frequency of Thoracic Aortic Aneurysms per year, we were able to calculate the nationwide inpatient hospital charges, the total average expenses affected by paraplegia during the first 12 months after the repair, the total average expenses after paraplegia for each subsequent year, mortality rate at 30 days and one year, and the number of extensive TAAAs ruptures. Results: The current nationwide inpatient hospital charges for type II or III TAAA repair cost $12484324 and $37612665 for endovascular repair and surgical repair respectively, and the total average expenses for patients affected by paraplegia during the first 12-month were $4882291 and $23179110 after endovascular repair and surgical repair respectively. The nationwide average expense after 10 years for patients undergoing surgical repair and affected by paraplegia is $33421910 and $6,316,183 for patients undergoing endovascular repair. Moreover, 55 patients with a type II or type III TAAA died after 30 days, and 100 after 1 year. The potential risk of type II or III TAAA ruptures is totally 1637 in a year. Conclusions: Major economic impacts of type II or III TAAA repairs in the United States have been identified. An endovascular repair excluding spinal cord injury and mortality with the same average costs as present endovascular treatments makes it possible to save at least $53189742 after one year, 100 lives of operated patients would be saved after one year, and 1637 type II and III TAAA ruptures would be avoided yearly. PMID:25478532

  18. [Current status and future of TEVAR for descending thoracic aortic aneurysm].

    PubMed

    Kichikawa, Kimihiko; Sakaguchi, Shoji; Itoh, Hirofumi; Ichihashi, Shigeo; Tabayashi, Nobuoki; Taniguchi, Shigeki; Higashiura, Wataru

    2009-09-01

    As a new option for treatment of thoracic aortic aneurysm, thoracic endovascular aneurysm repair (TEVAR) has become more popular recently in Japan, because TEVAR is less invasive and TAG and Tallent are approved as a commercially available device for descending thoracic aorta The results of TEVAR showed more favorable compared to open surgery. Incidence of paraplegia after TEVAR is lower than that of open surgery. However we performed spinal cord drainage to avoid paraplegia in patients with history of the aortic aneurysm repair or long segmental coverage with stent graft. It has higher risk of injury to the iliac artery compared to EVAR, and in patients with small iliac artery and/or severe calcified artery, iliac conduit should be made before TEVAR. To expand the indication of TEAVR and to obtain better outcome, team approach with borderless and improvement of devices should be required. TEAVR will become more predominant and safer treatment in the future. PMID:19827569

  19. Different expression levels of spartin cause broad spectrum of cellular consequences in human neuroblastoma cells.

    PubMed

    Milewska, Malgorzata; Byrne, Paula Catherine

    2015-09-01

    Hereditary spastic paraplegia describes a diverse group of neurodegenerative conditions characterised by progressive spasticity and weakness of the lower limbs. Mutations in the SPG20 gene encoding spartin cause an autosomal recessive hereditary spastic paraplegia known as Troyer syndrome. To evaluate the cellular consequences of sustained spartin depletion in neuronal cells, we established several clonal SH-SY5Y cell lines with different level of spartin knockdown. Here, we report that cells with modest spartin downregulation show signs of neuronal differentiation such as increased neuritogenesis and cytoskeleton rearrangement. Interestingly, we also indicate that permanent high level spartin depletion results in impaired cell growth and multiple mitochondrial aberrations, which we speculate, arise as a result of chronic oxidative stress. Our studies demonstrate that the scale of spartin downregulation is the major factor that determines the severity of cellular consequences observed and suggest that there is a critical level of spartin expression which must be maintained for proper cellular functions. PMID:25821002

  20. CT-guided transforaminal cervical and lumbar epidural injections.

    PubMed

    Depriester, C; Setbon, S; Larde, A; Malaquin, E; Vanden Abeele, B; Bocquet, J

    2012-09-01

    Transforaminal injections are widely used. Serious complications including strokes and paraplegia have been reported after transforaminal injections of corticosteroids, and the Afssaps (2011) has issued a warning about their use [1]. The needle must be positioned in the posterior aspect of foramen, and its correct placement validated by an injection of contrast product. It is preferable to choose cortivazol (Altim(®)) as the corticoid for injection. This procedure is simple, reproducible, and durably effective in 60 to 70% of cases. Complications and adverse effects are rare but potentially serious: allergies, blood pressure surge, vasovagal syncope, transient exacerbation of pain, infection, stroke, and paraplegia. The aim of this course is to stress the need for rigor - in the indication, the technical performance of the procedure, and the overall management of the patient. PMID:22925592

  1. Suppl\\'eance perceptive par \\'electro-stimulation linguale embarqu\\'ee : perspectives pour la pr\\'evention des escarres chez le bless\\'e m\\'edullaire

    E-print Network

    Chenu, Olivier; Moreau-Gaudry, Alexandre; Fleury, Anthony; Demongeot, Jacques; Payan, Yohan

    2007-01-01

    We introduce the innovative technologies, based on the concept of "sensory substitution", we are developing in the fields of biomedical engineering and human disability. Precisely, our goal is to design, develop and validate practical assistive biomedical and/or technical devices and/or rehabilitating procedures for persons with disabilities, using artificial tongue-placed tactile biofeedback systems. This paper proposes an application for pressure sores prevention in case of spinal cord injuries (persons with paraplegia, or tetraplegia).

  2. Carcinoma of the prostate: remission of paraparesis with inhibitors of bone resorption.

    PubMed Central

    Percival, R. C.; Watson, M. E.; Williams, J. L.; Kanis, J. A.

    1985-01-01

    We describe a patient with metastatic carcinoma of the prostate associated with paraplegia. The patient also had Paget's disease of bone elsewhere. Because the neurological lesion was thought to be due to Paget's disease, the patient was treated with inhibitors of bone resorption. Treatment rapidly induced clinical remission and inhibition of bone resorption, and withdrawal was associated with relapse. This suggests that such agents may be of value in the treatment of bone disease of prostatic carcinoma. Images Figure 1 PMID:3160014

  3. [Brentuximab vedotin and cord blood transplantation for primary refractory Hodgkin lymphoma following autologous hematopoietic stem cell transplantation].

    PubMed

    Meshitsuka, Sohsuke; Suzuki, Kenshi; Igeta, Yukifusa; Kawai, Sigeo; Kumasaka, Toshio; Tsukada, Nobuhiro

    2015-06-01

    We report a 26-year-old man with primary refractory nodular sclerosis Hodgkin lymphoma against ABVD, ICE and autologous peripheral blood stem cell transplantation (auto-PBSCT), presenting with multiple epidural spinal cord compressions, paraplegia, and generalized lymphadenopathy. We administrated four cycles of brentuximab vedotin to achieve a complete response, and then conducted cord blood transplantation. This case raises the possibility of a new strategy for refractory Hodgkin lymphoma showing residual lesions after auto-PBSCT. PMID:26256882

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

    PubMed

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

    2013-05-01

    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

  5. Atrial myxoma presenting as total occlusion of the abdominal aorta and its major four branches.

    PubMed

    Huang, Chun-Yang; Chang, Yu-Yao; Hsieh, Ming-Yu; Hsu, Chiao-Po

    2012-07-01

    The presentations of cardiac myxoma are diverse, from asymptomatic to a variety of symptoms due to embolization. Occlusion of abdominal aortic bifurcation by straddled myxoma is not common; however, obstructive level above renal artery is very rare. We present a patient with cardiac myxoma who presented with acute onset of paraplegia. The aorta was occluded from the level of the liver dome to the renal arteries, and catastrophic outcome (ischemia/reperfusion) following its removal. PMID:22824050

  6. Unusual course of an epidural rhabdomyosarcoma of the upper thoracic spine.

    PubMed

    Tsitsopoulos, P D; Tsonidis, C A; Nanasis, K A; Tsoleka, K D; Tavridis, G N

    1995-01-01

    This report deals with a case of rhabdomyosarcoma in the upper thoracic spine. It is of particular interest, not only for the rarity of type and location of this tumour, but for its clinical course, which presented fluctuations of neurological status, included an acute demonstration of complete paraplegia followed by full recovery after conservative treatment, and gradual relapsing of neurological deficit, one year later. PMID:8748814

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

    PubMed Central

    Cruz–Arámbulo, Robert; Nykamp, Stephanie

    2012-01-01

    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. PMID:22942443

  8. Epidurals, spinals and bleeding disorders in pregnancy: a review.

    PubMed

    Sage, D J

    1990-08-01

    Paraplegia caused by spinal haemorrhage is a very rare but disastrous complication of spinal or epidural insertion. The risk in uncomplicated surgical and obstetric patients is outlined. Bleeding disorders in pregnant patients may prevent the use of major regional anaesthesia. Factors which influence the choice of anaesthetic technique for patients with pregnancy-induced hypertension, von Willebrand's disease, and anticoagulation therapy, are discussed. PMID:2221324

  9. 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, standing and movement accounting for 67% improvement rate .

  10. Modeling Axonal Phenotypes with Human Pluripotent Stem Cells.

    PubMed

    Denton, Kyle R; Xu, Chong-Chong; Li, Xue-Jun

    2016-01-01

    Impaired axonal development and degeneration are implicated in many debilitating disorders, such as hereditary spastic paraplegia (HSP), amyotrophic lateral sclerosis (ALS), and periphery neuropathy. Human pluripotent stem cells (hPSCs) have provided researchers with an excellent resource for modeling human neuropathologic processes including axonal defects in vitro. There are a number of steps that are crucial when developing an hPSC-based model of a human disease, including generating induced pluripotent stem cells (iPSCs), differentiating those cells to affected cell types, and identifying disease-relevant phenotypes. Here, we describe these steps in detail, focusing on the neurodegenerative disorder HSP. PMID:25520289

  11. Rehabilitation and physical therapy for the neurologic veterinary patient.

    PubMed

    Sims, Cory; Waldron, Rennie; Marcellin-Little, Denis J

    2015-01-01

    A comprehensive physiotherapy plan for neurology patients manages pain, prevents secondary complications, and supports the health and function of musculoskeletal tissues during recovery. Neurologically impaired patients range in ability from complete immobility (tetraplegia/paraplegia), partial mobility (tetraparesis/paraparesis), mild ataxia, to pain only. Important considerations for the design of a physiotherapy program include access to the patient, level of staff support, and safety of staff, patient, and client during treatments. A thorough overview of the treatment plan and expected outcome should be discussed with the client at the onset of therapy and should be reviewed frequently, particularly as the patient's status changes. PMID:25440754

  12. 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.

  13. Spinal cord monitoring.

    PubMed

    Nuwer, M R

    1999-12-01

    Over the past two decades, intraoperative spinal cord monitoring has matured into a widely used clinical tool. It is used when the spinal cord is at risk for damage during a surgical procedure. This includes orthopedic, neurosurgical, and certain cardiothoracic procedures. Both somatosensory evoked potential (SEP) and direct motor pathway stimulation techniques are available. The SEP techniques are used most widely, are generally accepted, and have been shown to reduce surgical morbidity. A large multicenter study has shown that SEP monitoring reduces postoperative paraplegia by more than 50-60%. Techniques and literature on clinical applications are reviewed in this report. PMID:10567073

  14. The changing pattern of spinal arachnoiditis.

    PubMed Central

    Shaw, M D; Russell, J A; Grossart, K W

    1978-01-01

    Spinal arachnoiditis is a rare condition. Eighty cases, diagnosed during a period when 7600 spinal contrast investigations were undertaken, have been reviewed. The majority had suffered a previous spinal condition, the most common being lumbar disc disease. There has been a change in the distribution of arahnoiditis with the lumbar region now most frequently involved. This accounts for the persistence of radicular symptoms and the relatively low incidence of paraplegia when compared with earlier series. Surgery does not appear to have any role in the treatment. Images PMID:632824

  15. The effect of magnesium oral therapy on spasticity in a patient with multiple sclerosis.

    PubMed

    Rossier, P; van Erven, S; Wade, D T

    2000-11-01

    The effects of magnesium glycerophosphate oral therapy on spasticity was studied in a 35-year-old woman with severe spastic paraplegia resulting from multiple sclerosis (MS). We found a significant improvement in the spasticity after only 1 week from the onset of the treatment on the modified Ashworth scale, an improvement in the range of motion and in the measures of angles at resting position in lower limbs. No side-effects were reported and there was no weakness in the arms during the treatment. PMID:11136367

  16. [Epidural abscess in the spine extended from pulmonary zygomycosis during consolidation chemotherapy for acute lymphoblastic leukemia].

    PubMed

    Tuyumu, Keiko; Nakaya, Aya; Miyauchi, Jun; Okamoto, Shinichiro

    2011-08-01

    A 37-year-old woman with acute lymphoblastic leukemia developed fever and pneumonia during persistent neutropenia after consolidation chemotherapy. Pneumonia was rapidly followed by the formation of abscess in adjacent subcutaneous tissues, muscles and bones. She subsequently developed sudden onset of paraplegia and loss of all sensation below Th4. Epidural abscess was detected by MRI. Emergency drainage was performed, but the patient died 4 days after the operation. Rhizopus oryzae grew from culture of the epidural abscess. Since the incidence of zygomycosis appears to have increased over the recent years, clinicians should be aware of the possibility of zygomycosis in case of any infection that is resistant to antibiotics. PMID:21897081

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

    PubMed Central

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

    2014-01-01

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

  18. Novel SIL1 mutations cause cerebellar ataxia and atrophy in a French-Canadian family.

    PubMed

    Noreau, Anne; La Piana, Roberta; Marcoux, Camille; Dion, Patrick A; Brais, Bernard; Bernard, Geneviève; Rouleau, Guy A

    2015-10-01

    Two French-Canadian sibs with cerebellar ataxia and dysarthria were seen in our neurogenetics clinic. The older brother had global developmental delay and spastic paraplegia. Brain MRIs from these two affected individuals showed moderate to severe cerebellar atrophy. To identify the genetic basis for their disease, we conducted a whole exome sequencing (WES) investigation using genomic DNA prepared from the affected sibs and their healthy father. We identified two mutations in the SIL1 gene, which is reported to cause Marinesco-Sjögren syndrome. This study emphasizes how the diagnosis of patients with ataxic gait and cerebellar atrophy may benefit from WES to identify the genetic cause of their condition. PMID:26260654

  19. 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. PMID:22275666

  20. Genotype-phenotype correlation in L1 associated diseases.

    PubMed Central

    Fransen, E; Van Camp, G; D'Hooge, R; Vits, L; Willems, P J

    1998-01-01

    The neural cell adhesion molecule L1 (L1CAM) plays a key role during embryonic development of the nervous system and is involved in memory and learning. Mutations in the L1 gene are responsible for four X linked neurological conditions: X linked hydrocephalus (HSAS), MASA syndrome, complicated spastic paraplegia type 1 (SP-1), and X linked agenesis of the corpus callosum. As the clinical picture of these four L1 associated diseases shows considerable overlap and is characterised by Corpus callosum hypoplasia, mental Retardation, Adducted thumbs, Spastic paraplegia, and Hydrocephalus, these conditions have recently been lumped together into the CRASH syndrome. We investigate here whether a genotype-phenotype correlation exists in CRASH syndrome since its clinical spectrum is highly variable and numerous L1 mutations have been described. We found that (1) mutations in the extracellular part of L1 leading to truncation or absence of L1 cause a severe phenotype, (2) mutations in the cytoplasmic domain of L1 give rise to a milder phenotype than extracellular mutations, and (3) extracellular missense mutations affecting amino acids situated on the surface of a domain cause a milder phenotype than those affecting amino acids buried in the core of the domain. PMID:9610803

  1. The Troyer syndrome (SPG20) protein spartin interacts with Eps15

    SciTech Connect

    Bakowska, Joanna C.; Jenkins, Russell; Pendleton, James; Blackstone, Craig . E-mail: blackstc@ninds.nih.gov

    2005-09-09

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

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

    PubMed

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

    2011-01-01

    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

  3. An AP4B1 frameshift mutation in siblings with intellectual disability and spastic tetraplegia further delineates the AP-4 deficiency syndrome.

    PubMed

    Abdollahpour, Hengameh; Alawi, Malik; Kortüm, Fanny; Beckstette, Michael; Seemanova, Eva; Komárek, Vladimír; Rosenberger, Georg; Kutsche, Kerstin

    2015-02-01

    The recently proposed adaptor protein 4 (AP-4) deficiency syndrome comprises a group of congenital neurological disorders characterized by severe intellectual disability (ID), delayed or absent speech, hereditary spastic paraplegia, and growth retardation. AP-4 is a heterotetrameric protein complex with important functions in vesicle trafficking. Mutations in genes affecting different subunits of AP-4, including AP4B1, AP4E1, AP4S1, and AP4M1, have been reported in patients with the AP-4 deficiency phenotype. We describe two siblings from a non-consanguineous couple who presented with severe ID, absent speech, microcephaly, growth retardation, and progressive spastic tetraplegia. Whole-exome sequencing in the two patients identified the novel homozygous 2-bp deletion c.1160_1161delCA (p.(Thr387Argfs*30)) in AP4B1. Sanger sequencing confirmed the mutation in the siblings and revealed it in the heterozygous state in both parents. The AP4B1-associated phenotype has previously been assigned to spastic paraplegia-47. Identification of a novel AP4B1 alteration in two patients with clinical manifestations highly similar to other individuals with mutations affecting one of the four AP-4 subunits further supports the observation that loss of AP-4 assembly or functionality underlies the common clinical features in these patients and underscores the existence of the clinically recognizable AP-4 deficiency syndrome. PMID:24781758

  4. Decentralized cardiovascular autonomic control and cognitive deficits in persons with spinal cord injury

    PubMed Central

    Wecht, Jill M.; Bauman, William A.

    2013-01-01

    Spinal cord injury (SCI) results in motor and sensory impairments that can be identified with the American Spinal Injury Association (ASIA) Impairment Scale (AIS). Although, SCI may disrupt autonomic neural transmission, less is understood regarding the clinical impact of decentralized autonomic control. Cardiovascular regulation may be altered following SCI and the degree of impairment may or may not relate to the level of AIS injury classification. In general, persons with lesions above T1 present with bradycardia, hypotension, and orthostatic hypotension; functional changes which may interfere with rehabilitation efforts. Although many individuals with SCI above T1 remain overtly asymptomatic to hypotension, we have documented deficits in memory and attention processing speed in hypotensive individuals with SCI compared to a normotensive SCI cohort. Reduced resting cerebral blood flow (CBF) and diminished CBF responses to cognitive testing relate to test performance in hypotensive non-SCI, and preliminary evidence suggests a similar association in individuals with SCI. Persons with paraplegia below T7 generally present with a normal cardiovascular profile; however, our group and others have documented persistently elevated heart rate and increased arterial stiffness. In the non-SCI literature there is evidence supporting a link between increased arterial stiffness and cognitive deficits. Preliminary evidence suggests increased incidence of cognitive impairment in individuals with paraplegia, which we believe may relate to adverse cardiovascular changes. This report reviews relevant literature and discusses findings related to the possible association between decentralized cardiovascular autonomic control and cognitive dysfunction in persons with SCI. PMID:23809520

  5. Spinal cord ischemia after cardiac arrest.

    PubMed

    Imaizumi, H; Ujike, Y; Asai, Y; Kaneko, M; Chiba, S

    1994-01-01

    Subsequent to cardiac arrest, a 58-year-old man with intractable dysrhythmia and severe arteriosclerosis developed flaccid paraplegia, depressed deep tendon reflexes, and showed no pain or temperature sensation caudal to Th-7 in spite of completely intact proprioception and vibration sensation. An echocardiogram showed no clots or vegetation on the prosthetic valve and no thrombus in the left atrium or left ventricle. The patient's paraplegia was permanent, at least through a follow-up period of 2 years. These findings suggest that the etiology was spinal cord ischemia due to blood supply in the area of the anterior spinal artery (ASA); however, magnetic resonance T2-weighted imaging demonstrated signal abnormalities throughout the gray matter and in the adjacent center white matter. Somatosensory-evoked potentials (SEP) measure neural transmission in the afferent spinal cord pathway, which is located in the lateral and posterior columns of the white matter; these showed a delay in latency between Th-6 and Th-7. The spinal cord is as vulnerable to transient ischemia as the brain. Spinal cord ischemia after cardiac arrest results from principal damage in the anterior horn of the gray matter, the so-called ASA syndrome; however, the pathways of SEP and pathogenesis of the spinal cord ischemia need further investigation. PMID:7884198

  6. 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

  7. Cervical Osteomyelitis with Thoracic Myelitis and Meningitis in a Diabetic Patient

    PubMed Central

    Ohnishi, Yu-ichiro; Iwatsuki, Koichi; Ishida, Shiromaru; Yoshimine, Toshiki

    2015-01-01

    A 45-year-old man with a history of untreated diabetes mellitus had a persisting fever, back pain, and diarrhea. The primary care physician diagnosed the patient with the flu and gastroenteritis. The patient developed paraplegia for two weeks and was admitted to another hospital. The physician in this hospital suspected infectious meningitis and myelitis, and administered piperacillin and steroids without cerebrospinal fluid (CSF) examination. On referral to our hospital, he presented a high fever and complete paraplegia. The lumbar puncture revealed a yellowish CSF, polynucleosis, and hypoglycorrhachia. Bacteria were not detected on Gram’s staining and were not confirmed by CSF culture. Magnetic resonance imaging (MRI) showed no thoracolumbar lesion and suggested a cervical epidural abscess without any spinal cord compression. He was diagnosed as having osteomyelitis with meningitis and thoracic myelitis. The infection subsided with broad-spectrum antibiotics. After two weeks, bilateral sensorimotor disturbances of the upper extremities appeared. MRI findings showed the epidural abscess compressing the cervical spinal cord. We performed debridement of the epidural abscess. The infection was clinically controlled by using another antibiotic. One month after the infection subsided, a 360° reconstruction was performed. In this case, the misdiagnosis and the absence of CSF examination and culture to detect the pathogenic bacteria at an earlier stage in the patient’s disease course might have led to the exacerbation of the pathology. PMID:25983566

  8. Motor Evoked Potentials in 43 High Risk Spine Deformities

    PubMed Central

    Biscevic, Mirza; Biscevic, Sejla; Ljuca, Farid; Smrke, Barbara UR; Ozturk, Cagatay; Tiric-Campara, Merita

    2014-01-01

    ABSTRACT Introduction: Correction of pediatric spine deformities is challenging surgical procedures. This fragile group of patients has many risk factors, therefore prevention of most fearing complication-paraplegia is extremely important. Monitoring of transmission of neurophysiological impulses through motor and sensor pathways of spinal cord gives us an insight into cord's function, and predicts postoperative neurological status. Goal: Aim of this work is to present our experiences in monitoring of spinal cord motor function - MEP during surgical corrections of the hardest pediatric spine deformities, pointing on the most dangerous aspects. Material and methods: We analyzed incidence of MEP changes and postoperative neurological status in patients who had major spine correcting surgery in period April ‘11- April ‘14 on our Spine department. Results: Two of 43 patients or 4.6% in our group experienced significant MEP changes during their major spine reconstructive surgeries. We promptly reduced distractive forces, and MEP normalized, and there were no neurological deficit. Neuromonitoring is reliable method which allows us to “catch” early signs of neurological deficits, when they are still in reversible phase. Although IONM cannot provide complete protection of neurological deficit (it reduces risk of paraplegia about 75%), it at least afford a comfort to the surgeon being fear free that his patient is neurologically intact during long lasting procedures. PMID:25568569

  9. Size and blood flow of central and peripheral arteries in highly trained able-bodied and disabled athletes.

    PubMed

    Huonker, M; Schmid, A; Schmidt-Trucksass, A; Grathwohl, D; Keul, J

    2003-08-01

    In a cross-sectional study, central and peripheral arteries were investigated noninvasively in high-performance athletes and in untrained subjects. The diastolic inner vessel diameter (D) of the thoracic and abdominal aorta, the subclavian artery (Sub), and common femoral artery (Fem) were determined by duplex sonography in 18 able-bodied professional tennis players, 34 able-bodied elite road cyclist athletes, 26 athletes with paraplegia, 17 below-knee amputated athletes, and 30 able-bodied, untrained subjects. The vessel cross-sectional areas (CSA) were set in relation to body surface area (BSA), and the cross-section index (CS-index = CSA/BSA) was calculated. Volumetric blood flow was determined in Sub and Fem via a pulsed-wave Doppler system and was set in relation to heart rate to calculate the stroke flow. A significantly increased D of Sub was found in the racket arm of able-bodied tennis players compared with the opposite arm (19%). Fem of able-bodied road cyclist athletes and of the intact limb in below-knee amputated athletes showed similar increases. D of Fem was lower in athletes with paraplegia (37%) and in below-knee amputated athletes proximal to the lesion (21%) compared with able-bodied, untrained subjects; CS-indexes were reduced 57 and 31%, respectively. Athletes with paraplegia demonstrated a larger D (19%) and a larger CS-index in Sub (54%) than able-bodied, untrained subjects. No significant differences in D and CS-indexes of the thoracic and abdominal aorta were found between any of the groups. The changes measured in Sub and Fem were associated with corresponding alterations in blood flow and stroke flow in all groups. The study suggests that the size and blood flow volume of the proximal limb arteries are adjusted to the metabolic needs of the corresponding extremity musculature and underscore the impact of exercise training or disuse on the structure and the function of the arterial system. PMID:12433857

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

    E-print Network

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

    2007-01-01

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

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

    E-print Network

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

    2007-01-01

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

  12. Spina Bifida Cystica

    PubMed Central

    Lorber, John

    1972-01-01

    The disappointing results of treatment in 270 consecutive unselected cases of spina bifida admitted during a 27-month period are detailed. Massive effort has led to much avoidable suffering at an exorbitant cost in manpower and money. This study confirms the validity of those adverse prognostic criteria defined in an earlier study and which form a basis for selection. These are (1) thoracolumbar lesions, (2) severe paraplegia, (3) gross enlargement of head, (4) kyphosis, and (5) other severe congenital defects, or birth injuries. It is shown again that selection is possible on the first day of life on purely objective criteria; that it is essential for the benefit of all those affected—whether they are for treatment or no treatment; and that it is in the interest of their families and the community. ImagesFIG. 2.FIG. 3.FIG. 4.FIG. 5.FIG. 6.FIG. 7. PMID:4567074

  13. New domains of neural cell-adhesion molecule L1 implicated in X-linked hydrocephalus and MASA syndrome

    SciTech Connect

    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 first 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.

  14. A diagnostic challenge in a young woman with intractable hiccups and vomiting: a case of neuromyelitis optica

    PubMed Central

    Mandaliya, Rohan; Boigon, Margot; Smith, David G.; Bhutani, Suchit; Ali, Naveed; Hilton, Cheryl; Kelly, John; Ternopolska, Nataliya

    2015-01-01

    Intractable nausea and vomiting along with hiccups is a commonly encountered problem on any general medicine or gastroenterology service. These symptoms are usually not appreciated as the possible initial manifestation of neuromyelitis optica (NMO). Missing diagnosis at this early stage will lead to a delay in the treatment, and hence, irreversible complications including blindness and paraplegia could occur. We report a case of a 22-year-old young female who presented with intractable hiccups and vomiting. After extensive evaluation, she was found to have NMO which involved the area postrema, the vomiting center of the brain. Early diagnosis from the clinical picture aided by aquaporin-4 serologic testing is extremely important to allow early initiation of immunosuppressive therapy. Immunosuppression gives an opportunity to modify the disease at an earlier stage rather than waiting for evolution of disease to fulfill the diagnostic criteria of NMO. PMID:26486116

  15. Neuroprosthetic applications of electrical stimulation.

    PubMed

    Grill, W M; Kirsch, R F

    2000-01-01

    Neural prostheses are a developing technology that use electrical activation of the nervous system to restore function to individuals with neurological impairment. Neural prostheses function by electrical initiation of action potentials in nerve fibers that carry the signal to an endpoint where chemical neurotransmitters are released, either to affect an end organ or another neuron. Thus, in principle, any end organ under neural control is a candidate for neural prosthetic control. Applications have included stimulation in both the sensory and motor systems and range in scope from experimental trials with single individuals to commercially available devices. Outcomes of motor system neural prostheses include restoration of hand grasp and release in quadriplegia, restoration of standing and stepping in paraplegia, restoration of bladder function (continence, micturition) following spinal cord injury, and electrophrenic respiration in high-level quadriplegia. Neural prostheses restore function and provide greater independence to individuals with disability. PMID:11067578

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

    SciTech Connect

    Rousseau, Herve Elaassar, Omar; Marcheix, Bertrand; Cron, Christophe; Chabbert, Valerie; Combelles, Sophie; Dambrin, Camille; Leobon, Bertrand; Moreno, Ramiro; Otal, Philippe; Auriol, Julien

    2012-02-15

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

  17. Clinical assessment and magnetic resonance imaging of the shoulder of patients with spinal cord injury

    PubMed Central

    Alves, Alex Pereira; Terrabuio Junior, Alberto Antonio; Pimenta, Ciro Jabur; Medina, Giovanna Ignácio Subirá; Rimkus, Carolina de Medeiros; Cliquet Júnior, Alberto

    2012-01-01

    Objective To study the shoulder of this group of patients using magnetic resonance imaging to detect clinical and subclinical disorders and establish a rehabilitation program. Methods Nine patients with spinal cord injury followed in the Laboratory of Biomechanics and Rehabilitation of the Locomotive System at HC/UNICAMP were divided into two groups according to the presence of paraplegia and tetraplegia and were clinically assessed for correlation with the imaging exams. Results Normal results were found in 41% of the shoulders. Most common injuries were tendinopathy of the supraspinatus and acromioclavicular joint degeneration. Eighty percent of injured shoulders had combined lesions. Conclusion A great variety of causes of shoulder pain was identified in paraplegic and tetraplegic subjects. Routine clinical assessment and imaging studies of the shoulder may contribute to the evolution of rehabilitation and reduction of pain and musculoskeletal disorders. Level of Evidence II, Development of Diagnostic Criteria on Consecutive Patients, With Universally Applied Reference "Gold" Standard. PMID:24453620

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

    PubMed

    Kawanishi, Camilla Yuri; Greguol, Márcia

    2013-10-01

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

  19. Clinical Features of Spinal Cord Hemangioblastoma in a Dog

    PubMed Central

    Michaels, Jennifer; Thomas, William; Ferguson, Sylvia; Hecht, Silke

    2015-01-01

    A 2-year-old male, intact Yorkshire terrier presented with a 1-month history of progressive paraparesis. Neurological examination revealed paraplegia with absent deep pain perception, decreased right pelvic limb withdrawal reflex, and lumbar pain consistent with an L4–S2 neurolocalization. Magnetic resonance imaging (MRI) showed a single, well-demarcated, intramedullary mass centered over the L3–4 disk space. A hemilaminectomy was performed, and the mass was removed en bloc. Histopathological evaluation was consistent with a hemangioblastoma. Follow-up MRI 9?months after surgery showed no evidence of tumor recurrence, and the dog was ambulatory paraparetic at that time. This case is consistent with a previous histopathological report of spinal cord hemangioblastoma in a dog and provides additional clinical information regarding diagnosis, treatment, and outcome associated with this tumor type. PMID:26664967

  20. [Rehabilitation for cancer patients].

    PubMed

    Tanuma, Akira

    2013-09-01

    In Japan, the number of patients with cancer is increasing drastically with the increase in number of elderly people. Therefore, recently, the necessity of rehabilitation for cancer patients has been realized. Cancer rehabilitation can be classified as preventive, restorative, supportive, or palliative and is administered according to the degree of cancer progression. Rehabilitation is of great significance even for patients with progressive cancer as it helps maintain their quality of life. Various forms of impairment, disability, and handicap are associated with cancer rehabilitation. Examples of impairments that cancer patients experience are hemiplegia and higher brain dysfunction in brain tumor cases, paraplegia and quadriplegia in spinal or spinal cord tumor cases, neuropathy and radiculopathy in cases of tumor invasion, complications after surgery, peripheral neuropathy after chemotherapy, and dysphagia after radiotherapy. It is important to evaluate these impairments and the risks associated with rehabilitation. PMID:24047769

  1. Secondary structure analysis of swine pasivirus (family Picornaviridae) RNA reveals a type-IV IRES and a parechovirus-like 3' UTR organization.

    PubMed

    Boros, Ákos; Fenyvesi, Hajnalka; Pankovics, Péter; Biró, Hunor; Phan, Tung Gia; Delwart, Eric; Reuter, Gábor

    2015-05-01

    The potential RNA structures of the 5' and 3' untranslated regions (UTRs) and cis-acting replication elements (CREs) of a novel pasivirus (PaV) genotype (family Picornaviridae) were analysed. PaV-A3 (KM259923) was identified in a faecal sample from a domestic pig in Hungary with posterior paraplegia of unknown etiology. Based on likely structural features of the 5' UTR, the pasiviruses were inferred to possess Hepacivirus/Pestivirus-like type-IV IRES. The pasivirus CRE was mapped to the 2B genome region, similar to Ljungan virus. The secondary RNA structure of the pasivirus 3' UTR was structurally similar to that of human parechoviruses. The genome, CRE, and 3' UTR of pasiviruses provide further evidence of the common origin of the members of the genera Parechovirus and Pasivirus, although their different 5' UTR IRES types suggest that a recombination event occurred during the divergence these viruses. PMID:25716922

  2. [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. PMID:20192033

  3. Acute Spontaneous Spinal Subdural Hematoma with Vague Symptoms

    PubMed Central

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

    2014-01-01

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

  4. Endovascular treatment of distal thoracic aortic transection associated with severe thoracolumbar spinal fracture.

    PubMed

    Chock, Megan M; Aho, Johnathon; Naik, Nimesh; Clarke, Michelle; Heller, Stephanie; Oderich, Gustavo S

    2015-10-01

    Endovascular repair has become the first line of treatment in most patients with blunt aortic injury. The most common mechanism is deceleration injury affecting the aortic isthmus distal to the origin of the left subclavian artery. Injuries of the distal thoracic aorta are uncommon. We report the case of a 25-year-old male patient who presented with paraplegia and distal thoracic aortic pseudoaneurysm associated with severe thoracolumbar vertebral fracture and displacement after a motocross accident. Endovascular repair was performed using total percutaneous technique and conformable C-TAG thoracic stent-graft (WL Gore, Flagstaff, AZ). Following stent-graft placement and angiographic confirmation of absence of endoleak, thoracolumbar spinal fixation was performed in the same operative procedure. This case illustrates a multispecialty approach to complex aortic and vertebral injury and the high conformability of newer thoracic stent-grafts to adapt to tortuous anatomy. PMID:25406266

  5. Carcinomatous Myelitis and Meningitis after a Squamous Cell Carcinoma of the Lip

    PubMed Central

    Pougnet, Isabelle; Murati, Anne; Sarran, Anthony; Viens, Patrice; Sabatier, Renaud

    2014-01-01

    Background 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. Case Report 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. Conclusion 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. PMID:24575013

  6. Traumatic L5 Posterolateral Spondyloptosis: A Case Report and Review of the Literature.

    PubMed

    Gabel, Brandon C; Curtis, Erik; Gonda, David; Ciacci, Joseph

    2015-06-01

    Traumatic retrolisthesis of the lumbar spine is a rare clinical entity. Only a few case reports have shown retrolisthesis of the fractured fragment over the inferior vertebral body. Fracture dislocations of the spine are unstable injuries that require operative fixation to restore alignment and prevent progressive deformity. We present the case of a traumatic L5-S1 fracture dislocation with retrolisthesis of the L5 vertebral body over the superior aspect of S1 managed with anterior, middle, and posterior column reconstruction. The patient presented with paraplegia and bowel and bladder incontinence. Retrolisthesis fracture dislocations injuries are rare, and as such, there are no guidelines regarding their management. In our case, we performed an L5 vertebrectomy with anterior, middle, and posterior column reconstruction via a posterior approach using a lumbosacral-pelvic construct. The patient did not regain function in his distal lower extremities postoperatively. PMID:26180701

  7. Slow onset cauda equina syndrome: a case report *

    PubMed Central

    Crowther, ER

    1993-01-01

    Cauda equina syndrome (CES) is characterized by low back pain, sciatica, lower limb motor weakness and sensory deficits, saddle anaesthesia, bowel and bladder dysfunction and occasionally paraplegia. The syndrome is classified according to onset: rapid or slow. Rapid onset CES, because of its characteristic presentation is easily recognized. The slow, chronic progression and varying presenting signs and symptoms of slow onset CES often mimic mechanical low back pain and makes the diagnosis difficult in its early stages. The case of a 23-year-old female with slow onset cauda equina is presented to illustrate this. A discussion of lumbar spine anatomy as it relates to the clinical presentation of cauda equina syndrome and the influence of associated degenerative factors follows. The most common presenting signs and symptoms are reviewed with special emphasis on those which can help diagnose CES in its early stages. Patients prognosis following surgical decompression is highlighted. ImagesFigure 1aFigure 1bFigure 2

  8. Acute neurological signs as the predominant clinical manifestation in four dogs with Angiostrongylus vasorum infections in Denmark

    PubMed Central

    2011-01-01

    Four dogs with acute neurological signs caused by haemorrhages in the central nervous system were diagnosed with Angiostrongylus vasorum infection as the underlying aetiology. Two dogs presented with brain lesions, one dog with spinal cord lesions and one with lesions in both the brain and spinal cord. Only one dog presented with concurrent signs of classical pulmonary angiostrongylosis (respiratory distress, cough), and only two dogs displayed overt clinical signs of haemorrhages. Results of coagulation assays were inconsistent. Neurological signs reflected the site of pathology and included seizures, various cranial nerve deficits, vestibular signs, proprioceptive deficits, ataxia and paraplegia. One dog died and three were euthanised due to lack of improvement despite medical treatment. This emphasises canine angiostrongylosis as a potential cause of fatal lesions of the central nervous system and the importance of including A. vasorum as a differential diagnosis in young dogs with acute neurological signs in Denmark. PMID:21711538

  9. Unique Imaging Features of Spinal Neurenteric Cyst.

    PubMed

    Jung, Hyoung-Seok; Park, Sang-Min; Kim, Gang-Un; Kim, Mi Kyung; Song, Kwang-Sup

    2015-12-01

    A 50-year-old male presented with acutely progressed paraplegia. His magnetic resonance imaging demonstrated two well-demarcated components with opposite signals in one cystic lesion between the T1- and T2-weighted images at the T1 spine level. The patient showed immediately improved neurological symptoms after surgical intervention and the histopathological exam was compatible with a neurenteric cyst. On operation, two different viscous drainages from the cyst were confirmed. A unique similarity of image findings was found from a review of the pertinent literature. The common findings of spinal neurenteric cyst include an isointense or mildly hyperintense signal relative to cerebrospinal fluid for both T1- and T2-weighted images. However, albeit rarer, the signals of some part of the cyst could change into brightly hyperintensity on T1-weighted images and hypointensity on T2-weighted images due to the differing sedimentation of the more viscous contents in the cyst. PMID:26640637

  10. Unique Imaging Features of Spinal Neurenteric Cyst

    PubMed Central

    Jung, Hyoung-Seok; Park, Sang-Min; Kim, Gang-Un; Kim, Mi Kyung

    2015-01-01

    A 50-year-old male presented with acutely progressed paraplegia. His magnetic resonance imaging demonstrated two well-demarcated components with opposite signals in one cystic lesion between the T1- and T2-weighted images at the T1 spine level. The patient showed immediately improved neurological symptoms after surgical intervention and the histopathological exam was compatible with a neurenteric cyst. On operation, two different viscous drainages from the cyst were confirmed. A unique similarity of image findings was found from a review of the pertinent literature. The common findings of spinal neurenteric cyst include an isointense or mildly hyperintense signal relative to cerebrospinal fluid for both T1- and T2-weighted images. However, albeit rarer, the signals of some part of the cyst could change into brightly hyperintensity on T1-weighted images and hypointensity on T2-weighted images due to the differing sedimentation of the more viscous contents in the cyst. PMID:26640637

  11. Survey of Use of the Insufflator-Exsufflator in Patients With Spinal Cord Injury

    PubMed Central

    Schmitt, James K; Stiens, Steven; Trincher, Rose; Lam, Mylam; Sarkarati, Mehdii; Linder, Steven; Ho, Chester H

    2007-01-01

    Background/Objective: The insufflator-exsufflator has been shown to be effective in assisting cough in individuals with spinal cord injury. However, many institutions do not use this device. The study was performed to assess use of the device and attitudes among health care providers. Methods: We developed a questionnaire with 4 categories of questions: knowledge of the device, type of facility, clinical practice with the device, and patient and provider satisfaction. The questionnaire was mailed to members of the American Paraplegia Society. Results: Eighty-six questionnaires (16%) were returned. The device was being used in 49% of the institutions. The device was most commonly used with a tracheostomy; use did not correlate with size or type of facility. Patient and provider satisfaction with the insufflator-exsufflator was high. Conclusions: The insufflator-exsufflator is used as a means of removal of secretions in approximately one half of institutions polled. Satisfaction with the device is high. PMID:17591224

  12. 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. PMID:18817014

  13. What we have learned from the next-generation sequencing: Contributions to the genetic diagnoses and understanding of pathomechanisms of neurodegenerative diseases.

    PubMed

    Liu, Yo-Tsen; Lee, Yi-Chung; Soong, Bing-Wen

    2015-01-01

    Since its first availability in 2009, the next-generation sequencing (NGS) has been proved to be a powerful tool in identifying disease-associated variants in many neurological diseases, such as spinocerebellar ataxias, Charcot-Marie-Tooth disease, hereditary spastic paraplegia, and amyotrophic lateral sclerosis. Whole exome sequencing and whole genome sequencing are efficient for identifying variants in novel or unexpected genes responsible for inherited diseases, whereas targeted sequencing is useful in detecting variants in previously known disease-associated genes. The trove of genetic data yielded by NGS has made a significant impact on the clinical diagnoses while contributing hugely on the discovery of molecular pathomechanisms underlying these diseases. Nonetheless, elucidation of the pathogenic roles of the variants identified by NGS is challenging. Establishment of consensus guidelines and development of public genomic/phenotypic databases are thus vital to facilitate data sharing and validation. PMID:26059699

  14. Connexin: a potential novel target for protecting the central nervous system?

    PubMed Central

    Xie, Hong-yan; Cui, Yu; Deng, Fang; Feng, Jia-chun

    2015-01-01

    Connexin subunits are proteins that form gap junction channels, and play an important role in communication between adjacent cells. This review article discusses the function of connexins/hemichannels/gap junctions under physiological conditions, and summarizes the findings regarding the role of connexins/hemichannels/gap junctions in the physiological and pathological mechanisms underlying central nervous system diseases such as brain ischemia, traumatic brain and spinal cord injury, epilepsy, brain and spinal cord tumor, migraine, neuroautoimmune disease, Alzheimer's disease, Parkinson's disease, X-linked Charcot-Marie-Tooth disease, Pelizaeus-Merzbacher-like disease, spastic paraplegia and maxillofacial dysplasia. Connexins are considered to be a potential novel target for protecting the central nervous system. PMID:26170830

  15. 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; Mahmoud, Iman Gamal El Din; 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. PMID:24482476

  16. Exome Sequencing Links Corticospinal Motor Neuron Disease to Common Neurodegenerative Disorders

    PubMed Central

    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.

    2014-01-01

    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. PMID:24482476

  17. Management of Acute Aortic Syndrome and Chronic Aortic Dissection

    SciTech Connect

    Nordon, Ian M. Hinchliffe, Robert J.; Loftus, Ian M.; Morgan, Robert A.; Thompson, Matt M.

    2011-10-15

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

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

    PubMed Central

    Park, Seil; Park, Sung Wook

    2013-01-01

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

  19. "Ears of the lynx" sign in a marchiafava-bignami patient: structural basis and fiber-tracking DTI contribution to the understanding of this imaging abnormality.

    PubMed

    Pacheco, Felipe Torres; Rego, Milena Morais; do Rego, Jose Iram Mendonça; da Rocha, Antonio J

    2014-01-01

    The "ears of the lynx" sign was previously reported as a neuroimaging finding observed in patients with autosomal recessive hereditary spastic paraplegia in association with a thin corpus callosum (ARHSP-TCC). We report a patient with a chronic form of Marchiafava-Bignami disease (MBD) that presented with this imaging feature. Diffusion tensor imaging (DTI) and fiber-tracking data support that this finding is a consequence of the structural derangement, which enlarges a preexisting border zone of the bundles of fibers from the corpus callosum (CC) genu to the forceps minor and anterior corona radiata. Therefore, we assume that despite their pathological differences, damage to the anterior portion of the CC is responsible for the imaging similarities between MBD and ARHSP-TCC. PMID:23216703

  20. An Unusual Case of a Large Hematorrachis Associated with Multi-Level Osteoporotic Vertebral Compression Fractures; a Case Report

    PubMed Central

    Kumar, T.V. Ravi; Daksh, Gadi; Raghavendra, Rao; Mathew, Joseph Vinay

    2015-01-01

    Spinal epidural haemorrhage may present as back pain associated with radicular symptoms and can be a catastrophic clinical scenario with progression to paraplegia or even sudden death. Being a rare entity, it needs a high index of clinical suspicion to diagnose it. Fractures have been documented as a cause of hematorrachis but such hematomas only extend to one or two vertebral segments. Large epidural hematomas are usually associated with conditions like bleeding diathesis, arterio-venous malformations, plasma cell myeloma, and non-Hodgkin’s lymphoma. Surgical management with immediate evacuation of the hematoma is the usual line of management in patients with neurological deficits. Though rare, monitored and careful conservative management can lead to recovery of neurological symptoms and resolution of the hematoma. We report a case of a very large post traumatic epidural hematorrchis extending to 11 vertebral segments from D3 to L1 vertebral bodies, who had a gradual spontaneous recovery. PMID:26110182

  1. Movement and muscle activity pattern in wheelchair ambulation by persons with para-and tetraplegia.

    PubMed

    Schantz, P; Björkman, P; Sandberg, M; Andersson, E

    1999-06-01

    The patterns of movement and muscle activation in wheelchair ambulation have been studied in two groups: subjects with paraplegia (n = 4) and tetraplegia (n = 3). All subjects were physically active and experienced wheelchair users. The tests were done in the subjects' own wheelchairs and under free-wheeling conditions. The tasks studied were: self-chosen normal velocity, maximal velocity and maximally accelerated start. Muscle activation was registered by surface electromyography performed on several arm and shoulder muscles. The movement pattern was studied by goniometry of the shoulder and elbow joints, as well as by observing video recordings. Speed and arm cycle frequency were also recorded. The movement pattern was divided into three phases: pull, push and recovery. Relatively concordant muscle activation patterns were noted within the groups, whereas differences were noted between the groups with regard to muscle activation, length of the pull and push phases and the velocity-dependent adaptation. The subjects with tetraplegia were more dependent on the pull phase. The self-chosen normal and maximal speeds of the subjects with tetraplegia were approximately half those of the subjects with paraplegia. Three different types of recovery movements were noted as well as a velocity-dependent adaptation. Major trunk movements during the rim phase were only noted at the maximally accelerated start. In conclusion, the results point to both similarities and differences in the movement pattern and muscle activation in individuals with para- and tetraplegia under different ambulation conditions. The differences are of such a magnitude that they are important enough to consider when teaching wheelchair techniques and developing rehabilitation programmes for different groups of patients with spinal cord injuries. PMID:10380721

  2. The Sir Ludwig Guttmann lecture 2012: the contribution of Stoke Mandeville Hospital to spinal cord injuries.

    PubMed

    Frankel, H L

    2012-11-01

    This Ludwig Guttmann Lecture was presented at the 2012 meeting of the International Spinal Cord Society in London. It describes the contribution of Stoke Mandeville Hospital to the field of spinal cord injuries. Dr Ludwig Guttmann started the Spinal Unit at Stoke Mandeville Hospital in 1944 and introduced a novel, comprehensive method of care, which included early admission, prevention and treatment of spinal cord injury related complications, active rehabilitation and social reintegration. Soon a dedicated specialist team was assembled and training of visitors was encouraged, some of whom went on to start their own spinal units. Research went hand in hand with clinical work, and over the years more than 500 scientific contributions from Stoke Mandeville have been published in peer reviewed journals and books. Guttmann introduced sport as a means of physical therapy, which soon lead to organised Stoke Mandeville Games, first national in 1948, then international in 1952 and finally the Paralympic Games in 1960. Stoke Mandeville is regarded as the birthplace of the Paralympic movement, and Guttmann was knighted in 1966. Stoke Mandeville is also the birthplace of the International Medical Society of Paraplegia, later International Spinal Cord Society, which was formed during the International Stoke Mandeville Games in 1961, and of the Society's medical journal Paraplegia, later Spinal Cord, first published in 1963. Guttmann's followers have continued his philosophy and, with some new developments and advances, the present day National Spinal Injuries Centre at Stoke Mandeville Hospital provides comprehensive, multidisciplinary acute care, rehabilitation and life-long follow-up for patient with spinal cord injuries of all ages. PMID:23045299

  3. Successful Pedicled Anterolateral Thigh Flap Reconstruction for a Recurrent Ischial Pressure Ulcer: A Case With Multiple Recurrences Over a 7-year Follow-up.

    PubMed

    Wang, Chi-Yu; Shih, Yu-Jen; Chou, Chang-Yi; Chen, Tim-Mo; Chen, Shyi-Gen; Tzeng, Yuan-Sheng

    2015-06-01

    Ischial pressure ulcers are difficult ulcers to treat and have a low treatment success rate compared to sacral and trochanteric ulcers; regional flap failure further complicates the treatment. Reported here is a case of a 65-year-old man who experienced a spinal injury with paraplegia due to trauma 20 years ago. The patient experienced a recurrent ischial ulcer since 2007, and underwent several types of flap reconstruction with poor outcomes over a 7-year period. Therefore, the chosen intervention was a pedicled anterolateral thigh (pALT) fasciocutaneous flap reconstruction for the ischial ulcer via a subcutaneous route. Over the 10-month follow-up, the recurrent ischial ulcer healed without wound dehiscence. Island pALT reconstruction appears to be an alternative technique for treating recurrent ischial pressure ulcers. Though reconstruction of ischial ulcers via the pALT technique has been described previously, this may be the first case report to describe pALT flap in a patient with recurrent ischial ulcers after failed reconstructions using a gluteus maximus flap, V-Y advancement flap, and hatchet flap.Ischial pressure ulcers are difficult to treat and have a low treatment success rate1 compared to sacral and trochanteric ulcers. In addition, there are many different techniques that can be used to treat ischial pressure ulcers, including primary wound closure, gluteus maximus flaps, V-Y advancement flaps, or inferior gluteal artery perforator flaps. However, several experts have recently described using the pedicled anterolateral thigh (pALT) flap for reconstruction of recurrent ischial pressure ulcers.1,2 In the presented case, the authors followed a single patient with paraplegia with a recurrent ischial ulcer who had undergone several types of wound treatment over a 7-year period. The indurated ulcer was ultimately resolved by pALT reconstruction. PMID:26266282

  4. Polyradiculopathy and Gastroparesis due to Cytomegalovirus Infection in AIDS: A Case Report and Review of Literature

    PubMed Central

    Thongpooswan, Supat; Chyn, Eric; Alfishawy, Mostafa; Restrepo, Erfidia; Berman, Charles; Ahmed, Kawser; Muralidharan, Sethu

    2015-01-01

    Patient: Female, 46 Final Diagnosis: CMV gastroparesis and radiculopathy Symptoms: Nausea • paraplegia • urinary retention • vomiting Medication: — Clinical Procedure: Lumbar puncture Specialty: Infectious Diseases Objective: Unusual clinical course Background: Cytomegalovirus (CMV) infection has been well described as an opportunistic infection of patients with human immunodeficiency virus (HIV). To the best of our knowledge, this is the first case report of a patient with AIDS and lumbosacral polyradiculopathy, associated with gastroparesis resulting from CMV infection. Case Report: A 46-year-old Hispanic woman with a history of HIV for 10 years was admitted to our hospital for nausea, vomiting, urinary retention, and generalized weakness. Bilateral lower extremity examination revealed flaccid paraplegia, decreased sensations from the groin downwards, bilateral lower extremity areflexia, and absent plantar reflexes, with enlarged urinary bladder. CMV was detected in CSF by PCR, and cervical and lumbar magnetic resonance imaging (MRI) revealed intense nodular leptomeningeal enhancement from the lower thoracic cord and extending along the conus medullaris/filum terminalis and nerve roots. Gastric emptying scintigraphy revealed severe delayed gastric emptying time. Ganciclovir was initiated and her neurological symptoms and gastrological symptoms gradually improved. Over 8 weeks, nausea and vomiting resolved and the patient was able to walk before being discharged from the hospital. Conclusions: Polyradiculopathy and gastroparesis can result from CMV infection in AIDS patients. Whether the mechanism is secondary to viral infection or immune systems remains unclear. It is important for physicians to be aware of this uncommon presentation in the antiretroviral therapy (ART) era. CMV treatment should be initiated immediately once diagnosis is confirmed. PMID:26552851

  5. 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 ? 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 ?. 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

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

    PubMed

    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

    2015-09-01

    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 ? 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 ?. 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

  7. 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

  8. 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

  9. 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 Paraplegia of lower limbs 88 showed improvement in weight bearing, standing and movement accounting for 76% improvement rate.

  10. 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 lower limbs 44 showed improvement in weight bearing, standing and movement accounting for 76% improvement rate.

  11. The Alu-Rich Genomic Architecture of SPAST Predisposes to Diverse and Functionally Distinct Disease-Associated CNV Alleles

    PubMed Central

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

    2014-01-01

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

  12. Elephant trunk technique for hybrid aortic arch repair.

    PubMed

    Miyamoto, Yuji

    2014-03-01

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

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

    PubMed Central

    Chan, Sam Chi Chung; Chan, Alice Po Shan

    2013-01-01

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

  14. Non-Traumatic Spontaneous Spinal Subdural Hematoma in a Patient with Non-Valvular Atrial Fibrillation During Treatment with Rivaroxaban

    PubMed Central

    Castillo, Jessica M.; Afanador, Hayley F.; Manjarrez, Efren; Morales, Ximena A.

    2015-01-01

    Patient: Male, 69 Final Diagnosis: Spontaneous spinal subdural hematoma Symptoms: Paraplegia Medication: Rivaroxaban Clinical Procedure: — Specialty: General Internal Medicine • Hospital Medicine • Cardiology • Hematology • Neurology Objective: Diagnostic/therapeutic accidents Background: Spontaneous spinal subdural hematoma (SSDH) is a rare but disabling condition, accounting for only 4.1% of all intraspinal hematomas. Risk factors include arteriovenous malformations, coagulopathy, therapeutic anticoagulation, underlying neoplasms, or following spinal puncture. Vitamin K antagonists, antiplatelet agents, and heparinoids have been associated with SSDHs in prior reports. To the best of our knowledge, no cases have reported this association with the factor Xa inhibitor, rivaroxaban, and SSDHs. Case Report: We report the case of a 69-year-old Honduran man with a 5-year history of symptomatic palpitations due to non-valvular atrial fibrillation. He was initially refractory to pharmacologic therapy. He underwent cardioversion in February 2014. After cardioversion, he remained asymptomatic on flecainide. He was anticoagulated on rivaroxaban 20 mg daily without incident since early 2013 until presentation in August 2014. He presented with sudden onset of excruciating upper and lower back pain after minimal movement. This was immediately followed by bilateral lower extremity paresis rapidly progressing to paraplegia with bowel and bladder dysfunction over 15 minutes. Magnetic resonance imaging demonstrated an acute spinal subdural hematoma extending from T3 inferiorly to the conus medullaris. Six months after undergoing cervical and lumbar drainage procedures, he has not recovered bowel, bladder, or lower extremity neurologic function. Conclusions: Non-traumatic spontaneous spinal subdural hematoma is a rare neurological emergency that may occur during the use of rivaroxaban in patients with non-valvular atrial fibrillation. Physicians should suspect SSDH in patients on rivaroxaban with acute onset of severe back pain and neurologic symptoms to improve the odds of a favorable outcome. PMID:26090890

  15. Brain-computer interface controlled robotic gait orthosis

    PubMed Central

    2013-01-01

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

  16. 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

  17. Post traumatic paraplegics living in Athens: the impact of pressure sores and UTIs on everyday life activities.

    PubMed

    Sapountzi-Krepia, D; Soumilas, A; Papadakis, N; Sapkas, G; Nomicos, J; Theodossopoulou, E; Dimitriadou, A

    1998-06-01

    This paper contains the findings of a scientific research which was done on post-traumatic paraplegics who live in the area of Athens. Greece, and measured the impact of pressure sores and UTIs on their everyday life activities. The target population was 127 individuals out of which 98 were observed and interviewed. A semi-structured questionnaire which consisted of two parts used; the first part of the questionnaire included general questions whereas the second contained the Sarno Functional Life Scale (SFLS) which is a tool measuring the level of independence of disabled people. Sixty-two per cent of the population was male. The mean age of the sample population at the time they had the accident which caused the paraplegia was 31.5, while the median was 28.5. The majority of the subjects comes from the lower socioeconomic class. Traffic accidents accounted for the 55% of the occurrences of paraplegia, falls for 37%, surgical complication for 4% and athletic activities for the remaining 4%. Forty-nine percent of the sample had been hospitalised in a rehabilitation centre. However, the multiple regressions used did not reveal any statistically significant relation between the hospitalisation in a rehabilitation centre and the paraplegic's scores in any of the Sarno Functional Life Scale's (SFLS) variables. Instead, the multiple regressions employed yielded paraplegics' scores in the SFLS's everyday life activities that were negatively related to age (P = 0.004) and pressure sores (P = 0.021). The paraplegics' scores on the SFLS's indoors activities are positively related to the years since injury (P = 0.048) and health education on daily fluid consumption (P = 0.003). The scores of the subjects on the SFLS's outdoor activities are positively related to the years of education (P = 0.008), the years since injury (P = 0.011), while are negatively related to pressure sores (P = 0.034) and UTIs (0.044). The subjects' scores on the SFLS variables regarding social relations had a negative relation to sex, (female) (P = 0.0001), age (P = 0.001) and pressure sores (P = 0.019), while they have a positive relation with the years since injury (P = 0.024). PMID:9648201

  18. Myelin-associated glycoprotein gene mutation causes Pelizaeus-Merzbacher disease-like disorder.

    PubMed

    Lossos, Alexander; Elazar, Nimrod; Lerer, Israela; Schueler-Furman, Ora; Fellig, Yakov; Glick, Benjamin; Zimmerman, Bat-El; Azulay, Haim; Dotan, Shlomo; Goldberg, Sharon; Gomori, John M; Ponger, Penina; Newman, J P; Marreed, Hodaifah; Steck, Andreas J; Schaeren-Wiemers, Nicole; Mor, Nofar; Harel, Michal; Geiger, Tamar; Eshed-Eisenbach, Yael; Meiner, Vardiella; Peles, Elior

    2015-09-01

    Pelizaeus-Merzbacher disease is an X-linked hypomyelinating leukodystrophy caused by mutations or rearrangements in PLP1. It presents in infancy with nystagmus, jerky head movements, hypotonia and developmental delay evolving into spastic tetraplegia with optic atrophy and variable movement disorders. A clinically similar phenotype caused by recessive mutations in GJC2 is known as Pelizaeus-Merzbacher-like disease. Both genes encode proteins associated with myelin. We describe three siblings of a consanguineous family manifesting the typical infantile-onset Pelizaeus-Merzbacher disease-like phenotype slowly evolving into a form of complicated hereditary spastic paraplegia with mental retardation, dysarthria, optic atrophy and peripheral neuropathy in adulthood. Magnetic resonance imaging and spectroscopy were consistent with a demyelinating leukodystrophy. Using genetic linkage and exome sequencing, we identified a homozygous missense c.399C>G; p.S133R mutation in MAG. This gene, previously associated with hereditary spastic paraplegia, encodes myelin-associated glycoprotein, which is involved in myelin maintenance and glia-axon interaction. This mutation is predicted to destabilize the protein and affect its tertiary structure. Examination of the sural nerve biopsy sample obtained in childhood in the oldest sibling revealed complete absence of myelin-associated glycoprotein accompanied by ill-formed onion-bulb structures and a relatively thin myelin sheath of the affected axons. Immunofluorescence, cell surface labelling, biochemical analysis and mass spectrometry-based proteomics studies in a variety of cell types demonstrated a devastating effect of the mutation on post-translational processing, steady state expression and subcellular localization of myelin-associated glycoprotein. In contrast to the wild-type protein, the p.S133R mutant was retained in the endoplasmic reticulum and was subjected to endoplasmic reticulum-associated protein degradation by the proteasome. Our findings identify involvement of myelin-associated glycoprotein in this family with a disorder affecting the central and peripheral nervous system, and suggest that loss of the protein function is responsible for the unique clinical phenotype. PMID:26179919

  19. Subunit Interactions and Cooperativity in the Microtubule-severing AAA ATPase Spastin*

    PubMed Central

    Eckert, Thomas; Link, Susanne; Le, Doan Tuong-Van; Sobczak, Jean-Philippe; Gieseke, Anja; Richter, Klaus; Woehlke, Günther

    2012-01-01

    Spastin is a hexameric ring AAA ATPase that severs microtubules. To see whether the ring complex funnels the energy of multiple ATP hydrolysis events to the site of mechanical action, we investigate here the cooperativity of spastin. Several lines of evidence indicate that interactions among two subunits dominate the cooperative behavior: (i) the ATPase activity shows a sigmoidal dependence on the ATP concentration; (ii) ATP?S displays a mixed-inhibition behavior for normal ATP turnover; and (iii) inactive mutant subunits inhibit the activity of spastin in a hyperbolic dependence, characteristic for two interacting species. A quantitative model based on neighbor interactions fits mutant titration experiments well, suggesting that each subunit is mainly influenced by one of its neighbors. These observations are relevant for patients suffering from SPG4-type hereditary spastic paraplegia and explain why single amino acid exchanges lead to a dominant negative phenotype. In severing assays, wild type spastin is even more sensitive toward the presence of inactive mutants than in enzymatic assays, suggesting a weak coupling of ATPase and severing activity. PMID:22637577

  20. Spinal tuberculosis: a review.

    PubMed

    Garg, Ravindra Kumar; Somvanshi, Dilip Singh

    2011-01-01

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

  1. An obscure case of hepatic subcapsular hematoma.

    PubMed

    Ndzengue, Albert; Hammoudeh, Fadi; Brutus, Pierre; Ajah, Ofem; Purcell, Roland; Leadon, Joseph; Rafal, Richard B; Balmir, Simon; Enriquez, Danilo A; Posner, Gerald L; Jaffe, Eric A; Chandra, Pradeep

    2011-01-01

    Spontaneous liver bleeding is often reported in preeclampsia. It is otherwise rare and has been linked to gross anatomical lesions and coagulopathy. We report a case of subcapsular hematoma of the liver without any apparent lesion and in the absence of coagulopathy. A 41-year-old male, paraplegic for 16 years, presented to the emergency department 3 days after sudden onset of right upper quadrant and shoulder pain. He had been on vitamins and 5,000 units subcutaneous heparin 12-hourly at the nursing home for the last month. He was in no distress, afebrile, with stable vitals. Physical examination showed a diverting colostomy, tender hepatomegaly and sacral decubiti. A fecal occult blood test was negative. There was spastic paraplegia below the level of T12. Two days after admission, the patient was afebrile and hemodynamically stable. PTT, PT, liver profile, BUN and creatinine were all normal, however his hemoglobin had dropped from 11.3 to 7.6 g/dl. An abdominal CT scan revealed an isolated 9.0 × 1.8 cm subcapsular hematoma. The patient received blood transfusion in the intensive care unit and was discharged 7 days later. In conclusion, spontaneous liver hemorrhage occurs in the nonobstetrical population in the setting of gross anatomical lesions or coagulopathy. This is the first report of an isolated subcapsular liver hematoma. PMID:21552450

  2. Sexual Functioning in Men Living with a Spinal Cord Injury–A Narrative Literature Review

    PubMed Central

    Sunilkumar, MM; Boston, Patricia; Rajagopal, MR

    2015-01-01

    Background: Sexual dysfunction is a major concern for Indian men living with a spinal cord injury Objectives: To examine the literature related to sexuality traumatic cord injury and its impact on sexual functioning. Materials and Methods: 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. Results: 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. Conclusion: 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. PMID:26600694

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

    PubMed Central

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

    2014-01-01

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

  4. Glycosphingolipids are modulators of disease pathogenesis in amyotrophic lateral sclerosis.

    PubMed

    Dodge, James C; Treleaven, Christopher M; Pacheco, Joshua; Cooper, Samantha; Bao, Channa; Abraham, Marissa; Cromwell, Mandy; Sardi, S Pablo; Chuang, Wei-Lien; Sidman, Richard L; Cheng, Seng H; Shihabuddin, Lamya S

    2015-06-30

    Recent genetic evidence suggests that aberrant glycosphingolipid metabolism plays an important role in several neuromuscular diseases including hereditary spastic paraplegia, hereditary sensory neuropathy type 1, and non-5q spinal muscular atrophy. Here, we investigated whether altered glycosphingolipid metabolism is a modulator of disease course in amyotrophic lateral sclerosis (ALS). Levels of ceramide, glucosylceramide, galactocerebroside, lactosylceramide, globotriaosylceramide, and the gangliosides GM3 and GM1 were significantly elevated in spinal cords of ALS patients. Moreover, enzyme activities (glucocerebrosidase-1, glucocerebrosidase-2, hexosaminidase, galactosylceramidase, ?-galactosidase, and ?-galactosidase) mediating glycosphingolipid hydrolysis were also elevated up to threefold. Increased ceramide, glucosylceramide, GM3, and hexosaminidase activity were also found in SOD1(G93A) mice, a familial model of ALS. Inhibition of glucosylceramide synthesis accelerated disease course in SOD1(G93A) mice, whereas infusion of exogenous GM3 significantly slowed the onset of paralysis and increased survival. Our results suggest that glycosphingolipids are likely important participants in pathogenesis of ALS and merit further analysis as potential drug targets. PMID:26056266

  5. Glycosphingolipids are modulators of disease pathogenesis in amyotrophic lateral sclerosis

    PubMed Central

    Dodge, James C.; Treleaven, Christopher M.; Pacheco, Joshua; Cooper, Samantha; Bao, Channa; Abraham, Marissa; Cromwell, Mandy; Sardi, S. Pablo; Chuang, Wei-Lien; Sidman, Richard L.; Cheng, Seng H.; Shihabuddin, Lamya S.

    2015-01-01

    Recent genetic evidence suggests that aberrant glycosphingolipid metabolism plays an important role in several neuromuscular diseases including hereditary spastic paraplegia, hereditary sensory neuropathy type 1, and non-5q spinal muscular atrophy. Here, we investigated whether altered glycosphingolipid metabolism is a modulator of disease course in amyotrophic lateral sclerosis (ALS). Levels of ceramide, glucosylceramide, galactocerebroside, lactosylceramide, globotriaosylceramide, and the gangliosides GM3 and GM1 were significantly elevated in spinal cords of ALS patients. Moreover, enzyme activities (glucocerebrosidase-1, glucocerebrosidase-2, hexosaminidase, galactosylceramidase, ?-galactosidase, and ?-galactosidase) mediating glycosphingolipid hydrolysis were also elevated up to threefold. Increased ceramide, glucosylceramide, GM3, and hexosaminidase activity were also found in SOD1G93A mice, a familial model of ALS. Inhibition of glucosylceramide synthesis accelerated disease course in SOD1G93A mice, whereas infusion of exogenous GM3 significantly slowed the onset of paralysis and increased survival. Our results suggest that glycosphingolipids are likely important participants in pathogenesis of ALS and merit further analysis as potential drug targets. PMID:26056266

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

    SciTech Connect

    Brandt, Michael Walluscheck, Knut P.; Jahnke, Thomas; Attmann, Tim; Heller, Martin; Cremer, Jochen; Mueller-Huelsbeck, Stefan

    2006-10-15

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

  7. Endovascular repair of thoracic and abdominal aortic ruptures: a single-center experience

    PubMed Central

    ?slim, Filiz; Sal?k, Aysun Erbahçeci; Güven, Koray; Bakuy, Vedat; Çukurova, Zafer

    2014-01-01

    PURPOSE We aimed to present our preliminary single-center experience of the endovascular management of thoracic and abdominal aortic ruptures. MATERIALS AND METHODS Between September 2010 and May 2012, 11 consecutive patients (nine males, two females; age range, 26–80 years) with thoracic and abdominal aortic ruptures underwent endovascular repair in our unit. Thoracoabdominal computed tomography (CT) angiography was performed for diagnosis and follow-up. Patients were selected for endovascular repair by a cardiovascular surgeon, anesthesiologist, and interventional radiologist. All repairs were performed using commercially available stent-grafts. The patients were followed up with CT angiography before discharge, at six months, and yearly thereafter. RESULTS Three patients died by day 30. One patient died due to an unsuccessful procedure and hemodynamic instability; two patients died because of comorbidities. The other eight patients were followed for six to 24 months after the procedure. No endoleaks or late ruptures were observed during the follow-up period. The patient with iatrogenic thoracic aortic rupture developed paraplegia after the procedure. CONCLUSION Reduced mortality due to aortic rupture has been reported with the expanding use of endovascular repair. Reports of small centers are important because of the rarity of these pathologies, and because transferring patients with aortic rupture to a referral center is not usually possible. PMID:24412816

  8. Adiposity and spinal cord injury

    PubMed Central

    Gorgey, Ashraf S; Wells, Kathryn M; Austin, Timothy L

    2015-01-01

    The drastic changes in body composition following spinal cord injury (SCI) have been shown to play a significant role in cardiovascular and metabolic health. The pattern of storage and distribution of different types of adipose tissue may impact metabolic health variables similar to carbohydrate, lipid and bone metabolism. The use of magnetic resonance imaging provides insights on the interplay among different regional adipose tissue compartments and their role in developing chronic diseases. Regional adipose tissue can be either distributed centrally or peripherally into subcutaneous and ectopic sites. The primary ectopic adipose tissue sites are visceral, intramuscular and bone marrow. Dysfunction in the central nervous system following SCI impacts the pattern of distribution of adiposity especially between tetraplegia and paraplegia. The current editorial is focused primarily on introducing different types of adipose tissue and establishing scientific basis to develop appropriate dietary, rehabilitation or pharmaceutical interventions to manage the negative consequences of increasing adiposity after SCI. We have also summarized the clinical implications and future recommendations relevant to study adiposity after SCI. PMID:26396933

  9. Effect of Locomotor Training on Motor Recovery and Walking Ability in Patients with Incomplete Spinal Cord Injury: A Case Series

    PubMed Central

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

    2014-01-01

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

  10. Spinal cord injury: overview of experimental approaches used to restore locomotor activity.

    PubMed

    Fakhoury, Marc

    2015-01-01

    Spinal cord injury affects more than 2.5 million people worldwide and can lead to paraplegia and quadriplegia. Anatomical discontinuity in the spinal cord results in disruption of the impulse conduction that causes temporary or permanent changes in the cord's normal functions. Although axonal regeneration is limited, damage to the spinal cord is often accompanied by spontaneous plasticity and axon regeneration that help improve sensory and motor skills. The recovery process depends mainly on synaptic plasticity in the preexisting circuits and on the formation of new pathways through collateral sprouting into neighboring denervated territories. However, spontaneous recovery after spinal cord injury can go on for several years, and the degree of recovery is very limited. Therefore, the development of new approaches that could accelerate the gain of motor function is of high priority to patients with damaged spinal cord. Although there are no fully restorative treatments for spinal injury, various rehabilitative approaches have been tested in animal models and have reached clinical trials. In this paper, a closer look will be given at the potential therapies that could facilitate axonal regeneration and improve locomotor recovery after injury to the spinal cord. This article highlights the application of several interventions including locomotor training, molecular and cellular treatments, and spinal cord stimulation in the field of rehabilitation research. Studies investigating therapeutic approaches in both animal models and individuals with injured spinal cords will be presented. PMID:25870961

  11. Effects of repetitive transcranial magnetic stimulation on recovery of function after spinal cord injury.

    PubMed

    Tazoe, Toshiki; Perez, Monica A

    2015-04-01

    A major goal of rehabilitation strategies after spinal cord injury (SCI) is to enhance the recovery of function. One possible avenue to achieve this goal is to strengthen the efficacy of the residual neuronal pathways. Noninvasive repetitive transcranial magnetic stimulation (rTMS) has been used in patients with motor disorders as a tool to modulate activity of corticospinal, cortical, and subcortical pathways to promote functional recovery. This article reviews a series of studies published during the last decade that used rTMS in the acute and chronic stages of paraplegia and tetraplegia in humans with complete and incomplete SCI. In the studies, rTMS has been applied over the arm and leg representations of the primary motor cortex to target 3 main consequences of SCI: sensory and motor function impairments, spasticity, and neuropathic pain. Although some studies demonstrated that consecutive sessions of rTMS improve aspects of particular functions, other studies did not show similar effects. We discuss how rTMS parameters and postinjury reorganization in the corticospinal tract, motor cortical, and spinal cord circuits might be critical factors in understanding the advantages and disadvantages of using rTMS in patients with SCI. The available data highlight the limited information on the use of rTMS after SCI and the need to further understand the pathophysiology of neuronal structures affected by rTMS to maximize the potential beneficial effects of this technique in humans with SCI. PMID:25175159

  12. Selective dorsal rhizotomy for spastic diplegia secondary to stroke in an adult patient

    PubMed Central

    Eppinger, Melissa Ann; Berman, Casey Melissa; Mazzola, Catherine Anne

    2015-01-01

    Background: Selective dorsal rhizotomy (SDR) is often recommended for children with spastic paraparesis and cerebral palsy. SDR reduces spasticity in the lower extremities for these children with spastic paraplegia. However, SDR is infrequently recommended for adults with spasticity. Spastic diplegia in adult patients can be due to stroke, brain or spinal cord injury from trauma, infection, toxic-metabolic disorders, and other causes. Although rarely considered, SDR is an option for adult patients with spastic diplegia as well. Case Description: The authors describe a patient who underwent a SDR with a successful postoperative outcome. This man suffered a hypertensive and hemorrhagic stroke secondary to intravenous drug abuse at age 46. A SDR was performed after two failed intrathecal baclofen pump placements due to recurrent infections, likely resulting from his immunocompromised status. The patient underwent lumbar laminectomies and dorsal rhizotomies at levels L1-S1 bilaterally. Postoperatively, the patient's spasticity was significantly reduced. His Ashworth spasticity score decreased from 4/5 to 1/5, and the reduction in tone has been durable over 3 years. Conclusion: SDR in older patients with spastic paraparesis may be considered as a treatment option. PMID:26167363

  13. [Dermal sinus: a neurosurgical emergency].

    PubMed

    Lallemant, P; Forin, V

    2015-03-01

    Spinal dysraphisms include various types of congenital malformations. About 10% are dermal sinuses, i.e., a connection between the skin elements and intradural space through an open tract. The major complication of this malformation is a central nervous system infection that occurs most frequently before the age of 5 years. We report the case of a lumbosacral skin defect initially described as a coccygeal pit, which happened to be a dermal sinus with a tethered cord after ultrasound imaging in a newborn infant. No indication for surgery was recognized. Later, the infant experienced cerebral empyema and spinal cord edema when he was 5 months old, while a second infection, with a medullar abscess, occurred 7 months later. Both infections began with high fever and were complicated by neurologic deficits. An emergency surgery was performed during the second myelitis. The operative findings confirmed a dermal sinus and a tethered cord. Moreover, they found a dermoid cyst next to the tract. After 2 years of recovery, the child has neurologic deficits including lower limb paraplegia with neurological bladder and bowel. This observation recalls the importance of the differential diagnosis between a coccygeal pit and a dermal sinus, the latter being associated with a dermoid cyst in 50% of cases. Serious neurologic consequences due to the possible infectious complications can occur when a dermal sinus is neglected. A preventive operative excision of both the dermal sinus and a possible cyst is a surgical emergency for spinal dysraphism. PMID:25656457

  14. Arachnoiditis ossificans and syringomyelia: A unique presentation

    PubMed Central

    Opalak, Charles F.; Opalak, Michael E.

    2015-01-01

    Background: Arachnoiditis ossificans (AO) is a rare disorder that was differentiated from leptomeningeal calcification by Kaufman and Dunsmore in 1971. It generally presents with progressive lower extremity myelopathy. Though the underlying etiology has yet to be fully described, it has been associated with various predisposing factors including vascular malformations, previous intradural surgery, myelograms, and adhesive arachnoiditis. Associated conditions include syringomyelia and arachnoid cyst. The preferred diagnostic method is noncontrast computed tomography (CT). Surgical intervention is still controversial and can include decompression and duroplasty or durotomy. Case Description: The authors report the case of a 62-year-old male with a history of paraplegia who presented with a urinary tract infection and dysautonomia. His past surgical history was notable for a C4–C6 anterior fusion and an intrathecal phenol injection for spasticity. A magnetic resonance image (MR) also demonstrated a T6-conus syringx. At surgery, there was significant ossification of the arachnoid/dura, which was removed. After a drain was placed in the syrinx, there was a significant neurologic improvement. Conclusion: This case demonstrates a unique presentation of AO and highlights the need for CT imaging when a noncommunicating syringx is identified. In addition, surgical decompression can achieve good results when AO is associated with concurrent compressive lesions. PMID:26693389

  15. Sequence Alterations within CYP7B1 Implicate Defective Cholesterol Homeostasis in Motor-Neuron Degeneration

    PubMed Central

    Tsaousidou, Maria K.; Ouahchi, Karim; Warner, Tom T.; Yang, Yi; Simpson, Michael A.; Laing, Nigel G.; Wilkinson, Philip A.; Madrid, Ricardo E.; Patel, Heema; Hentati, Faycal; Patton, Michael A.; Hentati, Afif; Lamont, Philippa J.; Siddique, Teepu; Crosby, Andrew H.

    2008-01-01

    The hereditary spastic paraplegias (HSPs) are a genetically and clinically heterogeneous group of upper-motor-neuron degenerative diseases characterized by selective axonal loss in the corticospinal tracts and dorsal columns. Although numerous mechanisms involving defective subcellular transportation, mitochondrial malfunction, and increased oxidative stress have been proposed, the pathogenic basis underlying the neuronal loss is unknown. We have performed linkage analysis to refine the extent of the SPG5 disease locus and conducted sequence analysis of the genes located within this region. This identified sequence alterations in the cytochrome P450-7B1 (CYP7B1) associated with this pure form of HSP. In the liver, CYP7B1 offers an alternative pathway for cholesterol degradation and also provides the primary metabolic route for the modification of dehydroepiandrosterone neurosteroids in the brain. These findings provide the first direct evidence of a pivotal role of altered cholesterol metabolism in the pathogenesis of motor-neuron degenerative disease and identify a potential for therapeutic intervention in this form of HSP. PMID:18252231

  16. Novel mutational mechanism in man: Expansion of trinucleotide repeats

    SciTech Connect

    Ilarioshkin, S.N.; Ivanova-Smolenskaya, I.A.; Markova, E.D.

    1995-11-01

    An analysis of a novel, recently discovered class of mutations in man - an expansion, i.e., an increase of the copy number of intragenic unstable trinucleotide repeats - is presented. The expansion of trinucleotide X chromosome syndrome (two separate variants of the disease - FRAXA and FRAXE), myotonic dystrophy, spinal and bulbar Kennedy`s amyotrophy, Huntington`s chorea, type 1 spinocerebellar ataxia, and dentatorubral-pallidolyusian atrophy. The discovery of triplet expansion allows a satisfactory explanation on the molecular level of a series of unusual clinical genetic phenomena, such as anticipation, the {open_quotes}paternal transmission{close_quotes} effect, the {open_quotes}Sherman paradox,{close_quotes} and others. The common properties and the distinctions of unstable trinucleotide mutations in the nosologic forms mentioned above are analyzed comprehensively. These features include the mechanism by which these mutations cause disease, the time of their appearance in ontogenesis, and various clinical genetic correlations. The evolutionary origin of this class of mutations and, in particular, the role of alleles with an {open_quotes}intermediate{close_quotes} triplet number, which are the persistent reservoir of mutations arising de novo in a population, are also discussed. The possible implication of unstable trinucleotide repeats for a series of other hereditary diseases, such as type 2, spinocerebellar ataxia, Machado-Joseph disease, hereditary spastic paraplegia, essential tremor, schizophrenia, and others, is also suggested. 108 refs., 1 tab.

  17. Efficacy of dorsal longitudinal myelotomy in treating spinal spasticity: a review of 20 cases.

    PubMed

    Putty, T K; Shapiro, S A

    1991-09-01

    The authors report their experience using dorsal longitudinal myelotomy in treating spasticity in 20 patients with complete spinal cord injuries. These patients suffered from severe painful flexor/extensor spasms that prevented them from wheelchair ambulation and/or their decubitus ulcers healing. All were receiving large doses of various oral drugs, including baclofen, which had failed to control their spasticity, and all underwent a modification of a posterior T-myelotomy as first described by Bischof. All 20 patients enjoyed immediate complete relief of their painful spasms, although two (10%) eventually experienced return of their spasms and are thus classified as long-term failures. Seventeen patients succeeded in markedly reducing, or being completely weaned from, their antispasmodic medications. In 11 of 14 patients, nonhealing decubitus ulcers subsequently healed with treatment. Bladder function was unchanged from the preoperative status in all patients. Chronic intrathecal baclofen infusion has recently been reported as an effective treatment of the spasticity of paraplegia. The results of this study, along with previous reports advocating dorsal longitudinal myelotomy, suggest that this approach is an efficacious alternative to chronic baclofen infusion in reducing spasticity for complete paraplegics. Considering the cost of the infusion pump, along with the fact that chronic intrathecal baclofen therapy necessitates long-term medical supervision, it appears that myelotomy is superior for this select group of patients who have no hope of regaining voluntary motor function. PMID:1869941

  18. Atypical Aicardi-Goutieres syndrome: Is the WRN locus a modifier?

    PubMed Central

    Lesse, Davor; Saha, Bidisha; Hisama, Fuki; Kaymakamzade, Bahar; Nurlu, Gulay; Gursoy-Özdemir, Yasemin; Thiele, Holger; Nürnberg, Peter; Martin, George M.; Kubisch, Christian; Oshima, Junko

    2014-01-01

    We describe a 28-year-old Turkish man with consanguineous parents who presented with an aged appearance with prematurely gray hair and scleroderma-like skin, spastic paraplegia, and apparent disability. The proband and each of his parents were heterozygous for a mutation in WRN, which could not explain his symptoms. Exome sequencing of the proband’s blood DNA showed a homozygous c.626-1G>C mutation in intron 5 of the SAMHD1 gene, which encodes a triphosphohydrolase involved in the regulation of intracellular dNTP pools and which is mutated in Aicardi-Goutieres syndrome. The RNA studies confirmed aberrant splicing of exon 6, and family studies showed that both parents are heterozygous for this mutation. We conclude that mutations in SAMHD1 - in addition to causing an early-onset form of encephalopathy in Aicardi-Goutieres syndrome - may present with modest signs of accelerated aging similar to Werner syndrome. The extent to which heterozygosity at the WRN locus may modify the effect of biallelic SAMHD1 mutations is unknown. It is conceivable that synergistic effects of these two mutations might be responsible for the unusual phenotype. PMID:24989684

  19. Squamous cell carcinoma arising from a recurrent ischial pressure ulcer: a case report.

    PubMed

    Chou, Chang-Yi; Huang, Zheng-Yi; Chiao, Hao-Yu; Wang, Chi-Yu; Sun, Yu-Shan; Chen, Shyi-Gen; Chen, Tim-Mon; Chang, Shun-Cheng

    2015-02-01

    Marjolin's ulcer is the malignant transformation of long-standing chronic pressure ulcers and requires prompt diagnosis and treatment. A 46-year-old man with an 8-year history of traumatic spinal injury with paraplegia presented with a recurrent ischial pressure ulcer. The initial ulcer, which developed 6 years earlier, was a Stage IV sacral ulcer. The wound was debrided and pathology showed epithelial hyperplasia, acanthosis, hyperkatosis accompanied by mild inflammation, and fibrosis without any malignant transformation. The lesion was covered with a fasciocutaneous bipedicled flap. Four years later, the patient presented with a similar ulcer in the same location. Histology showed the presence of a well-differentiated squamous cell carcinoma (SCC). Following a wide excision, the lesion was covered with a gluteal maximal V-Y musculocutaneous advancement flap. At last follow-up 14 months postoperatively, there was no evidence of recurrence or metastatic disease. Clinicians must be aware of known risk factors for the development of SCC. PMID:25654781

  20. Sialylation regulates brain structure and function.

    PubMed

    Yoo, Seung-Wan; Motari, Mary G; Susuki, Keiichiro; Prendergast, Jillian; Mountney, Andrea; Hurtado, Andres; Schnaar, Ronald L

    2015-07-01

    Every cell expresses a molecularly diverse surface glycan coat (glycocalyx) comprising its interface with its cellular environment. In vertebrates, the terminal sugars of the glycocalyx are often sialic acids, 9-carbon backbone anionic sugars implicated in intermolecular and intercellular interactions. The vertebrate brain is particularly enriched in sialic acid-containing glycolipids termed gangliosides. Human congenital disorders of ganglioside biosynthesis result in paraplegia, epilepsy, and intellectual disability. To better understand sialoglycan functions in the nervous system, we studied brain anatomy, histology, biochemistry, and behavior in mice with engineered mutations in St3gal2 and St3gal3, sialyltransferase genes responsible for terminal sialylation of gangliosides and some glycoproteins. St3gal2/3 double-null mice displayed dysmyelination marked by a 40% reduction in major myelin proteins, 30% fewer myelinated axons, a 33% decrease in myelin thickness, and molecular disruptions at nodes of Ranvier. In part, these changes may be due to dysregulation of ganglioside-mediated oligodendroglial precursor cell proliferation. Neuronal markers were also reduced up to 40%, and hippocampal neurons had smaller dendritic arbors. Young adult St3gal2/3 double-null mice displayed impaired motor coordination, disturbed gait, and profound cognitive disability. Comparisons among sialyltransferase mutant mice provide insights into the functional roles of brain gangliosides and sialoglycoproteins consistent with related human congenital disorders. PMID:25846372

  1. A veterinary and behavioral analysis of dolphin killing methods currently used in the "drive hunt" in Taiji, Japan.

    PubMed

    Butterworth, Andrew; Brakes, Philippa; Vail, Courtney S; Reiss, Diana

    2013-01-01

    Annually in Japanese waters, small cetaceans are killed in "drive hunts" with quotas set by the government of Japan. The Taiji Fishing Cooperative in Japan has published the details of a new killing method that involves cutting (transecting) the spinal cord and purports to reduce time to death. The method involves the repeated insertion of a metal rod followed by the plugging of the wound to prevent blood loss into the water. To date, a paucity of data exists regarding these methods utilized in the drive hunts. Our veterinary and behavioral analysis of video documentation of this method indicates that it does not immediately lead to death and that the time to death data provided in the description of the method, based on termination of breathing and movement, is not supported by the available video data. The method employed causes damage to the vertebral blood vessels and the vascular rete from insertion of the rod that will lead to significant hemorrhage, but this alone would not produce a rapid death in a large mammal of this type. The method induces paraplegia (paralysis of the body) and death through trauma and gradual blood loss. This killing method does not conform to the recognized requirement for "immediate insensibility" and would not be tolerated or permitted in any regulated slaughterhouse process in the developed world. PMID:23544757

  2. 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

  3. Delayed Induction of Human NTE (PNPLA6) Rescues Neurodegeneration and Mobility Defects of Drosophila swiss cheese (sws) Mutants

    PubMed Central

    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. PMID:26671664

  4. Myelo-meningocele: A multi-disciplinary problem

    PubMed Central

    Nnamdi, Ibe Michael Onwuzuruike

    2014-01-01

    Background: Myelo-meningoceles are part of congenital afflictions of the spinal column. They arise from the failure of the neural tube to fuse properly during early embryonic growth. The causes and sequalae are multiple and, therefore, require multiple disciplines, to handle them. This study assessed the role of inter-disciplinary approach in the management of myelo-meningoceles. Materials and Methods: From 1975 to 2007, the author repaired 20 midline lumbar and lumbo-sacral myelo-meningoceles; 5 in Jamaica and 15 in Nigeria. There were 11 males and 9 females. Their ages, at operation, ranged from 1 to 168 days. All had urine and faecal incontinence and severe paraparesis to paraplegia. Skeletal deformities were present in 16 cases. The operations were carried out under routine general anaesthesia and in prone position. All cases were followed-up for up to 60 months, apart from one who died 4 days at home after discharge. Results: There were no deaths within the period of hospitalisation, usually about 14 days. Those followed-up have not made much improvement, though they were able to sit up without support and move around by shifting on their buttocks on the floor. Conclusion: We must continue to help these patients, but under the umbrella of specialised rehabilitation centres with the different specialists working together to make these patients attain a meaningful life and be useful to themselves and the society. PMID:24970975

  5. 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. PMID:24441006

  6. Dominant spinal muscular atrophy is caused by mutations in BICD2, an important golgin protein

    PubMed Central

    Martinez-Carrera, Lilian A.; Wirth, Brunhilde

    2015-01-01

    Spinal muscular atrophies (SMAs) are characterized by degeneration of spinal motor neurons and muscle weakness. Autosomal recessive SMA is the most common form and is caused by homozygous deletions/mutations of the SMN1 gene. However, families with dominant inherited SMA have been reported, for most of them the causal gene remains unknown. Recently, we and others have identified heterozygous mutations in BICD2 as causative for autosomal dominant SMA, lower extremity-predominant, 2 (SMALED2) and hereditary spastic paraplegia (HSP). BICD2 encodes the Bicaudal D2 protein, which is considered to be a golgin, due to its coiled-coil (CC) structure and interaction with the small GTPase RAB6A located at the Golgi apparatus. Golgins are resident proteins in the Golgi apparatus and form a matrix that helps to maintain the structure of this organelle. Golgins are also involved in the regulation of vesicle transport. In vitro overexpression experiments and studies of fibroblast cell lines derived from patients, showed fragmentation of the Golgi apparatus. In the current review, we will discuss possible causes for this disruption, and the consequences at cellular level, with a view to better understand the pathomechanism of this disease. PMID:26594138

  7. Endovascular Management of Thoracic Aortic Aneurysms

    SciTech Connect

    Fattori, Rossella Russo, Vincenzo; Lovato, Luigi; Buttazzi, Katia; Rinaldi, Giovanni

    2011-12-15

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

  8. Three Routes to Suppression of the Neurodegenerative Phenotypes Caused by Kinesin Heavy Chain Mutations

    PubMed Central

    Djagaeva, Inna; Rose, Debra J.; Lim, Angeline; Venter, Chris E.; Brendza, Katherine M.; Moua, Pangkong; Saxton, William M.

    2012-01-01

    Kinesin-1 is a motor protein that moves stepwise along microtubules by employing dimerized kinesin heavy chain (Khc) subunits that alternate cycles of microtubule binding, conformational change, and ATP hydrolysis. Mutations in the Drosophila Khc gene are known to cause distal paralysis and lethality preceded by the occurrence of dystrophic axon terminals, reduced axonal transport, organelle-filled axonal swellings, and impaired action potential propagation. Mutations in the equivalent human gene, Kif5A, result in similar problems that cause hereditary spastic paraplegia (HSP) and Charcot–Marie–Tooth type 2 (CMT2) distal neuropathies. By comparing the phenotypes and the complementation behaviors of a large set of Khc missense alleles, including one that is identical to a human Kif5A HSP allele, we identified three routes to suppression of Khc phenotypes: nutrient restriction, genetic background manipulation, and a remarkable intramolecular complementation between mutations known or likely to cause reciprocal changes in the rate of microtubule-stimulated ADP release by kinesin-1. Our results reveal the value of large-scale complementation analysis for gaining insight into protein structure–function relationships in vivo and point to possible paths for suppressing symptoms of HSP and related distal neuropathies. PMID:22714410

  9. Intramedullary conus metastasis from carcinoma lung

    PubMed Central

    Mavani, Sandip B.; Nadkarni, Trimurti D.; Goel, Naina A.

    2013-01-01

    A 46-year-old male presented with progressive paraparesis and sensory impairment in both lower limbs since 2 months. He had urinary and bowel incontinence. On examination he had flaccid paraplegia with a sensory level at 11th dorsal vertebral level. Magnetic resonance imaging (MRI) scans of the lumbosacral spine showed an enhancing intramedullary lesion in the conus. The patient underwent excision of the conus mass. Histopathology confirmed the tumor to represent a poorly differentiated metastatic carcinoma from an unknown primary. A positron emission tomography-computed tomography (PET-CT) scan of the whole body revealed hypermetabolic activity in the hilum of the right lung confirmed to be a lung carcinoma on a CT-guided biopsy. The patient was undergoing chemoradiation at 1 month follow-up. The author's literature search has yielded only four other case reports of conus metastasis of which only one is in English literature. The present case report and review of literature are presented. PMID:24381457

  10. Risk factors for periprosthetic joint infection after total joint arthroplasty: a systematic review and meta-analysis.

    PubMed

    Zhu, Y; Zhang, F; Chen, W; Liu, S; Zhang, Q; Zhang, Y

    2015-02-01

    Many of the mooted risk factors associated with periprosthetic joint infection (PJI) after total joint arthroplasty (TJA) remain controversial and are not well characterized. Online and manual searches were performed using Medline, Embase, Chinese National Knowledge Infrastructure and the Cochrane Central Database from January 1980 to March 2014). For inclusion, studies had to meet the quality assessment criteria of the CONSORT statement, and be concerned with evaluation of risk factors for PJI after TJA. Two reviewers extracted the relevant data independently and any disagreements were resolved by consensus. Fourteen studies were included in this meta-analysis. The following significant risk factors for PJI were identified: body mass index (both continuous and dichotomous variables); diabetes mellitus; corticosteroid therapy; hypoalbuminaemia; history of rheumatoid arthritis; blood transfusion; presence of a wound drain; wound dehiscence; superficial surgical site infection; coagulopathy; malignancy, immunodepression; National Nosocomial Infections Surveillance Score ?2; other nosocomial infection; prolonged operative time; and previous surgery. Factors that were not significantly associated with PJI were: cirrhosis; hypothyroidism; urinary tract infection; illicit drug abuse; alcohol abuse; hypercholesterolaemia; hypertension, ischaemic heart disease; peptic ulcer disease; hemiplegia or paraplegia; dementia; and operation performed by a staff surgeon (vs a trainee). Strategies to prevent PJI after TJA should focus, in particular, on those patients at greatest risk of infection according to their individual risk factors. PMID:25575769

  11. Long-Term Results of Endovascular Repair for Distal Arch and Descending Thoracic Aortic Aneurysms Treated by Custom-Made Endografts: Usefulness of Fenestrated Endografts

    PubMed Central

    Nakamura, Kunihide; Nagahama, Hiroyuki; Nina, Katsuhiko; Endou, Jouji; Kojima, Kazushi; Nishimura, Masanori; Ishii, Hirohito; Yokota, Atsuko

    2014-01-01

    Objective: We evaluated early and long-term results of atherosclerotic aneurysm repair with custom-made endografts. Materials and Methods: Eighty-one consecutive patients underwent thoracic endovascular aortic repair with custom-made endografts. Fenestrated grafts were used in 37 patients (45.7%) to maintain blood flow of the neck and a landing zone for as long as possible for distal arch or proximal descending aneurysms. The rates of perioperative mortality, stroke, paraplegia, and primary endoleaks were assessed to evaluate in-hospital safety. The rates of endoleak development, survival, and freedom from aortic-related death were assessed to evaluate long-term efficiency. Results: Twenty-four patients (29.6%) underwent urgent operations, and 38 (46.9%) underwent distal arch or proximal descending aortic aneurysm repair. There was one case (1.2%) of in-hospital mortality and no cases of stroke. Permanent spinal injury occurred in one patient (1.2%). Early and late endoleaks occurred in one and 16 patients, respectively. The actuarial survival rates were 88.9%, 64.9%, and 51.7% at 1, 5, and 10 years, respectively. The actuarial rates of freedom from endoleaks were 90.1%, 81.3%, and 68.6% at 1, 5, and 10 years, respectively. Conclusion: Early results of custom-made endografts were excellent, and fenestrated endografts were safe for distal arch and proximal descending aortic aneurysms. PMID:25593623

  12. Spinal dorsal dermal sinus tract: An experience of 21 cases

    PubMed Central

    Singh, Ishwar; Rohilla, Seema; Kumar, Prashant; Sharma, Saurabh

    2015-01-01

    Background: Spinal dorsal dermal sinus is a rare entity, which usually comes to clinical attention by cutaneous abnormalities, neurologic deficit, and/or infection. The present study was undertaken to know the clinical profile of these patients, to study associated anomalies and to assess the results of surgical intervention. Methods: Medical records of 21 patients treated for spinal dorsal dermal sinus from September 2007 to December 2013 were reviewed. Results: We had 21 patients with male: female ratio of 13:8. Only 2 patients were below 1-year of age, and most cases (15) were between 2 and 15 years (mean age = 8.2 years). Lumbar region (11 cases) was most frequently involved, followed by thoracic (4 cases), lumbosacral, and cervical region in 3 patients each. All of our patients presented with neurological deficits. Three patients were admitted with acute meningitis with acute onset paraplegia and had intraspinal abscess. The motor, sensory, and autonomic deficits were seen in 14, 6, and 8 patients, respectively. Scoliosis and congenital talipes equinovarus were the common associated anomalies. All patients underwent surgical exploration and repair of dysraphic state and excision of the sinus. Overall, 20 patients improved or neurological status stabilized and only 1 patient deteriorated. Postoperative wound infection was seen in 2 cases. Conclusions: All patients with spinal dorsal dermal sinuses should be offered aggressive surgical treatment in the form of total excision of sinus tract and correction of spinal malformation, as soon as diagnosed. PMID:26539316

  13. Mutation screen reveals novel variants and expands the phenotypes associated with DYNC1H1.

    PubMed

    Strickland, Alleene V; Schabhüttl, Maria; Offenbacher, Hans; Synofzik, Matthis; Hauser, Natalie S; Brunner-Krainz, Michaela; Gruber-Sedlmayr, Ursula; Moore, Steven A; Windhager, Reinhard; Bender, Benjamin; Harms, Matthew; Klebe, Stephan; Young, Peter; Kennerson, Marina; Garcia, Avencia Sanchez Mejias; Gonzalez, Michael A; Züchner, Stephan; Schule, Rebecca; Shy, Michael E; Auer-Grumbach, Michaela

    2015-09-01

    Dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1) encodes a necessary subunit of the cytoplasmic dynein complex, which traffics cargo along microtubules. Dominant DYNC1H1 mutations are implicated in neural diseases, including spinal muscular atrophy with lower extremity dominance (SMA-LED), intellectual disability with neuronal migration defects, malformations of cortical development, and Charcot-Marie-Tooth disease, type 2O. We hypothesized that additional variants could be found in these and novel motoneuron and related diseases. Therefore, we analyzed our database of 1024 whole exome sequencing samples of motoneuron and related diseases for novel single nucleotide variations. We filtered these results for significant variants, which were further screened using segregation analysis in available family members. Analysis revealed six novel, rare, and highly conserved variants. Three of these are likely pathogenic and encompass a broad phenotypic spectrum with distinct disease clusters. Our findings suggest that DYNC1H1 variants can cause not only lower, but also upper motor neuron disease. It thus adds DYNC1H1 to the growing list of spastic paraplegia related genes in microtubule-dependent motor protein pathways. PMID:26100331

  14. Overexpression of KLC2 due to a homozygous deletion in the non-coding region causes SPOAN syndrome.

    PubMed

    Melo, Uirá S; Macedo-Souza, Lucia I; Figueiredo, Thalita; Muotri, Alysson R; Gleeson, Joseph G; Coux, Gabriela; Armas, Pablo; Calcaterra, Nora B; Kitajima, João P; Amorim, Simone; Olávio, Thiago R; Griesi-Oliveira, Karina; Coatti, Giuliana C; Rocha, Clarissa R R; Martins-Pinheiro, Marinalva; Menck, Carlos F M; Zaki, Maha S; Kok, Fernando; Zatz, Mayana; Santos, Silvana

    2015-12-15

    SPOAN syndrome is a neurodegenerative disorder mainly characterized by spastic paraplegia, optic atrophy and neuropathy (SPOAN). Affected patients are wheelchair bound after 15 years old, with progressive joint contractures and spine deformities. SPOAN patients also have sub normal vision secondary to apparently non-progressive congenital optic atrophy. A potential causative gene was mapped at 11q13 ten years ago. Here we performed next-generation sequencing in SPOAN-derived samples. While whole-exome sequencing failed to identify the causative mutation, whole-genome sequencing allowed to detect a homozygous 216-bp deletion (chr11.hg19:g.66,024,557_66,024,773del) located at the non-coding upstream region of the KLC2 gene. Expression assays performed with patient's fibroblasts and motor neurons derived from SPOAN patients showed KLC2 overexpression. Luciferase assay in constructs with 216-bp deletion confirmed the overexpression of gene reporter, varying from 48 to 74%, as compared with wild-type. Knockdown and overexpression of klc2 in Danio rerio revealed mild to severe curly-tail phenotype, which is suggestive of a neuromuscular disorder. Overexpression of a gene caused by a small deletion in the non-coding region is a novel mechanism, which to the best of our knowledge, was never reported before in a recessive condition. Although the molecular mechanism of KLC2 up-regulation still remains to be uncovered, such example adds to the importance of non-coding regions in human pathology. PMID:26385635

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

    PubMed Central

    2011-01-01

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

  16. [Analysis of the quality of life in patients with spinal lesions in the Canton of Sarajevo].

    PubMed

    Vavra-Hadziahmetovi?, Narcisa

    2004-01-01

    The author present in the retrospective analysis 10 patients (52 females, 48 males) with the condition of paraplegy in Canton Sarajevo in the period 01.01.-31.12.2002. year. In all the patients were followed the total life and working activities as are proclaim by UN 1994. The standard rules for the equal possibilities of the persons with unableness what predicts the insurance of their rights from the medical care and additional services. The results of the examination show that there does not exist one program for the professional direction and that only 8 (16%) males and 2 (4%) females employed while the rest unemployed, prematurely retired people or it is about the children it schooling. Although the persons with paraplegia get qualified as the persons with unableness of the adaptation and the life--housing adaptation only portionally performed (entrance in the flat--house 30%, bathroom/WC 26%, the thresholds 60%). They are identical the situations and with use of the utilities: wheel chair--stand--beds (92%:2%:29%). The particular caution is by the parents, marital partner 32% and 27% by brother, sister or another family member. The results which concern life of the examinees in the community show that 16% of examinees live along. The identical is the situation when ace in question also the members in the association and attending of the tuition at schools or faculties. PMID:15202316

  17. 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

  18. Differences between immediate and late onset of spinal cord ischemia after open and endovascular aortic interventions.

    PubMed

    Davidovic, L; Ilic, N; Koncar, I

    2015-10-01

    Spinal cord ischemia remains the most impressive and colliding complication following open surgical and endovascular aortic procedures. Paraparesis and paraplegia are devastating, having a major invalidating impact on the patient's life. Also for the surgeon and the entire team this dramatic adverse event causes a significant concussion. Surgeons faced this problem in practice in the 1950s when this surgery started being applied. Even A. Carrel in 1910 said, "The main danger of the aortic operation does not come from the heart or from the aorta itself, but from the central nervous system". As the number of these surgeries grew, some were followed by the spinal cord ischemia. Now, in 21st century, problem of spinal cord ischemia still exists. By understanding the reasons of its development we shall be able to find more useful methods for prevention as well as for the treatment. The aim of this article was to search what is behind this dreadful complication, explaining different mechanisms which take part in its development during endovascular and open surgical treatment. PMID:25868970

  19. 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 ?/?-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.

  20. Lipoxin A4 ameliorates ischemia/reperfusion induced spinal cord injury in rabbit model

    PubMed Central

    Liu, Zhi-Qiang; Zhang, Hong-Bin; Wang, Jian; Xia, Li-Jian; Zhang, Wei

    2015-01-01

    Ischemia/reperfusion (I/R) induced spinal cord injury is an important pathologic mechanism leading to the paraplegia observed after surgery to repairaortic aneurysms. This study aims to investigate the neuroprotective effects of Lipoxin A4 and its potential mechanism in a rabbit model with I/R spinal cord injury. Forty-five rabbits were randomly divided into three groups: sham group, I/R group and Lipoxin A4 group. Rabbits were subject to 30 min aortic occlusion to induce transient spinal cord ischemia. All animals were sacrificed after neurological evaluation with modified Tarlov criteria at the 48th hour after reperfusion, and the spinal cord segments (L4-6) were harvested for histopathological examination, as well as local malondialdehyde (MDA) and total superoxide dismutase (SOD) activity analysis. All animals in the I/R group became paraplegic. While after 48-hour treatment, compared with I/R group, Lipoxin A4 significantly improved neurological function, reduced cell apoptosis and MDA levels as well as increased SOD activity (P < 0.05). These results suggest that Lipoxin A4 can ameliorate I/R induced spinal cord injury in Rabbit through its antiapoptosis and antioxidant activity. PMID:26550197

  1. Intrathecal Baclofen therapy in Germany: Proceedings of the IAB-Interdisciplinary Working Group for Movement Disorders Consensus Meeting.

    PubMed

    Dressler, D; Berweck, S; Chatzikalfas, A; Ebke, M; Frank, B; Hesse, S; Huber, M; Krauss, J K; Mücke, K-H; Nolte, A; Oelmann, H-D; Schönle, P W; Schmutzler, M; Pickenbrock, H; Van der Ven, C; Veelken, N; Vogel, M; Vogt, T; Saberi, F Adib

    2015-11-01

    Continuous intrathecal Baclofen application (ITB) through an intracorporeal pump system is widely used in adults and children with spasticity of spinal and supraspinal origin. Currently, about 1200 new ITB pump systems are implanted in Germany each year. ITB is based on an interdisciplinary approach with neurologists, rehabilitation specialists, paediatricians and neurosurgeons. We are presenting the proceedings of a consensus meeting organised by IAB-Interdisciplinary Working Group for Movement Disorders. The ITB pump system consists of the implantable pump with its drug reservoir, the refill port, an additional side port and a flexible catheter. Non-programmable pumps drive the Baclofen flow by the reservoir pressure. Programmable pumps additionally contain a radiofrequency control unit, an electrical pump and a battery. They have major advantages during the dose-finding phase. ITB doses vary widely between 10 and 2000 ?g/day. For spinal spasticity, they are typically in the order of 100-300 ?g/day. Hereditary spastic paraplegia seems to require particularly low doses, while dystonia and brain injury require particularly high ones. Best effects are documented for tonic paraspasticity of spinal origin and the least effects for phasic muscle hyperactivity disorders of supraspinal origin. Oral antispastics are mainly effective in mild spasticity. Botulinum toxin is most effective in focal spasticity. Myotomies and denervation operations are restricted to selected cases of focal spasticity. Due to its wide-spread distribution within the cerebrospinal fluid, ITB can tackle wide-spread and severe spasticity. PMID:26179478

  2. Endovascular Treatment of Descending Thoracic Aortic Aneurysms with the EndoFit Stent-Graft

    SciTech Connect

    Saratzis, N.; Saratzis, Athanasios Melas, N.; Ginis, G.; Lioupis, A.; Lykopoulos, D.; Lazaridis, J.; Kiskinis, Dimitrios

    2007-04-15

    Objective. To evaluate the mid-term feasibility, efficacy, and durability of descending thoracic aortic aneurysm (DTAA) exclusion using the EndoFit device (LeMaitre Vascular). Methods. Twenty-three (23) men (mean age 66 years) with a DTAA were admitted to our department for endovascular repair (21 were ASA III+ and 2 refused open repair) from January 2003 to July 2005. Results. Complete aneurysm exclusion was feasible in all subjects (100% technical success). The median follow-up was 18 months (range 8-40 months). A single stent-graft was used in 6 cases. The deployment of a second stent-graft was required in the remaining 17 patients. All endografts were attached proximally, beyond the left subclavian artery, leaving the aortic arch branches intact. No procedure-related deaths have occurred. A distal type I endoleak was detected in 2 cases on the 1 month follow-up CT scan, and was repaired with reintervention and deployment of an extension graft. A nonfatal acute myocardial infarction occurred in 1 patient in the sixth postoperative month. Graft migration, graft infection, paraplegia, cerebral or distal embolization, renal impairment or any other major complications were not observed. Conclusion. The treatment of DTAAs using the EndoFit stent-graft is technically feasible. Mid-term results in this series are promising.

  3. Souffle/Spastizin controls secretory vesicle maturation during zebrafish oogenesis.

    PubMed

    Kanagaraj, Palsamy; Gautier-Stein, Amandine; Riedel, Dietmar; Schomburg, Christoph; Cerdà, Joan; Vollack, Nadine; Dosch, Roland

    2014-06-01

    During oogenesis, the egg prepares for fertilization and early embryogenesis. As a consequence, vesicle transport is very active during vitellogenesis, and oocytes are an outstanding system to study regulators of membrane trafficking. Here, we combine zebrafish genetics and the oocyte model to identify the molecular lesion underlying the zebrafish souffle (suf) mutation. We demonstrate that suf encodes the homolog of the Hereditary Spastic Paraplegia (HSP) gene SPASTIZIN (SPG15). We show that in zebrafish oocytes suf mutants accumulate Rab11b-positive vesicles, but trafficking of recycling endosomes is not affected. Instead, we detect Suf/Spastizin on cortical granules, which undergo regulated secretion. We demonstrate genetically that Suf is essential for granule maturation into secretion competent dense-core vesicles describing a novel role for Suf in vesicle maturation. Interestingly, in suf mutants immature, secretory precursors accumulate, because they fail to pinch-off Clathrin-coated buds. Moreover, pharmacological inhibition of the abscission regulator Dynamin leads to an accumulation of immature secretory granules and mimics the suf phenotype. Our results identify a novel regulator of secretory vesicle formation in the zebrafish oocyte. In addition, we describe an uncharacterized cellular mechanism for Suf/Spastizin activity during secretion, which raises the possibility of novel therapeutic avenues for HSP research. PMID:24967841

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

    PubMed Central

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

    2013-01-01

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

  5. Oligomerization of ZFYVE27 (Protrudin) Is Necessary to Promote Neurite Extension

    PubMed Central

    Pantakani, D. V. Krishna; Czyzewska, Marta M.; Sikorska, Anna; Bodda, Chiranjeevi; Mannan, Ashraf U.

    2011-01-01

    ZFYVE27 (Protrudin) was originally identified as an interacting partner of spastin, which is most frequently mutated in hereditary spastic paraplegia. ZFYVE27 is a novel member of FYVE family, which is implicated in the formation of neurite extensions by promoting directional membrane trafficking in neurons. Now, through a yeast two-hybrid screen, we have identified that ZFYVE27 interacts with itself and the core interaction region resides within the third hydrophobic region (HR3) of the protein. We confirmed the ZFYVE27's self-interaction in the mammalian cells by co-immunoprecipitation and co-localization studies. To decipher the oligomeric nature of ZFYVE27, we performed sucrose gradient centrifugation and showed that ZFYVE27 oligomerizes into dimer/tetramer forms. Sub-cellular fractionation and Triton X-114 membrane phase separation analysis indicated that ZFYVE27 is a peripheral membrane protein. Furthermore, ZFYVE27 also binds to phosphatidylinositol 3-phosphate lipid moiety. Interestingly, cells expressing ZFYVE27?HR3 failed to produce protrusions instead caused swelling of cell soma. When ZFYVE27?HR3 was co-expressed with wild-type ZFYVE27 (ZFYVE27WT), it exerted a dominant negative effect on ZFYVE27WT as the cells co-expressing both proteins were also unable to induce protrusions and showed cytoplasmic swelling. Altogether, it is evident that a functionally active form of oligomer is crucial for ZFYVE27 ability to promote neurite extensions. PMID:22216323

  6. Polyradiculopathy and Gastroparesis due to Cytomegalovirus Infection in AIDS: A Case Report and Review of Literature.

    PubMed

    Thongpooswan, Supat; Chyn, Eric; Alfishawy, Mostafa; Restrepo, Erfidia; Berman, Charles; Ahmed, Kawser; Muralidharan, Sethu

    2015-01-01

    BACKGROUND Cytomegalovirus (CMV) infection has been well described as an opportunistic infection of patients with human immunodeficiency virus (HIV). To the best of our knowledge, this is the first case report of a patient with AIDS and lumbosacral polyradiculopathy, associated with gastroparesis resulting from CMV infection. CASE REPORT A 46-year-old Hispanic woman with a history of HIV for 10 years was admitted to our hospital for nausea, vomiting, urinary retention, and generalized weakness. Bilateral lower extremity examination revealed flaccid paraplegia, decreased sensations from the groin downwards, bilateral lower extremity areflexia, and absent plantar reflexes, with enlarged urinary bladder. CMV was detected in CSF by PCR, and cervical and lumbar magnetic resonance imaging (MRI) revealed intense nodular leptomeningeal enhancement from the lower thoracic cord and extending along the conus medullaris/filum terminalis and nerve roots. Gastric emptying scintigraphy revealed severe delayed gastric emptying time. Ganciclovir was initiated and her neurological symptoms and gastrological symptoms gradually improved. Over 8 weeks, nausea and vomiting resolved and the patient was able to walk before being discharged from the hospital. CONCLUSIONS Polyradiculopathy and gastroparesis can result from CMV infection in AIDS patients. Whether the mechanism is secondary to viral infection or immune systems remains unclear. It is important for physicians to be aware of this uncommon presentation in the antiretroviral therapy (ART) era. CMV treatment should be initiated immediately once diagnosis is confirmed. PMID:26552851

  7. 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

  8. 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

  9. Posttraumatic syringomyelia: profound neuronal loss, yet preserved function.

    PubMed

    Goldstein, B; Hammond, M C; Stiens, S A; Little, J W

    1998-01-01

    Posttraumatic syrinxes may extend many cord segments rostral to a spinal cord injury (SCI) and significantly dilate the spinal cord, yet few neurologic deficits may be noted. Careful physical examination may reveal ascending loss of pain and temperature without evident functional motor decline. We present a 49-year-old man with T4 paraplegia and a large posttraumatic syrinx who died 3 weeks after syringoperitoneal shunting. Neuropathologic study revealed a large bilateral syrinx cavity from T1 to C6 that tapered to a small unilateral syrinx at C2. Light microscopy of sections from T1 to C2 showed massive loss of intermediate to intermedio-lateral gray neurons and moderate reduction of motoneurons at T1 to C6 levels. Despite these findings, manual muscle testing results remained normal for wrist extensors and elbow extensors, and the patient continued to perform independent sliding board transfers. We conclude that this large progressive syrinx did not merely dissect neural elements apart but caused extensive neuronal damage. Loss of interneurons was evident in spinal segments with preserved strength and function. Possible mechanisms to explain the relatively minimal clinical deficits in view of the neuronal loss are discussed. PMID:9440427

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

    PubMed Central

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

    2013-01-01

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

  11. Traumatic lumbar artery rupture after lumbar spinal fracture dislocation causing hypovolemic shock: An endovascular treatment.

    PubMed

    Eun, Jong-Pil; Oh, Young-Min

    2015-10-01

    Recently, we observed a case of lumbar artery injury after trauma, which was treated by endovascular embolization. A 67-year-old woman who was injured in a traffic accident was brought to the emergency room. She was conscious and her hemodynamic condition was stable, but she had paraplegia below L1 dermatome. Contrast-enhanced computed tomography scan of abdomen and pelvis revealed fracture dislocation of L3/4 along with retroperitoneal hematomas. However, there was no evidence of traumatic injury in both thoracic and abdominal cavity. At that time, her blood pressure suddenly decreased to 60/40 mmHg and her mental status deteriorated. Also, her hemoglobin level was 5.4 g/dl. While her hemodynamic condition stabilized with massive fluid resuscitation including blood transfusion, an angiography was immediately performed to look for and embolize site of retroperitoneal hemorrhage. On the angiographic images, there was an active extravasation from ruptured left 3rd lumbar artery, and we performed complete embolization with GELFOAM and coil. Lumbar artery injury after trauma is rare and endovascular treatment is useful in case of hemodynamic instability. PMID:25958959

  12. Factors That Influence Employment After Spinal Cord Injury in South Korea

    PubMed Central

    Kang, Eun-Na; Shin, Hyung-Ik

    2014-01-01

    Objective To investigate employment status after spinal cord injury (SCI) and identify personal, family, and injury characteristics those affect their employment in South Korea. Methods Participants were 334 community-dwelling persons 20-64 years of age who had sustained SCI for more than one year. Investigators visited each participant's home to carry out the survey. Bivariate and binary logistic regression analyses were performed to identify personal, family, and injury characteristics that influenced employment after SCI. Results Employment rate decreased significantly from 82.5% to 27.5% after SCI. Logistic regression showed that the probability of employment was higher in men than women, and in individuals older than 45 years at the time of injury than those aged 31-45 years of age. Moreover, employment was higher in individuals injured for longer than 20 years than those injured for 1-5 years and in individuals with incomplete tetraplegia than those with complete paraplegia. Employment was lower in individuals with SCI caused by industrial accidents than those injured in non-industrial accidents. Conclusion Injury characteristics are the most important predictors of employment in persons with SCI. For persons with lower employment rate, individualized vocational rehabilitation and employment-support systems are required. PMID:24639924

  13. Neuroprotective effect of atorvastatin in spinal cord ischemia-reperfusion injury

    PubMed Central

    Nazli, Yunus; Colak, Necmettin; Alpay, Mehmet Fatih; Uysal, Sema; Uzunlar, Ali Kemal; Cakir, Omer

    2015-01-01

    OBJECTIVES: Prevention of the development of paraplegia during the repair of the damage caused by descending thoracic and thoracoabdominal aneurysms remains an important issue. Therefore, we investigated the protective effect of atorvastatin on ischemia-induced spinal cord injury in a rabbit model. METHOD: Thirty-two rabbits were divided into the following four equally sized groups: group I (control), group II (ischemia-reperfusion), group III (atorvastatin treatment) and group IV (atorvastatin withdrawal). Spinal cord ischemia was induced by clamping the aorta both below the left renal artery and above the iliac bifurcation. Seventy-two hours postoperatively, the motor function of the lower limbs of each animal was evaluated according to the Tarlov score. Spinal cord and blood samples were obtained for histopathological and biochemical analyses. RESULTS: All of the rabbits in group II exhibited severe neurological deficits. Atorvastatin treatment (groups III and IV) significantly reduced the level of motor dysfunction. No significant differences were observed between the motor function scores of groups III and IV at the evaluated time points. Light microscopic examination of spinal cord tissue samples obtained at the 72nd hour of reperfusion indicated greater tissue preservation in groups III and IV than in group II. CONCLUSION: This study demonstrates the considerable neuroprotective effect of atorvastatin on the neurological, biochemical and histopathological status of rabbits with ischemia-induced spinal cord injury. Moreover, the acute withdrawal of atorvastatin therapy following the induction of spinal cord ischemia did not increase the neuronal damage in this rabbit model. PMID:25672430

  14. Prevalence and pattern of spinocerebellar degenerations in northeastern Libya.

    PubMed

    Sridharan, R; Radhakrishnan, K; Ashok, P P; Mousa, M E

    1985-12-01

    An intensive search over a two-year period for cases of cerebellar and spinocerebellar degenerations in Benghazi, Libya, made through polyclinics, university hospitals and a centre for the handicapped, revealed a total of 52 patients, among whom 30 were index cases; the remainder were detected on family study. Twenty-five patients lived in Benghazi, giving a crude prevalence of 4.8/100 000 population. There were 24 patients (10 families) with hereditary spastic paraplegia (HSP), 13 (9 families) with early onset cerebellar ataxia with retained tendon reflexes (EOCA), 3 with Friedreich's ataxia (FA), 5 (1 family) with late onset cerebellar ataxia (LOCA) with pigmentary retinal degeneration and autosomal dominant inheritance, 6 single cases of LOCA and 1 with ataxia telangiectasia. There were 14 families with definite autosomal recessive inheritance and only 2 with dominant transmission. The large family size (average of 6.2 children per married woman in the patient group) and the high rate of consanguineous marriages contribute to the high incidence of familial cases, especially those with autosomal recessive inheritance. Nerve conduction studies were normal in HSP and abnormal in EOCA and FA. Computed tomographic scans revealed atrophy of the brainstem and cerebellum in 3 cases of EOCA and 2 with LOCA. No indigenous forms of the disease were observed and the clinical features differed little from the descriptions in literature. However, the relative rarity of patients with FA, in comparison with other types of hereditary ataxias, is striking. PMID:4075075

  15. Spinal Cord Stereotaxy: An Overview.

    PubMed

    Nadvornik, Pavel

    2015-07-01

    The origin of spinal cord stereotaxy can be traced back to the 19th-century work of Woroshiloff, the pioneer of brain stereotaxy. The development of clinical brain stereotaxy began in the mid-20th century, but spinal cord stereotaxy lagged behind. The first stereotactic spinal cord surgery was successfully performed by Hitchcock for pain treatment in the 1960s, and surgery for urinary bladder hyperspasticity performed by Nádvorník followed several years later. Other stereotactic surgeries of the spinal cord movement system could not be considered until Slovak anatomist ?ierny used animal experiments (with cats) to discover the exact location of motoneurons for the individual muscles in the anterior horns of the spinal cord. Having compared the data with the pattern of Riley's atlas based on microscopic investigation of the human spinal cord (only motoneuron groups without functional properties), the first stereotactic spinal cord atlas was transferred to human structures. With the construction of a universal spinal cord stereotactic device began a new era in spinal cord stereotaxy. The investigation of spinal cord movement functions will probably become the main focus of this discipline that aims to restore physiologic movement after spinal cord injury associated with paraplegia. PMID:25798803

  16. Longitudinally extensive transverse myelitis with anti-NMDA receptor antibodies during a systemic lupus erythematosus flare-up.

    PubMed

    Takei, Kentarou; Sato, Mineshige; Nakamura, Masashi; Shimizu, Hiroshi

    2015-01-01

    Transverse myelitis (TM) with systemic lupus erythematosus (SLE) has been linked to the presence of autoantibodies (eg, antiaquaporin 4 (AQP4) and anticardiolipin (aCL)) and SLE-induced secondary vasculitis, but the aetiology remains incompletely understood. A 48-year-old Japanese man with a 6-year history of poorly controlled SLE had stopped glucocorticoid therapy 1?year before admission. 3?days before admission, he developed flaccid paraplegia. Spinal MRI showed a longitudinally hyperintense T2 grey matter lesion from the level of Th4 to the conus medullaris, which was considered longitudinally extensive TM (LETM). We administered steroid pulse therapy (methyl-prednisolone 1000?mg/day) for 3?days and prednisolone 50?mg/day. The patient's flaccid paralysis gradually improved. We concluded that the patient's TM was caused by SLE flare-up, even though we could not completely rule out antiphospholipid syndrome. SLE myelitis is relatively rare and many aetiologies are possible for TM in SLE. PMID:26611483

  17. Molecular mechanisms of gap junction mutations in myelinating cells.

    PubMed

    Sargiannidou, Irene; Markoullis, Kyriaki; Kleopa, Kleopas A

    2010-09-01

    There is an emerging group of neurological disorders that result from genetic mutations affecting gap junction proteins in myelinating cells. The X-linked form of Charcot Marie Tooth disease (CMT1X) is caused by numerous mutations in the GJB1 gene encoding the gap junction protein connexin32 (Cx32), which is expressed in both Schwann cells in the PNS and oligodendrocytes in the CNS. Patients with CMT1X present mainly with a progressive peripheral neuropathy, showing mixed axonal and demyelinating features. In many cases there is also clinical or subclinical involvement of the CNS with acute or chronic phenotypes of encephalopathy. Furthermore, mutations in the GJA12/GJC2 gene encoding the gap junction protein Cx47, which is expressed in oligodendrocytes, have been identified in families with progressive leukodystrophy, known as Pelizaeus-Merzbacher-like disease, as well as in patients with hereditary spastic paraplegia. Recent studies have provided insights into the pattern of gap junction protein expression and function in CNS and PNS myelinating cells. Furthermore, in vitro and in vivo disease models have clarified some of the molecular and cellular mechanisms underlying these disorders. Here we provide an overview of the clinical, genetic, and neurobiological aspects of gap junction disorders affecting the nervous system. PMID:20607661

  18. Extended phenotypic spectrum of KIF5A mutations

    PubMed Central

    Liu, Yo-Tsen; Laurá, Matilde; Hersheson, Joshua; Horga, Alejandro; Jaunmuktane, Zane; Brandner, Sebastian; Pittman, Alan; Hughes, Deborah; Polke, James M.; Sweeney, Mary G.; Proukakis, Christos; Janssen, John C.; Auer-Grumbach, Michaela; Zuchner, Stephan; Shields, Kevin G.; Reilly, Mary M.

    2014-01-01

    Objective: To establish the phenotypic spectrum of KIF5A mutations and to investigate whether KIF5A mutations cause axonal neuropathy associated with hereditary spastic paraplegia (HSP) or typical Charcot-Marie-Tooth disease type 2 (CMT2). Methods: KIF5A sequencing of the motor-domain coding exons was performed in 186 patients with the clinical diagnosis of HSP and in 215 patients with typical CMT2. Another 66 patients with HSP or CMT2 with pyramidal signs were sequenced for all exons of KIF5A by targeted resequencing. One additional patient was genetically diagnosed by whole-exome sequencing. Results: Five KIF5A mutations were identified in 6 unrelated patients: R204W and D232N were novel mutations; R204Q, R280C, and R280H have been previously reported. Three patients had CMT2 as the predominant and presenting phenotype; 2 of them also had pyramidal signs. The other 3 patients presented with HSP but also had significant axonal neuropathy or other additional features. Conclusion: This is currently the largest study investigating KIF5A mutations. By combining next-generation sequencing and conventional sequencing, we confirm that KIF5A mutations can cause variable phenotypes ranging from HSP to CMT2. The identification of mutations in CMT2 broadens the phenotypic spectrum and underlines the importance of KIF5A mutations, which involve degeneration of both the central and peripheral nervous systems and should be tested in HSP and CMT2. PMID:25008398

  19. A New Mutation in Gjc2 Associated with Subclinical Leukodystrophy

    PubMed Central

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

    2014-01-01

    Recessive mutations in GJC2, the gene encoding connexin 47 (Cx47), cause Pelizaeus-Merzbacher-like disease type 1 (PMLD1), a severe dysmyelinating disorder. One recessive mutation (p.Ile33Met) has been associated with a much milder phenotype - Hereditary spastic paraplegia type 44 (SPG44). Here we present evidence that a novel Arg98Leu mutation causes an even milder phenotype - a subclinical leukodystrophy. The Arg98Leu mutant forms gap junction plaques in HeLa cells comparable to wild-type Cx47, but electrical coupling was 20-fold lower in cell pairs expressing Arg98Leu than for cell pairs expressing wild-type Cx47. On the other hand, coupling between Cx47Arg98Leu and Cx43WT expressing cells did not show such reductions. Single channel conductance and normalized steady state junctional conductance-junctional voltage (Gj-Vj) relations differed only slightly from those for wild-type Cx47. Our data suggest that that the minimal phenotype in this patient results from a reduced efficiency of opening of Cx47 channels between oligodendrocyte and oligodendrocyte with preserved coupling between oligodendrocyte and astrocyte, and support a partial loss of function model for the mild Cx47 associated disease phenotypes. PMID:25059390

  20. A novel mutation of AFG3L2 might cause dominant optic atrophy in patients with mild intellectual disability

    PubMed Central

    Charif, Majida; Roubertie, Agathe; Salime, Sara; Mamouni, Sonia; Goizet, Cyril; Hamel, Christian P.; Lenaers, Guy

    2015-01-01

    Dominant optic neuropathies causing fiber loss in the optic nerve are among the most frequent inherited mitochondrial diseases. In most genetically resolved cases, the disease is associated to a mutation in OPA1, which encodes an inner mitochondrial dynamin involved in network fusion, cristae structure and mitochondrial genome maintenance. OPA1 cleavage is regulated by two m-AAA proteases, SPG7 and AFG3L2, which are, respectively involved in Spastic Paraplegia 7 and Spino-Cerebellar Ataxia 28. Here, we identified a novel mutation c.1402C>T in AFG3L2, modifying the arginine 468 in cysteine in an evolutionary highly conserved arginine-finger motif, in a family with optic atrophy and mild intellectual disability. Ophthalmic examinations disclosed a loss of retinal nerve fibers on the temporal and nasal sides of the optic disk and a red–green dyschromatopsia. Thus, our results suggest that neuro-ophthalmological symptom as optic atrophy might be associated with AFG3L2 mutations, and should prompt the screening of this gene in patients with isolated and syndromic inherited optic neuropathies. PMID:26539208

  1. Volitional walking via upper limb muscle-controlled stimulation of the lumbar locomotor center in man.

    PubMed

    Sasada, Syusaku; Kato, Kenji; Kadowaki, Suguru; Groiss, Stefan J; Ugawa, Yoshikazu; Komiyama, Tomoyoshi; Nishimura, Yukio

    2014-08-13

    Gait disturbance in individuals with spinal cord lesion is attributed to the interruption of descending pathways to the spinal locomotor center, whereas neural circuits below and above the lesion maintain their functional capability. An artificial neural connection (ANC), which bridges supraspinal centers and locomotor networks in the lumbar spinal cord beyond the lesion site, may restore the functional impairment. To achieve an ANC that sends descending voluntary commands to the lumbar locomotor center and bypasses the thoracic spinal cord, upper limb muscle activity was converted to magnetic stimuli delivered noninvasively over the lumbar vertebra. Healthy participants were able to initiate and terminate walking-like behavior and to control the step cycle through an ANC controlled by volitional upper limb muscle activity. The walking-like behavior stopped just after the ANC was disconnected from the participants even when the participant continued to swing arms. Furthermore, additional simultaneous peripheral electrical stimulation to the foot via the ANC enhanced this walking-like behavior. Kinematics of the induced behaviors were identical to those observed in voluntary walking. These results demonstrate that the ANC induces volitionally controlled, walking-like behavior of the legs. This paradigm may be able to compensate for the dysfunction of descending pathways by sending commands to the preserved locomotor center at the lumbar spinal cord and may enable individuals with paraplegia to regain volitionally controlled walking. PMID:25122909

  2. ER network formation and membrane fusion by atlastin1/SPG3A disease variants

    PubMed Central

    Ulengin, Idil; Park, John J.; Lee, Tina H.

    2015-01-01

    At least 38 distinct missense mutations in the neuronal atlastin1/SPG3A GTPase are implicated in an autosomal dominant form of hereditary spastic paraplegia (HSP), a motor-neurological disorder manifested by lower limb weakness and spasticity and length-dependent axonopathy of corticospinal motor neurons. Because the atlastin GTPase is sufficient to catalyze membrane fusion and required to form the ER network, at least in nonneuronal cells, it is logically assumed that defects in ER membrane morphogenesis due to impaired fusion activity are the primary drivers of SPG3A-associated HSP. Here we analyzed a subset of established atlastin1/SPG3A disease variants using cell-based assays for atlastin-mediated ER network formation and biochemical assays for atlastin-catalyzed GTP hydrolysis, dimer formation, and membrane fusion. As anticipated, some variants exhibited clear deficits. Surprisingly however, at least two disease variants, one of which represents that most frequently identified in SPG3A HSP patients, displayed wild-type levels of activity in all assays. The same variants were also capable of co-redistributing ER-localized REEP1, a recently identified function of atlastins that requires its catalytic activity. Taken together, these findings indicate that a deficit in the membrane fusion activity of atlastin1 may be a key contributor, but is not required, for HSP causation. PMID:25761634

  3. Tick paralysis caused by Amblyomma maculatum on the Mexican Pacific Coast.

    PubMed

    Espinoza-Gomez, Francisco; Newton-Sanchez, Oscar; Flores-Cazares, Gabriel; De la Cruz-Ruiz, Miriam; Melnikov, Valery; Austria-Tejeda, Jabih; Rojas-Larios, Fabian

    2011-07-01

    Tick paralysis is a rare entity in which it is necessary to identify the cause and remove the arthropod to have a rapid remission of symptoms. In the absence of an early diagnosis, the outcome can be fatal, as toxins are released from the tick's saliva as it feeds. To the best of the authors' knowledge, this is the first clinical report of the disease in Mexico and Latin America. A 22-year-old man from a rural area, who was in contact with cattle, developed ascending flaccid paralysis secondary to Amblyomma maculatum tick toxin. He presented flaccid paraplegia and arreflexia that progressed until causing dyspnea. The clinical symptoms subsided 48 h after the ticks spontaneously detached. The ticks were discovered by nursing personnel while the patient was being transferred to a regional hospital with the diagnosis of Guillain-Barré syndrome. The patient was asymptomatic on discharge from hospital and showed no further motor deterioration at a 1-month follow-up. PMID:21395426

  4. 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

  5. Progressive Lower Extremity Weakness and Axonal Sensorimotor Polyneuropathy from a Mutation in KIF5A (c.611G>A;p.Arg204Gln)

    PubMed Central

    Jerath, Nivedita U.; Grider, Tiffany; Shy, Michael E.

    2015-01-01

    Introduction. Hereditary Spastic Paraplegia (HSP) is a rare hereditary disorder that primarily involves progressive spasticity of the legs (hamstrings, quadriceps, and calves). Methods. A 27-year-old gentleman was a fast runner and able to play soccer until age 9 when he developed slowly progressive weakness. He was wheelchair-bound by age 25. He was evaluated by laboratory testing, imaging, electrodiagnostics, and molecular genetics. Results. Electrodiagnostic testing revealed an axonal sensorimotor polyneuropathy. Genetic testing for HSP in 2003 was negative; repeat testing in 2013 revealed a mutation in KIF5A (c.611G>A;p.Arg204Gln). Conclusions. A recent advance in neurogenetics has allowed for more genes and mutations to be identified; over 76 different genetic loci for HSP and 59 gene products are currently known. Even though our patient had a sensorimotor polyneuropathy on electrodiagnostic testing and a 2003 HSP genetic panel that was negative, a repeat HSP genetic panel was performed in 2013 due to the advancement in neurogenetics. This revealed a mutation in KIF5A. PMID:26543653

  6. The AANA Foundation Malpractice Closed Claims Study: A Descriptive Analysis.

    PubMed

    Jordan, Lorraine M; Quraishi, Jihan A

    2015-10-01

    The AANA Foundation Closed Claims Researchers evaluated 245 closed claims spanning from 2003-2012. The majority of claims comprised CRNA providers whom are mainly male, independent contractors, certified between 1980-1999, and with malpractice coverage limits of $1 million/$3 million. The median age for all claimants was 50 years old, and 63.7% of claimants were female. For those claims where race was known, 54% of claimants were Caucasian. Most adverse events occurred in a hospital with an outpatient admission status. The majority of adverse events were identified as intra-anesthesia. The top five surgical procedures associated with these claims were orthopedic general surgery, cosmetic, obstetric, and neurologic procedures. An adverse event leading to death occurred in 35.1% of claims. Regardless of severity of injury, reviewers determined that 45.5% of negative outcomes were preventable, 32.7% of the anesthesia treatment was inappropriate, and 29% of negative outcomes were caused by CRNAs' actions. Reviewers found that no AANA Standards were breached in 45.7% of claims; however, Standards 4, 5, and 3 were the most common standards breached. The most costly severity classification was major permanent injury (ie, paraplegia, blindness, loss of two limbs, or brain ddamage) with a median payment of $299,810. PMID:26638452

  7. Schistosomiasis of the nervous system.

    PubMed

    Coyle, Christina Marie

    2013-01-01

    Schistosomiasis is a parasitic disease caused by blood flukes of the genus Schistosoma. Currently 200 million people worldwide are infected. Neurological manifestations are a result of the inflammatory response of the host to egg deposition in the brain and spinal cord and is usually seen in patients with recent infection with no evidence of systemic illness. Cerebral and cerebellar disease can result in headache, seizure, and increased intracranial pressure. Cerebral schistosomiasis is more common in Schistosoma japonicum, but increasing cases due to Schistosoma mansoni are being reported in the literature. Other complications of cerebral schistosomiasis include delirium, loss of consciousness, visual field impairment, focal motor deficits, and ataxia. Myelopathy is the most common neurological manifestation of Schistosoma mansoni and the conus medullaris and cauda equine are the most common sites of involvement. Severe disease can result in flaccid paraplegia with areflexia, sphincter dysfunction, and sensory disturbance. Early recognition and prompt treatment are essential when physicians are faced with schistosomiasis involving the central nervous system. Schistosomicidal drugs, such as praziquantel, steroids and surgery, are the mainstay of therapy for this severe form of schistosomiasis. PMID:23829918

  8. Dopa-responsive dystonia--clinical and genetic heterogeneity.

    PubMed

    Wijemanne, Subhashie; Jankovic, Joseph

    2015-07-01

    Dopa-responsive dystonia (DRD) encompasses a group of clinically and genetically heterogeneous disorders that typically manifest as limb-onset, diurnally fluctuating dystonia and exhibit a robust and sustained response to levodopa treatment. Autosomal dominant GTP cyclohydrolase 1 deficiency, also known as Segawa disease, is the most common and best-characterized condition that manifests as DRD, but a similar presentation can be seen with genetic abnormalities that lead to deficiencies in tyrosine hydroxylase, sepiapterin reductase or other enzymes that are involved in the biosynthesis of dopamine. In rare cases, DRD can result from conditions that do not affect the biosynthesis of dopamine; single case reports have shown that DRD can be a manifestation of hereditary spastic paraplegia type 11, spinocerebellar ataxia type 3 and ataxia telangiectasia. This heterogeneity of conditions that underlie DRD frequently leads to misdiagnosis, which delays the appropriate treatment with levodopa. Correct diagnosis at an early stage requires use of the appropriate diagnostic tests, which include a levodopa trial, genetic testing (including whole-exome sequencing), cerebrospinal fluid neurotransmitter analysis, the phenylalanine loading test, and enzyme activity measurements. The selection of tests for use depends on the clinical presentation and level of complexity. This Review presents the common and rarer causes of DRD and their clinical features, and considers the most appropriate approaches to ensure early diagnosis and treatment. PMID:26100751

  9. Unique Function of Kinesin Kif5A in Localization of Mitochondria in Axons

    PubMed Central

    Campbell, Philip D.; Shen, Kimberle; Sapio, Matthew R.; Glenn, Thomas D.; Talbot, William S.

    2014-01-01

    Mutations in Kinesin proteins (Kifs) are linked to various neurological diseases, but the specific and redundant functions of the vertebrate Kifs are incompletely understood. For example, Kif5A, but not other Kinesin-1 heavy-chain family members, is implicated in Charcot-Marie-Tooth disease (CMT) and Hereditary Spastic Paraplegia (HSP), but the mechanism of its involvement in the progressive axonal degeneration characteristic of these diseases is not well understood. We report that zebrafish kif5Aa mutants exhibit hyperexcitability, peripheral polyneuropathy, and axonal degeneration reminiscent of CMT and HSP. Strikingly, although kif5 genes are thought to act largely redundantly in other contexts, and zebrafish peripheral neurons express five kif5 genes, kif5Aa mutant peripheral sensory axons lack mitochondria and degenerate. We show that this Kif5Aa-specific function is cell autonomous and is mediated by its C-terminal tail, as only Kif5Aa and chimeric motors containing the Kif5Aa C-tail can rescue deficits. Finally, concurrent loss of the kinesin-3, kif1b, or its adaptor kbp, exacerbates axonal degeneration via a nonmitochondrial cargo common to Kif5Aa. Our results shed light on Kinesin complexity and reveal determinants of specific Kif5A functions in mitochondrial transport, adaptor binding, and axonal maintenance. PMID:25355224

  10. Neurodegeneration and microtubule dynamics: death by a thousand cuts

    PubMed Central

    Dubey, Jyoti; Ratnakaran, Neena; Koushika, Sandhya P.

    2015-01-01

    Microtubules form important cytoskeletal structures that play a role in establishing and maintaining neuronal polarity, regulating neuronal morphology, transporting cargo, and scaffolding signaling molecules to form signaling hubs. Within a neuronal cell, microtubules are found to have variable lengths and can be both stable and dynamic. Microtubule associated proteins, post-translational modifications of tubulin subunits, microtubule severing enzymes, and signaling molecules are all known to influence both stable and dynamic pools of microtubules. Microtubule dynamics, the process of interconversion between stable and dynamic pools, and the proportions of these two pools have the potential to influence a wide variety of cellular processes. Reduced microtubule stability has been observed in several neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS), and tauopathies like Progressive Supranuclear Palsy. Hyperstable microtubules, as seen in Hereditary Spastic Paraplegia (HSP), also lead to neurodegeneration. Therefore, the ratio of stable and dynamic microtubules is likely to be important for neuronal function and perturbation in microtubule dynamics might contribute to disease progression. PMID:26441521

  11. Hazards of mattresses, beds and bedding in deaths of infants.

    PubMed

    Gilbert-Barness, E; Hegstrand, L; Chandra, S; Emery, J L; Barness, L A; Franciosi, R; Huntington, R

    1991-03-01

    Of 52 infants who had died suddenly and were referred to autopsy, nine had lain on adult water beds for the first time; five had died as a result of accidents; two had died on water beds; two were in beds with widely spaced slats; and one had died as a result of strangulation. Three deaths were due to overlying. Three other infants had been placed on sheepskin rugs for the first time and were found dead shortly thereafter. These infants ranged in age from 2 to 9 months, except for a severely mentally retarded nine-year-old with spastic paraplegia. We believe that a general warning should be issued concerning water beds and that soft bedding should not be used for infants. Infants should not be placed unattended or left to sleep on water beds; only beds recommended for infants should be used. Overlying of a young infant is most likely to occur on a water bed, or if the parent is obese or has consumed alcohol. PMID:2063814

  12. Hippocrates: the forefather of neurology.

    PubMed

    Breitenfeld, T; Jurasic, M J; Breitenfeld, D

    2014-09-01

    Hippocrates is one of the most influential medical doctors of all times. He started observing and experimenting in times of mysticism and magic. He carried a holistic and humanitarian approach to the patient with examination as the principal approach-inspection, palpation and auscultation are still the most important tools in diagnosing algorithms of today. He had immense experience with the human body most likely due to numerous wound treatments he had performed; some even believe he performed autopsies despite the negative trend at the time. Hippocrates identified the brain as the analyst of the outside world, the interpreter of consciousness and the center of intelligence and willpower. Interestingly, Hippocrates was aware of many valid concepts in neurology; his treatise On the Sacred Disease was the most important for understanding neurology and epilepsy. His other ideas pioneered modern day neurology mentioning neurological diseases like apoplexy, spondylitis, hemiplegia, and paraplegia. Today, 10 % of neurological Pubmed and 7 % of neuroscience Scopus reviews mention Corpus Hippocraticum as one of the sources. Therefore, Hippocrates may be considered as the forefather of neurology. PMID:25027011

  13. Infectious aortitis and spondylodiscitis in patients with endovascular stents.

    PubMed

    d'Ettorre, G; Ceccarelli, G; Zaffiri, L; Falcone, M; Mastroianni, C M; Venditti, M; Vullo, V

    2009-04-01

    The infection of endovascular stents remains one of the most problematic complications of aortic surgery. This article describes the case of a 61-year-old male with ascendant and descendent aorta endovascular stents, hospitalized for pyrexia, weight loss and back pain. Blood culture was positive for Staphylococcus hominis resistant to oxacillin and ciprofloxacin. Spiral computed tomography, magnetic resonance imaging and leukocyte-labelled scintigraphy showed that the patient developed a perigraft infection which spondylodiscitis in correspondence of D7, D8 and D9 vertebras. The biopsy CT-scan guided of vertebral inflammed tissue revealed a coagulase-negative Staphylo-coccus and the presence of numerous neutrophilis granulocytes. The reintervention for substituting an infected graft was excluded due to the high risk of death or paraplegia. A therapy with vancomycin, rifampicin and ceftazidime was started. On the basis of clinical and radiological findings, it was decided to switch empirical antimicrobial therapy to levofloxacin, minocycline and teicoplanin and a reduction of inflammation indices was observed. The patient was discharged maintaining this chronic suppressive antimicrobial therapy with a 28-day cycle of linezolid with complete regression of pain, and normalization of inflammation blood indices. After, therapy switched to teicoplanin three times a week while maintaining good clinical and radiological features. In the present, due to the high risk in performing a surgical procedure, a conservative chronic suppressive antimicrobial therapy with teicoplanin allowed to control the infection on an outpatient basis, thereby reducing the costs. PMID:19390503

  14. A Muscle Synergy-Inspired Adaptive Control Scheme for a Hybrid Walking Neuroprosthesis

    PubMed Central

    Alibeji, Naji A.; Kirsch, Nicholas Andrew; Sharma, Nitin

    2015-01-01

    A hybrid neuroprosthesis that uses an electric motor-based wearable exoskeleton and functional electrical stimulation (FES) has a promising potential to restore walking in persons with paraplegia. A hybrid actuation structure introduces effector redundancy, making its automatic control a challenging task because multiple muscles and additional electric motor need to be coordinated. Inspired by the muscle synergy principle, we designed a low dimensional controller to control multiple effectors: FES of multiple muscles and electric motors. The resulting control system may be less complex and easier to control. To obtain the muscle synergy-inspired low dimensional control, a subject-specific gait model was optimized to compute optimal control signals for the multiple effectors. The optimal control signals were then dimensionally reduced by using principal component analysis to extract synergies. Then, an adaptive feedforward controller with an update law for the synergy activation was designed. In addition, feedback control was used to provide stability and robustness to the control design. The adaptive-feedforward and feedback control structure makes the low dimensional controller more robust to disturbances and variations in the model parameters and may help to compensate for other time-varying phenomena (e.g., muscle fatigue). This is proven by using a Lyapunov stability analysis, which yielded semi-global uniformly ultimately bounded tracking. Computer simulations were performed to test the new controller on a 4-degree of freedom gait model.

  15. An Interlaminotomy New Zealand White Rabbit Model to Evaluate Novel Epidural Strategies.

    PubMed

    Nevzati, Edin; Soleman, Jehuda; Schöpf, Salome Aglaia; Coluccia, Daniel; Fandino, Javier; Marbacher, Serge

    2015-11-01

    Objective?The New Zealand White (NZW) rabbit model is an established animal model for examining surgical methods to prevent epidural scar formation after spine surgery. As most approaches include complete laminectomy of the rabbit vertebra, this procedure is associated with high morbidity and mortality rates. We examined a less invasive technique, the microsurgical interlaminotomy, for testing epidural substance application in the rabbit spine. Methods?Surgery was performed in the cadaver rabbit spine to evaluate the approach before performing it in NZW rabbits. All surgical procedures were performed under an operation microscope. Female rabbits with a mean weight of 4770?g?±?240?g were used. Neurologic symptoms were analyzed based on predefined scores. After resection of the spinal process, the caudal part of the upper lamina was resected using a drill and a 1-mm Kerrison punch. The yellow ligament was resected resulting in a dural exposure of ? 5?×?10 mm. Results?Eight pilot interlaminotomies were performed on three cadaveric spines to establish the surgical approach. Twenty-one NZW rabbits were then operated on using the interlaminotomy model. Three rabbits (14.3%) died during surgery due to anesthesia-related complications. Two rabbits (9.5%) showed partial paresis of the lower extremities and one (4.8%) a complete paraplegia. The remaining 15 rabbits (71.4%) had an uneventful recovery without neurologic symptoms. The mean surgical duration was 88 +/- 28 minutes. Conclusion?The rabbit interlaminotomy model is associated with few neurologic deficits and a relatively short operating time. PMID:26351871

  16. Survey of human mitochondrial diseases using new genomic/proteomic tools

    PubMed Central

    Plasterer, Thomas N; Smith, Temple F; Mohr, Scott C

    2001-01-01

    Background We have constructed Bayesian prior-based, amino-acid sequence profiles for the complete yeast mitochondrial proteome and used them to develop methods for identifying and characterizing the context of protein mutations that give rise to human mitochondrial diseases. (Bayesian priors are conditional probabilities that allow the estimation of the likelihood of an event - such as an amino-acid substitution - on the basis of prior occurrences of similar events.) Because these profiles can assemble sets of taxonomically very diverse homologs, they enable identification of the structurally and/or functionally most critical sites in the proteins on the basis of the degree of sequence conservation. These profiles can also find distant homologs with determined three-dimensional structures that aid in the interpretation of effects of missense mutations. Results This survey reports such an analysis for 15 missense mutations, one insertion and three deletions involved in Leber's hereditary optic neuropathy, Leigh syndrome, mitochondrial neurogastrointestinal encephalomyopathy, Mohr-Tranebjaerg syndrome, iron-storage disorders related to Friedreich's ataxia, and hereditary spastic paraplegia. We present structural correlations for seven of the mutations. Conclusions Of the 19 mutations analyzed, 14 involved changes in very highly conserved parts of the affected proteins. Five out of seven structural correlations provided reasonable explanations for the malfunctions. As additional genetic and structural data become available, this methodology can be extended. It has the potential for assisting in identifying new disease-related genes. Furthermore, profiles with structural homologs can generate mechanistic hypotheses concerning the underlying biochemical processes - and why they break down as a result of the mutations. PMID:11423010

  17. Endovascular Repair versus Open Repair for Isolated Descending Thoracic Aortic Aneurysm

    PubMed Central

    Lee, Hyung Chae; Joo, Hyun-Chel; Lee, Seung Hyun; Lee, Sak; Chang, Byung-Chul; Yoo, Kyung-Jong

    2015-01-01

    Purpose To compare the outcomes of thoracic endovascular aortic repair (TEVAR) with those of open repair for descending thoracic aortic aneurysms (DTAA). Materials and Methods We compared the outcomes of 114 patients with DTAA and proximal landing zones 3 or 4 after TEVAR to those of 53 patients after conventional open repairs. Thirty-day and late mortality were the primary endpoints, and early morbidities, aneurysm-related death, and re-intervention were the secondary endpoints. Results The TEVAR group was older and had more incidences of dissecting aneurysm. The mean follow-up was 36±26 months (follow-up rate, 97.8%). The 30-day mortality in the TEVAR and open repair groups were 3.5% and 9.4% (p=0.11). Perioperative stroke and paraplegia incidences were similar between the groups [5.3% vs. 7.5% (p=0.56) and 7.5% vs. 3.5% (p=0.26), respectively]. Respiratory failure occurred more in the open repair group (1.8% vs. 26.4%, p<0.01). The incidence of acute kidney injury requiring dialysis was higher in the open repair group (1.8% vs. 9.4%, p<0.01). The cumulative survival rate was higher in the TEVAR group at 2 to 5 years (79.6% vs. 58.3%, p=0.03). The free from re-intervention was lower in the TEVAR group (65.3% vs. 100%, p=0.02), and the free from aneurysm-related death in the TEVAR and open repair groups were 88.5% and 86.1% (p=0.45). Conclusion TEVAR is safe and effective for treating DTAAs with improved perioperative and long-term outcomes compared with open repair. PMID:26069110

  18. Blood redistribution and circulatory responses to submaximal arm exercise in persons with spinal cord injury.

    PubMed

    Hopman, M T; Monroe, M; Dueck, C; Phillips, W T; Skinner, J S

    1998-09-01

    The purpose of this study was to evaluate responses to submaximal arm exercise (20%, 40%, and 60% of peak power output) using four conditions to support the circulatory redistribution in persons with spinal cord injury (SCI). Five males with tetraplegia (TP) and four males with paraplegia (PR) exercised 1) sitting, 2) supine, and 3) sitting with the addition of a) an anti-gravity suit (anti-G), b) elastic stockings and abdominal binder, and c) functional electrical stimulation of the leg muscles. Compared to sitting, the following significant changes were observed: in the supine position, heart rate (HR) decreased (PR: 104 vs 118 b/min, TP: 76 vs 92 b/min) and stroke volume (SV) increased (PR: 132 vs 116 ml, TP: 96 vs 83 ml). The anti-G suit induced a decrease in heart rate (PR: 104 vs 118 b/min, TP: 87 vs 92 b/min) and a decrease in oxygen uptake (VO2) in PR. Stockings only affected TP, i.e. a decrease in heart rate with 5 b/min and an increase in stroke volume with 13 ml/beat. Functional electrical stimulation produced an increase in VO2 (PR: 1.00 vs 0.95 l/min, TP: 0.68 vs 0.53 l/min) and a rise in stroke volume in TP. Results indicate that the methods employed to support the circulatory redistribution have different working mechanisms and, in addition, that the effects are different for TP and PR probably because of differences in active muscle mass, sympathetic impairment and blood pressure values. PMID:9782544

  19. [A Case of Foix-Alajouanine Syndrome due to Perimedullary AVF: Remission and Aggravation Mechanism Considered by an Open Surgical Biopsy and Intraoperative ICG Angiography].

    PubMed

    Maruyama, Fumiaki; Akasaki, Yasuharu; Watanabe, Mitsuyoshi; Arai, Takao; Isoshima, Akira; Nagashima, Hiroyasu; Murayama, Yuichi

    2015-08-01

    Foix-Alajouanine syndrome (FAS), also known as congestive myelopathy due to spinal vascular malformations, presents with paraplegia, sensory disturbance of lower limbs, and dysfunction of the bladder and rectum. Although FAS is characterized by a subacute onset of neurological symptoms that may wax and wane over a few years, the progression mechanism remains unclear. We report a case of FAS due to an angiographically occult arteriovenous fistula (AVF) that was diagnosed by an open surgical biopsy and intraoperative indocyanine green (ICG) angiography. The patient was a 74-year-old female who presented with a one-year history of gradually progressive gait disturbance, weakness, and decreased sensation in her legs associated with bladder and rectum dysfunction. MRI showed intramedullary T1 hypointensity, T2 hyperintensity at level Th4-12, and intramedullary enhancing with a Gd-DTPA lesion at level Th8-12. A true-FISP image of the MRI revealed an abnormal tortuous vessel in the dorsal spinal subarachnoid space, but digital subtraction angiography of the spine at the C1-L5 level showed no abnormality. The patient also underwent Th8-12 laminectomy for open biopsy. ICG angiography revealed blood flow stagnation in an abnormally enlarged posterior spinal vein. Histological findings indicated necrotizing myelopathy and stenosis with wall thickening of the posterior spinal vein. We hypothesized that the progression mechanism in the present case may have resulted from histological changes in the draining veins of an AVF. Intraoperative ICG angiography may be a valuable method, not only for diagnosing AVFs but also for determining the existence and pathological characteristics of FAS. PMID:26224468

  20. Treatment of middle-super thoracic fractures associated with the sternum fracture

    PubMed Central

    Huang, Zheyuan; Chen, Fengrong; Huang, Jianming; Jian, Guojian; Gong, Hao; Xu, Tianrui; Wang, Bowen; Chen, Ruisong; Chen, Xiaolin; Ye, Zhiyang; Wang, Jun; Xie, Desheng; Liu, Haoyuan

    2015-01-01

    To analyze the characteristics and treatment of middle-super thoracic fractures associated with the sternum fracture, twenty six patients with middle-super thoracic fractures associated with the sternum fracture were retrospectively reviewed. The intimate information of patients including age, gender, cause of injury, site of the sternal fracture, level and type of thoracic vertebral fracture, spinal cord injury and associated injuries were included in the analysis. There were 12 compressed fractures, 11 fracture-dislocations, two burst fracture and one burst-dislocation in this study. Six patients had a complete lesion of the spinal cord, nine sustained a neurologically incomplete injury and 11 were neurologically intact. Nine patients were treated non-operatively and 17 were underwent surgery. All patients were followed up for 8~99 months. Our results showed that road traffic accidents (RTA) and fall were the dominated in the causes. All six patients with a complete paralytic lesion were not recovered with any significant function. Four out of eleven neurologically intact patients had local pain although ten of them remained normal function and one patient turn up tardive paralysis. One of nine patients with incomplete paraplegia returned to normal and four recovered with some function. These study suggested that the sternum is one of the important parts in constructing thoracic cage and plays an important role in maintain the stabilization of the thoracic vertebra. Because of the unique anatomy and biomechanics of the thoracic cage, the classification commonly applied to thoracic vertebra fractures is not suitable for middle-super thoracic fractures associated with the sternum fracture. Middle-super thoracic fractures associated with the sternum fracture was marked by violent force, severe fractures of spine, severe injuries of spinal cord and high incidence of associated injuries. These cases confirm the existence and clinical relevance of the fourth column of the thoracic spine and its role for spinal stability in the patient with middle-super thoracic fracture. PMID:26309652

  1. Early Results of Endovascular Treatment of the Thoracic Aorta Using the Valiant Endograft

    SciTech Connect

    Thompson, Matt Ivaz, Stella; Cheshire, Nicholas; Fattori, Rosella; Rousseau, Herve; Heijmen, Robin; Beregi, Jean-Paul; Thony, Frederic; Horne, Gillian; Morgan, Robert; Loftus, Ian

    2007-11-15

    Endovascular repair of the thoracic aorta has been adopted as the first-line therapy for much pathology. Initial results from the early-generation endografts have highlighted the potential of this technique. Newer-generation endografts have now been introduced into clinical practice and careful assessment of their performance should be mandatory. This study describes the initial experience with the Valiant endograft and makes comparisons with similar series documenting previous-generation endografts. Data were retrospectively collected on 180 patients treated with the Valiant endograft at seven European centers between March 2005 and October 2006. The patient cohort consisted of 66 patients with thoracic aneurysms, 22 with thoracoabdominal aneurysms, 19 with an acute aortic syndrome, 52 with aneurysmal degeneration of a chronic dissection, and 21 patients with traumatic aortic transection. The overall 30-day mortality for the series was 7.2%, with a stroke rate of 3.8% and a paraplegia rate of 3.3%. Subgroup analysis demonstrated that mortality differed significantly between different indications; thoracic aneurysms (6.1%), thoracoabdominal aneurysms (27.3%), acute aortic syndrome (10.5%), chronic dissections (1.9%), and acute transections (0%). Adjunctive surgical procedures were required in 63 patients, and 51% of patients had grafts deployed proximal to the left subclavian artery. Comparison with a series of earlier-generation grafts demonstrated a significant increase in complexity of procedure as assessed by graft implantation site, number of grafts and patient comorbidity. The data demonstrate acceptable results for a new-generation endograft in series of patients with diverse thoracic aortic pathology. Comparison of clinical outcomes between different endografts poses considerable challenges due to differing case complexity.

  2. Hybrid Repair of Complex Thoracic Aortic Arch Pathology: Long-Term Outcomes of Extra-anatomic Bypass Grafting of the Supra-aortic Trunk

    SciTech Connect

    Lotfi, S. Clough, R. E.; Ali, T.; Salter, R.; Young, C. P.; Bell, R.; Modarai, B.; Taylor, P.

    2013-02-15

    Hybrid repair constitutes supra-aortic debranching before thoracic endovascular aortic repair (TEVAR). It offers improved short-term outcome compared with open surgery; however, longer-term studies are required to assess patient outcomes and patency of the extra-anatomic bypass grafts. A prospectively maintained database of 380 elective and urgent patients who had undergone TEVAR (1997-2011) was analyzed retrospectively. Fifty-one patients (34 males; 17 females) underwent hybrid repair. Median age was 71 (range, 18-90) years with mean follow-up of 15 (range, 0-61) months. Perioperative complications included death: 10 % (5/51), stroke: 12 % (6/51), paraplegia: 6 % (3/51), endoleak: 16 % (8/51), rupture: 4 % (2/51), upper-limb ischemia: 2 % (1/51), bypass graft occlusion: 4 % (2/51), and cardiopulmonary complications in 14 % (7/51). Three patients (6 %) required emergency intervention for retrograde dissection: (2 aortic root repairs; 2 innominate stents). Early reintervention was performed for type 1 endoleak in two patients (2 proximal cuff extensions). One patient underwent innominate stenting and revision of their bypass for symptomatic restenosis. At 48 months, survival was 73 %. Endoleak was detected in three (6 %) patients (type 1 = 2; type 2 = 1) requiring debranching with proximal stent graft (n = 2) and proximal extension cuff (n = 1). One patient had a fatal rupture of a mycotic aneurysm and two arch aneurysms expanded. No bypass graft occluded after the perioperative period. Hybrid operations to treat aortic arch disease can be performed with results comparable to open surgery. The longer-term outcomes demonstrate low rates of reintervention and high rates of graft patency.

  3. The site of a missense mutation in the extracellular Ig or FN domains of L1CAM influences infant mortality and the severity of X linked hydrocephalus.

    PubMed Central

    Michaelis, R C; Du, Y Z; Schwartz, C E

    1998-01-01

    The L1 cell adhesion molecule (L1CAM) plays an important role in axon growth, fasciculation, and neural migration. Mutations in the L1CAM gene produce a phenotype characterised by X linked hydrocephalus, mental retardation, spastic paraplegia, adducted thumbs, and agenesis of the corpus callosum. We have conducted a detailed analysis of the phenotypic effects of missense mutations in the extracellular portion of L1CAM, following a study that differentiated between "key" amino acid residues critical for maintaining the conformation of the extracellular immunoglobulin type C-like (Ig) or fibronectin type III-like (FN) domains and surface residues of less certain significance. We have analysed the data from 71 published cases and seven patients whose mutations were detected in our laboratory to determine if the site of a missense mutation in the Ig or FN domains correlated with the severity of hydrocephalus, presence of adducted thumbs, or survival past infancy. Mutations affecting the key residues in either type of domain were more likely to produce a phenotype with severe hydrocephalus, adducted thumbs, and lifespan less than one year than were mutations affecting surface residues. In addition, mutations affecting the FN domains were more likely than those affecting Ig domains to produce a phenotype with severe hydrocephalus, with less certain effects on adducted thumbs and lifespan. Mutations in key residues of the FN domains were particularly deleterious to infant survival. These data provide information that may be useful in predicting some aspects of the phenotypic effects of certain L1CAM mutations. PMID:9832035

  4. Socio-economic outcome after blunt orthopaedic trauma: Implications on injury prevention

    PubMed Central

    2011-01-01

    Background Several large studies have identified factors associated with long-term outcome after orthopaedic injuries. However, long-term social and economic implications have not been published so far. The aim of this investigation is to study the long-term socio-economic consequences of patients sustaining severe trauma. Methods Patients treated at a level one trauma center were invited for a follow-up (at least 10 years) examination. There were 637 patients who responded and were examined. Inclusion criteria included injury severity score (ISS) ? 16 points, presence of lower and upper extremity fractures, and age between 3 and 60 years. Exclusion criteria included the presence of amputations and paraplegia. The socio-economic outcome was evaluated in three age groups: group I (< 18 years), group II (19 - 50 years), and group III (> 50 years). The following parameters were analyzed using a standardized questionnaire: financial losses, net income losses, pension precaution losses, need for a bank loan, and the decrease in number of friends. Results 510 patients matched all study criteria, and breakdown of groups were as follows: 140 patients in group I, 341 patients in group II, and 29 patients in group III. Financial losses were reported in all age groups (20%-44%). Younger patients (group I) were associated with less income losses when compared with other groups (p < 0.05). Financial deterioration was more frequently reported in age group II (p < 0.05). Social consequences (number of friends decreased) were predominantly stated in patients younger than 18 years old (p < 0.05). Conclusions Economic consequences are reported by polytraumatized patients even ten or more years after injury. Financial losses appear to be common in patients between 19 and 50 years. In contrast, social deprivation appears to be most pronounced in the younger age groups. Early socio-economic support and measures of injury prevention should focus on these specific age groups. PMID:21569475

  5. Sepsis of the hip due to pressure sore in spinal cord injured patients: advocacy for a one-stage surgical procedure.

    PubMed

    Le Fort, M; Rome-Saulnier, J; Lejeune, F; Bellier-Waast, F; Touchais, S; Kieny, P; Duteille, F; Perrouin-Verbe, B

    2014-11-01

    Study design:Retrospective study reporting characteristics and management of septic arthritis of the hip due to pressure sores in spinal cord-injured patients.Objectives:To describe clinical and biological data of septic arthritis of the hip and its treating management.Setting:The database of the regional SCI referral center, Nantes, France.Methods:We retrospectively collected data from 33 cases of septic arthritis of the hip in the medical files of 26 patients.Results:We analyzed 33 cases of septic arthritis of the hip treated in one French referent center for spinal cord-injured patients from January 1988 to December 2009. Most patients had a thoracic complete paraplegia and nearly two-third (17 out of 26) had no systematic follow-up. In 25 out of 33 cases, the septic arthritis of the hip was due to a trochanteric pressure sore. The causal pressure sore was most frequently associated with a persistent drainage. The standard radiological examination led to the diagnosis in 30 cases and, in 7 questionable cases, magnetic resonance imaging was more contributory. Surgery always consisted of a wide carcinological-like excision and of a subtrochanteric proximal femoral resection including both greater and lesser trochanters. A musculocutaneous flap was realized for all cases and the choice of the muscle depended on the localization of the causal pressure sore but also of the remaining choices, as most of the patients had already undergone a prior surgery. An antibiotic treatment was adapted to multiple samples during surgery.Conclusion:We do advocate for a one-stage procedure including a subtrochanteric proximal femoral resection and a musculocutaneous flap.Spinal Cord advance online publication, 4 November 2014; doi:10.1038/sc.2014.170. PMID:25366526

  6. An ayurvedic approach in the management of Guillain-Barre syndrome: A case study

    PubMed Central

    Nakanekar, Amit; Bhople, Sunanda; Gulhane, Harshad; Rathod, Suraj; Gulhane, Jayant; Bonde, Pravin

    2015-01-01

    Guillain-Barre syndrome is an acute, frequently severe and fulminant polyradiculopathy that is autoimmune in nature. Guillain Barre syndrome is a rare disorder that causes immune systems to attack peripheral nervous system (PNS). A 46 year old male patient, presenting with sudden onset, complete paralysis of all four limbs (quadriplegia), unable to walk, stand, sit, difficulty in deglutition (dysphagia) and dysarthia, was having foley's catheter and Ryle's Tube brought by relative to Out Door Patient Department (OPD) of Government Ayurvedic Hospital, Nagpur; He was provisionally diagnosed as subacute sensory motor paraplegia. Previously patient admitted and treated in Government Medical College (GMC) Nagpur but did not show any sign of improvement so patient was admitted and treated with Ayurvedic treatment for about 50 days. As per Ayurvedic classics, this condition can be correlated with sarv?? gagatav?tavy?dhi (~v?ta disorder affecting all parts of the body), which is apatarpa?a in nature (~diseases with deprived nourishment of body tissue) preceded by jvara (~(H/O fever before onset of GBS). Hence, the principle of treatment is santarpa?a cikits? (~nourishing treatment). Santarpa?a (~nourishing treatment) includes bahyopakramas (~nourishing external treatment modalities), such as abhya?ga (~oleation therapy) and ?a??ika??lipi??asveda (~sudation using of hot and processed ?a??ika rice), karmabasti (~medicated enema) ?irodh?r? (gentle pouring of medicated liquid over forehead) and jvaraghna cikits? (~treatment of fever) using various Ayurvedic herbomineral compounds. Remarkable results were observed in the form of improvement in the muscle power from zero to five of all four limbs with improvement in speech. There was no difficulty post treatment in deglutition, sitting, standing and walking; and now patient has near to normal movements. PMID:26600668

  7. Lack of seipin in neurons results in anxiety- and depression-like behaviors via down regulation of PPAR?.

    PubMed

    Zhou, Libin; Yin, Jun; Wang, Conghui; Liao, Jiawei; Liu, George; Chen, Ling

    2014-08-01

    The Seipin gene was originally found to be responsible for type 2 congenital lipodystrophy and involved in lipid droplet formation. Seipin is highly expressed in the central nervous system as well. Seipin mutations have been identified in motor neuron diseases such as Silver syndrome and spastic paraplegia. In this study, we generated neuron-specific seipin knockout mice (seipin-nKO) to investigate the influence of seipin deficiency on locomotion and affective behaviors. In comparison with control mice, 8-week-old male seipin-nKO mice, but not female mice, displayed anxiety- and depression-like behaviors as assessed by open-field, elevated plus-maze, forced swim and tail suspension tests. However, neither male nor female seipin-nKO mice showed locomotion deficits in swimming tank and rotarod tests. Interestingly, the mRNA and protein levels of peroxisome proliferator-activated receptor gamma (PPAR?) in the hippocampus and cortex were lower in male seipin-nKO mice, but not female mice, than controls. In seipin-nKO mice, plasma levels of sex hormones including 17?-estradiol (E2) in females and testosterone in males as well as corticosterone were not altered compared with controls. The treatment of male seipin-nKO mice with E2 ameliorated the anxiety- and depression-like behaviors and remarkably increased PPAR? levels. The PPAR? agonist rosiglitazone alleviated affective disorders in male seipin-nKO mice. Notably, anxiety- and depression-like behaviors appeared in female seipin-nKO mice after ovariectomy, which was associated with low PPAR? expression. Collectively, these results indicate that neuronal seipin deficiency causing reduced PPAR? levels leads to affective disorders in male mice that are rescued by E2-increased PPAR? expression. PMID:24651066

  8. Trunk Robot Rehabilitation Training with Active Stepping Reorganizes and Enriches Trunk Motor Cortex Representations in Spinal Transected Rats

    PubMed Central

    Oza, Chintan S.

    2015-01-01

    Trunk motor control is crucial for postural stability and propulsion after low thoracic spinal cord injury (SCI) in animals and humans. Robotic rehabilitation aimed at trunk shows promise in SCI animal models and patients. However, little is known about the effect of SCI and robot rehabilitation of trunk on cortical motor representations. We previously showed reorganization of trunk motor cortex after adult SCI. Non-stepping training also exacerbated some SCI-driven plastic changes. Here we examine effects of robot rehabilitation that promotes recovery of hindlimb weight support functions on trunk motor cortex representations. Adult rats spinal transected as neonates (NTX rats) at the T9/10 level significantly improve function with our robot rehabilitation paradigm, whereas treadmill-only trained do not. We used intracortical microstimulation to map motor cortex in two NTX groups: (1) treadmill trained (control group); and (2) robot-assisted treadmill trained (improved function group). We found significant robot rehabilitation-driven changes in motor cortex: (1) caudal trunk motor areas expanded; (2) trunk coactivation at cortex sites increased; (3) richness of trunk cortex motor representations, as examined by cumulative entropy and mutual information for different trunk representations, increased; (4) trunk motor representations in the cortex moved toward more normal topography; and (5) trunk and forelimb motor representations that SCI-driven plasticity and compensations had caused to overlap were segregated. We conclude that effective robot rehabilitation training induces significant reorganization of trunk motor cortex and partially reverses some plastic changes that may be adaptive in non-stepping paraplegia after SCI. PMID:25948267

  9. An Investigation of Bilateral Symmetry During Manual Wheelchair Propulsion

    PubMed Central

    Soltau, Shelby L.; Slowik, Jonathan S.; Requejo, Philip S.; Mulroy, Sara J.; Neptune, Richard R.

    2015-01-01

    Studies of manual wheelchair propulsion often assume bilateral symmetry to simplify data collection, processing, and analysis. However, the validity of this assumption is unclear. Most investigations of wheelchair propulsion symmetry have been limited by a relatively small sample size and a focus on a single propulsion condition (e.g., level propulsion at self-selected speed). The purpose of this study was to evaluate bilateral symmetry during manual wheelchair propulsion in a large group of subjects across different propulsion conditions. Three-dimensional kinematics and handrim kinetics along with spatiotemporal variables were collected and processed from 80 subjects with paraplegia while propelling their wheelchairs on a stationary ergometer during three different conditions: level propulsion at their self-selected speed (free), level propulsion at their fastest comfortable speed (fast), and propulsion on an 8% grade at their level, self-selected speed (graded). All kinematic variables had significant side-to-side differences, primarily in the graded condition. Push angle was the only spatiotemporal variable with a significant side-to-side difference, and only during the graded condition. No kinetic variables had significant side-to-side differences. The magnitudes of the kinematic differences were low, with only one difference exceeding 5°. With differences of such small magnitude, the bilateral symmetry assumption appears to be reasonable during manual wheelchair propulsion in subjects without significant upper-extremity pain or impairment. However, larger asymmetries may exist in individuals with secondary injuries and pain in their upper extremity and different etiologies of their neurological impairment. PMID:26125019

  10. An Investigation of Bilateral Symmetry During Manual Wheelchair Propulsion.

    PubMed

    Soltau, Shelby L; Slowik, Jonathan S; Requejo, Philip S; Mulroy, Sara J; Neptune, Richard R

    2015-01-01

    Studies of manual wheelchair propulsion often assume bilateral symmetry to simplify data collection, processing, and analysis. However, the validity of this assumption is unclear. Most investigations of wheelchair propulsion symmetry have been limited by a relatively small sample size and a focus on a single propulsion condition (e.g., level propulsion at self-selected speed). The purpose of this study was to evaluate bilateral symmetry during manual wheelchair propulsion in a large group of subjects across different propulsion conditions. Three-dimensional kinematics and handrim kinetics along with spatiotemporal variables were collected and processed from 80 subjects with paraplegia while propelling their wheelchairs on a stationary ergometer during three different conditions: level propulsion at their self-selected speed (free), level propulsion at their fastest comfortable speed (fast), and propulsion on an 8% grade at their level, self-selected speed (graded). All kinematic variables had significant side-to-side differences, primarily in the graded condition. Push angle was the only spatiotemporal variable with a significant side-to-side difference, and only during the graded condition. No kinetic variables had significant side-to-side differences. The magnitudes of the kinematic differences were low, with only one difference exceeding 5°. With differences of such small magnitude, the bilateral symmetry assumption appears to be reasonable during manual wheelchair propulsion in subjects without significant upper-extremity pain or impairment. However, larger asymmetries may exist in individuals with secondary injuries and pain in their upper extremity and different etiologies of their neurological impairment. PMID:26125019

  11. Antibodies to MOG in adults with inflammatory demyelinating disease of the CNS

    PubMed Central

    Woodhall, Mark R.; Kim, Ji-Sun; Kim, Seong-Joon; Park, Kyung Seok; Vincent, Angela; Lee, Kwang-Woo

    2015-01-01

    Objective: To evaluate the clinical relevance of myelin oligodendrocyte glycoprotein antibody (MOG-Ab) in a cohort of adults with inflammatory demyelinating disease (IDD) of the CNS. Methods: Live cell-based assays for MOG-Ab (IgG1 subset) and antibody to aquaporin-4 (AQP4-Ab) were performed in a cohort of 270 adult patients with IDD and 72 controls. Patients were first grouped by positive antibody result as MOG-Ab or AQP4-Ab, and the remainder were grouped by published diagnostic criteria. Results: Seventeen patients with IDD (6.3%) had MOG-Abs and 49 patients (18.1%) had AQP4-Abs; none had both antibodies. The MOG-Ab patients predominantly manifested with isolated symptoms of optic neuritis (83%). One-third of these patients experienced relapses, which involved only the optic nerve, and all relapsed within 1 year of disease onset. At onset, MRI in the MOG-Ab group uniquely demonstrated perineural enhancement, extending to the soft tissues around the optic nerves (33%). Although about 30% of MOG-Ab patients had brain MRI lesions, they had fewer periventricular lesions than the 26 patients with relapsing-remitting multiple sclerosis (MS); none of these lesions were ovoid or perpendicular to the ventricle. Moreover, MOG-Ab patients did not meet the diagnostic criteria for definite neuromyelitis optica (NMO) and had less spinal cord involvement than the AQP4-Ab group. Four patients (23.5%) had poor visual outcomes (<0.2) or paraplegia. Conclusions: MOG-Abs may be a disease-specific biomarker in adult patients with IDD who have a disease distinct from NMO or MS. The radiologic as well as clinical manifestations of MOG-Ab patients can be useful in their differential diagnosis. PMID:26516628

  12. Clinical predictors of recovery after blunt spinal cord trauma: systematic review.

    PubMed

    Al-Habib, Amro F; Attabib, Najmedden; Ball, Jonathon; Bajammal, Sohail; Casha, Steve; Hurlbert, R John

    2011-08-01

    Several clinical, imaging, and therapeutic factors affecting recovery following spinal cord injury (SCI) have been described. A systematic review of the topic is still lacking. Our primary aim was to systematically review clinical factors that may predict neurological and functional recovery following blunt traumatic SCI in adults. Such work would help guide clinical care and direct future research. Both Medline and Embase (to April 2008) were searched using index terms for various forms of SCI, paraplegia, or quadri/tetraplegia, and functional and neurological recovery. The search was limited to published articles that were in English and included human subjects. Article selection included class I and II evidence, blunt traumatic SCI, injury level above L1-2, baseline assessment within 72?h of injury, use of American Spinal Injury Association (ASIA) scoring system for clinical assessment, and functional and neurological outcome. A total of 1526 and 1912 citations were located from Medline and Embase, respectively. Two surgeons reviewed the titles, abstracts, and full text articles for each database. Ten articles were identified, only one of which was level 1 evidence. Age and gender were identified as two patient-related predictors. While motor and functional recovery decreased with advancing age for complete SCI, there was no correlation considering incomplete ones. Therefore, treatment should not be restructured based on age in incomplete SCI. Among injury-related predictors, severity of SCI was the most significant. Complete injuries correlated with increased mortality and worse neurological and functional outcomes. Other predictors included SCI level, energy transmitted by the injury, and baseline electrophysiological testing. PMID:19831845

  13. Clinical Predictors of Recovery after Blunt Spinal Cord Trauma: Systematic Review

    PubMed Central

    Al-Habib, Amro F.; Attabib, Najmedden; Ball, Jonathon; Bajammal, Sohail; Casha, Steve

    2011-01-01

    Abstract Several clinical, imaging, and therapeutic factors affecting recovery following spinal cord injury (SCI) have been described. A systematic review of the topic is still lacking. Our primary aim was to systematically review clinical factors that may predict neurological and functional recovery following blunt traumatic SCI in adults. Such work would help guide clinical care and direct future research. Both Medline and Embase (to April 2008) were searched using index terms for various forms of SCI, paraplegia, or quadri/tetraplegia, and functional and neurological recovery. The search was limited to published articles that were in English and included human subjects. Article selection included class I and II evidence, blunt traumatic SCI, injury level above L1-2, baseline assessment within 72?h of injury, use of American Spinal Injury Association (ASIA) scoring system for clinical assessment, and functional and neurological outcome. A total of 1526 and 1912 citations were located from Medline and Embase, respectively. Two surgeons reviewed the titles, abstracts, and full text articles for each database. Ten articles were identified, only one of which was level 1 evidence. Age and gender were identified as two patient-related predictors. While motor and functional recovery decreased with advancing age for complete SCI, there was no correlation considering incomplete ones. Therefore, treatment should not be restructured based on age in incomplete SCI. Among injury-related predictors, severity of SCI was the most significant. Complete injuries correlated with increased mortality and worse neurological and functional outcomes. Other predictors included SCI level, energy transmitted by the injury, and baseline electrophysiological testing. PMID:19831845

  14. Intravenous colistin-induced acute respiratory failure: A case report and a review of literature

    PubMed Central

    Shrestha, Amardeep; Soriano, Sheryll Mae; Song, Mingchen; Chihara, Shingo

    2014-01-01

    The emergence of multi-drug-resistant gram negative bacillary infections has regained popularity of ancient drugs such as polymyxins. We report a case of acute respiratory failure induced by use of intravenous colistimethate, which is one of the forms of polymyxin. The patient is a 31 year old female with paraplegia due to spina bifida who underwent excisional debridement of large lumbosacral decubitus ulcer with osteomyelitis infected with pan-resistant Pseudomonas aeruginosa and MRSA. Six days after initiation of intravenous colistimethate and vancomycin, she developed acute respiratory failure requiring mechanical ventilation. Pan-culture was negative including a chest radiograph. V/Q scan showed low probability for pulmonary embolism. Echocardiogram showed normal right ventricle with no strain or pulmonary hypertension. Colistimethate was discontinued. Within 24 hours, she was extubated. In the early years after introduction of polymyxin, there were several reports of acute respiratory paralysis. The mechanism is thought to be noncompetitive myoneuronal presynaptic blockade of acetylcholine release. Though a direct causal relationship for respiratory failure is often difficult to establish in current era with multiple co morbidities, the timeframe of apnea, acuity of onset as well as rapid recovery in our case clearly point out the causal relationship. In addition, our patient also developed acute renal failure, presumably due to colistimethate induced nephrotoxicity, a possible contributing factor for her acute respiratory failure. In summary, colistimethate can induce acute neurotoxicity including respiratory muscular weakness and acute respiratory failure. Clinicians should consider its toxicity in the differential diagnosis of acute respiratory failure especially in critically ill patients. PMID:25337492

  15. The course of spinal tuberculosis (Pott disease): results of the multinational, multicentre Backbone-2 study.

    PubMed

    Batirel, A; Erdem, H; Sengoz, G; Pehlivanoglu, F; Ramosaco, E; Gülsün, S; Tekin, R; Mete, B; Balkan, I I; Sevgi, D Y; Giannitsioti, E; Fragou, A; Kaya, S; Cetin, B; Oktenoglu, T; Celik, A D; Karaca, B; Horasan, E S; Ulug, M; Senbayrak, S; Kaya, S; Arslanalp, E; Hasbun, R; Ates-Guler, S; Willke, A; Senol, S; Inan, D; Güclü, E; Ertem, G T; Koc, M M; Tasbakan, M; Ocal, G; Kocagoz, S; Kusoglu, H; Güven, T; Baran, A I; Dede, B; Karadag, F Y; Yilmaz, H; Aslan, G; Al-Gallad, D A; Cesur, S; El-Sokkary, R; Sirmatel, F; Savasci, U; Karaahmetoglu, G; Vahaboglu, H

    2015-11-01

    We aimed to describe clinical, laboratory, diagnostic and therapeutic features of spinal tuberculosis (ST), also known as Pott disease. A total of 314 patients with ST from 35 centres in Turkey, Egypt, Albania and Greece were included. Median duration from initial symptoms to the time of diagnosis was 78 days. The most common complications presented before diagnosis were abscesses (69%), neurologic deficits (40%), spinal instability (21%) and spinal deformity (16%). Lumbar (56%), thoracic (49%) and thoracolumbar (13%) vertebrae were the most commonly involved sites of infection. Although 51% of the patients had multiple levels of vertebral involvement, 8% had noncontiguous involvement of multiple vertebral bodies. The causative agent was identified in 41% of cases. Histopathologic examination was performed in 200 patients (64%), and 74% were consistent with tuberculosis. Medical treatment alone was implemented in 103 patients (33%), while 211 patients (67%) underwent diagnostic and/or therapeutic surgical intervention. Ten percent of the patients required more than one surgical intervention. Mortality occurred in 7 patients (2%), and 77 (25%) developed sequelae. The distribution of the posttreatment sequelae were as follows: 11% kyphosis, 6% Gibbus deformity, 5% scoliosis, 5% paraparesis, 5% paraplegia and 4% loss of sensation. Older age, presence of neurologic deficit and spinal deformity were predictors of unfavourable outcome. ST results in significant morbidity as a result of its insidious course and delayed diagnosis because of diagnostic and therapeutic challenges. ST should be considered in the differential diagnosis of patients with vertebral osteomyelitis, especially in tuberculosis-endemic regions. Early establishment of definitive aetiologic diagnosis and appropriate treatment are of paramount importance to prevent development of sequelae. PMID:26232534

  16. Spastin Binds to Lipid Droplets and Affects Lipid Metabolism

    PubMed Central

    Papadopoulos, Chrisovalantis; Orso, Genny; Mancuso, Giuseppe; Herholz, Marija; Gumeni, Sentiljana; Tadepalle, Nimesha; Jüngst, Christian; Tzschichholz, Anne; Schauss, Astrid; Höning, Stefan; Trifunovic, Aleksandra; Daga, Andrea; Rugarli, Elena I.

    2015-01-01

    Mutations in SPAST, encoding spastin, are the most common cause of autosomal dominant hereditary spastic paraplegia (HSP). HSP is characterized by weakness and spasticity of the lower limbs, owing to progressive retrograde degeneration of the long corticospinal axons. Spastin is a conserved microtubule (MT)-severing protein, involved in processes requiring rearrangement of the cytoskeleton in concert to membrane remodeling, such as neurite branching, axonal growth, midbody abscission, and endosome tubulation. Two isoforms of spastin are synthesized from alternative initiation codons (M1 and M87). We now show that spastin-M1 can sort from the endoplasmic reticulum (ER) to pre- and mature lipid droplets (LDs). A hydrophobic motif comprised of amino acids 57 through 86 of spastin was sufficient to direct a reporter protein to LDs, while mutation of arginine 65 to glycine abolished LD targeting. Increased levels of spastin-M1 expression reduced the number but increased the size of LDs. Expression of a mutant unable to bind and sever MTs caused clustering of LDs. Consistent with these findings, ubiquitous overexpression of Dspastin in Drosophila led to bigger and less numerous LDs in the fat bodies and increased triacylglycerol levels. In contrast, Dspastin overexpression increased LD number when expressed specifically in skeletal muscles or nerves. Downregulation of Dspastin and expression of a dominant-negative variant decreased LD number in Drosophila nerves, skeletal muscle and fat bodies, and reduced triacylglycerol levels in the larvae. Moreover, we found reduced amount of fat stores in intestinal cells of worms in which the spas-1 homologue was either depleted by RNA interference or deleted. Taken together, our data uncovers an evolutionarily conserved role of spastin as a positive regulator of LD metabolism and open up the possibility that dysfunction of LDs in axons may contribute to the pathogenesis of HSP. PMID:25875445

  17. ?-Glucosidase 2 (GBA2) activity and imino sugar pharmacology.

    PubMed

    Ridley, Christina M; Thur, Karen E; Shanahan, Jessica; Thillaiappan, Nagendra Babu; Shen, Ann; Uhl, Karly; Walden, Charlotte M; Rahim, Ahad A; Waddington, Simon N; Platt, Frances M; van der Spoel, Aarnoud C

    2013-09-01

    ?-Glucosidase 2 (GBA2) is an enzyme that cleaves the membrane lipid glucosylceramide into glucose and ceramide. The GBA2 gene is mutated in genetic neurological diseases (hereditary spastic paraplegia and cerebellar ataxia). Pharmacologically, GBA2 is reversibly inhibited by alkylated imino sugars that are in clinical use or are being developed for this purpose. We have addressed the ambiguity surrounding one of the defining characteristics of GBA2, which is its sensitivity to inhibition by conduritol B epoxide (CBE). We found that CBE inhibited GBA2, in vitro and in live cells, in a time-dependent fashion, which is typical for mechanism-based enzyme inactivators. Compared with the well characterized impact of CBE on the lysosomal glucosylceramide-degrading enzyme (glucocerebrosidase, GBA), CBE inactivated GBA2 less efficiently, due to a lower affinity for this enzyme (higher KI) and a lower rate of enzyme inactivation (k(inact)). In contrast to CBE, N-butyldeoxygalactonojirimycin exclusively inhibited GBA2. Accordingly, we propose to redefine GBA2 activity as the ?-glucosidase that is sensitive to inhibition by N-butyldeoxygalactonojirimycin. Revised as such, GBA2 activity 1) was optimal at pH 5.5-6.0; 2) accounted for a much higher proportion of detergent-independent membrane-associated ?-glucosidase activity; 3) was more variable among mouse tissues and neuroblastoma and monocyte cell lines; and 4) was more sensitive to inhibition by N-butyldeoxynojirimycin (miglustat, Zavesca®), in comparison with earlier studies. Our evaluation of GBA2 makes it possible to assess its activity more accurately, which will be helpful in analyzing its physiological roles and involvement in disease and in the pharmacological profiling of monosaccharide mimetics. PMID:23880767

  18. Segmental distribution of the motor neuron columns that supply the rat hindlimb: A muscle/motor neuron tract-tracing analysis targeting the motor end plates.

    PubMed

    Mohan, R; Tosolini, A P; Morris, R

    2015-10-29

    Spinal cord injury (SCI) that disrupts input from higher brain centers to the lumbar region of the spinal cord results in paraplegia, one of the most debilitating conditions affecting locomotion. Non-human primates have long been considered to be the most appropriate animal to model lower limb dysfunction. More recently, however, there has been a wealth of scientific information gathered in the rat regarding the central control of locomotion. Moreover, rodent models of SCI at lumbar levels have been widely used to validate therapeutic scenarios aimed at the restoration of locomotor activities. Despite the growing use of the rat as a model of locomotor dysfunction, knowledge regarding the anatomical relationship between spinal cord motor neurons and the hindlimb muscles that they innervate is incomplete. Previous studies performed in our laboratory have shown the details of the muscle/motor neuron topographical relationship for the mouse forelimb and hindlimb as well as for the rat forelimb. The present analysis aims to characterize the segmental distribution of the motor neuron pools that innervate the muscles of the rat hindlimb, hence completing this series of studies. The location of the motor end plate (MEP) regions on the main muscles of the rat hindlimb was first revealed with acetylcholinesterase histochemistry. For each muscle under scrutiny, injections of Fluoro-Gold were then performed along the length of the MEP region. Targeting the MEPs gave rise to columns of motor neurons that span more spinal cord segments than previously reported. The importance of this study is discussed in terms of its application to gene therapy for SCI. PMID:26304758

  19. Spinal deformity in children treated for neuroblastoma

    SciTech Connect

    Mayfield, J.K.; Riseborough, E.J.; Jaffe, N.; Nehme, M.E.

    1981-02-01

    Of seventy-four children who were treated at a mean age of seventeen months for neuroblastoma and survived more than five years, fifty-six had spinal deformity due either to the disease or to the treatment after a mean follow-up of 12.9 years. Of these fifty-six, 50 per cent had post-radiation scoliosis, and 16 per cent had post-radiation kyphosis, most frequently at the thoracolumbar junction, at the time of follow-up. Two kyphotic thoracolumbar curve patterns were identified: an angular kyphosis with a short radius of curvature and its apex at the twelfth thoracic and first lumbar vertebrae, and a thoracic kyphosis with a long radius of curvature that extended into the lumbar spine. The post-radiation deformity - both the scoliosis and the kyphosis - progressed with growth, the scoliosis at a rate of 1 degree per year and the kyphosis at a rate of 3 degrees per year. Epidural spread of the neuroblastoma was associated with most of the cases of severe scoliosis and kyphosis. The deformity was due either to the laminectomy or to the paraplegia acting in conjunction with the radiation. Eighteen per cent of 419 children with this malignant disease survived more than five years, and of the survivors, 20 per cent had spinal deformity severe enough to warrant treatment. The factors associated with the development of spinal deformity in patient treated for neuroblastoma were: orthovoltage radiation exceeding 3000 rads, asymmetrical radiation of the spine, thoracolumbar kyphosis, and epidural spread of the tumor.

  20. Mitochondrial Hsp60 Chaperonopathy Causes an Autosomal-Recessive Neurodegenerative Disorder Linked to Brain Hypomyelination and Leukodystrophy

    PubMed Central

    Magen, Daniella; Georgopoulos, Costa; Bross, Peter; Ang, Debbie; Segev, Yardena; Goldsher, Dorit; Nemirovski, Alexandra; Shahar, Eli; Ravid, Sarit; Luder, Anthony; Heno, Bayan; Gershoni-Baruch, Ruth; Skorecki, Karl; Mandel, Hanna

    2008-01-01

    Hypomyelinating leukodystrophies (HMLs) are disorders involving aberrant myelin formation. The prototype of primary HMLs is the X-linked Pelizaeus-Merzbacher disease (PMD) caused by mutations in PLP1. Recently, homozygous mutations in GJA12 encoding connexin 47 were found in patients with autosomal-recessive Pelizaeus-Merzbacher-like disease (PMLD). However, many patients of both genders with PMLD carry neither PLP1 nor GJA12 mutations. We report a consanguineous Israeli Bedouin kindred with clinical and radiological findings compatible with PMLD, in which linkage to PLP1 and GJA12 was excluded. Using homozygosity mapping and mutation analysis, we have identified a homozygous missense mutation (D29G) not previously described in HSPD1, encoding the mitochondrial heat-shock protein 60 (Hsp60) in all affected individuals. The D29G mutation completely segregates with the disease-associated phenotype. The pathogenic effect of D29G on Hsp60-chaperonin activity was verified by an in vivo E. coli complementation assay, which demonstrated compromised ability of the D29G-Hsp60 mutant protein to support E. coli survival, especially at high temperatures. The disorder, which we have termed MitCHAP-60 disease, can be distinguished from spastic paraplegia 13 (SPG13), another Hsp60-associated autosomal-dominant neurodegenerative disorder, by its autosomal-recessive inheritance pattern, as well as by its early-onset, profound cerebral involvement and lethality. Our findings suggest that Hsp60 defects can cause neurodegenerative pathologies of varying severity, not previously suspected on the basis of the SPG13 phenotype. These findings should help to clarify the important role of Hsp60 in myelinogenesis and neurodegeneration. PMID:18571143

  1. The clinical spectrum of inherited diseases involved in the synthesis and remodeling of complex lipids. A tentative overview.

    PubMed

    Garcia-Cazorla, Àngels; Mochel, Fanny; Lamari, Foudil; Saudubray, Jean-Marie

    2015-01-01

    Over one hundred diseases related to inherited defects of complex lipids synthesis and remodeling are now reported. Most of them were described within the last 5 years. New descriptions and phenotypes are expanding rapidly. While the associated clinical phenotype is currently difficult to outline, with only a few patients identified, it appears that all organs and systems may be affected. The main clinical presentations can be divided into (1) Diseases affecting the central and peripheral nervous system. Complex lipid synthesis disorders produce prominent motor manifestations due to upper and/or lower motoneuron degeneration. Motor signs are often complex, associated with other neurological and extra-neurological signs. Three neurological phenotypes, spastic paraparesis, neurodegeneration with brain iron accumulation and peripheral neuropathies, deserve special attention. Many apparently well clinically defined syndromes are not distinct entities, but rather clusters on a continuous spectrum, like for the PNPLA6-associated diseases, extending from Boucher-Neuhauser syndrome via Gordon Holmes syndrome to spastic ataxia and pure hereditary spastic paraplegia; (2) Muscular/cardiac presentations; (3) Skin symptoms mostly represented by syndromic (neurocutaneous) and non syndromic ichthyosis; (4) Retinal dystrophies with syndromic and non syndromic retinitis pigmentosa, Leber congenital amaurosis, cone rod dystrophy, Stargardt disease; (5) Congenital bone dysplasia and segmental overgrowth disorders with congenital lipomatosis; (6) Liver presentations characterized mainly by transient neonatal cholestatic jaundice and non alcoholic liver steatosis with hypertriglyceridemia; and (7) Renal and immune presentations. Lipidomics and molecular functional studies could help to elucidate the mechanism(s) of dominant versus recessive inheritance observed for the same gene in a growing number of these disorders. PMID:25413954

  2. Examining health-care utilization in the first year following spinal cord injury.

    PubMed

    Skelton, Felicia; Hoffman, Jeanne M; Reyes, Maria; Burns, Stephen P

    2015-11-01

    Objective To identify factors associated with health-care utilization during the first year after inpatient rehabilitation (IR) in individuals with traumatic spinal cord injury (SCI). Design Prospective cohort. Methods One hundred and sixty-eight patients were prospectively enrolled and followed over 1 year after discharge from an SCI Model System IR program. Telephone follow-up occurred at 3, 6, 9, and 12 months. Participants were grouped into four impairment levels (C1-4 American Spinal Injury Association (ASIA) Impairment Scale (AIS) A-C, C5-C8 AIS A-C, paraplegia AIS A-C, and all AIS D). Three domains of health-care utilization were examined: hospital care, outpatient provider visits, and home services. Results Health-care utilization in the first year following IR was high with 45% of subjects reporting re-hospitalization. Twenty percent of patients were initially discharged to a skilled nursing facility (SNF), and an additional 10% required SNF care during this first year. Overall, those with C1-4 AIS A-C used the most services. Participants discharged home used less health care compared to those discharged elsewhere. SCI due to falls (vs. vehicular crashes) was associated with fewer in-home service visits. Age, sex, race, and education were unrelated to higher use. Conclusion Those with greater neurological impairment or not discharged home after IR had higher health-care utilization, while age was not associated with utilization. Targeted efforts to reduce genitourinary and respiratory complications may reduce the need for hospital care in the first year after IR. PMID:25299152

  3. Racial and Ethnic Disparities in Functioning at Discharge and Follow-Up Among Patients With Motor Complete Spinal Cord Injury

    PubMed Central

    Fyffe, Denise C.; Deutsch, Anne; Botticello, Amanda L.; Kirshblum, Steven; Ottenbacher, Kenneth J.

    2015-01-01

    Objective To examine racial and ethnic differences in self-care and mobility outcomes for persons with a motor complete, traumatic spinal cord injury (SCI) at discharge and 1-year follow-up. Design Retrospective cohort study. Setting Sixteen rehabilitation centers contributing to the Spinal Cord Injury Model Systems (SCIMS) database. Participants Adults with traumatic, motor complete SCI (N=1766; American Spinal Injury Association Impairment Scale grade A or B) enrolled in the SCIMS between 2000 and 2011. Selected cases had complete self-reported data on race and ethnicity (non-Hispanic white, non-Hispanic black, or Hispanic) and motor FIM scores assessed at inpatient rehabilitation admission, discharge, and 1-year follow-up. Interventions Not applicable. Main Outcome Measures Functional outcomes were measured by FIM self-care and mobility scores on a 1 to 7 FIM scale, at discharge and 1-year follow-up. Results Multiple regression models stratified by neurologic category and adjusted for sociodemographic and injury characteristics assessed racial and ethnic group differences in FIM self-care and mobility change scores at discharge and 1-year follow-up. At discharge, non-Hispanic black participants with tetraplegia and paraplegia had significantly poorer gains in FIM self-care and mobility scores relative to non-Hispanic white and Hispanic participants. At 1-year follow-up, similar FIM self-care and mobility change scores were found across racial and ethnic groups within each neurologic category. Conclusions Non-Hispanic white and Hispanic participants had comparatively more improvement in self-care and mobility during inpatient rehabilitation compared with non-Hispanic black participants. At 1-year follow-up, no differences in self-care and mobility outcomes were observed across racial and ethnic groups. Additional research is needed to identify potential modifiable factors that may contribute to racially and ethnically different patterns of functional outcomes observed during inpatient rehabilitation. PMID:25093999

  4. ?-Glucosidase 2 (GBA2) Activity and Imino Sugar Pharmacology*

    PubMed Central

    Ridley, Christina M.; Thur, Karen E.; Shanahan, Jessica; Thillaiappan, Nagendra Babu; Shen, Ann; Uhl, Karly; Walden, Charlotte M.; Rahim, Ahad A.; Waddington, Simon N.; Platt, Frances M.; van der Spoel, Aarnoud C.

    2013-01-01

    ?-Glucosidase 2 (GBA2) is an enzyme that cleaves the membrane lipid glucosylceramide into glucose and ceramide. The GBA2 gene is mutated in genetic neurological diseases (hereditary spastic paraplegia and cerebellar ataxia). Pharmacologically, GBA2 is reversibly inhibited by alkylated imino sugars that are in clinical use or are being developed for this purpose. We have addressed the ambiguity surrounding one of the defining characteristics of GBA2, which is its sensitivity to inhibition by conduritol B epoxide (CBE). We found that CBE inhibited GBA2, in vitro and in live cells, in a time-dependent fashion, which is typical for mechanism-based enzyme inactivators. Compared with the well characterized impact of CBE on the lysosomal glucosylceramide-degrading enzyme (glucocerebrosidase, GBA), CBE inactivated GBA2 less efficiently, due to a lower affinity for this enzyme (higher KI) and a lower rate of enzyme inactivation (kinact). In contrast to CBE, N-butyldeoxygalactonojirimycin exclusively inhibited GBA2. Accordingly, we propose to redefine GBA2 activity as the ?-glucosidase that is sensitive to inhibition by N-butyldeoxygalactonojirimycin. Revised as such, GBA2 activity 1) was optimal at pH 5.5–6.0; 2) accounted for a much higher proportion of detergent-independent membrane-associated ?-glucosidase activity; 3) was more variable among mouse tissues and neuroblastoma and monocyte cell lines; and 4) was more sensitive to inhibition by N-butyldeoxynojirimycin (miglustat, Zavesca®), in comparison with earlier studies. Our evaluation of GBA2 makes it possible to assess its activity more accurately, which will be helpful in analyzing its physiological roles and involvement in disease and in the pharmacological profiling of monosaccharide mimetics. PMID:23880767

  5. Spastin binds to lipid droplets and affects lipid metabolism.

    PubMed

    Papadopoulos, Chrisovalantis; Orso, Genny; Mancuso, Giuseppe; Herholz, Marija; Gumeni, Sentiljana; Tadepalle, Nimesha; Jüngst, Christian; Tzschichholz, Anne; Schauss, Astrid; Höning, Stefan; Trifunovic, Aleksandra; Daga, Andrea; Rugarli, Elena I

    2015-04-01

    Mutations in SPAST, encoding spastin, are the most common cause of autosomal dominant hereditary spastic paraplegia (HSP). HSP is characterized by weakness and spasticity of the lower limbs, owing to progressive retrograde degeneration of the long corticospinal axons. Spastin is a conserved microtubule (MT)-severing protein, involved in processes requiring rearrangement of the cytoskeleton in concert to membrane remodeling, such as neurite branching, axonal growth, midbody abscission, and endosome tubulation. Two isoforms of spastin are synthesized from alternative initiation codons (M1 and M87). We now show that spastin-M1 can sort from the endoplasmic reticulum (ER) to pre- and mature lipid droplets (LDs). A hydrophobic motif comprised of amino acids 57 through 86 of spastin was sufficient to direct a reporter protein to LDs, while mutation of arginine 65 to glycine abolished LD targeting. Increased levels of spastin-M1 expression reduced the number but increased the size of LDs. Expression of a mutant unable to bind and sever MTs caused clustering of LDs. Consistent with these findings, ubiquitous overexpression of Dspastin in Drosophila led to bigger and less numerous LDs in the fat bodies and increased triacylglycerol levels. In contrast, Dspastin overexpression increased LD number when expressed specifically in skeletal muscles or nerves. Downregulation of Dspastin and expression of a dominant-negative variant decreased LD number in Drosophila nerves, skeletal muscle and fat bodies, and reduced triacylglycerol levels in the larvae. Moreover, we found reduced amount of fat stores in intestinal cells of worms in which the spas-1 homologue was either depleted by RNA interference or deleted. Taken together, our data uncovers an evolutionarily conserved role of spastin as a positive regulator of LD metabolism and open up the possibility that dysfunction of LDs in axons may contribute to the pathogenesis of HSP. PMID:25875445

  6. Bridging defects in chronic spinal cord injury using peripheral nerve grafts combined with a chitosan-laminin scaffold and enhancing regeneration through them by co-transplantation with bone-marrow-derived mesenchymal stem cells: Case series of 14 patients

    PubMed Central

    Amr, Sherif M.; Gouda, Ashraf; Koptan, Wael T.; Galal, Ahmad A.; Abdel-Fattah, Dina Sabry; Rashed, Laila A.; Atta, Hazem M.; Abdel-Aziz, Mohammad T.

    2014-01-01

    Objective To investigate the effect of bridging defects in chronic spinal cord injury using peripheral nerve grafts combined with a chitosan-laminin scaffold and enhancing regeneration through them by co-transplantation with bone-marrow-derived mesenchymal stem cells. Methods In 14 patients with chronic paraplegia caused by spinal cord injury, cord defects were grafted and stem cells injected into the whole construct and contained using a chitosan-laminin paste. Patients were evaluated using the International Standards for Classification of Spinal Cord Injuries. Results Chitosan disintegration leading to post-operative seroma formation was a complication. Motor level improved four levels in 2 cases and two levels in 12 cases. Sensory-level improved six levels in two cases, five levels in five cases, four levels in three cases, and three levels in four cases. A four-level neurological improvement was recorded in 2 cases and a two-level neurological improvement occurred in 12 cases. The American Spinal Impairment Association (ASIA) impairment scale improved from A to C in 12 cases and from A to B in 2 cases. Although motor power improvement was recorded in the abdominal muscles (2 grades), hip flexors (3 grades), hip adductors (3 grades), knee extensors (2–3 grades), ankle dorsiflexors (1–2 grades), long toe extensors (1–2 grades), and plantar flexors (0–2 grades), this improvement was too low to enable them to stand erect and hold their knees extended while walking unaided. Conclusion Mesenchymal stem cell-derived neural stem cell-like cell transplantation enhances recovery in chronic spinal cord injuries with defects bridged by sural nerve grafts combined with a chitosan-laminin scaffold. PMID:24090088

  7. Endovascular repair of thoracoabdominal aneurysms: results of the first 48 cases

    PubMed Central

    Lanziotti, Luiz; Cunha, Rodrigo; d’Utra, Guilherme

    2012-01-01

    Background In 2006, we began our experience with a novel technology for fully endovascular thoracoabdominal aneurysm repair, based on a custom-made, branched stent graft design. After 48 cases, we have learned and achieved substantial progress both in technical and in clinical skills. This paper describes the partial results of this ongoing experience. Methods Patients in this series were selected for the presence of thoracoabdominal aortic aneurysms, with or without dissection, which was present in one patient. The observation of extensive anatomical variations in several patients prompted changes in many of the basic stent graft configurations, which are also described. Results Between August 2006 and June 2012, 48 patients were treated consecutively with custom-made branch stent grafts. The five patients with the longest follow-up available so far are at 71, 65, 60, 54 and 51 months post-procedure. The operative mortality rate, defined as death during or within a month of surgical hospitalization, was 21% (10 patients); each case is described herein. During postoperative follow up, nine patients died from causes not directly related to aneurysmal disease, at 3, 18, 20, 22, 24, 24, 37, 44 and 46 months. The main causes of death were myocardial infarction (four cases), cancer (two cases), gastrointestinal hemorrhage (one case), ischemic stroke (one case), and sepsis (one case). Permanent paraplegia occurred in one patient. Conclusions It is still too soon to compare the results of endovascular repair of thoracoabdominal aneurysms with those of open surgical series. Despite the active and rapid progress currently observed for the endovascular method, it is still far from reaching its state-of-the-art plateau or becoming a gold standard. Further technological and technical advances in endovascular stent grafting seem to have a clear potential to provide very satisfactory operative outcomes for thoracoabdominal aortic aneurysms. PMID:23977512

  8. Longitudinal relationship between wheelchair exercise capacity and life satisfaction in patients with spinal cord injury: A cohort study in the Netherlands.

    PubMed

    van Koppenhagen, Casper Floris; Post, Marcel; de Groot, Sonja; van Leeuwen, Christel; van Asbeck, Floris; Stolwijk-Swüste, Janneke; van der Woude, Lucas; Lindeman, Eline

    2014-05-01

    Objective To examine the relationship between wheelchair exercise capacity and life satisfaction in persons with spinal cord injury from the start of active inpatient rehabilitation up to 5 years after discharge. Design Prospective cohort study. Subjects Persons with spinal cord injury, aged 18-65 years, and wheelchair dependent at least for long distances. Method Measurements at the start of active rehabilitation, after 3 months, at discharge from inpatient rehabilitation, and 1 and 5 years after discharge. A peak wheelchair exercise test was performed to record peak oxygen uptake (VO2peak) and peak power output (POpeak). Life satisfaction was measured as current life satisfaction and change of life satisfaction in comparison with life after spinal cord injury. Relationships between (changes in) exercise capacity and (changes in) life satisfaction were analyzed random coefficient analysis, corrected for possible confounders (age, gender, level of lesion, functional status, secondary impairments, pain, and sports activity) if necessary. Results Of 225 persons included, 130 attended two or more peak exercise tests, who were include in the analyses. Mean age at start was 39 years, 75% were male, 73% had paraplegia, and 76% had a traumatic lesion. Mean POpeak increased during the study from 32.9 to 55.9 Watts, mean VO2peak from 1.02  to 1.38 l/minute, and mean life satisfaction from 5.7 to 7.8. An increase of POpeak with 10 W was associated with a 0.3-point increase of life satisfaction (P = 0.01). An increase of VO2peak with 0.1 l/minute was associated with a 0.1-point increase of life satisfaction (P = 0.049). Conclusion High(er) wheelchair exercise capacity is related to high(er) life satisfaction in spinal cord injury patients. PMID:24621019

  9. The kinesin-3, unc-104 regulates dendrite morphogenesis and synaptic development in Drosophila.

    PubMed

    Kern, Jeannine V; Zhang, Yao V; Kramer, Stella; Brenman, Jay E; Rasse, Tobias M

    2013-09-01

    Kinesin-based transport is important for synaptogenesis, neuroplasticity, and maintaining synaptic function. In an anatomical screen of neurodevelopmental mutants, we identified the exchange of a conserved residue (R561H) in the forkhead-associated domain of the kinesin-3 family member Unc-104/KIF1A as the genetic cause for defects in synaptic terminal- and dendrite morphogenesis. Previous structure-based analysis suggested that the corresponding residue in KIF1A might be involved in stabilizing the activated state of kinesin-3 dimers. Herein we provide the first in vivo evidence for the functional importance of R561. The R561H allele (unc-104(bris)) is not embryonic lethal, which allowed us to investigate consequences of disturbed Unc-104 function on postembryonic synapse development and larval behavior. We demonstrate that Unc-104 regulates the reliable apposition of active zones and postsynaptic densities, possibly by controlling site-specific delivery of its cargo. Next, we identified a role for Unc-104 in restraining neuromuscular junction growth and coordinating dendrite branch morphogenesis, suggesting that Unc-104 is also involved in dendritic transport. Mutations in KIF1A/unc-104 have been associated with hereditary spastic paraplegia and hereditary sensory and autonomic neuropathy type 2. However, we did not observe synapse retraction or dystonic posterior paralysis. Overall, our study demonstrates the specificity of defects caused by selective impairments of distinct molecular motors and highlights the critical importance of Unc-104 for the maturation of neuronal structures during embryonic development, larval synaptic terminal outgrowth, and dendrite morphogenesis. PMID:23770702

  10. Altered glycolipid and glycerophospholipid signaling drive inflammatory cascades in adrenomyeloneuropathy.

    PubMed

    Ruiz, Montserrat; Jové, Mariona; Schlüter, Agatha; Casasnovas, Carlos; Villarroya, Francesc; Guilera, Cristina; Ortega, Francisco J; Naudí, Alba; Pamplona, Reinald; Gimeno, Ramón; Fourcade, Stéphane; Portero-Otín, Manuel; Pujol, Aurora

    2015-12-15

    X-linked adrenomyeloneuropathy (AMN) is an inherited neurometabolic disorder caused by malfunction of the ABCD1 gene, characterized by slowly progressing spastic paraplegia affecting corticospinal tracts, and adrenal insufficiency. AMN is the most common phenotypic manifestation of adrenoleukodystrophy (X-ALD). In some cases, an inflammatory cerebral demyelination occurs associated to poor prognosis in cerebral AMN (cAMN). Though ABCD1 codes for a peroxisomal transporter of very long-chain fatty acids, the molecular mechanisms that govern disease onset and progression, or its transformation to a cerebral, inflammatory demyelinating form, remain largely unknown. Here we used an integrated -omics approach to identify novel biomarkers and altered network dynamic characteristic of, and possibly driving, the disease. We combined an untargeted metabolome assay of plasma and peripheral blood mononuclear cells (PBMC) of AMN patients, which used liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (LC-Q-TOF), with a functional genomics analysis of spinal cords of Abcd1(-) mouse. The results uncovered altered nodes in lipid-driven proinflammatory cascades, such as glycosphingolipid and glycerophospholipid synthesis, governed by the ?-1,4-galactosyltransferase (B4GALT6), the phospholipase 2? (PLA2G4C) and the choline/ethanolamine phosphotransferase (CEPT1) enzymes. Confirmatory investigations revealed a non-classic, inflammatory profile, consisting on the one hand of raised plasma levels of several eicosanoids derived from arachidonic acid through PLA2G4C activity, together with also the proinflammatory cytokines IL6, IL8, MCP-1 and tumor necrosis factor-?. In contrast, we detected a more protective, Th2-shifted response in PBMC. Thus, our findings illustrate a previously unreported connection between ABCD1 dysfunction, glyco- and glycerolipid-driven inflammatory signaling and a fine-tuned inflammatory response underlying a disease considered non-inflammatory. PMID:26370417

  11. Gene dosage-dependent rescue of HSP neurite defects in SPG4 patients’ neurons

    PubMed Central

    Havlicek, Steven; Kohl, Zacharias; Mishra, Himanshu K.; Prots, Iryna; Eberhardt, Esther; Denguir, Naime; Wend, Holger; Plötz, Sonja; Boyer, Leah; Marchetto, Maria C.N.; Aigner, Stefan; Sticht, Heinrich; Groemer, Teja W.; Hehr, Ute; Lampert, Angelika; Schlötzer-Schrehardt, Ursula; Winkler, Jürgen; Gage, Fred H.; Winner, Beate

    2014-01-01

    The hereditary spastic paraplegias (HSPs) are a heterogeneous group of motorneuron diseases characterized by progressive spasticity and paresis of the lower limbs. Mutations in Spastic Gait 4 (SPG4), encoding spastin, are the most frequent cause of HSP. To understand how mutations in SPG4 affect human neurons, we generated human induced pluripotent stem cells (hiPSCs) from fibroblasts of two patients carrying a c.1684C>T nonsense mutation and from two controls. These SPG4 and control hiPSCs were able to differentiate into neurons and glia at comparable efficiency. All known spastin isoforms were reduced in SPG4 neuronal cells. The complexity of SPG4 neurites was decreased, which was paralleled by an imbalance of axonal transport with less retrograde movement. Prominent neurite swellings with disrupted microtubules were present in SPG4 neurons at an ultrastructural level. While some of these swellings contain acetylated and detyrosinated tubulin, these tubulin modifications were unchanged in total cell lysates of SPG4 neurons. Upregulation of another microtubule-severing protein, p60 katanin, may partially compensate for microtubuli dynamics in SPG4 neurons. Overexpression of the M1 or M87 spastin isoforms restored neurite length, branching, numbers of primary neurites and reduced swellings in SPG4 neuronal cells. We conclude that neurite complexity and maintenance in HSP patient-derived neurons are critically sensitive to spastin gene dosage. Our data show that elevation of single spastin isoform levels is sufficient to restore neurite complexity and reduce neurite swellings in patient cells. Furthermore, our human model offers an ideal platform for pharmacological screenings with the goal to restore physiological spastin levels in SPG4 patients. PMID:24381312

  12. Regeneration of Xenopus laevis spinal cord requires Sox2/3 expressing cells.

    PubMed

    Muñoz, Rosana; Edwards-Faret, Gabriela; Moreno, Mauricio; Zuñiga, Nikole; Cline, Hollis; Larraín, Juan

    2015-12-15

    Spinal cord regeneration is very inefficient in humans, causing paraplegia and quadriplegia. Studying model organisms that can regenerate the spinal cord in response to injury could be useful for understanding the cellular and molecular mechanisms that explain why this process fails in humans. Here, we use Xenopus laevis as a model organism to study spinal cord repair. Histological and functional analyses showed that larvae at pre-metamorphic stages restore anatomical continuity of the spinal cord and recover swimming after complete spinal cord transection. These regenerative capabilities decrease with onset of metamorphosis. The ability to study regenerative and non-regenerative stages in Xenopus laevis makes it a unique model system to study regeneration. We studied the response of Sox2(/)3 expressing cells to spinal cord injury and their function in the regenerative process. We found that cells expressing Sox2 and/or Sox3 are present in the ventricular zone of regenerative animals and decrease in non-regenerative froglets. Bromodeoxyuridine (BrdU) experiments and in vivo time-lapse imaging studies using green fluorescent protein (GFP) expression driven by the Sox3 promoter showed a rapid, transient and massive proliferation of Sox2(/)3(+) cells in response to injury in the regenerative stages. The in vivo imaging also demonstrated that Sox2(/)3(+) neural progenitor cells generate neurons in response to injury. In contrast, these cells showed a delayed and very limited response in non-regenerative froglets. Sox2 knockdown and overexpression of a dominant negative form of Sox2 disrupts locomotor and anatomical-histological recovery. We also found that neurogenesis markers increase in response to injury in regenerative but not in non-regenerative animals. We conclude that Sox2 is necessary for spinal cord regeneration and suggest a model whereby spinal cord injury activates proliferation of Sox2/3 expressing cells and their differentiation into neurons, a mechanism that is lost in non-regenerative froglets. PMID:25797152

  13. Variant non ketotic hyperglycinemia is caused by mutations in LIAS, BOLA3 and the novel gene GLRX5

    PubMed Central

    Baker, Peter R.; Friederich, Marisa W.; Swanson, Michael A.; Shaikh, Tamim; Bhattacharya, Kaustuv; Scharer, Gunter H.; Aicher, Joseph; Creadon-Swindell, Geralyn; Geiger, Elizabeth; MacLean, Kenneth N.; Lee, Wang-Tso; Deshpande, Charu; Freckmann, Mary-Louise; Shih, Ling-Yu; Wasserstein, Melissa; Rasmussen, Malene B.; Lund, Allan M.; Procopis, Peter; Cameron, Jessie M.; Robinson, Brian H.; Brown, Garry K.; Brown, Ruth M.; Compton, Alison G.; Dieckmann, Carol L.; Collard, Renata; Coughlin, Curtis R.; Spector, Elaine; Wempe, Michael F.

    2014-01-01

    Patients with nonketotic hyperglycinemia and deficient glycine cleavage enzyme activity, but without mutations in AMT, GLDC or GCSH, the genes encoding its constituent proteins, constitute a clinical group which we call ‘variant nonketotic hyperglycinemia’. We hypothesize that in some patients the aetiology involves genetic mutations that result in a deficiency of the cofactor lipoate, and sequenced genes involved in lipoate synthesis and iron-sulphur cluster biogenesis. Of 11 individuals identified with variant nonketotic hyperglycinemia, we were able to determine the genetic aetiology in eight patients and delineate the clinical and biochemical phenotypes. Mutations were identified in the genes for lipoate synthase (LIAS), BolA type 3 (BOLA3), and a novel gene glutaredoxin 5 (GLRX5). Patients with GLRX5-associated variant nonketotic hyperglycinemia had normal development with childhood-onset spastic paraplegia, spinal lesion, and optic atrophy. Clinical features of BOLA3-associated variant nonketotic hyperglycinemia include severe neurodegeneration after a period of normal development. Additional features include leukodystrophy, cardiomyopathy and optic atrophy. Patients with lipoate synthase-deficient variant nonketotic hyperglycinemia varied in severity from mild static encephalopathy to Leigh disease and cortical involvement. All patients had high serum and borderline elevated cerebrospinal fluid glycine and cerebrospinal fluid:plasma glycine ratio, and deficient glycine cleavage enzyme activity. They had low pyruvate dehydrogenase enzyme activity but most did not have lactic acidosis. Patients were deficient in lipoylation of mitochondrial proteins. There were minimal and inconsistent changes in cellular iron handling, and respiratory chain activity was unaffected. Identified mutations were phylogenetically conserved, and transfection with native genes corrected the biochemical deficiency proving pathogenicity. Treatments of cells with lipoate and with mitochondrially-targeted lipoate were unsuccessful at correcting the deficiency. The recognition of variant nonketotic hyperglycinemia is important for physicians evaluating patients with abnormalities in glycine as this will affect the genetic causation and genetic counselling, and provide prognostic information on the expected phenotypic course. PMID:24334290

  14. Quality of Life and Related Factors Among People With Spinal Cord Injuries in Tehran, Iran

    PubMed Central

    Moghimian, Maryam; Kashani, Fahimeh; Cheraghi, Mohammad Ali; Mohammadnejad, Esmaeil

    2015-01-01

    Background: Spinal Cord Injury (SCI) is one of the biggest health problems. Disabilities resulting from injuries such as spinal disability requires special attention because of their potential reduced to cause adverse effects in different systems of the body. Today, improving the Quality of Life (QOL) in patients with SCIs is an important goal of treatment. Objectives: The purpose of this study was to determine the QOL and related factors among people with SCIs. Patients and Methods: In this cross-sectional descriptive study, 106 patients with SCI were selected through sampling based on census. Data were collected using a demographic questionnaire and a Short-Form 36 (SF-36) health survey questionnaire for measuring the QOL among patients. Data were analyzed using SPSS 14 software and descriptive and inferential statistics. P < 0.05 was considered statistically significant. Results: The mean QOL in these patients was 37.1 ± 1.7 years (21 - 65 years) and mean disease duration was 7.3±6 years. The most common injury was paraplegia. Most of the patients have moderate QOL (54.7 %). The results showed a significant relationship between QOL and marital status and employment status (P < 0.05). Also, results showed a significant relationship between QOL and education levels (P = 0.002), age (P = 0.001), and duration of illness (P = 0.001).The highest and lowest scores were 64 ± 7.1 and 36 ± 5.3 for understanding General Health (GH) and role physical, respectively. Conclusions: The results show that patients with SCI have a moderate health-related QOL Determining the QOL is needed to focus on the strengths and weaknesses of patients with spinal cord injuries. Planning principles is recommended in order to reform the disability. PMID:26557639

  15. Hybrid FES-robot cooperative control of ambulatory gait rehabilitation exoskeleton.

    PubMed

    del-Ama, Antonio J; Gil-Agudo, Angel; Pons, José L; Moreno, Juan C

    2014-01-01

    Robotic and functional electrical stimulation (FES) approaches are used for rehabilitation of walking impairment of spinal cord injured individuals. Although devices are commercially available, there are still issues that remain to be solved. Control of hybrid exoskeletons aims at blending robotic exoskeletons and electrical stimulation to overcome the drawbacks of each approach while preserving their advantages. Hybrid actuation and control have a considerable potential for walking rehabilitation but there is a need of novel control strategies of hybrid systems that adequately manage the balance between FES and robotic controllers. Combination of FES and robotic control is a challenging issue, due to the non-linear behavior of muscle under stimulation and the lack of developments in the field of hybrid control. In this article, a cooperative control strategy of a hybrid exoskeleton is presented. This strategy is designed to overcome the main disadvantages of muscular stimulation: electromechanical delay and change in muscle performance over time, and to balance muscular and robotic actuation during walking.Experimental results in healthy subjects show the ability of the hybrid FES-robot cooperative control to balance power contribution between exoskeleton and muscle stimulation. The robotic exoskeleton decreases assistance while adequate knee kinematics are guaranteed. A new technique to monitor muscle performance is employed, which allows to estimate muscle fatigue and implement muscle fatigue management strategies. Kinesis is therefore the first ambulatory hybrid exoskeleton that can effectively balance robotic and FES actuation during walking. This represents a new opportunity to implement new rehabilitation interventions to induce locomotor activity in patients with paraplegia.Acronym list: 10 mWT: ten meters walking test; 6 MWT: six minutes walking test; FSM: finite-state machine; t-FSM: time-domain FSM; c-FSM: cycle-domain FSM; FES: functional electrical stimulation; HKAFO: hip-knee-ankle-foot orthosis; ILC: iterative error-based learning control; MFE: muscle fatigue estimator; NILC: Normalized stimulation output from ILC controller; PID: Proportional-Integral-derivative Control; PW: Stimulation pulse width; QUEST: Quebec User Evaluation of Satisfaction with assistive Technology; SCI: Spinal cord injury; TTI: torque-time integral; VAS: Visual Analog Scale. PMID:24594302

  16. Hybrid FES-robot cooperative control of ambulatory gait rehabilitation exoskeleton

    PubMed Central

    2014-01-01

    Robotic and functional electrical stimulation (FES) approaches are used for rehabilitation of walking impairment of spinal cord injured individuals. Although devices are commercially available, there are still issues that remain to be solved. Control of hybrid exoskeletons aims at blending robotic exoskeletons and electrical stimulation to overcome the drawbacks of each approach while preserving their advantages. Hybrid actuation and control have a considerable potential for walking rehabilitation but there is a need of novel control strategies of hybrid systems that adequately manage the balance between FES and robotic controllers. Combination of FES and robotic control is a challenging issue, due to the non-linear behavior of muscle under stimulation and the lack of developments in the field of hybrid control. In this article, a cooperative control strategy of a hybrid exoskeleton is presented. This strategy is designed to overcome the main disadvantages of muscular stimulation: electromechanical delay and change in muscle performance over time, and to balance muscular and robotic actuation during walking. Experimental results in healthy subjects show the ability of the hybrid FES-robot cooperative control to balance power contribution between exoskeleton and muscle stimulation. The robotic exoskeleton decreases assistance while adequate knee kinematics are guaranteed. A new technique to monitor muscle performance is employed, which allows to estimate muscle fatigue and implement muscle fatigue management strategies. Kinesis is therefore the first ambulatory hybrid exoskeleton that can effectively balance robotic and FES actuation during walking. This represents a new opportunity to implement new rehabilitation interventions to induce locomotor activity in patients with paraplegia. Acronym list: 10mWT: ten meters walking test; 6MWT: six minutes walking test; FSM: finite-state machine; t-FSM: time-domain FSM; c-FSM: cycle-domain FSM; FES: functional electrical stimulation; HKAFO: hip-knee-ankle-foot orthosis; ILC: iterative error-based learning control; MFE: muscle fatigue estimator; NILC: Normalized stimulation output from ILC controller; PID: Proportional-Integral-derivative Control; PW: Stimulation pulse width; QUEST: Quebec User Evaluation of Satisfaction with assistive Technology; SCI: Spinal cord injury; TTI: torque-time integral; VAS: Visual Analog Scale. PMID:24594302

  17. Staged hybrid approach using proximal TEVAR and distal open repair for the treatment of extensive thoracoabdominal aortic aneurysms

    PubMed Central

    Johnston, William F.; Upchurch, Gilbert R.; Tracci, Margaret C.; Cherry, Kenneth J.; Ailawadi, Gorav; Kern, John A.

    2012-01-01

    Objective Repair of patients with extent I and II thoracoabdominal aortic aneurysms (TAAAs) is associated with significant morbidity and mortality, while repair of more distal extent III and IV TAAAs has a lower risk of mortality and paraplegia. Therefore, we describe an approach using thoracic endovascular repair (TEVAR) as the index operation to convert extent I and II TAAAs to extent III and IV TAAAs amenable to subsequent open aortic repair to minimize patient risk. Methods Between July 2007 and March 2012, 10 staged hybrid operations were performed to treat 1 extent I and 9 extent II TAAAs. Aortic aneurysm pathology included 5 chronic type B dissections, 3 acute type B dissections, and 2 penetrating aortic ulcers. Initially, the proximal descending thoracic aorta was repaired with TEVAR for coverage of the most proximal fenestration or penetrating ulcer, with 7 elective and 3 emergent repairs. Interval open distal aortic replacement was performed either in a short-term planned setting or for progressive dilation of the distal aortic segment. In the open repair, the proximal end of the graft was sewn directly to the distal end of the TEVAR and outer wall of the aorta. Results Average patient age was 48 years with the majority of patients male (60%). Risk factors included hypertension (80%), current tobacco use (50%), and Marfan syndrome (30%). Postoperative complications following TEVAR included endoleaks [type IA (n=1); type II (n=3)], pleural effusions (n=3), and acute kidney injury (n=1). Endovascular re-interventions were required in 3 cases. In dissection cases, persistent filling of the false lumen was common and associated with distal thoracic aortic dilation. Complications of open repair included acute kidney injury (n=2) but no cardiac, pulmonary, or neurologic morbidity. Median time between TEVAR and open repair was 14 weeks. Most importantly, there was no mortality or neurologic deficit after either procedure with a median follow up of 35 weeks. Conclusions A staged hybrid approach to extensive TAAAs combining proximal TEVAR followed by interval open distal TAAA repair is safe and appears to be an effective alternative to traditional open repair. This approach may decrease the significant morbidity associated with single stage open extent I and II TAAA repairs and may be applicable to many TAAA etiologies. PMID:22832268

  18. Cervical spine collar clearance in the obtunded adult blunt trauma patient: A systematic review and practice management guideline from the Eastern Association for the Surgery of Trauma

    PubMed Central

    Patel, Mayur B.; Humble, Stephen S.; Cullinane, Daniel C.; Day, Matthew A.; Jawa, Randeep S.; Devin, Clinton J.; Delozier, Margaret S.; Smith, Lou M.; Smith, Miya A.; Capella, Jeannette M.; Long, Andrea M.; Cheng, Joseph S.; Leath, Taylor C.; Falck-Ytter, Yngve; Haut, Elliott R.; Como, John J.

    2015-01-01

    BACKGROUND With the use of the framework advocated by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group, our aims were to perform a systematic review and to develop evidence-based recommendations that may be used to answer the following PICO [Population, Intervention, Comparator, Outcomes] question: In the obtunded adult blunt trauma patient, should cervical collar removal be performed after a negative high-quality cervical spine (C-spine) computed tomography (CT) result alone or after a negative high-quality C-spine CT result combined with adjunct imaging, to reduce peri-clearance events, such as new neurologic change, unstable C-spine injury, stable C-spine injury, need for post-clearance imaging, false-negative CT imaging result on re-review, pressure ulcers, and time to cervical collar clearance? METHODS Our protocol was registered with the PROSPERO international prospective register of systematic reviews on August 23, 2013 (Registration Number: CRD42013005461). Eligibility criteria consisted of adult blunt trauma patients 16 years or older, who underwent C-spine CT with axial thickness of less than 3 mm and who were obtunded using any definition. Quantitative synthesis via meta-analysis was not possible because of pre-post, partial-cohort, quasi-experimental study design limitations and the consequential incomplete diagnostic accuracy data. RESULTS Of five articles with a total follow-up of 1,017 included subjects, none reported new neurologic changes (paraplegia or quadriplegia) after cervical collar removal. There is a worst-case 9% (161 of 1,718 subjects in 11 studies) cumulative literature incidence of stable injuries and a 91% negative predictive value of no injury, after coupling a negative high-quality C-spine CT result with 1.5-T magnetic resonance imaging, upright x-rays, flexion-extension CT, and/or clinical follow-up. Similarly, there is a best-case 0% (0 of 1,718 subjects in 11 studies) cumulative literature incidence of unstable injuries after negative initial imaging result with a high-quality C-spine CT. CONCLUSION In obtunded adult blunt trauma patients, we conditionally recommend cervical collar removal after a negative high-quality C-spine CT scan result alone. LEVEL OF EVIDENCE Systematic review, level III. PMID:25757133

  19. Human Disease-Drug Network Based on Genomic Expression Profiles

    PubMed Central

    Hu, Guanghui; Agarwal, Pankaj

    2009-01-01

    Background Drug repositioning offers the possibility of faster development times and reduced risks in drug discovery. With the rapid development of high-throughput technologies and ever-increasing accumulation of whole genome-level datasets, an increasing number of diseases and drugs can be comprehensively characterized by the changes they induce in gene expression, protein, metabolites and phenotypes. Methodology/Principal Findings We performed a systematic, large-scale analysis of genomic expression profiles of human diseases and drugs to create a disease-drug network. A network of 170,027 significant interactions was extracted from the ?24.5 million comparisons between ?7,000 publicly available transcriptomic profiles. The network includes 645 disease-disease, 5,008 disease-drug, and 164,374 drug-drug relationships. At least 60% of the disease-disease pairs were in the same disease area as determined by the Medical Subject Headings (MeSH) disease classification tree. The remaining can drive a molecular level nosology by discovering relationships between seemingly unrelated diseases, such as a connection between bipolar disorder and hereditary spastic paraplegia, and a connection between actinic keratosis and cancer. Among the 5,008 disease-drug links, connections with negative scores suggest new indications for existing drugs, such as the use of some antimalaria drugs for Crohn's disease, and a variety of existing drugs for Huntington's disease; while the positive scoring connections can aid in drug side effect identification, such as tamoxifen's undesired carcinogenic property. From the ?37K drug-drug relationships, we discover relationships that aid in target and pathway deconvolution, such as 1) KCNMA1 as a potential molecular target of lobeline, and 2) both apoptotic DNA fragmentation and G2/M DNA damage checkpoint regulation as potential pathway targets of daunorubicin. Conclusions/Significance We have automatically generated thousands of disease and drug expression profiles using GEO datasets, and constructed a large scale disease-drug network for effective and efficient drug repositioning as well as drug target/pathway identification. PMID:19657382

  20. Mitochondrial optic neuropathies – Disease mechanisms and therapeutic strategies

    PubMed Central

    Yu-Wai-Man, Patrick; Griffiths, Philip G.; Chinnery, Patrick F.

    2011-01-01

    Leber hereditary optic neuropathy (LHON) and autosomal-dominant optic atrophy (DOA) are the two most common inherited optic neuropathies in the general population. Both disorders share striking pathological similarities, marked by the selective loss of retinal ganglion cells (RGCs) and the early involvement of the papillomacular bundle. Three mitochondrial DNA (mtDNA) point mutations; m.3460G>A, m.11778G>A, and m.14484T>C account for over 90% of LHON cases, and in DOA, the majority of affected families harbour mutations in the OPA1 gene, which codes for a mitochondrial inner membrane protein. Optic nerve degeneration in LHON and DOA is therefore due to disturbed mitochondrial function and a predominantly complex I respiratory chain defect has been identified using both in vitro and in vivo biochemical assays. However, the trigger for RGC loss is much more complex than a simple bioenergetic crisis and other important disease mechanisms have emerged relating to mitochondrial network dynamics, mtDNA maintenance, axonal transport, and the involvement of the cytoskeleton in maintaining a differential mitochondrial gradient at sites such as the lamina cribosa. The downstream consequences of these mitochondrial disturbances are likely to be influenced by the local cellular milieu. The vulnerability of RGCs in LHON and DOA could derive not only from tissue-specific, genetically-determined biological factors, but also from an increased susceptibility to exogenous influences such as light exposure, smoking, and pharmacological agents with putative mitochondrial toxic effects. Our concept of inherited mitochondrial optic neuropathies has evolved over the past decade, with the observation that patients with LHON and DOA can manifest a much broader phenotypic spectrum than pure optic nerve involvement. Interestingly, these phenotypes are sometimes clinically indistinguishable from other neurodegenerative disorders such as Charcot-Marie-Tooth disease, hereditary spastic paraplegia, and multiple sclerosis, where mitochondrial dysfunction is also thought to be an important pathophysiological player. A number of vertebrate and invertebrate disease models has recently been established to circumvent the lack of human tissues, and these have already provided considerable insight by allowing direct RGC experimentation. The ultimate goal is to translate these research advances into clinical practice and new treatment strategies are currently being investigated to improve the visual prognosis for patients with mitochondrial optic neuropathies. PMID:21112411

  1. Polymeric biomaterials for nerve regeneration applications: From promoting cellular organization to the delivery of bioactive molecules

    NASA Astrophysics Data System (ADS)

    Delgado-Rivera, Roberto L.

    Thousands of new cases of injury to the central nervous system (CNS) occur each year in the USA and all over the world. However, despite recent advances, at present there is no cure for the resulting paraplegia or quadriplegia. This research is directed towards engineering biomaterial platforms to promote cellular organization at the surface of polymer scaffolds that will be conducive to proper regeneration of injured CNS. In addition, the formulation of a delivery system for neuroactive molecules using polymer-based materials will be evaluated to establish its potential to treat CNS disorders. Initial studies involved the chemical modification of an electrospun nonwoven matrix of nanofibers with fibroblast growth factor 2 (FGF-2). Nanofibers alone up-regulated FGF-2, albeit to a lesser extent than nanofibers covalently modified with FGF-2. These results underscore the importance of both surface topography and growth factor presentation on cellular function. Moreover, that FGF-2 modified nanofibrillar scaffolds may demonstrate utility in tissue engineering applications for replacement and regeneration of damaged tissue following CNS injury or disease. Subsequent research efforts focused on a novel micropatterning technique called microscale plasma-initiated patterning (microPIP). This patterning method uses a polydimethylsiloxane (PDMS) stamp to selectively protect regions of an underlying substrate from oxygen plasma treatment resulting in hydrophobic and hydrophilic regions. FGF-2 and laminin-1 were applied to an electrospun polyamide nanofibrillar matrix following plasma treatment. In this work it, was possible to demonstrate that textured surfaces, such as nanofibrillar scaffolds, can be micropatterned to provide external chemical cues for cellular organization. Finally, a microsphere system capable of encapsulating proteins while minimizing the mechanisms of protein degradation and providing a controlled release was investigated. Microspheres were comprised of a salicylic-acid based poly(anhydride-ester) (PAE), a biodegradable polymer that incorporates salicylic acid into the polymer backbone (PolyAspirin). The use of microspheres formulated from PolyAspirin as a delivery vehicle can be advantageous due its ability of performing a dual delivery; biomolecule (protein) and drug. By combining these two properties, it will be possible to release neurotrophic factors to induce a biological response while mitigating inflammatory pathways due to the localized delivery of salicylic acid.

  2. Safety and Efficacy of At-Home Robotic Locomotion Therapy in Individuals with Chronic Incomplete Spinal Cord Injury: A Prospective, Pre-Post Intervention, Proof-of-Concept Study

    PubMed Central

    Rupp, Rüdiger; Schließmann, Daniel; Plewa, Harry; Schuld, Christian; Gerner, Hans Jürgen; Weidner, Norbert; Hofer, Eberhard P.; Knestel, Markus

    2015-01-01

    Background The compact Motorized orthosis for home rehabilitation of Gait (MoreGait) was developed for continuation of locomotion training at home. MoreGait generates afferent stimuli of walking with the user in a semi-supine position and provides feedback about deviations from the reference walking pattern. Objective Prospective, pre-post intervention, proof-of-concept study to test the feasibility of an unsupervised home-based application of five MoreGait prototypes in subjects with incomplete spinal cord injury (iSCI). Methods Twenty-five (5 tetraplegia, 20 paraplegia) participants with chronic (mean time since injury: 5.8 ± 5.4 (standard deviation, SD) years) sensorimotor iSCI (7 ASIA Impairment Scale (AIS) C, 18 AIS D; Walking Index for Spinal Cord Injury (WISCI II): Interquartile range 9 to 16) completed the training (45 minutes / day, at least 4 days / week, 8 weeks). Baseline status was documented 4 and 2 weeks before and at training onset. Training effects were assessed after 4 and 8 weeks of therapy. Results After therapy, 9 of 25 study participants improved with respect to the dependency on walking aids assessed by the WISCI II. For all individuals, the short-distance walking velocity measured by the 10-Meter Walk Test showed significant improvements compared to baseline (100%) for both self-selected (Mean 139.4% ± 35.5% (SD)) and maximum (Mean 143.1% ± 40.6% (SD)) speed conditions as well as the endurance estimated with the six-minute walk test (Mean 166.6% ± 72.1% (SD)). One device-related adverse event (pressure sore on the big toe) occurred in over 800 training sessions. Conclusions Home-based robotic locomotion training with MoreGait is feasible and safe. The magnitude of functional improvements achieved by MoreGait in individuals with iSCI is well within the range of complex locomotion robots used in hospitals. Thus, unsupervised MoreGait training potentially represents an option to prolong effective training aiming at recovery of locomotor function beyond in-patient rehabilitation. Trial Registration German Clinical Trials Register (DKRS) DRKS00005587 PMID:25803577

  3. Ten-Year Follow-Up of Endovascular Aneurysm Treatment with Talent Stent-Grafts

    SciTech Connect

    Pitton, Michael B. Scheschkowski, Tobias; Ring, Markus; Herber, Sascha; Oberholzer, Katja; Leicher-Dueber, Annegret; Neufang, Achim; Schmiedt, Walther; Dueber, Christoph

    2009-09-15

    The purpose of this study was to evaluate the clinical results, complications, and secondary interventions during long-term follow-up after endovascular aneurysm repair (EVAR) and to investigate the impact of endoleak sizes on aneurysm shrinkage. From 1997 to March 2007, 127 patients (12 female, 115 male; age, 73.0 {+-} 7.2 years) with abdominal aortic aneurysms were treated with Talent stent-grafts. Follow-up included clinical visits, contrast-enhanced MDCT, and radiographs at 3, 6, and 12 months and then annually. Results were analyzed with respect to clinical outcome, secondary interventions, endoleak rate and management, and change in aneurysm size. There was no need for primary conversion surgery. Thirty-day mortality was 1.6% (two myocardial infarctions). Procedure-related morbidity was 2.4% (paraplegia, partial infarction of one kidney, and inguinal bleeding requiring surgery). Mean follow-up was 47.7 {+-} 34.2 months (range, 0-123 months). Thirty-nine patients died during follow-up; three of the deaths were related to aneurysm (aneurysm rupture due to endoleak, n = 1; secondary surgical reintervention n = 2). During follow-up, a total of 29 secondary procedures were performed in 19 patients, including 14 percutaneous procedures (10 patients) and 15 surgical procedures (12 patients), including 4 cases with late conversion to open aortic repair (stent-graft infection, n = 1; migration, endoleak, or endotension, n = 3). Overall mean survival was 84.5 {+-} 4.7 months. Mean survival and freedom from any event was 66.7 {+-} 4.5 months. MRI depicted significantly more endoleaks compared to MDCT (23.5% vs. 14.3%; P < 0.01). Patients in whom all aneurysm side branches were occluded prior to stent-grafting showed a significantly reduced incidence of large endoleaks. Endoleaks >10% of the aneurysm area were associated with reduced aneurysm shrinkage compared to no endoleaks or <10% endoleaks ({Delta} at 3 years, -1.8% vs. -12.0%; P < 0.05). In conclusion, endovascular aneurysm treatment with Talent stent-grafts demonstrated encouraging long-term results with moderate secondary intervention rates. Primary occlusion of all aortic side branches reduced the incidence of large endoleaks. Large endoleaks significantly impaired aneurysm shrinkage, whereas small endoleaks did not.

  4. Functional recovery in spinal cord injured rats using polypyrrole/iodine implants and treadmill training.

    PubMed

    Alvarez-Mejia, Laura; Morales, Juan; Cruz, Guillermo J; Olayo, María-Guadalupe; Olayo, Roberto; Díaz-Ruíz, Araceli; Ríos, Camilo; Mondragón-Lozano, Rodrigo; Sánchez-Torres, Stephanie; Morales-Guadarrama, Axayacatl; Fabela-Sánchez, Omar; Salgado-Ceballos, Hermelinda

    2015-07-01

    Currently, there is no universally accepted treatment for traumatic spinal cord injury (TSCI), a pathology that can cause paraplegia or quadriplegia. Due to the complexity of TSCI, more than one therapeutic strategy may be necessary to regain lost functions. Therefore, the present study proposes the use of implants of mesoparticles (MPs) of polypyrrole/iodine (PPy/I) synthesized by plasma for neuroprotection promotion and functional recovery in combination with treadmill training (TT) for neuroplasticity promotion and maintenance of muscle tone. PPy/I films were synthesized by plasma and pulverized to obtain MPs. Rats with a TSCI produced by the NYU impactor were divided into four groups: Vehicle (saline solution); MPs (PPy/I implant); Vehicle-TT (saline solution + TT); and MPs-TT (PPy/I implant + TT). The vehicle or MPs (30 ?L) were injected into the lesion site 48 h after a TSCI. Four days later, TT was carried out 5 days a week for 2 months. Functional recovery was evaluated weekly using the BBB motor scale for 9 weeks and tissue protection using histological and morphometric analysis thereafter. Although the MPs of PPy/I increased nerve tissue preservation (P = 0.03) and promoted functional recovery (P = 0.015), combination with TT did not produce better neuroprotection, but significantly improved functional results (P = 0.000) when comparing with the vehicle group. So, use these therapeutic strategies by separately could stimulate specific mechanisms of neuroprotection and neuroregeneration, but when using together they could mainly potentiate different mechanisms of neuronal plasticity in the preserved spinal cord tissue after a TSCI and produce a significant functional recovery. The implant of mesoparticles of polypyrrole/iodine into the injured spinal cord displayed good integration into the nervous tissue without a response of rejection, as well as an increased in the amount of preserved tissue and a better functional recovery than the group without transplant after a traumatic spinal cord injury by contusion in rats. The relevance of the present results is that polypyrrole/iodine implants were synthesized by plasma instead by conventional chemical or electrochemical methods. Synthesis by plasma modifies physicochemical properties of polypyrrole/iodine implants, which can be responsible of the histological response and functional results. Furthermore, no additional molecules or trophic factors or cells were added to the implant for obtain such results. Even more, when the implant was used together with physical rehabilitation, better functional recovery was obtained than that observed when these strategies were used by separately. PMID:26169188

  5. [Hyperbaric therapy and diving medicine - diving medicine - present state and prospects].

    PubMed

    Winkler, Bernd; Muth, Claus-Martin; Piepho, Tim

    2015-10-01

    The diving accident (decompression incident, DCI) occurs in the decompression phase of dives. The DCI can either be caused by an arterial gas embolism (AGE) subsequent to a pulmonary barotrauma or by the formation of inert gas bubbles subsequent to a reduction of ambient pressure during the ascent from depth. In contrast to the traditional assumption that decompression incidents only occur if decompression rules are neglected, recent data indicate that a vast amount of diving accidents occur even though divers adhered to the rules. Hence, there is a large inter- and intraindividual variability in the predisposition for diving accidents.Within the past few years, the molecular understanding of the pathophysiology of diving accidents has improved considerably. It is now well accepted that pro-inflammatory and pro-coagulatory mechanisms play a central role. Moreover, microparticles are increasingly discussed in the pathogenesis of diving accidents. These new molecular findings have not yet resulted in new therapeutic approaches. However, new approaches of preconditioning before the dive have been developed which are intended to reduce the risk of diving accidents.The symptoms of a diving accident show a large variability and range. They reach from pruritus over tension in the female breast, marbled skin and pain in the joints to severe neurological disability like paraplegia or hemiplegia. Furthermore, pulmonary symptoms can be a result of a pulmonary gas embolism and/or a tension pneumothorax. Extreme cases can also manifest as generalized, difficult-to-treat seizures, loss of consciousness or even death.The evidence-based therapy of diving accidents consists of an immediate application of 100% inspiratory O2. This can be performed via a demand valve, face mask with reservoir bag or ventilation bag connected to a reservoir bag. Fluid substitution is performed by i. v. infusion of 500-1000ml/h of cristalloids. If consciousness is not impaired, the diver is positioned in a supine position, in case of impaired or absent consciousness in a lateral recovery position. Especially in severe cases of DCI a fast transfer to a qualified hyperbaric center and the earliest possible hyperbaric O2-therapy is essential. PMID:26510109

  6. “Open” repair of ruptured thoracoabdominal aortic aneurysm (experience of 51 cases)

    PubMed Central

    Zanetti, Piero Paolo; Walas, Ryszard; Cebotaru, Theodor; Popa, Calin; Vintila, Bogdan; Steiu, Flaviu

    2015-01-01

    Introduction Surgical treatment of toracoabdominal aortic aneurysms (TAAA) represents a difficult problem for the vascular surgeon and may become a formidable challenge in an emergency procedure. In patient with hemodynamic instability, protective measures as cerebral spinal fluid drainage and bio-pump against spinal cord, visceral and renal ischemia, may be ineffective or impracticable. Material and methods We report our experience of 51 emergency-operated patients with TAAA out of 660 treated between 1994 and 2014; 48 patients (94%) were hemodynamically unstable, 3 (6%) were hemodynamically stable. The TAAA patients were evaluated, according to Crawford classification, as: 18 type I, 13 type II, 15 type III, 5 type IV. Results Overall mortality was 23 cases out of 51 (43.1%); 8 deaths occurred during the surgical procedure and 14 in the postoperative period. Early deaths, subdivided by Crawford TAAA classification, were: type I 9/18 (50%), type II 9/13 (69.2%), type III 7/15 (46.6%), type IV 3/5 (60%). Paraplegia-paraparesis developed in 6 cases out of 43 (16.2%), excluding 8 deaths during the operative procedure. Acute renal failure was observed in 8 out of 43 patients (18.6%). Dialysis was found to be a risk factor for hospital mortality (p = 0.03). Pulmonary insufficiency was diagnosed in 15 patients out of 43 (34.8%), and 5 patients (15.5%) needed tracheostomy, out of whom 3 died (p = 0.04%). Postoperative bleeding was present in 8 cases out of 43 (18.6%). Inferior laryngeal nerve palsy was present in 6 cases out of 43 (13.5%). The follow-up period comprised 1-3-5-10 years postoperative follow-up. The actuarial survival rate of patients discharged from hospital was respectively 75%, 63%, 48%, 35%. Conclusions In the literature there are very few studies published on emergency treatment for TAAA. Having usually low numbers of patients in the groups wider experiences are still needed to give more light on the pathophysiology and surgical treatment of this type of TAAA, which are still being treated according to the individual surgeon's experience. PMID:26336493

  7. Clinically relevant intronic splicing enhancer mutation in myelin proteolipid protein leads to progressive microglia and astrocyte activation in white and gray matter regions of the brain

    PubMed Central

    2013-01-01

    Introduction Mutations in proteolipid protein (PLP), the most abundant myelin protein in the CNS, cause the X-linked dysmyelinating leukodystrophies, Pelizaeus-Merzbacher disease (PMD) and spastic paraplegia type 2 (SPG2). Point mutations, deletion, and duplication of the PLP1 gene cause PMD/SPG2 with varying clinical presentation. Deletion of an intronic splicing enhancer (ISEdel) within intron 3 of the PLP1 gene is associated with a mild form of PMD. Clinical and preclinical studies have indicated that mutations in myelin proteins, including PLP, can induce neuroinflammation, but the temporal and spatial onset of the reactive glia response in a clinically relevant mild form of PMD has not been defined. Methods A PLP-ISEdel knockin mouse was used to examine the behavioral and neuroinflammatory consequences of a deletion within intron 3 of the PLP gene, at two time points (two and four months old) early in the pathological progression. Mice were characterized functionally using the open field task, elevated plus maze, and nesting behavior. Quantitative neuropathological analysis was for markers of astrocytes (GFAP), microglia (IBA1, CD68, MHCII) and axons (APP). The Aperio ScanScope was used to generate a digital, high magnification photomicrograph of entire brain sections. These digital slides were used to quantify the immunohistochemical staining in ten different brain regions to assess the regional heterogeneity in the reactive astrocyte and microglial response. Results The PLP-ISEdel mice exhibited behavioral deficits in the open field and nesting behavior at two months, which did not worsen by four months of age. A marker of axonal injury (APP) increased from two months to four months of age. Striking was the robust reactive astrocyte and microglia response which was also progressive. In the two-month-old mice, the astrocyte and microglia reactivity was most apparent in white matter rich regions of the brain. By four months of age the gliosis had become widespread and included both white as well as gray matter regions of the brain. Conclusions Our results indicate, along with other preclinical models of PMD, that an early reactive glia response occurs following mutations in the PLP gene, which may represent a potentially clinically relevant, oligodendrocyte-independent therapeutic target for PMD. PMID:24314267

  8. Mitochondrial dynamics and inherited peripheral nerve diseases.

    PubMed

    Pareyson, Davide; Saveri, Paola; Sagnelli, Anna; Piscosquito, Giuseppe

    2015-06-01

    Peripheral nerves have peculiar energetic requirements because of considerable length of axons and therefore correct mitochondria functioning and distribution along nerves is fundamental. Mitochondrial dynamics refers to the continuous change in size, shape, and position of mitochondria within cells. Abnormalities of mitochondrial dynamics produced by mutations in proteins involved in mitochondrial fusion (mitofusin-2, MFN2), fission (ganglioside-induced differentiation-associated protein-1, GDAP1), and mitochondrial axonal transport usually present with a Charcot-Marie-Tooth disease (CMT) phenotype. MFN2 mutations cause CMT type 2A by altering mitochondrial fusion and trafficking along the axonal microtubule system. CMT2A is an axonal autosomal dominant CMT type which in most cases is characterized by early onset and rather severe course. GDAP1 mutations also alter fission, fusion and transport of mitochondria and are associated either with recessive demyelinating (CMT4A) and axonal CMT (AR-CMT2K) and, less commonly, with dominant, milder, axonal CMT (CMT2K). OPA1 (Optic Atrophy-1) is involved in fusion of mitochondrial inner membrane, and its heterozygous mutations lead to early-onset and progressive dominant optic atrophy which may be complicated by other neurological symptoms including peripheral neuropathy. Mutations in several proteins fundamental for the axonal transport or forming the axonal cytoskeleton result in peripheral neuropathy, i.e., CMT, distal hereditary motor neuropathy (dHMN) or hereditary sensory and autonomic neuropathy (HSAN), as well as in hereditary spastic paraplegia. Indeed, mitochondrial transport involves directly or indirectly components of the kinesin superfamily (KIF5A, KIF1A, KIF1B), responsible of anterograde transport, and of the dynein complex and related proteins (DYNC1H1, dynactin, dynamin-2), implicated in retrograde flow. Microtubules, neurofilaments, and chaperones such as heat shock proteins (HSPs) also have a fundamental role in mitochondrial transport and mutations in some of related encoding genes cause peripheral neuropathy (TUBB3, NEFL, HSPB1, HSPB8, HSPB3, DNAJB2). In this review, we address the abnormalities in mitochondrial dynamics and their role in determining CMT disease and related neuropathies. PMID:25847151

  9. [Neuropsychiatric manifestations ushering pernicious anemia].

    PubMed

    Mrabet, S; Ellouze, F; Ellini, S; Mrad, M F

    2015-12-01

    Biermer disease or pernicious anemia is an autoimmune atrophic gastritis characterized by the lack of secretion of gastric intrinsic factor. This leads to an insufficient absorption of vitamin B12 in the ileum. Clinical manifestations are mainly hematologic. Neuropsychiatric manifestations are known but are less frequent especially early in the disease. Inaugural neuropsychiatric arrays are rare and various thus making diagnosis difficult. In this article, we report through two clinical cases different neuropsychiatric manifestations revealing pernicious anemia. Mrs. C.O., aged 56, presented after surgery for gallstones, an acute psychiatric array associated with gait disorders. She had no history of neurological or psychiatric problems. The psychiatric interview revealed delirious syndrome, depressive symptoms and anxiety. Neurological examination noted a flaccid paraplegia with peripheral neuropathic syndrome and myoclonus in the upper limbs. At the full blood count, a macrocytosis (VGM: 112.2fl) without anemia was found. The level of vitamin B12 in the blood was low. Cerebro-spinal MRI was suggestive of a neuro-Biermer and showed hypersignal in the cervical cord on T2-weighted sagittal section. In axial section, hypersignal appears at the posterior columns in the form of V. There were no brain abnormalities. A sensorimotor axonal polyneuropathy was diagnosed. The patient received vitamin B12 intramuscularly for ten days associated with neuroleptic treatment. Mrs. R.M., aged 40, was brought to the psychiatry consultation for acute behavioral disorders progressively worsening over a month. An anxiety syndrome, depressive syndrome and delirious syndrome were identified. Neurological examination showed a posterior cordonal syndrome with quadripyramidal syndrome. Full blood count showed a macrocytic anemia. Serum B12 level was collapsed. Cerebro-spinal MRI was normal. She received vitamin B12 with clinical and biological improvement. Features of pernicious anemia vary according to studies and age range. Digestive and hematological manifestations are well known. Neurological and psychiatric manifestations of pernicious anemia were also described in the early literature. They can be the initial symptoms or the only ones. However, inaugural neuropsychiatric features are often unrecognized. The most common psychiatric symptoms were depression, mania, psychotic symptoms, cognitive impairment and obsessive compulsive disorder. Neurological involvement includes mainly combined spinal sclerosis, peripheral neuropathy and dementia. Cerebellar ataxia and movement disorders are reported less often. Severity of neuropsychiatric features and therapeutic efficacy depends on the duration of signs and level of B12 deficiency. Macrocytic anemia may lack. Neuropsychiatric manifestations could be isolated or be the first manifestation of vitamin deficiency and occur without any hematological or gastrointestinal context. Pernicious anemia and serum B12 assay should be discussed in all patients with organic mental disorders, atypical psychiatric symptoms and fluctuation of symptomatology. Nevertheless, B12 level could be normal in genuine pernicious anemia diseases and macrocytic anemia may lack. Substitutive vitaminotherapy is required when diagnosis is strongly suspected and etiologic assessment is negative. PMID:26345354

  10. [Figures of first laureates of the Wiktor Dega medal (XXXVII Jubilee Congress of Polish Orthopaedic and Traumatologic Society, 10-13 September 2008)].

    PubMed

    Nowakowski, Andrzej; Rapa?a, Kazimierz

    2008-01-01

    Figures of two outstanding orthopaedists Professor Stefan Malawski and Professor Jerzy Król rewarded with the medal of the name of Wiktor Degi were described. The medal is being granted by the Chapter of the Medal as regarding for outstanding achievements for the Polish and world orthopaedics and rehabilitation. Profesor Stefan Kazimierz Malawski was born 26. 12. 1920 in the Vilnius area. In Vilnius he stated his medical studies, which he continued in Lwow and graduated in 1946 at the Marie Curie Sk?odowska in Lublin. Professor Malawski's main field of interest were related to the problems related to tuberculosis of bones and joints and trauma of the lumbar and cervical spine. In the problems of bone tuberculosis he remains an unquestioned authority in Poland. His deep understanding of these clinical problems can be found in his text-book "Tuberculosis of bones and joints", which was printed in 1976. The information pertaining diagnosis and surgical treatment remain extremely valuable today. Another field of interest of Professor Malawski are pathologies of the spine. Disc disease, neoplasms of the spine, spinal stenosis and infections of the spine, spondylolisthesis are among many of his interests. This very wide field of interest can be dound in his 3 tome publication Spondyloorthopedics. His 166 papars printed in Poland and abroad bear proof of the Professors wide field of interest and deep knowledge. Professor Malawski was the first surgeon in Poland to perform surgery on the front elements of the spine in tuberculotic paraplegia. In 1958 he implemented surgical treatment of spine tumor--both primary and metastatic, by resecting them and stabilizing the spine with grafts. In the early 70's he focused on spinal stenosis. In the years 1982-1986 he was the Chairman of the Board of the Polish Orthopedic and Trauma Society. Professor Malawski introdued a modern set of Rules and Regulations, greatly simplifying the decision making process during General assemblies of the Society. Professor Malawski is undoubtedly a great successor to the active way of surgical thinking introduced by professor Adam Gruca. Professor Jerzy Król is among the greatest Polish orthopedic surgeons. He was born on 21st February 1926 in Baranowice (Nowogródek woiwodship). He graduated from high school in the underground schooling system during the Second World War, receiving his maturity exam in 1945 from the Konarski High Scool School of the Western Lands in Czestochowa. In 1945 the professor started his medical studies at Adam Mickiewicz University of Poznan, where he graduated in 1949. In 1950 he started his medical career in in Orthopedic Department of Poznan head by professor Wiktor Dega. Professor Król is the author of over 100 medical papers printed in national and international journals. His key fields of interest are congenital dislocation of the hip, hip arthroplasty, scoliosis and rehabilitaton and prosthesis problems. In 1968 he performed the first scoliosis correction with the Harrington rod in Poland as well as the implantation of the first McKee-Ferara hip prosthesis. He is the co-author of the text-book Orthopedics and Rehabilitation, Medical Rehabilitation and a number of WHO text books: Community Health Worker and Guide for prevention of Deformities in Poliomyelitis. He also took part in the publishing of the WHO text-book Rehabilitation Surgery, for which he received the Ministry of Health Award. He overlooked 7 Ph.D thesis and 4 papers qualifying for assistant professor. Between 1972 and 1995 professor Król worked as a WHO expert, as member of the Expert Committee for Rehabilitation. Between 1986-1987 head was the director of the Orthopedics and Rehabilitation Institute in Poznan. He resigned from this function due to his work with WHO in Madagaskar. After his return he was the head of the Orthopedic Department in Poznan University of Medical Sciennces until October 1996 when he retired. PMID:19241890