Sample records for paraplegia

  1. Genetics Home Reference: Spastic paraplegia type 11

    MedlinePLUS

    ... OMIM Genetic disorder catalog Conditions > Spastic paraplegia type 11 On this page: Description Genetic changes Inheritance Diagnosis ... Reviewed April 2009 What is spastic paraplegia type 11? Spastic paraplegia type 11 is part of a ...

  2. Genetics Home Reference: Spastic paraplegia type 15

    MedlinePLUS

    ... over time. Additionally, there is often a loss (atrophy) of nerve cells in several parts of the ... definitions help with understanding spastic paraplegia type 15? atrophy ; autophagy ; autosomal ; autosomal recessive ; bradykinesia ; breakdown ; cell ; cell ...

  3. 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.

  4. Walking dreams in congenital and acquired paraplegia.

    PubMed

    Saurat, Marie-Thérèse; Agbakou, Maité; Attigui, Patricia; Golmard, Jean-Louis; Arnulf, Isabelle

    2011-12-01

    To test if dreams contain remote or never-experienced motor skills, we collected during 6 weeks dream reports from 15 paraplegics and 15 healthy subjects. In 9/10 subjects with spinal cord injury and in 5/5 with congenital paraplegia, voluntary leg movements were reported during dream, including feelings of walking (46%), running (8.6%), dancing (8%), standing up (6.3%), bicycling (6.3%), and practicing sports (skiing, playing basketball, swimming). Paraplegia patients experienced walking dreams (38.2%) just as often as controls (28.7%). There was no correlation between the frequency of walking dreams and the duration of paraplegia. In contrast, patients were rarely paraplegic in dreams. Subjects who had never walked or stopped walking 4-64 years prior to this study still experience walking in their dreams, suggesting that a cerebral walking program, either genetic or more probably developed via mirror neurons (activated when observing others performing an action) is reactivated during sleep. PMID:21704532

  5. Paraplegia after intercostal neurolysis with phenol

    PubMed Central

    Gollapalli, Lakshman; Muppuri, Rudramanaidu

    2014-01-01

    In patients with advanced stages of cancer, severe pain is commonly encountered and is very difficult to treat. It affects the quality of life of the patient and the families involved. Pain can be managed using analgesics and adjuvant therapy. However, studies have shown that at least 10%–15% of patients fail to control pain adequately and will experience severe pain. We discuss the case of a 66-year-old female with metastatic adenoid cystic carcinoma of the left submandibular gland and developed paraplegia following intercostal neurolysis with phenol. After a successful diagnostic T6 to T12 intercostal nerve block, the patient was scheduled for an intercostal neurolytic block. We injected 2 mL of 10% aqueous phenol at each level on the left from the T6 to T12 ribs. One hour after the procedure, the patient developed bilateral lower extremity weakness with difficulty moving. A physical examination showed the absence of sensation to pinpricks and vibration from T10 to S5 and an absence of anal sphincter tone and sensation. Magnetic resonance images of the thoracic and lumbar spine showed leptomeningeal metastatic disease and myelitis. We postulate that the paraplegia could be from phenol diffusing along either the spinal nerves or the paravertebral venous plexus into the subarachnoid space. This case report points to the risks involved with phenol neurolysis close to the spine, and we propose alternative methods to minimize neurological complications. PMID:25429238

  6. Spinal Arteriovenous Fistula with Progressive Paraplegia after Spinal Anaesthesia

    PubMed Central

    Argyrakis, Nikolaos; Matis, Georgios K.; Mpata-Tshibemba, Stephanie

    2014-01-01

    A case of an iatrogenic spinal arteriovenous fistula with progressive paraplegia in a young woman is reported. The fistula was eventually created after repetitive lumbar punctures performed in the process of spinal anaesthesia. Her symptoms were progressed to paraplegia over a period of 2 years. The digital subtraction angiography demonstrated a single-hole fistula, involving the anterior spinal artery and vein. The lesion was occluded by embolization with immediate improvement. The potential mechanism is discussed. PMID:24653807

  7. Factors influencing bone loss in paraplegia

    PubMed Central

    Dionyssiotis, Y; Lyritis, G P; Mavrogenis, A F; Papagelopoulos, P J

    2011-01-01

    Background and aim: Significant bone loss develops in the first months and continues years after spinal cord injury. A cross – sectional comparative study was performed to evaluate factors influencing bone loss in spinal cord injured men with paraplegia. Patients and Methods: We studied 31 paraplegic men in chronic stage (>1.5 years) in comparison with 30 able-bodied men of similar age, height, and weight. The paraplegic men were allocated into 2 subgroups based on the neurological level of injury; high paraplegics (n=16, T4-T7 neurological level of injury) and low paraplegics (n=15, T8-T12 neurological level of injury). The influence of positive and negative factors (spasticity, standing-therapeutic walking, and duration of paralysis) on bone structures was evaluated by pQCT measurement of the total, trabecular and cortical bone mineral density (BMDtot, BMDtrab, BMDcort, respectively) and cortical thickness (THIcort) at the distal tibial epiphysis and the tibial diaphysis at 4% and 38% proximal to the distal end of the tibia. The stress strain index (SSI) was measured at 14% (SSI2) and at 38% (SSI3) of the tibial diaphysis, and the difference SSI3 - SSI2 (?SSI3-2) was calculated. Results: In all paraplegics, bone mineral density parameters were significantly reduced compared to the control group (BMDtot: p<0.0005, BMDtrab: p<0.0005, BMDcort: p=0.029, THIcort: p=0.019, SSI2: p=0.009, SSI3: p=0.003, respectively). Paraplegics who used standing frames or long brace orthoses had statistically significant higher bone mass and geometric parameters (BMDtrab: p=0.03, BMDtot: p=0.01, THIcort: p=0.013, respectively), while spasticity did not protect bone. The duration of paralysis was significantly related to trabecular bone loss (r=-0.5, p=0.05) and cortical thickness (r=-0.6, p=0.006) in high paraplegics and to ?SSI3-2 in low paraplegics (r=0.534, p=0.03). Conclusions: The neurological level of injury adversely affects bone strength in paralyzed lower extremities such as the distal tibia. Standing or therapeutic walking could possibly have a positive effect in cortical and trabecular bone in paraplegia. PMID:21607037

  8. Manifesting heterozygosity in sex-linked spastic paraplegia?

    Microsoft Academic Search

    I D Young; I F Pye; J R Moore

    1984-01-01

    An unusual form of hereditary spastic paraplegia is described. Affected females have a late-onset slowly progressive spastic paraparesis. Affected males show oligophrenia with a rapidly progressive spastic quadriplegia. The mode of inheritance is consistent with sex-linkage, with partial manifestation in female carriers.

  9. A reinvenção da sexualidade masculina na paraplegia adquirida

    Microsoft Academic Search

    Luiz Carlos Avelino da Silva; Paulo Albertini

    2007-01-01

    RESUMO Neste trabalho a sexualidade masculina é discutida a partir da condição de um homem com lesão medular. Seu objetivo foi investigar o impacto da paraplegia adquirida na sexualidade masculina. Metodologicamente adotou-se uma aborda- gem qualitativa e coletou-se a história de vida por meio de entrevistas. As princi- pais conclusões apontam para um deslocamento das representações da masculi- nidade associadas

  10. Lipid Profiles of Persons With Paraplegia and Tetraplegia: Sex Differences

    PubMed Central

    Schmid, Andreas; Knöebber, Judith; Vogt, Stefan; König, Daniel; Deibert, Peter; Bültermann, Dirk; Heinrich, Lothar; Baumstark, Manfred W; Berg, Aloys; Storch, Max-Jürgen

    2008-01-01

    Background/Objective: To examine the lipoprotein profiles of men and women with paraplegia and tetraplegia. Impairment of the sympathetic nervous system (dependent on the level of injury) and the extent of physical capacity and activity were correlated with the lipid profile in men with spinal cord injury (SCI). Sex-related differences of the lipoprotein profiles could be found in nondisabled and premenopausal women with SCI mainly because of the different effects of sexual hormones. Methods: Lipoprotein profiles of 112 participants with SCI (32 premenopausal women, 80 men) were analyzed and correlated to sex, lesion level, and physical performance capacity. Results: Women with tetraplegia or paraplegia showed significantly higher levels of high-density lipoprotein and lower ratios of total cholesterol to high-density lipoprotein-cholesterol compared with men with corresponding lesion levels, without a difference in peak oxygen consumption. Concentrations of very-low-density lipoproteins were lower in women with paraplegia than in men with paraplegia; no differences were found in total cholesterol, low-density lipoprotein-cholesterol, and triglycerides. Sex-independent elevations in total cholesterol and low-density lipoprotein-cholesterol were associated with paraplegia, and sex-independent elevations in triglyceride levels were associated with tetraplegia. Conclusions: Persons with SCI showed sex-related differences in their lipoprotein profiles. Independent of physical fitness, the lipoprotein profile of premenopausal women with SCI did not exhibit the adverse lipoprotein characteristics observed in men with SCI, probably because of the influence of sexual hormones independent of lesion level. PMID:18795478

  11. Physical Activity Levels Are Low in Free-Living Adults with Chronic Paraplegia

    Microsoft Academic Search

    Andrea C. Buchholz; Colleen F. McGillivray; Paul B. Pencharz

    2003-01-01

    Objectives: To compare physical activity levels (PALs) of free-living adults with chronic paraplegia with World Health Organization recommendations and to compare energy expenditure between persons with complete vs. incomplete paraplegia.Research Methods and Procedures: Twenty-seven euthyroid adults (17 men and 10 women) with paraplegia (12.5 ± 9.5 years since onset; 17 with complete lesions and 10 with incomplete lesions) participated in

  12. Proteolipid protein 1 gene sequencing of hereditary spastic paraplegia?

    PubMed Central

    Gao, Yu; Chi, Lumei; Jin, Yinshi; Nan, Guangxian

    2012-01-01

    PCR amplification and sequencing of whole blood DNA from an individual with hereditary spastic paraplegia, as well as family members, revealed a fragment of proteolipid protein 1 (PLP1) gene exon 1, which excluded the possibility of isomer 1 expression for this family. The fragment sequence of exon 3 and exon 5 was consistent with the proteolipid protein 1 sequence at NCBI. In the proband samples, a PLP1 point mutation in exon 4 was detected at the basic group of position 844, T?C, phenylalanine?leucine. In proband samples from a male cousin, the basic group at position 844 was C, but gene sequencing signals revealed mixed signals of T and C, indicating possible mutation at this locus. Results demonstrated that changes in PLP1 exon 4 amino acids were associated with onset of hereditary spastic paraplegia.

  13. Acute flaccid paraplegia: a rare complication of meningococcal meningitis

    Microsoft Academic Search

    M F A Rathore; Z A Gill; A A Malik; F Farooq; MFA Rathore

    2008-01-01

    Study design:A case report of spinal cord dysfunction following meningococcal meningitis.Objectives:To describe a rare complication of meningococcal meningitis.Setting:Spinal Unit, Armed Forces Institute of Rehabilitation Medicine, Rawalpindi, Pakistan.Methods:A young healthy male developed meningococcal meningitis followed by acute onset low thoracic flaccid paraplegia with complete motor and sensory loss and sphincter disturbance. He responded well to antibiotics but was not investigated for

  14. Hereditary spastic paraplegia: clinical principles and genetic advances.

    PubMed

    Fink, John K

    2014-07-01

    Hereditary spastic paraplegia (HSP) refers to inherited disorders in which spastic gait is either the only feature or is a major syndrome feature. There are more than 70 genetic types of HSP. Neuropathological studies, albeit limited to only a few genetic types of HSP, have identified axon degeneration involving the distal ends of the corticospinal tracts and fasciculus gracilis fibers. In this review, the author highlights the clinical and genetic features of HSP. PMID:25192507

  15. Spinal dural arteriovenous fistula presenting with paraplegia following lumbar puncture.

    PubMed

    Koerts, Guus; Vanthuyne, Vincent; Delavallee, Maxime; Rooijakkers, Herbert; Raftopoulos, Christian

    2013-07-01

    Spinal dural arteriovenous fistulas are rare lesions with an annual incidence of 1 per 100,000 population. In patients with this disease, an abnormal vascular dural shunt exists between a dural branch of a segmental artery and a subdural radicular vein that drains the perimedullary venous system, leading to venous hypertension and secondary congestive myelopathy. Generally, patients present with progressive paraparesis, urinary disturbances, and gait ataxia. In this report the authors describe a 61-year-old woman with a spinal dural arteriovenous fistula who developed an acute paraplegia after a nontraumatic lumbar puncture. The possible underlying mechanisms and treatment options are discussed. PMID:23641674

  16. Mortality and paraplegia after thoracoabdominal aortic aneurysm repair: a risk factor analysis

    Microsoft Academic Search

    Joseph S. Coselli; Scott A. LeMaire; Charles C. Miller III; Zachary C. Schmittling; Cüneyt Köksoy; José Pagan; Patrick E. Curling

    2000-01-01

    Background. Recent recommendations regarding thoracoabdominal aortic aneurysm (TAAA) management have emphasized individualized treatment based on balancing a patient’s calculated risk of rupture with their anticipated risk of postoperative death or paraplegia. The purpose of this study was to enhance this risk-benefit decision by providing contemporary results and determining which preoperative risk factors currently predict mortality and paraplegia after TAAA surgery.Methods.

  17. Spinal extra-dural metastasis from Merkel cell carcinoma: a rare cause of paraplegia

    Microsoft Academic Search

    Kamath Vijay; Krishna Venkateswaran; Ajoy P. Shetty; S. Rajasekaran

    2008-01-01

    We report a rare case of Merkel cell carcinoma with extra-dural spinal metastasis causing paraplegia. There are only four\\u000a reported cases in literature. A 57-year-old lady presented with a breast lump, multiple truncal skin swellings, low back pain\\u000a and rapidly progressive paraplegia. MRI showed multiple epidural soft tissue masses causing neural compression. A biopsy from\\u000a the truncal skin lesion was

  18. Paraplegia differentially increases arterial blood pressure related cardiovascular disease risk factors in normotensive and hypertensive rats

    Microsoft Academic Search

    David W. Rodenbaugh; Heidi L. Collins; Stephen E. DiCarlo

    2003-01-01

    Older individuals (>50 years of age) are increasingly sustaining spinal cord injuries (SCI) and often have pre-existing medical conditions, including hypertension. Furthermore, the life expectancy of individuals with paraplegia has increased to near that of able-bodied individuals. Thus, chronic diseases associated with aging (e.g. hypertension) are increasing in this population. We tested the hypothesis that paraplegia differentially increases blood pressure

  19. Evaluation of activity monitors in manual wheelchair users with paraplegia

    PubMed Central

    Hiremath, Shivayogi V.; Ding, Dan

    2011-01-01

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

  20. Spastic paraplegia proteins spastizin and spatacsin mediate autophagic lysosome reformation

    PubMed Central

    Chang, Jaerak; Lee, Seongju; Blackstone, Craig

    2014-01-01

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

  1. Novel medical bathing with traditional Chinese herb formula alleviates paraplegia spasticity.

    PubMed

    Liu, Xin; Meng, Qingxi; Yu, Dapeng; Zhao, Xiwu; Zhao, Tingbao

    2014-06-01

    Paraplegia spasm is a kind of chronic disease which lacks effective treatment; the patients have to endure long-term pain, which is a tough problem for nursing practice. Lots of potential candidate medicines are under investigation, and a new Chinese herb formula is introduced in the current study. In the present study, we chose six different well-known Chinese herbs to form a formula, and boiled them into the water with an optimized ratio to make bath water; 80 paraplegic patients received this medicinal bath, and 80 patients received perfume water bath as placebo group. Compared with placebo control patients, the herb-treated patients have significant reduction in paraplegia spasm, visual analogue scale score, clinician global impression and sleep disorder. This novel six-combined formula traditional medicine could be beneficial for alleviating paraplegia spasm, but the underlying action mechanism deserves further study. PMID:24621269

  2. 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. [and others

    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.

  3. Carcinoid tumor mistaken for persistent neurogenic bowel symptoms in a patient with paraplegia: A case report

    Microsoft Academic Search

    Kanakadurga Rao Poduri; Edward M. Schnitzer

    2001-01-01

    Poduri KR, Schnitzer EM. Carcinoid tumor mistaken for persistent neurogenic bowel symptoms in a patient with paraplegia: a case report. Arch Phys Med Rehabil 2001;82:996-9. Neurogenic bowel in spinal cord injury (SCI) can present with constipation and diarrhea as ongoing problems. Usually, these manifestations are adequately controlled with modification in the bowel program. When these symptoms persist, other causes should

  4. 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 ...

  5. Spastic paraplegia associated with addison's disease: Adult variant of adreno-leukodystrophy

    Microsoft Academic Search

    H. Budka; E. Sluga; W.-D. Heiss

    1976-01-01

    Clinical and pathological features of an adult variant of adreno-leukodystrophy (ALD) are presented. A male with clinical and laboratory signs of Addison's disease (AD) developed at age 22 a slowly progressing paraplegia with slight sensory deficits in both legs and bladder and sphincter dysfunctions; he died at age 24 in an AD crisis. Autopsy revealed hyperplasia of lymphatic tissues, lymphocytic

  6. 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"…

  7. Work values: a comparison of non-disabled persons with persons with paraplegia.

    PubMed

    Ville, I; Ravaud, J F

    1998-04-01

    A number of studies focus on factors that might explain the low level of employment of persons with paraplegia without questioning the social representations connected to work. Being employed is considered a priori as beneficial, constituting an important objective for rehabilitation. However sociologists have recently pointed out that work, as a means of self fulfilment, is a 'constructed' rather than a 'natural' category. The comparisons of the representations of work given by two groups: persons with paraplegia (n = 350), and non-disabled persons (n = 327) show that persons with paraplegia are more likely than non-disabled persons to consider work as a source of personal fulfilment and social recognition and less likely to positively value the fact of not-working. In addition, a demonstrated satisfaction with not working, among persons of working age, is clearly more significant among non-disabled persons than among persons with paraplegia. Among these, some of them who have generally made up their mind about not working declare that they feel satisfied being unoccupied. This satisfaction is explained, in part, by expressed representations of work. The authors suggest a reflection on the place of work in rehabilitation programmes. PMID:9571379

  8. Flaccid paraplegia: a feature of spinal cord lesions in Holmes-Adie syndrome and tabes dorsalis.

    PubMed Central

    Swash, M; Earl, C J

    1975-01-01

    In a patient with Holmes-Adie syndrome, and in another with tabes dorsalis, a transverse cord lesion resulted in a severe, but flaccid paraplegia with absent tendon reflexes. Flexor spasms were severe in both patients, but spasticity was absent. The significance of these observations is discussed in relation to the functional and anatomical disorder in these two syndromes. PMID:1141918

  9. Very early onset and severe complicated phenotype caused by a new spastic paraplegia 3A gene mutation.

    PubMed

    Fusco, Carlo; Frattini, Daniele; Farnetti, Enrico; Nicoli, Davide; Casali, Bruno; Della Giustina, Elvio

    2012-10-01

    Spastic paraplegia 3A is the second most common form of hereditary autosomal dominant spastic paraplegia. This form is mainly associated with an early age of onset and pure phenotype, although recently complicated forms were reported. We describe a patient carrying a new C>T P344S>CT mutation in exon 10 of the spastic paraplegia 3A gene with unusual, complicated, and extremely severe phenotype. At the last neurologic examination performed at 17 years of life, the patient disclosed spastic tetraparesis, sensorimotor axonal neuropathy, cognitive and cranial nerve impairment, mild pes cavus, and distal amyotrophy. PMID:22378671

  10. 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

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

    PubMed

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

    2014-04-01

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

  12. A Rare Hyperextension Injury in Thoracic Spine Presenting with Delayed Paraplegia

    PubMed Central

    Shin, Dong-Eun; Yoon, Hyung-Ku; Lee, Jun-Ku; Cha, Yoon-Sik

    2013-01-01

    Hyperextension injury in the thoracic spine is uncommon with only a few cases documented in the literature. The mechanism of these injuries is hyperextension combined with axial or shearing force. These types of injuries are associated with a high risk of dural tears and paraplegia. A 91-year-old female presented with acute back pain from a hyperextension injury in thoracic spine with no neurological deficit. Lumbar magnetic resonance imaging showed a intervertebral disc rupture. On day 20 of hospitalization, the herniated intervertebral disc compressed the spinal cord with incomplete paraplegia. Hyperextension injuries involving the three columns are very unstable and we recommend surgical treatment as soon as possible, not only because of the initial trauma, but a ruptured disc herniation can damage the spinal cord. PMID:23741551

  13. Clinical Evaluation of Percutaneous Vertebroplasty in a Patient with Paraplegia and Immobilization Syndrome: A Case Report

    PubMed Central

    Masala, Salvatore; Calabria, Eros; De Vivo, Dominique; Neroni, Luca; Simonetti, Giovanni

    2013-01-01

    We will discuss a potential role of percutaneous vertebroplasty (PVP) in the management of a patient with immobilization syndrome due to paraplegia and vertebral osteoporotic fractures. While PVP is commonly used for the treatment of osteoporotic thoracolumbar vertebral compression fractures, its role in vertebral stabilization in patient with immobilization syndrome has not been reported in the literature. A 73-year-old woman affected by immobilization syndrome due to paraplegia and vertebral osteoporotic fractures was treated with PVP of vertebrae D12, L1, and L4. After PVP, the patient did not need any antalgic therapy, and there was a significant improvement regarding mobilization, performance of physiological functions, daily management of personal care, and treatment of decubitus ulcers, increasing life quality and psychological well-being. PMID:23573449

  14. Spinal tuberculosis--the commonest cause of non-traumatic paraplegia in Papua New Guinea.

    PubMed

    Scrimgeour, E M; Kaven, J; Gajdusek, D C

    1987-07-01

    A retrospective study was undertaken of 53 cases of non-traumatic paraplegia admitted to two major hospitals in Papua New Guinea (PNG) from 1975-1982; 19 of these cases were examined. The mean age of the patients was 29 years (range: 2-70 years). Spinal tuberculosis was the commonest cause of paraplegia (83%), followed by neoplasia (7.5%). Two cases of chronic idiopathic arachnoiditis were noted but nutritional myelopathy was not diagnosed. Thirty-one (70%) of the 44 tuberculosis patients responded to treatment and were ambulant at discharge but only 18% were known to have completed 18 months' chemotherapy and 23% defaulted. The introduction of short-term chemotherapy regimens using rifampicin should improve future management of spinal tuberculosis in PNG. PMID:3433337

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

    PubMed Central

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

    2009-01-01

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

  16. Nonlinear modeling of FES-supported standing-up in paraplegia for selection of feedback sensors

    Microsoft Academic Search

    Roman Kamnik; Jian Qing Shi; Roderick Murray-Smith; Tadej Bajd

    2005-01-01

    This paper presents analysis of the standing-up manoeuvre in paraplegia considering the body supportive forces as a potential feedback source in functional electrical stimulation (FES)-assisted standing-up. The analysis investigates the significance of arm, feet, and seat reaction signals to the human body center-of-mass (COM) trajectory reconstruction. The standing-up behavior of eight paraplegic subjects was analyzed, measuring the motion kinematics and

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

    Microsoft Academic Search

    Ken Inoue

    2005-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  19. AP5Z1/SPG48 frequency in autosomal recessive and sporadic spastic paraplegia

    PubMed Central

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

    2014-01-01

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

  20. 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

  1. TDP-43 Pathology in a Case of Hereditary Spastic Paraplegia with a NIPA1/SPG6 Mutation

    PubMed Central

    Martinez-Lage, Maria; Molina-Porcel, Laura; Falcone, Dana; McCluskey, Leo; Lee, Virginia M.-Y.; Van Deerlin, Vivianna M.; Trojanowski, John Q.

    2012-01-01

    Mutations in NIPA1 (non-imprinted in Prader-Willi/Angelman syndrome) have been described as a cause of autosomal dominant hereditary spastic paraplegia (HSP) known as SPG6 (spastic paraplegia-6). We present the first neuropathological description of a patient with a NIPA1 mutation, and clinical phenotype of complicated HSP with motor neuron disease-like syndrome and cognitive decline. Postmortem examination revealed degeneration of lateral corticospinal tracts and dorsal columns with motor neuron loss. TDP-43 immunostaining showed widespread spinal cord and cerebral skein-like and round neuronal cytoplasmic inclusions. We ruled out NIPA1 mutations in 419 additional cases of motor neuron disease. These findings suggest that hereditary spastic paraplegia due to NIPA1 mutations could represent a TDP-43 proteinopathy. PMID:22302102

  2. Assessment of intraoperative motor evoked potentials for predicting postoperative paraplegia in thoracic and thoracoabdominal aortic aneurysm repair

    Microsoft Academic Search

    Toshinori HoriuchiMasahiko; Masahiko Kawaguchi; Satoki Inoue; Hironobu Hayashi; Ryuichi Abe; Nobuoki Tabayashi; Shigeki Taniguchi; Hitoshi Furuya

    2011-01-01

    Purpose  Monitoring motor evoked potentials (MEPs) has been recognized as a highly reliable method to detect intraoperative spinal\\u000a cord ischemia (SCI) in aortic repair. However, the data regarding the sensitivity and specificity of MEPs for predicting postoperative\\u000a paraplegia are limited. We retrospectively assessed the value of intraoperative MEP amplitudes for predicting postoperative\\u000a paraplegia.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  The medical records of 44 patients were reviewed.

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

    Microsoft Academic Search

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

    2009-01-01

    Purpose  To evaluate the quality of life (QoL) and self-esteem of paraplegic persons.\\u000a \\u000a \\u000a \\u000a Methods  The sample consisted of 60 outpatients with traumatic paraplegia living in São Paulo, Brazil, from whom clinical and demographic\\u000a data were obtained. QoL was assessed by the 36-item Short-Form (SF-36) health survey questionnaire, and self-esteem was measured\\u000a by Rosenberg’s Self-Esteem (RSE) scale. Statistical analysis was performed using Student’s

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

    Microsoft Academic Search

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

    2011-01-01

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

  6. Exome sequencing is a useful diagnostic tool for complicated forms of hereditary spastic paraplegia.

    PubMed

    Bettencourt, C; López-Sendón, J L; García-Caldentey, J; Rizzu, P; Bakker, I M C; Shomroni, O; Quintáns, B; Dávila, J R; Bevova, M R; Sobrido, M-J; Heutink, P; de Yébenes, J G

    2014-02-01

    Hereditary spastic paraplegias constitute a heterogeneous group of neurodegenerative diseases encompassing pure and complicated forms, for which at least 52 loci and 31 causative genes have been identified. Although mutations in the SPAST gene explain approximately 40% of the pure autosomal dominant forms, molecular diagnosis can be challenging for the sporadic and recessive forms, which are often complicated and clinically overlap with a broad number of movement disorders. The validity of exome sequencing as a routine diagnostic approach in the movement disorder clinic needs to be assessed. The main goal of this study was to explore the usefulness of an exome analysis for the diagnosis of a complicated form of spastic paraplegia. Whole-exome sequencing was performed in two Spanish siblings with a neurodegenerative syndrome including upper and lower motor neuron, ocular and cerebellar signs. Exome sequencing revealed that both patients carry a novel homozygous nonsense mutation in exon 15 of the SPG11 gene (c.2678G>A; p.W893X), which was not found in 584 Spanish control chromosomes. After many years of follow-up and multiple time-consuming genetic testing, we were able to diagnose these patients by making use of whole-exome sequencing, showing that this is a cost-efficient diagnostic tool for the movement disorder specialist. PMID:23438842

  7. Structural basis of microtubule severing by the hereditary spastic paraplegia protein spastin

    PubMed Central

    Roll-Mecak, Antonina; Vale, Ronald D.

    2010-01-01

    Spastin, the most common locus for mutations in hereditary spastic paraplegias1, and katanin are related microtubule-severing AAA ATPases2–6 involved in constructing neuronal7–10 and noncentrosomal7,11 microtubule arrays and in segregating chromosomes12,13. The mechanism by which spastin and katanin break and destabilize microtubules is unknown, in part owing to the lack of structural information on these enzymes. Here we report the X-ray crystal structure of the Drosophila spastin AAA domain and provide a model for the active spastin hexamer generated using small-angle X-ray scattering combined with atomic docking. The spastin hexamer forms a ring with a prominent central pore and six radiating arms that may dock onto the microtubule. Helices unique to the microtubule-severing AAA ATPases surround the entrances to the pore on either side of the ring, and three highly conserved loops line the pore lumen. Mutagenesis reveals essential roles for these structural elements in the severing reaction. Peptide and antibody inhibition experiments further show that spastin may dismantle microtubules by recognizing specific features in the carboxy-terminal tail of tubulin. Collectively, our data support a model in which spastin pulls the C terminus of tubulin through its central pore, generating a mechanical force that destabilizes tubulin–tubulin interactions within the microtubule lattice. Our work also provides insights into the structural defects in spastin that arise from mutations identified in hereditary spastic paraplegia patients. PMID:18202664

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

    PubMed

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

    2013-10-01

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

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

    PubMed Central

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

    2013-01-01

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

  10. 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…

  11. [A case of thoracic disc herniation with sudden onset paraplegia on toilet straining: case report].

    PubMed

    Yano, Shunsuke; Hida, Kazutoshi; Seki, Toshitaka; Iwasaki, Yoshinobu; Akino, Minoru; Saitou, Hisatoshi

    2003-12-01

    Thoracic disc herniation is less common rather than cervical or lumbar herniation. Cases of sudden onset without trauma are especially rare. Generally, the neurological onset of disc herniation is caused by mechanical cord compression due to a protruded disc, and its onset is usually gradual. Ischemia is also considered as a factor of neurological onset. We report a case of a 78-year-old male with sudden paraplegia while straining at the toilet. T2 weighted MR image on admission showed mild disc protrusion at the level of Th8-9 and intramedullary high signal intensity below the Th8-9 level. We speculate that Valsalva-like maneuver had led to the congestion of vertebral venous plexus or compression of the anterior spinal artery, and spinal ischemia occurred. PMID:14719443

  12. Acute Paraplegia Secondary to Thoracic Disc Herniation of the Adjacent Segment Following Thoracolumbar Fusion and Instrumentation

    PubMed Central

    Assaker, Richard; Musharrafieh, Ramzi Sharif

    2013-01-01

    Proximal junctional disease is a well-recognized postoperative phenomenon in adults who are undergoing long thoracolumbar fusion and instrumentation, and is attributed to increased a junctional stress concentration. In general, the onset of symptoms in these patients is insidious and the disease progresses slowly. We report on a contrary case of rapidly progressing paraplegia secondary to acute disc herniation at the proximal adjacent segment after long posterior thoracolumbar fusion with cement augmentation at the upper instrumented vertebra and the supra-adjacent vertebra. The patient was treated with a discectomy through the costo-transverse approach combined with extension of the posterior instrumentation. The patient's neurological status improved markedly. Stress concentration at the proximal junction disc space may have caused accelerated disc degeneration which in turn lead to this complication. PMID:23508671

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

    PubMed

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

    2007-07-01

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

  14. [Spontaneous spinal epidural haematoma causing rapid flaccid paraplegia in a healthy 25-year-old patient].

    PubMed

    Colsy, M; Argote, C; Raimbault, M; Touchard, P

    2007-06-01

    Although clinical presentation of a spinal epidural compressive haematoma is well recognized, causing acute radicular pain shortly followed by cord compression syndrome, its aetiology may pose a quandary. Rare and most commonly seen after trauma, spinal surgery, epidural anaesthesia, anticoagulation therapy, vascular malformation or coagulopathy (haemophilia), spinal epidural haematoma (SHE) can be spontaneous. Surgical decompression remains the mainstay treatment especially when the prognosis depends on the interval to surgery and the severity of preoperative neurological deficit. We report the case of a healthy 25-year-old man who presented, three days after an acute back pain, a flaccid paraplegia with urinary retention. Magnetic resonance imaging of the spinal column identified a compressive SHE extending from T3 to T6, requiring an early laminectomy. After decompression, clinical outcome revealed a complete recovery excepted some mild sensibility trouble remains. PMID:17462853

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

    SciTech Connect

    Fink, J.K.; Wu, C.B.; Jones, S.M.; Lesicki, A.; Reinglass, T. [Univ. of Michigan, Ann Arbor, MI (United States); Sharp, G.B.; Lange, B.M. [Arkansas Children`s Hospital, Little Rock, AR (United States); Varvil, T.; Otterud, B.; Leppert, M. [Univ. of Utah, Salt Lake City, UT (United States)

    1995-01-01

    Autosomal dominant, uncomplicated familial spastic paraplegia (FSP) is a genetically heterogeneous disorder characterized by insidiously progressive lower-extremity spasticity. Recently, a locus on chromosome 14q was shown to be tightly linked with the disorder in one of three families. We performed linkage analysis in a kindred with autosomal dominant uncomplicated FSP. After excluding the chromosome 14q locus, we observed tight linkage of the disorder to a group of markers on chromosome 15q (maximum two-point lod score 9.70; {theta} = .05). Our results clearly establish the existence of a locus for autosomal dominant FSP in the centromeric region of chromosome 15q. Comparing clinical and genetic features in FSP families linked to chromosome 14q with those linked to chromosome 15q may provide insight into the pathophysiology of this disorder. 34 refs., 1 fig., 1 tab.

  16. 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

  17. Spastic paraplegia type 7 is associated with multiple mitochondrial DNA deletions.

    PubMed

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

    2014-01-01

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

  18. 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

  19. Spastic Paraplegia Type 7 Is Associated with Multiple Mitochondrial DNA Deletions

    PubMed Central

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

    2014-01-01

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

  20. Lysosomal abnormalities in hereditary spastic paraplegia types SPG15 and SPG11

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    Hussain, Tahziba

    2014-01-01

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

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

    PubMed

    Fink, John K

    2013-09-01

    Hereditary spastic paraplegia (HSP) is a syndrome designation describing inherited disorders in which lower extremity weakness and spasticity are the predominant symptoms. There are more than 50 genetic types of HSP. HSP affects individuals of diverse ethnic groups with prevalence estimates ranging from 1.2 to 9.6 per 100,000. Symptoms may begin at any age. Gait impairment that begins after childhood usually worsens very slowly over many years. Gait impairment that begins in infancy and early childhood may not worsen significantly. Postmortem studies consistently identify degeneration of corticospinal tract axons (maximal in the thoracic spinal cord) and degeneration of fasciculus gracilis fibers (maximal in the cervico-medullary region). HSP syndromes thus appear to involve motor-sensory axon degeneration affecting predominantly (but not exclusively) the distal ends of long central nervous system (CNS) axons. In general, proteins encoded by HSP genes have diverse functions including (1) axon transport (e.g. SPG30/KIF1A, SPG10/KIF5A and possibly SPG4/Spastin); (2) endoplasmic reticulum morphology (e.g. SPG3A/Atlastin, SPG4/Spastin, SPG12/reticulon 2, and SPG31/REEP1, all of which interact); (3) mitochondrial function (e.g. SPG13/chaperonin 60/heat-shock protein 60, SPG7/paraplegin; and mitochondrial ATP6); (4) myelin formation (e.g. SPG2/Proteolipid protein and SPG42/Connexin 47); (5) protein folding and ER-stress response (SPG6/NIPA1, SPG8/K1AA0196 (Strumpellin), SGP17/BSCL2 (Seipin), "mutilating sensory neuropathy with spastic paraplegia" owing to CcT5 mutation and presumably SPG18/ERLIN2); (6) corticospinal tract and other neurodevelopment (e.g. SPG1/L1 cell adhesion molecule and SPG22/thyroid transporter MCT8); (7) fatty acid and phospholipid metabolism (e.g. SPG28/DDHD1, SPG35/FA2H, SPG39/NTE, SPG54/DDHD2, and SPG56/CYP2U1); and (8) endosome membrane trafficking and vesicle formation (e.g. SPG47/AP4B1, SPG48/KIAA0415, SPG50/AP4M1, SPG51/AP4E, SPG52/AP4S1, and VSPG53/VPS37A). The availability of animal models (including bovine, murine, zebrafish, Drosophila, and C. elegans) for many types of HSP permits exploration of disease mechanisms and potential treatments. This review highlights emerging concepts of this large group of clinically similar disorders. PMID:23897027

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

    PubMed Central

    Fink, John K.

    2014-01-01

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

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

    PubMed Central

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

    2006-01-01

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

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

    PubMed

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

    2006-01-01

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

  6. 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

  7. Spastic paraplegia, optic atrophy, and neuropathy: new observations, locus refinement, and exclusion of candidate genes.

    PubMed

    Macedo-Souza, Lúcia Inês; Kok, Fernando; Santos, Silvana; Licinio, Luciana; Lezirovitz, Karina; Cavaçana, Natale; Bueno, Clarissa; Amorim, Simone; Pessoa, André; Graciani, Zodja; Ferreira, Aurea; Prazeres, Abdísio; de Melo, Aurea Nogueira; Otto, Paulo Alberto; Zatz, Mayana

    2009-05-01

    SPOAN is an autosomal recessive neurodegenerative disorder which was recently characterized by our group in a large inbred Brazilian family with 25 affected individuals. This condition is clinically defined by: 1. congenital optic atrophy; 2. progressive spastic paraplegia with onset in infancy; and 3. progressive motor and sensory axonal neuropathy. Overall, we are now aware of 68 SPOAN patients (45 females and 23 males, with age ranging from 5 to 72 years), 44 of which are presented here for the first time. They were all born in the same geographic micro region. Those 68 patients belong to 43 sibships, 40 of which exhibit parental consanguinity. Sixty-one patients were fully clinically evaluated and 64 were included in the genetic investigation. All molecularly studied patients are homozygotes for D11S1889 at 11q13. This enabled us to reduce the critical region for the SPOAN gene from 4.8 to 2.3 Mb, with a maximum two point lod score of 33.2 (with marker D11S987) and of 27.0 (with marker D11S1889). Three genes located in this newly defined critical region were sequenced, but no pathogenic mutation was detected. The gene responsible for SPOAN remains elusive. PMID:19344448

  8. PMCA4 (ATP2B4) Mutation in Familial Spastic Paraplegia

    PubMed Central

    Tse, Zero Ho-Man; Kung, Michelle Hiu-Wai; Sham, Pak-Chung; Ho, Shu-Leong

    2014-01-01

    Familial spastic paraplegia (FSP) is a heterogeneous group of disorders characterized primarily by progressive lower limb spasticity and weakness. More than 50 disease loci have been described with different modes of inheritance. In this study, we identified a novel missense mutation (c.803G>A, p.R268Q) in the plasma membrane calcium ATPase (PMCA4, or ATP2B4) gene in a Chinese family with autosomal dominant FSP using whole-exome sequencing and confirmed with Sanger sequencing. This mutation co-segregated with the phenotype in the six family members studied and is predicted to be pathogenic when multiple deleteriousness predictions were combined. This novel R268Q mutation was not present in over 7,000 subjects in public databases, and over 1,000 Han Chinese in our database. Prediction of potential functional consequence of R268Q mutation on PMCA4 by computational modeling revealed that this mutation is located in protein aggregation-prone segment susceptible to protein misfolding. Analysis for thermodynamic protein stability indicated that this mutation destabilizes the PMCA4 protein structure with higher folding free energy. As PMCA4 functions to maintain neuronal calcium homeostasis, our result showed that calcium dysregulation may be associated with the pathogenesis of FSP. PMID:25119969

  9. How "healthy" is circuit resistance training following paraplegia? Kinematic analysis associated with shoulder mechanical impingement risk.

    PubMed

    Riek, Linda M; Ludewig, Paula M; Nawoczenski, Deborah A

    2013-01-01

    The purpose of the study was to determine whether wheelchair-based circuit resistance training (CRT) exercises place the shoulder at risk for mechanical impingement. Using a novel approach, we created a mechanical impingement risk score for each exercise by combining scapular and glenohumeral kinematic and exposure data. In a case series design, 18 individuals (25-76 yr old) with paraplegia and without substantial shoulder pain participated. The mean mechanical impingement risk scores at 45-60 degrees humerothoracic elevation were rank-ordered from lowest to highest risk as per subacromial mechanical impingement risk: overhead press (0.6 +/- 0.5 points), lat pulldown (1.2 +/- 0.5 points), chest press (2.4 +/- 2.8 points), row (2.7 +/- 1.6 points), and rickshaw (3.4 +/- 2.3 points). The mean mechanical impingement risk scores at 105-120 degrees humerothoracic elevation were rank-ordered from lowest to highest risk as per internal mechanical impingement risk: lat pulldown (1.2 +/- 0.5 points) and overhead press (1.3 +/- 0.5 points). In conclusion, mechanical impingement risk scores provided a mechanism to capture risk associated with CRT. The rickshaw had the highest subacromial mechanical risk, whereas the overhead press and lat pulldown had the highest internal mechanical impingement risk. The rickshaw was highlighted as the most concerning exercise because it had the greatest combination of magnitude and exposure corresponding with increased subacromial mechanical impingement risk. PMID:24030158

  10. Root cause analysis of paraplegia following transforaminal epidural steroid injections: the 'unsafe' triangle.

    PubMed

    Glaser, Scott E; Shah, Rinoo V

    2010-01-01

    The utilization rate of transforaminal epidural steroid injections (TFESIs), an elective diagnostic and therapeutic spinal procedure, has risen dramatically over the past decade. In 2006 alone, greater than 300,000 thoracolumbar TFESIs were performed on Medicare beneficiaries. Despite the purported superiority of the transforaminal route, compared to other modes of epidural injection, TFESIs are associated with potential hazards. The artery of Adamkiewicz (ARM) might enter any mid thoracic, lower thoracic, or lumbar foramen; the exact level, in a specific patient, will be unknown to the proceduralist. The authors propose that the "safe triangle" approach to transforaminal epidural injections is not safe (TFESIs). Injury to the ARM can lead to paraplegia, independent of operator skill or adjuvant safety initiatives (digital subtraction angiography, local anesthetic test dose). Injury to the ARM is a "black swan" event. The authors believe that catastrophic injury may be averted when performing TFESIs by avoiding the "un-safe," superoanterior triangle in the foramen and that transforaminal injections should be performed at the inferior aspect of the foramen, known as Kambin's triangle. PMID:20495587

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

    PubMed Central

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

    2012-01-01

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

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

    SciTech Connect

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

    1997-03-01

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

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

    SciTech Connect

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

    1994-09-01

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

  14. Interaction between AP-5 and the hereditary spastic paraplegia proteins SPG11 and SPG15

    PubMed Central

    Hirst, Jennifer; Borner, Georg H. H.; Edgar, James; Hein, Marco Y.; Mann, Matthias; Buchholz, Frank; Antrobus, Robin; Robinson, Margaret S.

    2013-01-01

    The AP-5 complex is a recently identified but evolutionarily ancient member of the family of heterotetrameric adaptor proteins (AP complexes). It is associated with two proteins that are mutated in patients with hereditary spastic paraplegia, SPG11 and SPG15. Here we show that the four AP-5 subunits can be coimmunoprecipitated with SPG11 and SPG15, both from cytosol and from detergent-extracted membranes, with a stoichiometry of ?1:1:1:1:1:1. Knockdowns of SPG11 or SPG15 phenocopy knockdowns of AP-5 subunits: all six knockdowns cause the cation-independent mannose 6-phosphate receptor to become trapped in clusters of early endosomes. In addition, AP-5, SPG11, and SPG15 colocalize on a late endosomal/lysosomal compartment. Both SPG11 and SPG15 have predicted secondary structures containing ?-solenoids related to those of clathrin heavy chain and COPI subunits. SPG11 also has an N-terminal, ?-propeller–like domain, which interacts in vitro with AP-5. We propose that AP-5, SPG15, and SPG11 form a coat-like complex, with AP-5 involved in protein sorting, SPG15 facilitating the docking of the coat onto membranes by interacting with PI3P via its FYVE domain, and SPG11 (possibly together with SPG15) forming a scaffold. PMID:23825025

  15. Carcinoid tumor mistaken for persistent neurogenic bowel symptoms in a patient with paraplegia: a case report.

    PubMed

    Poduri, K R; Schnitzer, E M

    2001-07-01

    Neurogenic bowel in spinal cord injury (SCI) can present with constipation and diarrhea as ongoing problems. Usually, these manifestations are adequately controlled with modification in the bowel program. When these symptoms persist, other causes should be considered. This case report describes a jejunal carcinoid tumor with colonic extension that was diagnosed in a paraplegic patient with persistent constipation and diarrhea. A 39-year-old man sustained a T1 paraplegia with neurogenic bowel and bladder dysfunction from a gunshot wound. His bowels were initially managed adequately with digital disimpaction. Over the next 8 years, he had intermittent constipation that was managed with the addition of various suppositories. He then developed progressively worsening constipation, and other gastrointestinal (GI) symptoms. Although his symptoms initially resolved with medical management, the constipation worsened. Upper endoscopy revealed a submucosal bulge in the duodenal bulb. A month later, gallstones were found on renal ultrasound performed to evaluate recurrent urinary tract infections. He underwent cholecystectomy, but his GI symptoms persisted over the next several months. Repeat upper endoscopy subsequently revealed an ulcerated tumor at the duodenojejunal flexure. An upper-GI scan with small bowel follow through showed a proximal jejunal mass. The patient underwent laparotomy with resection of the mass. Final pathologic diagnosis was malignant carcinoid tumor. This case shows the importance of entertaining other clinical entities in patients with SCI when constipation and diarrhea persist despite adequate management. PMID:11441392

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

    PubMed Central

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

    2013-01-01

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

  17. A preliminary assessment of legged mobility provided by a lower limb exoskeleton for persons with paraplegia.

    PubMed

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

    2014-05-01

    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

  18. Cross-clamping of the thoracic aorta. Influence of aortic shunts, laminectomy, papaverine, calcium channel blocker, allopurinol, and superoxide dismutase on spinal cord blood flow and paraplegia in baboons.

    PubMed Central

    Svensson, L G; Von Ritter, C M; Groeneveld, H T; Rickards, E S; Hunter, S J; Robinson, M F; Hinder, R A

    1986-01-01

    There is a high incidence of paraplegia associated with thoracic aortic cross-clamping, even when cardiopulmonary bypass or shunts are used. In 56 adult baboons, spinal cord blood flow (SCBF), vascular anatomy, and paraplegia rates were evaluated. Tissue blood flow was measured by radioactive microspheres. Various procedures were used to increase SCBF and to prevent ischemia-reperfusion injury. It was found that the rate of paraplegia was inversely correlated with neural tissue ischemia (SCBF) and directly correlated with reperfusion hyperemia. Two methods completely prevented paraplegia. These two methods were a thoracic shunt with occlusion of the infrarenal aorta or cerebrospinal fluid drainage plus intrathecal papaverine injection, both of which were associated with an increased SCBF. Furthermore, papaverine dilated the anterior spinal artery (ASA) (p = 0.007) and increased the blood flow through the lower ASA. Whereas procedures utilizing a calcium channel blocker (flunarizine), allopurinol, superoxide dismutase (SOD), laminectomy alone, and a thoracoabdominal shunt not perfusing the arteria radicularis magna (ARM) all failed to prevent paraplegia, allopurinol (p = 0.026) and SOD (p = 0.004) did prevent gastric stress lesions, indicating that their failure to prevent paraplegia was not due to a lack of activity. Of great clinical interest is that, if a shunt is used and the ARM is perfused, infrarenal aortic cross-clamping increases SCBF, thus preventing paraplegia. Intrathecal application of papaverine proved to be even more effective in increasing SCBF and also completely prevented paraplegia. As this is a safer procedure than the insertion of shunts, this is the method of choice for the prevention of paraplegia associated with thoracic aortic cross-clamping. The preliminary trial using intrathecal papaverine in human beings has thus far shown no adverse side effects from the drug, and no paraplegia has occurred. PMID:3729582

  19. The effect of an anti-G suit on cardiovascular responses to exercise in persons with paraplegia.

    PubMed

    Hopman, M T; Oeseburg, B; Binkhorst, R A

    1992-09-01

    The purpose of this study was to determine whether external pressure on legs and abdomen could prevent venous blood pooling in persons with paraplegia and thus positively affect their cardiovascular responses to arm exercise. To investigate this, five male subjects with paraplegia (P), with complete lesions between T6 and T12, and five male control subjects who were wheelchair bound (C) (due to a chronic lower extremity disability), performed submaximal arm-cranking exercise at 20%, 40%, and 60% of their maximal power output (Wmax), with and without an antigravity (anti-G) suit inflated to 52 mm Hg (1 psi). For P, higher preexercise systolic pressure (127 vs 117 mm Hg) was seen with the anti-G suit. At 40 and 60% Wmax, significantly lower heart rates (at 40% = 5.7%; at 60% = 10.6%) at similar cardiac outputs were seen for P with an anti-G suit. Although not significant, P also demonstrated higher stroke volumes at 40% (4.8%) and 60% (5.0%) Wmax with external pressure. For C, no differences in preexercise blood pressure or cardiovascular responses at all three exercise levels were seen with or without the anti-G suit. These data suggest that an inflated anti-G suit is able to prevent venous blood pooling and offers hemodynamic benefits in persons with paraplegia during submaximal arm-cranking exercise. In addition, this study reports a possible alternative to hosiery or functional neuromuscular stimulation that could be applied to all subjects with spinal cord injuries regardless of type or duration of the lesion or of muscle-atrophy. PMID:1406199

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

    PubMed Central

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

    2011-01-01

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

  1. Paraplegia complicating selective steroid injections of the lumbar spine. Report of five cases and review of the literature

    Microsoft Academic Search

    Marc Wybier; Sandrine Gaudart; David Petrover; Emmanuel Houdart; Jean-Denis Laredo

    2010-01-01

    Background  Selective steroid injections of the lumbar spine carry a risk of paraplegia of sudden onset. Seven cases have been reported\\u000a in the English literature since 2002.\\u000a \\u000a \\u000a \\u000a Materials and methods  Five new cases have been analyzed, all coming from Paris area centers. Injections were performed between 2003 and 2008. The\\u000a following items were searched for: location of a previous lumbar spine surgery

  2. A pregnant woman with metastatic papillary thyroid carcinoma and paraplegia: Multiple considerations involved in the management.

    PubMed

    Basu, Sandip; Kand, Purushottam

    2011-01-01

    A 35 years old primigravida hailing from a humble, rural background with no previous history related to thyroid carcinoma, presented with acute paraparesis at the last trimester of pregnancy and was diagnosed to harbor metastatic papillary thyroid carcinoma (PTC) following magnetic resonance imaging (MRI) of the spine with guided biopsy, which demonstrated near complete collapse of D5 and D10 vertebral bodies with altered signal on the D4 to D6 and D9 to D11 vertebral bodies, in addition to a gravid uterus and a large goiter. There was also evidence of bilateral nodular lesions in the lung parenchyma and a fairly large hepatic lesion in segment 8 of the liver . Histopathology revealed metastatic follicular variant of thyroid papillary carcinoma. This case with challenging presentation had multiple issues to be resolved during its management: a) acute paraparesis and the requirement of radioiodine ((131)I) treatment soon after total thyroidectomy, b) her first valuable pregnancy that required to be managed successfully, c) the poor general condition, d) the abstinence from iodine containing medications, in relation to the Cesarean section planned, e) the timing of total thyroidectomy, f) postnatal care of the newborn and g) radioprotective measures. All were important considerations in the management of this patient. Iodine restricted diet and medications were recommended and were communicated to the obstetricians involved in the patient. The patient underwent Cesarean section and total thyroidectomy at the same sitting. The newborn baby was healthy and was started on artificial feeding. Recombinant TSH primed protocol was not considered immediately in view of a major surgery being undertaken and the poor general condition, so that the patient would not require frequent support during the isolation period. In the first 3 weeks of the postoperative period, she was put on T3 substitution and after a 2 weeks gap was given (131)I and whole body diagnostic scan was undertaken 48h after the administration of (131)I scan dose. Both the diagnostic and post (131)I treatment scan demonstrated multiple foci of (131)I uptake in the skeleton, lungs and liver. Following discharge from the isolation ward, adequate separation from the infant was ensured and the childcare was undertaken by relatives. The patient had a remarkable improvement clinically. During the next 3-½ years she was treated 2 more times with (131)I with cumulative doses of about 25.9GBq. The last post-treatment scan is depicted in. She has been presently ambulatory with complete resolution of paraplegia and a significantly better quality of life without any requirement of support, despite the presence of extensive skeletal disease. A recent review entitled "Approach to the pregnant patient with thyroid cancer", addresses this topic as a separate category. Similar emphasis has also been given by other authors while dealing with these patients. In our experience, patients with PTC metastatic lesions in the vertebrae show better response compared to those with large flat bone metastases likely related to the small size of the former. In conclusion, a teamwork of surgeons, obstetricians, nuclear medicine physicians as well as the strong support by the relatives, was necessary to favorably treat this patient with metastatic PTC, paraplegia and pregnancy. PMID:22087461

  3. 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

  4. Evaluation of loss of function as an explanation for SPG4-based hereditary spastic paraplegia

    PubMed Central

    Solowska, Joanna M.; Garbern, James Y.; Baas, Peter W.

    2010-01-01

    The spectrum of mutations (missense, non-sense and splice-site) associated with hereditary spastic paraplegia 4 (HSP-SPG4) (SPG4:OMIM#182601) has suggested that this autosomal dominant disease results from loss of function. Because the protein encoded by SPG4, termed spastin, is a microtubule-severing enzyme, a loss-of-function scenario for the disease suggests that corticospinal axons degenerate due to inadequate microtubule severing resulting from inactivation of one spastin allele. Lending more complexity to the situation, there are two major isoforms of spastin (M1 and M87) translated from two start codons. M87 is widely expressed, while M1 is appreciably detected only in adult spinal cord. Here, we focused on four HSP-associated mutations of the SPG4 gene located outside of the AAA region essential for microtubule severing. We found that none of these mutations affected the enzymatic activity or expression levels of either M1 or M87. Three of the mutations resulted in dominant-negative activity of M1. Surprisingly, the S44L mutation, which is asymptomatic when present heterozygously, conferred dominant-negative activity, while the E112K mutation, which is symptomatic when present heterozygously, did not. Clinical symptoms reported for patients carrying the dominant-negative mutations L195V or 46Stop are not more severe than those reported for patients carrying the non-dominant-negative E112K mutation. These results indicate that there are cases of HSP-SPG4 that cannot be explained by insufficient spastin microtubule-severing activity. PMID:20430936

  5. Evaluation of loss of function as an explanation for SPG4-based hereditary spastic paraplegia.

    PubMed

    Solowska, Joanna M; Garbern, James Y; Baas, Peter W

    2010-07-15

    The spectrum of mutations (missense, non-sense and splice-site) associated with hereditary spastic paraplegia 4 (HSP-SPG4) (SPG4:OMIM#182601) has suggested that this autosomal dominant disease results from loss of function. Because the protein encoded by SPG4, termed spastin, is a microtubule-severing enzyme, a loss-of-function scenario for the disease suggests that corticospinal axons degenerate due to inadequate microtubule severing resulting from inactivation of one spastin allele. Lending more complexity to the situation, there are two major isoforms of spastin (M1 and M87) translated from two start codons. M87 is widely expressed, while M1 is appreciably detected only in adult spinal cord. Here, we focused on four HSP-associated mutations of the SPG4 gene located outside of the AAA region essential for microtubule severing. We found that none of these mutations affected the enzymatic activity or expression levels of either M1 or M87. Three of the mutations resulted in dominant-negative activity of M1. Surprisingly, the S44L mutation, which is asymptomatic when present heterozygously, conferred dominant-negative activity, while the E112K mutation, which is symptomatic when present heterozygously, did not. Clinical symptoms reported for patients carrying the dominant-negative mutations L195V or 46Stop are not more severe than those reported for patients carrying the non-dominant-negative E112K mutation. These results indicate that there are cases of HSP-SPG4 that cannot be explained by insufficient spastin microtubule-severing activity. PMID:20430936

  6. 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.

  7. Mutations in the ER-shaping protein reticulon 2 cause the axon-degenerative disorder hereditary spastic paraplegia type 12

    PubMed Central

    Montenegro, Gladys; Rebelo, Adriana P.; Connell, James; Allison, Rachel; Babalini, Carla; D’Aloia, Michela; Montieri, Pasqua; Schüle, Rebecca; Ishiura, Hiroyuki; Price, Justin; Strickland, Alleene; Gonzalez, Michael A.; Baumbach-Reardon, Lisa; Deconinck, Tine; Huang, Jia; Bernardi, Giorgio; Vance, Jeffery M.; Rogers, Mark T.; Tsuji, Shoji; De Jonghe, Peter; Pericak-Vance, Margaret A.; Schöls, Ludger; Orlacchio, Antonio; Reid, Evan; Züchner, Stephan

    2012-01-01

    Hereditary spastic paraplegias (HSPs) are a group of genetically heterogeneous neurodegenerative conditions. They are characterized by progressive spastic paralysis of the legs as a result of selective, length-dependent degeneration of the axons of the corticospinal tract. Mutations in 3 genes encoding proteins that work together to shape the ER into sheets and tubules — receptor accessory protein 1 (REEP1), atlastin-1 (ATL1), and spastin (SPAST) — have been found to underlie many cases of HSP in Northern Europe and North America. Applying Sanger and exome sequencing, we have now identified 3 mutations in reticulon 2 (RTN2), which encodes a member of the reticulon family of prototypic ER-shaping proteins, in families with spastic paraplegia 12 (SPG12). These autosomal dominant mutations included a complete deletion of RTN2 and a frameshift mutation predicted to produce a highly truncated protein. Wild-type reticulon 2, but not the truncated protein potentially encoded by the frameshift allele, localized to the ER. RTN2 interacted with spastin, and this interaction required a hydrophobic region in spastin that is involved in ER localization and that is predicted to form a curvature-inducing/sensing hairpin loop domain. Our results directly implicate a reticulon protein in axonopathy, show that this protein participates in a network of interactions among HSP proteins involved in ER shaping, and further support the hypothesis that abnormal ER morphogenesis is a pathogenic mechanism in HSP. PMID:22232211

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

    PubMed Central

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

    2012-01-01

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

  9. Characterization of Alu and recombination-associated motifs mediating a large homozygous SPG7 gene rearrangement causing hereditary spastic paraplegia.

    PubMed

    López, Eva; Casasnovas, Carlos; Giménez, Javier; Matilla-Dueñas, Antoni; Sánchez, Ivelisse; Volpini, Víctor

    2015-04-01

    Spastic paraplegia type 7 (SPG7) is one of the most common forms of autosomal recessive hereditary spastic paraplegia (AR-HSP). Although over 77 different mutations have been identified in SPG7 patients, only 9 gross deletions have been reported with only a few of them being fully characterized. Here, we present a detailed description of a large homozygous intragenic SPG7 gene rearrangement involving a 5144-base pair (bp) genomic loss (c. 1450-446_1779?+?746 delinsAAAGTGCT) encompassing exons 11 to 13, identified in a Spanish AR-HSP family. Analysis of the deletion junction sequences revealed that the 5' breakpoint of this SPG7 gene deletion was located within highly homologous Alu sequences where the 3' breakpoint appears to be flanked by the core crossover hotspot instigator (chi)-like sequence (GCTGG). Furthermore, an 8-bp (AAAGTTGCT) conserved sequence at the breakpoint junction was identified, suggesting that the most likely mechanism for the occurrence of this rearrangement is by Alu microhomology and chi-like recombination-associated motif-mediated multiple exon deletion. Our results are consistent with non-allelic homologous recombination and non-homologous end joining in deletion mutagenesis for the generation of rearrangements. This study provides more evidence associating repeated elements as a genetic mechanism underlying neurodegenerative disorders, highlighting their importance in human diseases. PMID:25398481

  10. Novel SPAST deletion and reduced DPY30 expression in a Spastic Paraplegia type 4 kindred

    PubMed Central

    2014-01-01

    Background The hereditary spastic paraplegias (HSPs) are pleiomorphic disorders of motor pathway and a large number of affected genes have been discovered. Yet, mutations in SPG4/SPAST represent the most frequent molecular etiology in autosomal dominant (AD) patients and sporadic cases. We describe a large, AD-HSP Sardinian family where 5 out of several living members harbored a novel deletion affecting also the 5?UTR of SPAST and resulting in reduced expression of DPY30, the gene located upstream SPAST in a head-to-head manner. Case presentation A 54-year-old woman manifested leg stiffness at age 39 and required a cane to walk at age 50. Neurological examination disclosed mild spasticity and weakness in the legs, hyperreflexia in all limbs, and bilateral Babinski sign. She also complained of urinary urgency, but no additional neurological symptoms or signs were detected at examination. The clinical examination of 24 additional relatives disclosed three further affected individuals, two men and one woman. In the four symptomatic patients the initial manifestations were walking abnormalities and leg stiffness with a mean age at onset (SD) of 46.75 (5.44) years (range 39–51). The mean disease duration was 13.2 (13.4) years (range 6–35), and it correlated well with clinical severity (SPRS score) (r?=?0.975, p?=?0.005). One patient was confined to bed and displayed knee and ankle contractures, another case needed a cane to walk, and two individuals were able to walk without aids. Interestingly, a patient had also had a miscarriage during her first pregnancy. Gene testing revealed an heterozygous deletion spanning from the 5?-UTR to intron 4 of SPAST in the affected individuals and in one clinically unaffected woman. In three affected patients, the deletion also determined low mRNA levels of SPAST and DPY30, a component of the Set1-like multiprotein histone methyltransferase complex located upstream, head-to-head with SPAST. Conclusion Together with data described in a Japanese family, our findings seem to suggest that genes close to spastin might be candidates in modulating the clinical phenotype. This report endorses future research on the role of neighboring genes as potential players in SPG4 disease variability. PMID:24690193

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-01-01

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

  13. [Central necrosis of the lumbo-sacral segment of the spinal cord associated with multiple cholesterin emboli, clinically presenting as acute paraplegia].

    PubMed

    Yoshimura, M; Uchigata, M; Shimizu, S; Sakamoto, T; Murayama, S

    2000-10-01

    A seventy-six-year-old man suddenly suffered from paraplegia and pain in both legs. He had been maintained on hemodialysis and committed a suicide attempt by cutting the shunt at the paraplegic attack. He was brought to the emergency ward for the treatment of hemorrhagic preshock. Neurological examination demonstrated flaccid paraplegia, loss of tendon reflex in the lower extremities, dissociated sensory loss below the fourth lumbar level; and incontinence in defecation. MRI showed T2 shortening in the ventral spinal cord caudal below the level of the eleventh thoracic cord. Postmortem examination confirmed ischemic infarct in the central area of the spinal cord, associated with disseminated cholesterin emboli in the small arteries. This case was the first MRI demonstration of central necrosis caused by cholesterin emboli, and may emphasize the significance of cholesterin emboli in the spinal arterial disorders in the aged. PMID:11296370

  14. Decreased expression of the mitochondrial matrix proteases Lon and ClpP in cells from a patient with hereditary spastic paraplegia (SPG13)

    Microsoft Academic Search

    J. Hansen; T. J. Corydon; J. Palmfeldt; A. Dürr; B. Fontaine; M. N. Nielsen; J. H. Christensen; N. Gregersen; P. Bross

    2008-01-01

    The mitochondrial chaperonin heat shock protein 60 (Hsp60) assists the folding of a subset of proteins localized in mitochondria and is an essential component of the mitochondrial protein quality control system. Mutations in the HSPD1 gene that encodes Hsp60 have been identified in patients with an autosomal dominant form of hereditary spastic paraplegia (SPG13), a late-onset neurodegenerative disorder characterized by

  15. The effect of lower body positive pressure on the cardiovascular response to exercise in sedentary and endurance-trained persons with paraplegia

    Microsoft Academic Search

    Roger Kaprielian; Michael J. Plyley; Panagiota Klentrou; Leonard S. Goodman; Jack M. Goodman

    1998-01-01

    Exercise intolerance in persons with paraplegia (PARAS) is thought to be secondary to insufficient venous return and a subnormal\\u000a cardiac output at a given oxygen uptake. However, these issues have not been resolved fully. This study utilized lower-body\\u000a positive pressure (LBPP) as an intervention during arm crank exercise in PARAS in order to examine this issue. Endurance-trained\\u000a (TP, n= 7)

  16. Endogenous spar tin, mutated in hereditary spastic paraplegia, has a complex subcellular localization suggesting diverse roles in neurons

    SciTech Connect

    Robay, Dimitri [Medical Genetics, St. George's, University of London, Cranmer Terrace, London SW17 0RE (United Kingdom); Patel, Heema [Medical Genetics, St. George's, University of London, Cranmer Terrace, London SW17 0RE (United Kingdom); Simpson, Michael A. [Medical Genetics, St. George's, University of London, Cranmer Terrace, London SW17 0RE (United Kingdom); Brown, Nigel A. [Basic Medical Sciences, St. George's, University of London, Cranmer Terrace, London SW17 0RE (United Kingdom); Crosby, Andrew H. [Medical Genetics, St. George's, University of London, Cranmer Terrace, London SW17 0RE (United Kingdom)]. E-mail: acrosby@sgul.ac.uk

    2006-09-10

    Mutation of spartin (SPG20) underlies a complicated form of hereditary spastic paraplegia, a disorder principally defined by the degeneration of upper motor neurons. Using a polyclonal antibody against spartin to gain insight into the function of the endogenous molecule, we show that the endogenous molecule is present in two main isoforms of 85 kDa and 100 kDa, and 75 kDa and 85 kDa in human and murine, respectively, with restricted subcellular localization. Immunohistochemical studies on human and mouse embryo sections and in vitro cell studies indicate that spartin is likely to possess both nuclear and cytoplasmic functions. The nuclear expression of spartin closely mirrors that of the snRNP (small nuclear ribonucleoprotein) marker {alpha}-Sm, a component of the spliceosome. Spartin is also enriched at the centrosome within mitotic structures. Notably we show that spartin protein undergoes dynamic positional changes in differentiating human SH-SY5Y cells. In undifferentiated non-neuronal cells, spartin displays a nuclear and diffuse cytosolic profile, whereas spartin transiently accumulates in the trans-Golgi network and subsequently decorates discrete puncta along neurites in terminally differentiated neuroblastic cells. Investigation of these spartin-positive vesicles reveals that a large proportion colocalizes with the synaptic vesicle marker synaptotagmin. Spartin is also enriched in synaptic-like structures and in synaptic vesicle-enriched fraction.

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

    PubMed Central

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

    2010-01-01

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

  18. 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

  19. Full body gait analysis may improve diagnostic discrimination between hereditary spastic paraplegia and spastic diplegia: a preliminary study.

    PubMed

    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 but not the upper-body, where numerous compensations during walking occur. The aim of this study was to compare the full-body movements of HSP and SD groups and, in particular, the movement of the upper limbs. Ten HSP and 12 SD patients were evaluated through a CGA (VICON 460 and Mx3+; ViconPeak(®), Oxford, UK) between 2008 and 2012. The kinematic parameters were computed using the ViconPeak(®) software (Plug-In-Gait). In addition, the mean amplitude of normalised (by the patient's height) arm swing was calculated. All patients were asked to walk at a self-selected speed along a 10-m walkway. The mean kinematic parameters for the two populations were analysed with Mann-Whitney comparison tests, with a significant P-value set at 0.05. The results demonstrated that HSP patients used more spine movement to compensate for lower limb movement alterations, whereas SD patients used their arms for compensation. SD patients had increased shoulder movements in the sagittal plane (Flexion/extension angle) and frontal plane (elevation angle) compared to HSP patients. These arm postures are similar to the description of the guard position that toddlers exhibit during the first weeks of walking. To increase speed, SD patients have larger arm swings in the sagittal, frontal and transversal planes. Upper-body kinematics, and more specifically arm movements and spine movements, may support the differential diagnosis of HSP and SD. PMID:23085499

  20. Identification of the SPG15 Gene, Encoding Spastizin, as a Frequent Cause of Complicated Autosomal-Recessive Spastic Paraplegia, Including Kjellin Syndrome

    PubMed Central

    Hanein, Sylvain; Martin, Elodie; Boukhris, Amir; Byrne, Paula; Goizet, Cyril; Hamri, Abdelmadjid; Benomar, Ali; Lossos, Alexander; Denora, Paola; Fernandez, José; Elleuch, Nizar; Forlani, Sylvie; Durr, Alexandra; Feki, Imed; Hutchinson, Michael; Santorelli, Filippo M.; Mhiri, Chokri; Brice, Alexis; Stevanin, Giovanni

    2008-01-01

    Hereditary spastic paraplegias (HSPs) are genetically and phenotypically heterogeneous disorders. Both “uncomplicated” and “complicated” forms have been described with various modes of inheritance. Sixteen loci for autosomal-recessive “complicated” HSP have been mapped. The SPG15 locus was first reported to account for a rare form of spastic paraplegia variably associated with mental impairment, pigmented maculopathy, dysarthria, cerebellar signs, and distal amyotrophy, sometimes designated as Kjellin syndrome. Here, we report the refinement of SPG15 to a 2.64 Mb genetic interval on chromosome 14q23.3-q24.2 and the identification of ZFYVE26, which encodes a zinc-finger protein with a FYVE domain that we named spastizin, as the cause of SPG15. Six different truncating mutations were found to segregate with the disease in eight families with a phenotype that included variable clinical features of Kjellin syndrome. ZFYVE26 mRNA was widely distributed in human tissues, as well as in rat embryos, suggesting a possible role of this gene during embryonic development. In the adult rodent brain, its expression profile closely resembled that of SPG11, another gene responsible for complicated HSP. In cultured cells, spastizin colocalized partially with markers of endoplasmic reticulum and endosomes, suggesting a role in intracellular trafficking. PMID:18394578

  1. Hypokalemic Paraplegia in Pregnancy

    PubMed Central

    TV, Srividya; Gopal, N

    2014-01-01

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

  2. Hypokalemic paraplegia in pregnancy.

    PubMed

    Kulkarni, Maitri; Tv, Srividya; Gopal, N

    2014-06-01

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

  3. Hereditary Spastic Paraplegia

    MedlinePLUS

    ... vision due to cataracts and problems with the optic nerve and retina of the eye, ataxia (lack ... identified which underlie various forms of HSP, and specialized genetic testing and diagnosis are available at some ...

  4. Acute paraplegia after chiropraxis

    Microsoft Academic Search

    Antonio Lopez-Gonzalez; Maria Peris-Celda

    2011-01-01

    Spinal manipulation is a form of back and other musculoskeletal pain treatment that often involves a high-velocity thrust,\\u000a a technique in which the joints are adjusted rapidly. The main objective of chiropractors is to correct spinal malalignment\\u000a and relieve the nerves, allowing them to function optimally (Ernst In: Expert Rev Neurother 7:1451–1452, 2007; Oppenheim et al. In: Spine J 5:660–666,

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

    PubMed

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

    2014-12-15

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

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

    PubMed Central

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

    2012-01-01

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

  7. The EAAT2 (GLT-1) gene in motor neuron disease: absence of mutations in amyotrophic lateral sclerosis and a point mutation in patients with hereditary spastic paraplegia

    PubMed Central

    Meyer, T.; Munch, C.; Volkel, H.; Booms, P.; Ludolph, A.

    1998-01-01

    OBJECTIVES—To investigate if sequence alterations of the excitatory amino acid transporter gene EAAT2 (GLT-1) may be a contributory factor to the pathogenesis of motor system degeneration. EAAT2 serves as a candidate gene as its reduced expression was reported in patients with amyotrophic lateral sclerosis (ALS). Furthermore, neurolathyrism, a motor neuron disease clinically related to hereditary spastic paraplegia (HSP), has been associated with an exogenous excitotoxin.?METHODS—Sequence alterations were screened for in the coding region of EAAT2 in 55 patients with ALS and one family with autosomal dominant HSP (AD-HSP).?RESULTS—In ALS, no sequence alteration in the EAAT2 gene have been found. Interestingly, a heterozygous A79G mutation of the EAAT2 gene was detected in two of seven affected patients with AD-HSP in the same kindred. The absence of cosegregation with the familial disease showed that the detected variant was not the cause of disease. The A79G sequence variant was not found in 55 patients with ALS or in 50 non-neurological controls.?CONCLUSION—The allelic variant of the EAAT2 gene in conjunction with the primary gene defect may be a modifying factor for the highly variable AD-HSP phenotype.?? PMID:9771796

  8. Decreased expression of the mitochondrial matrix proteases Lon and ClpP in cells from a patient with hereditary spastic paraplegia (SPG13).

    PubMed

    Hansen, J; Corydon, T J; Palmfeldt, J; Dürr, A; Fontaine, B; Nielsen, M N; Christensen, J H; Gregersen, N; Bross, P

    2008-05-01

    The mitochondrial chaperonin heat shock protein 60 (Hsp60) assists the folding of a subset of proteins localized in mitochondria and is an essential component of the mitochondrial protein quality control system. Mutations in the HSPD1 gene that encodes Hsp60 have been identified in patients with an autosomal dominant form of hereditary spastic paraplegia (SPG13), a late-onset neurodegenerative disorder characterized by a progressive paraparesis of the lower limbs. The disease-associated Hsp60-(p.Val98Ile) protein, encoded by the c.292G>A HSPD1 allele, has reduced chaperonin activity, but how its expression affects mitochondrial functions has not been investigated. We have studied mitochondrial function and expression of genes encoding mitochondrial chaperones and proteases in a human lymphoblastoid cell line and fibroblast cells from a patient who is heterozygous for the c.292G>A HSPD1 allele. We found that both the c.292G>A RNA transcript and the corresponding Hsp60-(p.Val98Ile) protein were present at comparable levels to their wild-type counterparts in SPG13 patient cells. Compared with control cells, we found no significant cellular or mitochondrial dysfunctions in SPG13 patient cells by assessing the mitochondrial membrane potential, cell viability, and sensitivity toward oxidative stress. However, a decreased expression of the mitochondrial protein quality control proteases Lon and ClpP, both at the RNA and protein level, was demonstrated in SPG13 patient cells. We propose that decreased levels of mitochondrial proteases Lon and ClpP may allow Hsp60 substrate proteins to go through more folding attempts instead of being prematurely degraded, thereby supporting productive folding in cells with reduced Hsp60 chaperonin activity. In conclusion, our studies with SPG13 patient cells expressing the functionally impaired mutant Hsp60 chaperonin suggest that reduction of the degradative activity of the protein quality control system may represent a previously unrecognized cellular adaptation to reduced chaperone function. PMID:18378094

  9. 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

  10. Paraplegia following lumbosacral steroid epidural injections.

    PubMed

    AbdeleRahman, Kader Tawfiq; Rakocevic, Goran

    2014-09-01

    Spinal cord ischemia is a rare but possible neurological complication following routine conservative treatment of lumbosacral radiculopathy. A case of a 46 year old woman with chronic L5 radiculopathy, who developed spinal cord ischemia following epidural steroid injection, is reported. Two months after the epidural injection, she required crutches for walking and had neurogenic bladder and bowel. PMID:25200706

  11. 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 ...

  12. [Primary amyloidosis of the spine presenting with acute paraplegia].

    PubMed

    Ajlani, H; Zaouia, K; Chtourou, A; Elleuch, M; Bellil, S; Sellami, S

    2008-09-01

    Primary amylosis is rarely located in bone, exceptionally in the spine. The radiographic presentation is polymorphous. Magnetic resonance imaging is currently the best imaging technique. Spinal amyloidosis can exceptionally lead to cord compression requiring rapid surgical release. PMID:18774025

  13. Circuit resistance training in persons with complete paraplegia

    Microsoft Academic Search

    Patrick L. Jacobs; Edward T. Mahoney; Mark S. Nash; Barth A. Green

    Abstract—Background\\/Objective: We assessed the metabolic and heart rate (HR) responses to a ,single session of circuit resistance training (CRT) in six subjects with complete ,para- plegia (T5–T12levels) in order to determine the caloric cost of the exercise. Methods: Subjects underwent ,isoinertial weight training exercises with interspersed periods of high-cadence, low-resistance arm ergometry (AE). Following protocol famil- iarization, subjects completed one

  14. Study of Proper Tuning of Prosthetic Limb Control System with Paraplegia and Fatigue Condition

    Microsoft Academic Search

    Biswarup Neogi; Rajkumar Darbar; Subrata Mondal; Baidyanath Gorai; Sinchan Ghosh; Achintya Das; D. N. Tibarewala

    2011-01-01

    Prosthetic Control in living system is an ever- growing important phenomenon in today's world. The artificial limb thus is required to be well connected to the concerned nervous system which is in immediate contact with the limb concerned, and finally to the brain system which constitutes the overall control of the total living system including that artificially generated limb. This

  15. 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

  16. 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

  17. The Experience of Four Individuals with Paraplegia Enrolled in an Outpatient Interdisciplinary Sexuality Program

    Microsoft Academic Search

    Marika J. Hess; Sigmund Hough; Elizabeth Tammaro

    2007-01-01

    Spinal cord injury has a significant impact on an individual’s physical, emotional, as well as sexual functioning. Four consecutive\\u000a males with spinal cord injury were referred to the outpatient spinal cord injury sexuality program at an urban Veterans Affairs\\u000a Medical Center and seen by an interdisciplinary team comprised of a nurse, physician and psychologist. They felt that their\\u000a questions had

  18. Management of Marjolin's ulcer in a chronic pressure sore secondary to paraplegia: a radical surgical solution.

    PubMed

    Fairbairn, Neil G; Hamilton, Stuart A

    2011-10-01

    Marjolin's ulcer refers to malignant degeneration in a chronic wound. Although originally described in an area of burns scar, many other chronic wounds such as osteomyelitis sinus tracts, venous stasis ulcers and chronic pressure sores have the potential to undergo malignant transformation. We present an interesting case of malignant degeneration in a male paraplegic patient with chronic sacral and ischial pressure sores. By discussing our radical surgical solution to this problem, we aim to highlight the importance of prompt diagnosis. PMID:21827630

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

    PubMed

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

    1986-10-01

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

  20. Sexual adjustment and quality of relationships in spinal paraplegia: A controlled study

    Microsoft Academic Search

    Margareta Kreuter; Marianne Sullivan; Agneta Siösteen

    1996-01-01

    Objective: To identify determinants of sexual adjustment by persons with spinal cord injury (SCI) and quality of the relationship compared with persons in the general populationDesign: Controlled survey.Setting: Postdischarge community setting.Participants: A consecutive series of 252 persons admitted to our spinal unit between November 1982 and July 1991 with traumatic SCI were contacted, 85 of whom persons were excluded: 36

  1. Correlation between neurological recovery and magnetic resonance imaging in Pott's paraplegia

    PubMed Central

    Gupta, Anil Kumar; Kumar, Chandan; Kumar, Praveen; Verma, Ashok Kumar; Nath, Rohit; Kulkarni, Chaitanya D

    2014-01-01

    Background: Spinal cord/nerve root compression secondary to a tubercular epidural abscess leads to neurological deficit. Depending on the extent and duration of compression, the end result after treatment may vary from complete recovery to permanent deficit. ASIA has been used extensively to correlate between MRI and neurological status due to traumatic spine injuries. MRI has stood as an invaluable diagnostic tool out of the entire range of current imaging modalities. However, inspite of considerable literature on the applications of MRI in spinal tuberculosis, there have been few studies to assess the relationship between the MRI findings and the neurological deficit as assessed by clinical examination. Aims: The objective of this study was to ascertain whether the findings of magnetic resonance imaging (MRI) correlate well with the actual neurological recovery status using the American Spinal Injury Association impairment scale (ASIA) in patients with spinal compression secondary to tuberculous spondylitis. Materials and Methods: 60 patients (mean age 43.6 years) diagnosed as spinal tuberculosis by MRI/cytology/histopathology were examined and classified into ASIA impairment scale A-E based on the ASIA and again reclassified after 6 months of therapy to assess functional recovery. Similarly, they underwent MR imaging at the start and at the completion of 6 months of therapy to assess the structural recovery. The MRI features of recovery were correlated with the actual neurological recovery as ascertained by the ASIA. Results: Before starting treatment 1 patient (2.08%) was in ASIA A, 2 (4.16%) were in ASIA B, 9 (18.75%) were in ASIA C, 36 (75%) were in ASIA D and 12 (20%) were in ASIA E. There was a significant difference in the epidural abscess thickness, thecal compression and cord compression between ambulatory (ASIA D and ASIA E) and non ambulatory patients (ASIA A, ASIA B and ASIA C). After 6 months of therapy 30 (90%) patients in ASIA D and 5 (55.5%) in ASIA C had complete neurological recovery. Both patients from ASIA B improved to ASIA D. Single patient who was in ASIA A before treatment remained non ambulatory (ASIA C) after treatment. Overall 33 (78.5%) patients showed complete recovery at final followup. Out of all the MRI features, only size of epidural abscess was found to be a poor prognostic factor for recovery of neurological deficit. Conclusions: There are several parameters on MRI which correlate with the severity of neurological impairment according to ASIA score and resolution of those features on treatment is also correlated well with neurological recovery. PMID:25143639

  2. [Experiences and results in primary management of patients with traumatic paraplegia].

    PubMed

    Pätzug, P

    1989-01-01

    In the years from 1980 to 1987 124 patients in the age of 12 to 87 years suffering from traumatico-spinal cord injuries were treated in the County Hospital of Dresden-Friedrichstadt. The average of age amounts 36.1 years. Our level of medical attendance as to non-operative as well as operative treatment of the spinal injury including the providence of typical complications and the results are displayed here. The letality of the whole group was 25%. The analysis is displayed in the groups of age, by the localisations of the spinal injury and by the causes of death. PMID:2741577

  3. Development of a tissue-engineered composite implant for treating traumatic paraplegia in rats

    Microsoft Academic Search

    S. Rochkind; A. Shahar; D. Fliss; D. El-Ani; L. Astachov; T. Hayon; M. Alon; R. Zamostiano; O. Ayalon; I. E. Biton; Y. Cohen; R. Halperin; D. Schneider; A. Oron; Z. Nevo

    2006-01-01

    This study was designed to assess a new composite implant to induce regeneration of injured spinal cord in paraplegic rats following complete cord transection. Neuronal xenogeneic cells from biopsies of adult nasal olfactory mucosa (NOM) of human origin, or spinal cords of human embryos, were cultured in two consecutive stages: stationary cultures in a viscous semi-solid gel (NVR-N-Gel) and in

  4. Intramedullary Hemorrhage in a Neonate After Lumbar Puncture Resulting in Paraplegia: A Case Report

    Microsoft Academic Search

    R. S. Tubbs; M. D. Smyth; J. C. Wellons; W. J. Oakes

    2004-01-01

    ABSTRACT. We present the case of a premature infant with decreased spontaneous movement of the lower ex- tremities. Imaging was demonstrative of a lesion of the conus medullaris. Operatively and with histologic con- firmation, the mass was determined to be a blood clot originating from the conus. Retrospectively, the patient had a known lumbar puncture. There were no clotting abnormalities

  5. Incomplete paraplegia following use of heroin: a case report and review of the literature

    Microsoft Academic Search

    Stamatios A. Papadakis; Eleni C. Bambourda; Stefanos Papadakis; Michalis Minas; George Sapkas

    2004-01-01

    Neurological complications involving the lumbar spine following intravenous injection of heroin was observed in a 28-year-old man. On admission, steroids were administrated, and the patient had a complete recovery after an interval of 2 days. There have been more than 46 cases reported in the literature with similar findings to the one presented here. The mechanism of neuropathology of heroin

  6. Thoracic vertebral hemangioma causing paraplegia in Klippel-Trenaunay-Weber syndrome: case report.

    PubMed

    Okutan, Ozerk; Yildirim, Timur; Isik, Serdar; Gokce, Berna; Saygili, Bar?s; Konakli, Ethem Bes

    2013-01-01

    Vertebral hemangiomas are the most common tumours of the vertebral column. Generally, these tumours are asymptomatic but some patients complain of back pain and develop neurologic symptoms due to extraosseous extension. Vertebral hemangiomas can extend extradurally causing neurological impairment as a result of compression of the spinal cord and nerve roots. Vertebral hemangiomas may be multiple and detectable as a component of the Klippel-Trenaunay-Weber syndrome. Although this syndrome consists of deep venous thrombosis, lymphatic anomalies, cutaneous capillary malformations, and hypertrophy of soft tissue and bone on extremities, its clinical presentation may be very variable. We present a unique case of vertebral hemangioma causing spinal cord compression due to the extradural extension that also had deep venous thrombosis, hematuria, hypophyseal cyst and ventricle asymmetry, diagnosed as the Klippel-Trenaunay-Weber syndrome. PMID:24101274

  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. 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…

  9. Interference of different types of seats on postural control system during a forward-reaching task in individuals with paraplegia.

    PubMed

    de Abreu, Daniela Cristina Carvalho; Takara, Kelly; Metring, Nathália Lopes; Reis, Júlia Guimarães; Cliquet, Alberto

    2012-09-01

    We aimed to evaluate the influence of different types of wheelchair seats on paraplegic individuals' postural control using a maximum anterior reaching test. Balance evaluations during 50, 75, and 90% of each individual's maximum reach in the forward direction using two different cushions on seat (one foam and one gel) and a no-cushion condition were carried out on 11 individuals with a spinal cord injury (SCI) and six individuals without SCI. Trunk anterior displacement and the time spent to perform the test were assessed. No differences were found for the three types of seats in terms of trunk anterior displacement and the time spent to perform the test when intragroup comparisons were made in both groups (P>0.05). The intergroup comparison showed that body displacement was less prominent and the time spent to perform the test was more prolonged for individuals with SCI (P<0.05), which suggests a postural control deficit. The seat type did not affect the ability of the postural control system to maintain balance during the forward-reaching task. PMID:22517377

  10. 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

  11. A decentralized adaptive fuzzy robust strategy for control of upright standing posture in paraplegia using functional electrical stimulation.

    PubMed

    Kobravi, Hamid-Reza; Erfanian, Abbas

    2012-01-01

    In this paper, we present a novel decentralized robust methodology for control of quiet upright posture during arm-free paraplegic standing using functional electrical stimulation (FES). Each muscle-joint complex is considered as a subsystem and individual controllers are designed for each one. Each controller operates solely on its associated subsystem, with no exchange of information between them, and the interaction between the subsystems are taken as external disturbances. In order to achieve robustness with respect to external disturbances, unmodeled dynamics, model uncertainty and time-varying properties of muscle-joint dynamics, a robust control framework is proposed. The method is based on the synergistic combination of an adaptive nonlinear compensator with sliding mode control (SMC). Fuzzy logic system is used to represent unknown system dynamics for implementing SMC and an adaptive updating law is designed for online estimating the system parameters such that the global stability and asymptotic convergence to zero of tracking errors is guaranteed. The proposed controller requires no prior knowledge about the dynamics of system to be controlled and no offline learning phase. The results of experiments on three paraplegic subjects show that the proposed control strategy is able to maintain the vertical standing posture using only FES control of ankle dorsiflexion and plantarflexion without using upper limbs for support and to compensate the effect of external disturbances and muscle fatigue. PMID:21764350

  12. Oscillatory firing of single human sphincteric alpha 2 and alpha 3-motoneurons reflexly activated for the continence of urinary bladder and rectum. Restoration of bladder function in paraplegia.

    PubMed

    Schalow, G

    1991-09-01

    1. By recording with 2 pairs of wire electrodes from human sacral nerve roots (S3-S5) rhythmic as well as occasional firing was observed in alpha 2 and alpha 3-motoneurons in response to physiologic stimulation of the urinary bladder and the anal canal. The rhythmic firing consisted of periodically occurring impulse trains, most likely produced by true spinal oscillators which drove the motoneurons. 2. Alpha 2-motoneurons, innervating fast fatigue-resistant muscle fibres, were observed to fire with impulse trains of about 2 to 4 action potentials (Ap's). These impulse trains occurred every 110 to 170 msec (5-9 Hz). Alpha 3-motoneurons, innervating slow fatigue-resistant muscle fibres, fired about every 1400 msec (approximately 0.7 Hz) with impulse trains of about 11 to 60 Ap's. Alpha 1-motoneurons, innervating fast fatigue muscle fibres, and gamma-motoneurons were not observed in the continuous oscillatory firing mode. 3. Sphincteric motoneurons were observed most likely in the oscillatory firing mode in response to the sustained stretch (reflex) of the external and sphincter or to retrograde filling of the bladder (urethro-sphincteric guarding reflex), in order to preserve continence. A urethral sphincteric alpha 2-motoneuron increased its mean activity from 0.5 to 18 Ap's/sec during retrograde filling by changing its firing pattern from the occasional spike mode via the transient oscillatory firing mode to the continuous oscillatory mode. Up to a filling of the bladder of 500 ml the mean activity of the stretch receptors, measuring probably mural tension, increased roughly proportionally and the sphincteric motoneuron increased its activity to about 1 Ap/sec in the occasional spike mode. Up to 600 ml, the motoneuron responded in the transient oscillatory mode with mean activities of up to 5 Ap's/sec. With higher bladder fillings, the flow receptors afferents fired additionally, probably according to pressure symptoms, and the motoneuron switched into the continuous oscillatory firing mode and increased its activity up to 18 Ap's/sec at 700 ml. When the bladder was about 800 ml full, the stretch afferent activity decreased, the flow receptor activity increased strongly and the alpha 2-motoneuron activity decreased; the overflow incontinence had probably started. Micturition was not observed, probably because of brain death. 4. It is suggested that one adequate stimulus for an alpha 2-motoneuron of the external anal sphincter to jump into the oscillatory firing mode, was the activity from secondary spindle afferent (SP2) fibres from external anal sphincter muscle spindles.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1935758

  13. Spinal cord compression due to primary intramedullary tuberculoma of the spinal cord presenting as paraplegia: A case report and literature review

    PubMed Central

    Mishra, Sudhansu Sekhar; Das, Deepak; Das, Srikanta; Mohanta, Itibrata; Tripathy, Soubhagya Ranjan

    2015-01-01

    Background: Spinal cord compression can be due to various causes but spinal intramedullary tuberculoma is a rare cause. We report a case that had an intramedullary spinal cord tuberculomas in which the diagnosis was made histologically, without evidence of symptoms of systemic tuberculosis. This lesion, located in the thoracic region, mimicked as an intramedullary tumor radiologically. Case Description: The patient was a 25-year-old male who presented with a history of progressive paraparesis. Initial diagnosis was made as an intramedullary tumor by magnetic resonance imaging (MRI). The treatment of the patient involved is complete surgical excision of intramedullary lesion followed by appropriate antituberculous therapy. Postoperatively, his neurological symptoms were dramatically improved. With combination of both surgical and medical treatments, excellent clinical outcome was obtained. Conclusion: This case illustrates the risk of misdiagnosis and the importance of histological confirmation of a pathological lesion as spinal cord tuberculoma prior to surgical therapy, which should be kept in mind as a differential diagnosis of the intramedullary spinal cord tumors.

  14. Relationships of oxygen uptake, heart rate, and ratings of perceived exertion in persons with paraplegia during functional neuromuscular stimulation assisted ambulation

    Microsoft Academic Search

    Patrick L Jacobs; K John Klose; Rosalind Guest; Belinda Needham-Shropshire; James G Broton; Barth A Green

    1997-01-01

    Previous reports have described significant limitations in the daily use of functional neuromuscular stimulation (FNS) ambulation systems by persons with spinal cord injuries (SCI). The potential application of these devices to provide physiological benefits as an exercise modality has prompted a reconsideration of the technology. However, the acute physiological effects related to the use of FNS systems have not been

  15. 38 CFR 17.44 - Hospital care for certain retirees with chronic disability (Executive Orders 10122, 10400 and...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...psychiatric disorders, poliomyelitis with residuals, neurological disabilities, diseases of the nervous system, severe injuries to the nervous system, including quadriplegia, hemiplegia and paraplegia, tuberculosis, blindness and...

  16. 38 CFR 17.44 - Hospital care for certain retirees with chronic disability (Executive Orders 10122, 10400 and...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...psychiatric disorders, poliomyelitis with residuals, neurological disabilities, diseases of the nervous system, severe injuries to the nervous system, including quadriplegia, hemiplegia and paraplegia, tuberculosis, blindness and...

  17. 38 CFR 17.44 - Hospital care for certain retirees with chronic disability (Executive Orders 10122, 10400 and...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...psychiatric disorders, poliomyelitis with residuals, neurological disabilities, diseases of the nervous system, severe injuries to the nervous system, including quadriplegia, hemiplegia and paraplegia, tuberculosis, blindness and...

  18. 38 CFR 17.44 - Hospital care for certain retirees with chronic disability (Executive Orders 10122, 10400 and...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...psychiatric disorders, poliomyelitis with residuals, neurological disabilities, diseases of the nervous system, severe injuries to the nervous system, including quadriplegia, hemiplegia and paraplegia, tuberculosis, blindness and...

  19. 38 CFR 17.44 - Hospital care for certain retirees with chronic disability (Executive Orders 10122, 10400 and...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...psychiatric disorders, poliomyelitis with residuals, neurological disabilities, diseases of the nervous system, severe injuries to the nervous system, including quadriplegia, hemiplegia and paraplegia, tuberculosis, blindness and...

  20. 34 CFR 350.5 - What definitions apply?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...arthritis, autism, blindness, burn injury, cancer, cerebral palsy, cystic fibrosis, deafness, head injury, heart disease, hemiplegia...paraplegia, quadriplegia, other spinal cord impairments, sickle cell...

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

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...arthritis, autism, blindness, burn injury, cancer, cerebral palsy, cystic fibrosis, deafness, head injury, heart disease, hemiplegia...paraplegia, quadriplegia and other spinal cord conditions, sickle-cell...

  2. Localised necrosis of scrotum (Fournier's gangrene) in a spinal cord injury patient – a case report

    Microsoft Academic Search

    Subramanian Vaidyanathan; Bakul M Soni; Peter L Hughes; Paul Mansour; Gurpreet Singh; James Darroch; Tun Oo

    2002-01-01

    BACKGROUND: Men with spinal cord injury (SCI) appear to have a greater incidence of bacterial colonisation of genital skin as compared to neurologically normal controls. We report a male patient with paraplegia who developed rapidly progressive infection of scrotal skin, which resulted in localised necrosis of scrotum (Fournier's gangrene). CASE PRESENTATION: This male patient developed paraplegia at T-8 level 21

  3. TICK PARALYSIS IN A WESTERN HARVEST MOUSE (Reithrodontomys megalotis)

    Microsoft Academic Search

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

    1980-01-01

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

  4. Tick paralysis in a western harvest mouse.

    PubMed

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

    1980-04-01

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

  5. Genetics Home Reference: Dandy-Walker syndrome

    MedlinePLUS

    ... contains the cerebellum and the brainstem, called the posterior fossa, is abnormally large. These abnormalities often result ... neurological ; palsy ; paraplegia ; pattern of inheritance ; polydactyly ; population ; posterior ; sporadic ; syndactyly ; syndrome ; teratogens ; tissue ; trisomy ; urogenital tract ; ...

  6. Opportuni)es for Change The Role of Medical Professionals in

    E-print Network

    flu" ­ Chronic illness: renal, cardiac & lung disease, arthri=s, bipolar disorder, cancer, HIV ­ Fixed loss: blindness, amputa=on, paraplegia, mental retarda=on, malforma history · Supervisor never called: "They will handle it" · Weak supervisor · Teasing by co

  7. 16 CFR 1116.2 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...to any degree or with any residual disorder (e.g. epilepsy), and brain or brain stem injury including coma and spinal cord injuries; (v) Paraplegia, quadriplegia, or permanent paralysis or paresis, to any degree; (vi)...

  8. 16 CFR 1116.2 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...to any degree or with any residual disorder (e.g. epilepsy), and brain or brain stem injury including coma and spinal cord injuries; (v) Paraplegia, quadriplegia, or permanent paralysis or paresis, to any degree; (vi)...

  9. 16 CFR 1116.2 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...to any degree or with any residual disorder (e.g. epilepsy), and brain or brain stem injury including coma and spinal cord injuries; (v) Paraplegia, quadriplegia, or permanent paralysis or paresis, to any degree; (vi)...

  10. 16 CFR 1116.2 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...to any degree or with any residual disorder (e.g. epilepsy), and brain or brain stem injury including coma and spinal cord injuries; (v) Paraplegia, quadriplegia, or permanent paralysis or paresis, to any degree; (vi)...

  11. RESEARCH Open Access Implanted functional electrical stimulation: case

    E-print Network

    Paris-Sud XI, Université de

    RESEARCH Open Access Implanted functional electrical stimulation: case report of a paraplegic and Charles Fattal2 Abstract Backgrounds: Experience of an implanted functional electrical stimulation, Paraplegia, Gait, Functional electrical stimulation Background As reported in the literature, patients

  12. Genetics Home Reference: Troyer syndrome

    MedlinePLUS

    ... the degeneration and death of muscle cells and motor neurons (specialized nerve cells that control muscle movement) throughout a person's lifetime, leading to a slow progressive decline in muscle and nerve function. The ... nervous system ; paraparesis ; paraplegia ; peripheral ; ...

  13. Primary Lateral Sclerosis

    MedlinePLUS

    ... When symptoms begin, PLS may be mistaken for amyotrophic lateral sclerosis (ALS) or spastic paraplegia. Most neurologists follow an affected ... 1-877-773-4483) Fax: 877-SPF-GIVE ALS Association 1275 K Street, N.W. Suite 1050 ...

  14. RESEARCH PERSPECTIVE Grand Challenge Competition to Predict In Vivo Knee Loads

    E-print Network

    Delp, Scott

    mobility limitations and decreased quality of life. Computational models that accurately represent of life. Osteoarthritis, osteoporosis, stroke, cerebral palsy, and paraplegia are common clinical examples of Orthopaedics & Rehabilitation, University of Florida, Gainesville, Florida, 4 Auckland Bioengineering Institute

  15. 16 CFR 1116.2 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...one internal organ; (iv) Permanent brain injury to any degree or with any residual disorder (e.g. epilepsy), and brain or brain stem injury including coma and spinal cord injuries; (v) Paraplegia, quadriplegia, or...

  16. Post-exercise heart rate recovery in individuals with spinal cord injury

    Microsoft Academic Search

    J N Myers; L Hsu; D Hadley; M Y Lee; B J Kiratli

    2010-01-01

    Study design:Prospective comparison of spinal cord injured (SCI) subjects and ambulatory subjects.Objectives:To determine the effects of the presence and level of SCI on heart rate recovery (HRR).Setting:Outpatient SCI center.Methods:HRR was determined in 63 SCI subjects (26 with tetraplegia, 22 with high-level paraplegia, 15 with low-level paraplegia) and 26 ambulatory subjects. To adjust for differences in heart rate reserve between groups

  17. Effect of the free radical scavenger MCI186 on spinal cord reperfusion after transient ischemia in the rabbit

    Microsoft Academic Search

    Kenichi Hashizume; Toshihiko Ueda; Hideyuki Shimizu; Atsuo Mori; Ryohei Yozu

    2005-01-01

    Objective: Paraplegia remains a serious complication of aortic operations. The production of free radicals during reperfusion\\u000a after transient ischemia is believed to induce secondary spinal neuronal injury, resulting in paraplegia. The aim of the present\\u000a study was to clarify the protective effect and method of administration of antioxidants on the neurological and histological\\u000a outcome in the animal model for reperfusion

  18. 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

  19. Neurological Complications Following Endoluminal Repair of Thoracic Aortic Disease

    SciTech Connect

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

    2007-09-15

    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.

  20. Multimodal MRI-Based Study in Patients with SPG4 Mutations

    PubMed Central

    Rezende, Thiago J. R.; de Albuquerque, Milena; Lamas, Gustavo M.; Martinez, Alberto R. M.; Campos, Brunno M.; Casseb, Raphael F.; Silva, Cynthia B.; Branco, Lucas M. T.; D'Abreu, Anelyssa; Lopes-Cendes, Iscia; Cendes, Fernando; França, Marcondes C.

    2015-01-01

    Mutations in the SPG4 gene (SPG4-HSP) are the most frequent cause of hereditary spastic paraplegia, but the extent of the neurodegeneration related to the disease is not yet known. Therefore, our objective is to identify regions of the central nervous system damaged in patients with SPG4-HSP using a multi-modal neuroimaging approach. In addition, we aimed to identify possible clinical correlates of such damage. Eleven patients (mean age 46.0 ± 15.0 years, 8 men) with molecular confirmation of hereditary spastic paraplegia, and 23 matched healthy controls (mean age 51.4 ± 14.1years, 17 men) underwent MRI scans in a 3T scanner. We used 3D T1 images to perform volumetric measurements of the brain and spinal cord. We then performed tract-based spatial statistics and tractography analyses of diffusion tensor images to assess microstructural integrity of white matter tracts. Disease severity was quantified with the Spastic Paraplegia Rating Scale. Correlations were then carried out between MRI metrics and clinical data. Volumetric analyses did not identify macroscopic abnormalities in the brain of hereditary spastic paraplegia patients. In contrast, we found extensive fractional anisotropy reduction in the corticospinal tracts, cingulate gyri and splenium of the corpus callosum. Spinal cord morphometry identified atrophy without flattening in the group of patients with hereditary spastic paraplegia. Fractional anisotropy of the corpus callosum and pyramidal tracts did correlate with disease severity. Hereditary spastic paraplegia is characterized by relative sparing of the cortical mantle and remarkable damage to the distal portions of the corticospinal tracts, extending into the spinal cord. PMID:25658484

  1. Trainings- and Measurement System for FES- Cycling

    Microsoft Academic Search

    W. Reichenfelser; H. Hackl; S. Mina; S. Hanke; P. Lugner; M. Gföhler

    Due to Functional Electrical Stimulation (FES) of lower limb muscles persons with complete or incomplete paraplegia can perform a cycling movement. To quantify the progress of therapy and rehabilitation it is helpful to examine the induced forces during pedalling and the development of these forces over the period of rehabilita- tion. Therefore a trainings- and measurement- system for FES- cycling

  2. Hip angle induced modulation of H reflex amplitude, latency and duration in spinal cord injured humans

    E-print Network

    Abstract Objectives: To investigate the modulation of the soleus H reflex in spinal cord injured (SCI that imposing 108 of hip extension resulted in a significant facilitation in the size of the soleus H reflex. Keywords: Rehabilitation; Motor control; Muscle afferents; Paraplegia; Reflex modulation; Spasticity 1

  3. 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

  4. Journal of Neuroscience Methods 162 (2007) 198205 In vivo assay of presynaptic microtubule cytoskeleton

    E-print Network

    Broadie, Kendal S.

    ) and Fragile X Syndrome (FXS). However, previous studies have been restricted to indirect assays of synaptic, and the development and maintenance of synaptic transmission in both pre- and post-synaptic compartments (Barth et al neurological diseases, including Fragile X Syndrome (FXS) and Hereditary Spastic Paraplegia (HSP) (Huot et al

  5. A small de novo 16q24.1 duplication in a woman with severe clinical features Sylvia Qumner-Redon1,2

    E-print Network

    Brest, Université de

    with mental retardation, spastic paraplegia, severe epilepsy, a narrow and arched palate, malar hypoplasia.1, duplication, mental retardation, Array-CGH, QFM-PCR. inserm-00788405,version1-14Feb2013 #12;Introduction Chromosomal abnormalities are a major cause of mental retardation. Unbalanced karyotypes are estimated

  6. Cardiovascular consequences of loss of supraspinal control of the sympathetic nervous system after spinal cord injury

    Microsoft Academic Search

    Robert W. Teasell; J. Malcolm O. Arnold; Andrei Krassioukov; Gail A. Delaney

    2000-01-01

    Teasell RW, Arnold JMO, Krassioukov A, Delaney GA. Cardiovascular consequences of loss of supraspinal control of the sympathetic nervous system after spinal cord injury. Arch Phys Med Rehabil 2000;81:506-16. Spinal cord injury (SCI) with resultant quadriplegia or high paraplegia is associated with significant dysfunction of the sympathetic nervous system. This alteration of sympathetic nervous system activity occurs as a consequence

  7. Energetics in the pathogenesis of neurodegenerative diseases

    Microsoft Academic Search

    M. Flint Beal

    2000-01-01

    Mitochondria have been linked to both necrotic and apoptotic cell death, which are thought to have a major role in the pathogenesis of neurodegenerative diseases. Recent evidence shows that nuclear gene defects affecting mitochondrial function have a role in the pathogenesis of Friedreich’s ataxia, Wilson’s disease and hereditary spastic paraplegia. There is also accumulating evidence that mitochondrial dysfunction might have

  8. Pathophysiology of Hydrocephalus

    Microsoft Academic Search

    Giuseppe Cinalli; Pietro Spennato; Maria Consiglio Buonocore; Emilio Cianciulli; Matthieu Vinchon; Spyros Sgouros

    The three major clinical manifestations of spina bifida (hydrocephalus, paraplegia and urinary and bowel incontinence) are\\u000a easily observable and have been described since ancient times, though they were not described in relationship to spina bifida\\u000a until the seventeenth century [1].

  9. Genome Biology 2006, 7:301 commentreviewsreportsdepositedresearchinteractionsinformationrefereedresearch

    E-print Network

    of organisms, includ- ing Saccharomyces cerevisiae, Caenorhabditis elegans, Danio rerio, Drosophila melanogaster and humans. Chris Sanderson (University of Liverpool, UK) described how the focused application in hereditary spastic paraplegia, which is most commonly caused by mutations in the gene (SG4) for the protein

  10. Navigating a Robotic Wheelchair in a Railway Station during Rush Hour

    Microsoft Academic Search

    Erwin Prassler; Jens Scholz; Paolo Fiorini

    1999-01-01

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

  11. Influence of pre-exercise glucose ingestion of two concentrations on paraplegic athletes

    Microsoft Academic Search

    Owen Spendiff; Ian Campbell

    2005-01-01

    In this study, we assessed the influence that pre-exercise glucose ingestion of two concentrations has on the physiological responses of paraplegic athletes. Eight men with paraplegia ingested a drink containing 4% (low) or 11% (high) carbohydrate in a randomized double-blind crossover design, 20 min before exercise. The participants performed wheelchair exercise at 65% of peak oxygen uptake for 1 h

  12. The impact of assuming the primary caregiver role following traumatic spinal cord injury: An interpretative phenomenological analysis of the spouse's experience

    Microsoft Academic Search

    Adele Dickson; Grainne O’Brien; Richard Ward; David Allan; Ronan O’Carroll

    2010-01-01

    This study aimed to explore the lived experience of assuming the primary caregiver role in a group of spouses of individuals living with a traumatic spinal cord injury (SCI) (injuries ranged from paraplegia to quadriplegia). Individual in-depth interviews were conducted with 11 participants who were both the spouse and primary caregiver of an individual with a SCI; of these, 10

  13. Molecular pathways of oligodendrocyte apoptosis revealed by mutations in the proteolipid protein gene

    Microsoft Academic Search

    Cherie Southwood; Alexander Gow

    2001-01-01

    A decade after the genetic link was established between mutations in the proteo- lipid protein gene and two leukodystrophies, Pelizaeus-Merzbacher disease and spastic paraplegia, the molecular mechanisms underlying pathogenesis are beginning to come to light. Data from animal models of these diseases suggest that the absence of proteolipid protein gene products in the central nervous system confers a relatively mild

  14. 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).…

  15. 38 CFR 4.71a - Schedule of ratings-musculoskeletal system.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...for subpar. L. Code L-1 h, i (38 CFR 3.350(b)). Paraplegia with loss of use of both lower extremities and loss of anal and bladder sphincter control qualifies for subpar. O. Code O-2 (38 CFR 3.350(e)(2)). Where there are...

  16. 38 CFR 4.71a - Schedule of ratings-musculoskeletal system.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...for subpar. L. Code L-1 h, i (38 CFR 3.350(b)). Paraplegia with loss of use of both lower extremities and loss of anal and bladder sphincter control qualifies for subpar. O. Code O-2 (38 CFR 3.350(e)(2)). Where there are...

  17. 38 CFR 4.71a - Schedule of ratings-musculoskeletal system.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...for subpar. L. Code L-1 h, i (38 CFR 3.350(b)). Paraplegia with loss of use of both lower extremities and loss of anal and bladder sphincter control qualifies for subpar. O. Code O-2 (38 CFR 3.350(e)(2)). Where there are...

  18. Applying fuzzy logic to control cycling movement induced by functional electrical stimulation

    Microsoft Academic Search

    Jia-Jin J. Chen; Nan-Ying Yu; Ding-Gau Huang; Bao-Ting Ann; Gwo-Ching Chang

    1997-01-01

    This study examines the design of a rational stimulation pattern for electrical stimulation and a robust closed-loop control scheme to improve cycling system efficacy for subjects with paraplegia. The stimulation patterns were designed by analyzing gravitation potential needed for the cycling movement of the lower limbs against a frictionless cycling ergometer and the response delay of electrically stimulated muscles. To

  19. Mechanical and Aerospace Engineering

    E-print Network

    enhanced mobility and/or functionality for persons with lower limb loss, upper limb loss prosthesis for lower extremity amputees, the development of a multigrasp hand for upper extremity amputees, and the development of a lower limb exoskeleton for legged mobility assistance in individuals with paraplegia

  20. Identification of the Drosophila melanogaster homolog of the human spastin gene

    Microsoft Academic Search

    Lars Kammermeier; Jürg Spring; Michael Stierwald; Jean-Marc Burgunder; Heinrich Reichert

    2003-01-01

    The human SPG4 locus encodes the spastin gene, which is responsible for the most prevalent form of autosomal dominant hereditary spastic paraplegia (AD-HSP), a neurodegenerative disorder. Here we identify the predicted gene product CG5977 as the Drosophila homolog of the human spastin gene, with much higher sequence similarities than any other related AAA domain protein in the fly. Furthermore we

  1. The Fly as a Model for Neurodegenerative Diseases: Is It Worth the Jump?

    Microsoft Academic Search

    Ruben J. Cauchi; Marcel van den Heuvel

    2006-01-01

    Neurodegenerative diseases are responsible for agonizing symptoms that take their toll on the fragile human life. Aberrant protein processing and accumulation are considered to be the culprits of many classical neurodegenerative diseases such as Alzheimer’s disease, tauopathies, Parkinson’s disease, amyotrophic lateral sclerosis, hereditary spastic paraplegia and various polyglutamine diseases. However, recently it has been shown that toxic RNA species or

  2. 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,…

  3. Allan-Herndon syndrome. I. Clinical studies.

    PubMed Central

    Stevenson, R E; Goodman, H O; Schwartz, C E; Simensen, R J; McLean, W T; Herndon, C N

    1990-01-01

    A large family with X-linked mental retardation, originally reported in 1944 by Allan, Herndon, and Dudley, has been reinvestigated. Twenty-nine males have been affected in seven generations. Clinical features include severe mental retardation, dysarthria, ataxia, athetoid movements, muscle hypoplasia, and spastic paraplegia with hyperreflexia, clonus, and Babinski reflexes. The facies appear elongated with normal head circumference, bitemporal narrowing, and large, simple ears. Contractures develop at both small and large joint. Statural growth is normal and macroorchidism does not occur. Longevity is not impaired. High-resolution chromosomes, serum creatine kinase, and amino acids are normal. This condition, termed the Allan-Herndon syndrome, appears distinct from other X-linked disorders having mental retardation, muscle hypoplasia, and spastic paraplegia. Images Figure 2 Figure 3 PMID:2393019

  4. [Diagnosis and therapy of acute traumatic aortic rupture].

    PubMed

    Reidemeister, J C; Sadony, V; Rohm, N; Doetsch, N; Zerkowski, H R

    1990-01-01

    Aortic transection is defined as complete or partial dehiscence of the aortic wall layers. Aortic transections are seen in 16% of all lethal traffic accidents. The quality of the first emergency care outside hospital and the organization of rescue systems result in an increasing number of patients (espec. with life-threatening multiple injuries incl. atypical aortic lesions) reaching a trauma-center. Guide-lines for surgical indications are: 1. emergency-operation in case of symptomatic transection incl. simultaneous surgery of concommitant lesions. 2. Urgent operation following primary hemodynamic stabilisation in cases of isolated or asymptomatic transection. 3. In cases of concommitant lesions with surgical priority, delayed operation of asymptomatic transection. The perioperative letality claims up to 20%. Next of operative complication paraplegia remains the most deleterious problem. Despite different methods of protection on the spinal cord the incidence of paraplegia persists in the range of 5-10%. PMID:1983601

  5. Interscalene Regional Anesthesia in the Prevention of Autonomic Hyperreflexia in a Quadriplegic Patient Undergoing Shoulder Surgery

    Microsoft Academic Search

    Ali Habibi; Clifford Schmeising; J. C. Gerancher

    1999-01-01

    he patient was a 23-yr-old woman who had suf- fered a cervical spinal cord injury while playing basketball at age 16 yr. Her medical history was significant for C3-4 paraplegia and paralyzed right hemidiaphragm. She had a history of repeated epi- sodes of severe right upper extremity muscle spasms that sometimes woke her from sleep. The shoulder bruising that followed

  6. A preliminary study of reliability of impedance measurement to detect iatrogenic initial pedicle perforation (in the porcine model)

    Microsoft Academic Search

    Ciaran Bolger; C. Carozzo; T. Roger; Linda McEvoy; Jabir Nagaria; Gerard Vanacker; Maurice Bourlion

    2006-01-01

    Accidental perforation of the vertebral pedicle wall is a well-known complication associated with standard approach of pedicle\\u000a screw insertion. Depending on detection criteria, more than 20% of screws are reported misplaced. Serious clinical consequences,\\u000a from dysesthesia to paraplegia, although not common, may result from these misplaced screws. Many techniques have been described\\u000a to address this issue such as somatosensory evoked

  7. Surgical Repair of Retrograde Type A Aortic Dissection after Thoracic Endovascular Aortic Repair

    PubMed Central

    Kim, Chang-Young; Kim, Yeon Soo; Ryoo, Ji Yoon

    2014-01-01

    It is expected that the stent graft will become an alternative method for treating aortic diseases or reducing the extent of surgery; therefore, thoracic endovascular aortic repair has widened its indications. However, it can have rare but serious complications such as paraplegia and retrograde type A aortic dissection. Here, we report a surgical repair of retrograde type A aortic dissection that was performed after thoracic endovascular aortic repair. PMID:24570865

  8. Remote monitoring of sitting behaviors for community-dwelling manual wheelchair users with spinal cord injury

    Microsoft Academic Search

    Y-S Yang; G-L Chang; M-J Hsu; J-J Chang

    2009-01-01

    Study design:A case series study.Objectives:To describe the sitting behaviors in community-dwelling manual wheelchair users (MWUs) with spinal cord injury (SCI) by using a custom data logger and to compare the sitting time parameters between the groups with paraplegia and tetraplegia.Setting:Data were collected from the MWUs living in the community area of Kaohsiung, Taiwan.Methods:A custom data logger with six force sensor

  9. Reported pressure ulcer prevention and management techniques by persons with spinal cord injury

    Microsoft Academic Search

    Susan L. Garber; Diana H. Rintala; C. Don Rossi; Karen A. Hart; Marcus J. Fuhrer

    1996-01-01

    Objective: The purpose of this study was to identify factors that resulted in severe pressure ulcers in a community-based sample of 23 persons with spinal cord injury (SCI).Design: A correlational design was used.Subjects: Twenty men and three women, 57% with tetraplegia and 43% with paraplegia, participated. Adult participants with an ulcer of 12 weeks' duration or less were recruited from

  10. The neuroprotective effects of intrathecal administration of the selective N-type calcium channel blocker ziconotide in a rat model of spinal ischemia

    Microsoft Academic Search

    Lindsay H. Burns; Zhen Jin; S. Scott Bowersox

    1999-01-01

    Purpose: Spinal cord ischemia and resulting paraplegia represent a major complication associated with surgical repair of the thoracoabdominal aorta. Although the mechanism of spinal neuronal degeneration during ischemia is unclear, it may involve excessive calcium influx via N-type voltage-sensitive calcium channels (VSCCs). The neuroprotective capacity of intrathecal (IT) administration of the selective N-type VSCC blocker ziconotide, previously shown to be

  11. Three-dimensional kinematics of wheelchair propulsion

    Microsoft Academic Search

    S. S. Rao; E. L. Bontrager; J. K. Gronley; C. J. Newsam; J. Perry

    1996-01-01

    A three-dimensional (3-D biomechanical model was used to determine upper extremity kinematics of 16 male subjects with low-level paraplegia while performing wheelchair propulsion (WCP). A six-camera VICON motion analysis system was used to acquire the coordinate data of ten anatomic markers. Joint axes for the wrist and elbow were defined along with the planes of motion for the upper arm

  12. Propulsion patterns and pushrim biomechanics in manual wheelchair propulsion

    Microsoft Academic Search

    Michael L. Boninger; Aaron L. Souza; Rory A. Cooper; Shirley G. Fitzgerald; Alicia M. Koontz; Brian T. Fay

    2002-01-01

    Boninger ML, Souza AL, Cooper RA, Fitzgerald SG, Koontz AM, Fay BT. Propulsion patterns and pushrim biomechanics in manual wheelchair propulsion. Arch Phys Med Rehabil 2002;83:718-23. Objectives: To classify stroke patterns of manual wheelchair users and to determine if different patterns of propulsion lead to different biomechanics. Design: Case series. Setting: Biomechanics laboratory. Participants: Thirty-eight individuals with paraplegia who use

  13. Acute varicella-zoster virus ventriculitis and mengingo-myelo-radiculitis in acquired immunodeficiency syndrome

    Microsoft Academic Search

    F. Chrétien; F. Gray; M. C. Lescs; C. Geny; M. L. Dubreuil-Lemaire; F. Ricolfi; M. Baudrimont; Yo Levy; A. Sobel; H. V. Vinters

    1993-01-01

    A 30-year-old AIDS patient with no history of cutaneous eruption, presented with rapidly progressive flaccid paraplegia, hypoesthesia, urinary retention, moderate psychomotor slowing and fever (39.8°C), leading to death within 1 week. CD4 count was 290\\/mm3. Cerebrospinal fluid contained 210 white blood cells and 238 mg\\/100 ml protein. Neuropathology revealed HIV encephalitis and diffuse ventriculitis with Cowdry type A inclusions in

  14. Effect of spinal cord injury upon prostate: adenocarcinoma of prostate in a spinal cord injury patient - a case report

    Microsoft Academic Search

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

    2009-01-01

    INTRODUCTION: Following spinal cord injury, prostate undergoes atrophy probably due to interruption of neuro-hormonal pathways. The incidence of carcinoma of prostate is lower in patients with spinal cord injury above T-10 than in those with lesion below T-10. CASE PRESENTATION: A Caucasian male sustained T-4 paraplegia in 1991 at the age of 59-years. He had long-term indwelling urethral catheter. In

  15. Surgical outcome of posterior short segment trans-pedicle screw fixation for thoracolumbar fractures

    PubMed Central

    Khare, Shailendra; Sharma, Vijay

    2013-01-01

    Background Vast majority of spine fractures in thoracolumbar region are unstable and often associated with neurological deficit. With the advancement of technology, these fractures are now more often managed operatively. The present study aimed at evaluating the role of open reduction & internal fixation using pedicle screws and short segment fixation in patients with Thoracic and Lumbar spine fractures. Design In this prospective study, 25 patients in age group of 15–65 years (mean age 28.25 years) with thoracolumbar fractures with associated neurological deficit or compression fractures with loss of more than 50% vertebral height or angulations more than 20° with or without neurological deficit were included. The results were evaluated based on restoration and maintenance of vertebral body height, spinal lordosis/kyphosis and evaluation of the neurological recovery which was done at regular intervals using Frankel's grading. Results The mean follow-up period was 20.3 months. The average preoperative kyphotic angle as measured by Cobbs method was 20° which improved to 7.8° following instrumentation. The average preoperative vertebral height was 58.65% which improved to 78.55% postoperatively. Preoperatively, only 20% of patients had useful paraplegia (Frankel grade D and E) while 80% had useless paraplegia (Frankel's grade C and below). Following surgery, 60% patients had useful paraplegia while 40% had useless paraplegia. Conclusion Short segment trans-pedicle posterior fixation is helpful for not only stabilization of the fractures and restoration of anatomy, but also maintaining the same over a period with good functional outcome. PMID:24396235

  16. Acute spinal cord compression due to epidural lipomatosis complicated by an abscess: magnetic resonance and pathology findings

    PubMed Central

    Pipitone, Nicolò; De Carli, Nicola; Vecchia, Luigi; Bartoletti, Stefano C.

    2010-01-01

    A 68-year-old male presented with rapidly progressive paraplegia. MR images of the thoracic spine were interpreted as being consistent with an abscess within an epidural lipomatosis compressing the spinal cord. Laminectomy was performed, and a large amount of pus was drained from the epidural lipomatosis, from which Staphylococcus aureus was isolated. This is the first reported case of an abscess involving an epidural lipomatosis. PMID:20372939

  17. Intramedullary melanotic schwannoma of the conus medullaris: a case report

    Microsoft Academic Search

    H Mouchaty; R Conti; A M Buccoliero; P Conti

    2008-01-01

    Study design:A case of a very rare type of schwannoma is reported. It is the sixth reported case of intramedullary melanotic schwannoma and the only one localized in the conus.Methods:A 56-year-old woman was treated in this department for a C5–C6 spondylodiscitis. After 6 months her arms showed a rapid recovery, but her incomplete flaccid paraplegia remained stable. Magnetic resonance imaging

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

    PubMed Central

    Neto, Frederico Ribeiro; Lopes, Guilherme Henrique

    2011-01-01

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

  19. Virtual reality system in conjunction with neurorobotics and neuroprosthetics for rehabilitation in cerebrovascular accidents and spinal cord injuries

    Microsoft Academic Search

    A. De Mauro; E. Carrasco; D. Oyarzun; A. Ardanza; C. Paloc; A. Gil; J. Florez

    2010-01-01

    Cerebrovascular accidents (CVA) and spinal cord injuries (SCI) are the most common causes of paralysis and paresis with reported prevalence of 12,000 cases per million and 800 cases per million, respectively. Disabilities that follow CVA (hemiplegia) or SCI (paraplegia, tetraplegia) severely impair motor functions (e.g., standing, walking, reaching and grasping) and thereby prevent the affected individuals from healthy-like, full and

  20. Intravitreal ranibizumab injection for choroidal neovascularization in Strümpell-Lorrain Syndrome.

    PubMed

    Tran, T H C; Baglin, G; Querques, G

    2012-05-01

    Strümpell-Lorrain syndrome, or hereditary spastic paraplegia is a genetic disease of the central nervous system affecting the spinal cord and cerebellum. It represents a clinically heterogenous group of neurodegenerative disorders characterized by progressive spasticity and hyperreflexia of the lower limbs. Ocular abnormalities include keratitis, macular pigmentary abnormalities, juxtafoveolar retinal telangiectasis and choroidal neovascularization. We report the first case of choroidal neovascularization associated with Strüpell-Lorrain syndrome treated successfully with intravitreal ranibizumab injection. PMID:22463854

  1. Radiological Evaluation of Myelomeningocele — Chiari II Malformation

    Microsoft Academic Search

    Charles Raybaud; Elka Miller

    Myelomeningocele (MMC) is a malformation characterized by the failure of closure of the neural tube, usually (but not only)\\u000a at the lumbo-sacral level. Synonyms are spina bifida aperta, open spinal dysra — phism, and Chiari II malformation complex.\\u000a MMC is typically associated with a metamerically consistent paraplegia, a posterior fossa deformity known as the Chiari II\\u000a malformation, hydrocephalus, and a

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  4. Axon–glial interaction in the CNS: what we have learned from mouse models of Pelizaeus–Merzbacher disease

    PubMed Central

    Gruenenfelder, Fredrik I; Thomson, Gemma; Penderis, Jacques; Edgar, Julia M

    2011-01-01

    In the central nervous system (CNS) the majority of axons are surrounded by a myelin sheath, which is produced by oligodendrocytes. Myelin is a lipid-rich insulating material that facilitates the rapid conduction of electrical impulses along the myelinated nerve fibre. Proteolipid protein and its isoform DM20 constitute the most abundant protein component of CNS myelin. Mutations in the PLP1 gene encoding these myelin proteins cause Pelizaeus–Merzbacher disease and the related allelic disorder, spastic paraplegia type 2. Animal models of these diseases, particularly models lacking or overexpressing Plp1, have shed light on the interplay between axons and oligodendrocytes, and how one component influences the other. PMID:21401588

  5. Spontaneous spinal cord infarction secondary to embolism from an aortic aneurysm mimicking as cauda equina due to disc prolapse: a case report

    PubMed Central

    Ghoz, Ali; Singh, Vinay Kumar; Saed, Elrasheid; Abdunabi, Murad

    2009-01-01

    Spinal “stroke” is an uncommon cause of paraplegia. Spinal cord infarction from unruptured aortic aneurysm is rare. When encountered it poses diagnostic challenge to the clinician due to its rarity, which may lead to incorrect or delayed diagnosis. We report a case of 62-year-old man presenting to casualty as caudaequina syndrome due to spinal cord infarction secondary to emboli from an infra renal abdominal aortic aneurysm. To the authors knowledge this is first case of its kind and has not been reported in literature. Patient had improvement in proximal motor function following repair of the aneurysm, although he remained doubly incontinent in six months follow up. PMID:19829969

  6. Unusual cause of neuropathy: extensive dural spread of primary cervical osteosarcoma.

    PubMed

    Ponnampalam, Stephen N; Tan, Wilkinson Yj; Wazir, Nayyer Naveed; George, John

    2012-01-01

    We report a very rare case of a high grade osteosarcoma of the cervical spine in a 62-year-old woman. She presented with a relatively short history of a swelling in the posterior neck and cervical lymphadenopathy. This was associated with hoarseness of the voice, significant weight loss, and right upper arm radicular symptoms initially, progressing to paraplegia. Based on MR and CT imaging of the neck and an excision biopsy of an enlarged right supraclavicular lymph node, the histology revealed a high grade primary osteosarcoma of the cervical spine. PMID:23986826

  7. Unusual cause of neuropathy: extensive dural spread of primary cervical osteosarcoma

    PubMed Central

    Ponnampalam, Stephen N; Tan, Wilkinson YJ; Wazir, Nayyer Naveed; George, John

    2012-01-01

    We report a very rare case of a high grade osteosarcoma of the cervical spine in a 62-year-old woman. She presented with a relatively short history of a swelling in the posterior neck and cervical lymphadenopathy. This was associated with hoarseness of the voice, significant weight loss, and right upper arm radicular symptoms initially, progressing to paraplegia. Based on MR and CT imaging of the neck and an excision biopsy of an enlarged right supraclavicular lymph node, the histology revealed a high grade primary osteosarcoma of the cervical spine. PMID:23986826

  8. 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.

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

    SciTech Connect

    Fransen, E.; Vits, L.; Van Camp, G.; Willems, P.J. [Univ. of Antwerp (Belgium)] [Univ. of Antwerp (Belgium)

    1996-07-12

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

  10. 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

  11. Progressive myelopathy, a consequence of intra-thecal chemotherapy: Case report and review of the literature.

    PubMed

    Chukwu, B F; Ukekwe, I F; Ezenwosu, O U; Ani, C O; Ikefuna, A N; Emodi, I J

    2015-01-01

    Intra-thecal chemotherapy is a recognized therapy for hematological malignancies such as acute lymphoblastic leukemia (ALL). Despite the advantage of these drugs in treating or preventing central nervous system disease, they are not without complications. The authors describe a 12-year-old girl with ALL, who developed progressive myelopathy following intra-thecal administration of cytosine arabinoside. Initial presentation was urine and fecal retention that progressed to paraplegia, and finally encephalopathy. magnetic resonance imaging of the neuroaxis showed T2-weighted foci of increased signal intensity within the substance of the cervical cord indicative of myelopathy. Physicians should be wary of this rare complication of intra-thecal chemotherapy. PMID:25772933

  12. Spinal Cord Compression Revealing an Intraosseous Schwannoma

    PubMed Central

    Metoui, Leila; Ajili, Faïda; Maiza, Mouna; Ben Ammar, Mehdi; Gharsallah, Imen; M'sakni, Issam; Louzir, Bassem; Othmani, Salah

    2013-01-01

    A 68-year-old female presented with inflammatory lumbalgia and cruralgia. Physical examination revealed a lumbar stiffness without neurological deficit. Secondarily, paraplegia and urinary retention appeared. Magnetic resonance imaging showed a vertebral compaction of L3 vertebra with medullar compression. Emergent surgery revealed an epidural tumor involving largely the L3 vertebral body. Histology found schwannoma with positive protein S100 on the immunohistochemical study. Metastasis screening revealed bilateral nodular lesions of the lungs and a trochanter high scintigraphic signal. It was a malignant schwannoma. The patient underwent radiotherapy in addition to the total tumor resection. PMID:24381595

  13. The migration of a broken luque rod: a case report.

    PubMed

    Hirano, Kenichi; Deguchi, Masao; Kanamono, Toshihisa

    2007-04-01

    An exceedingly rare complication of Luque segmental spinal instrumentation in spinal fractures is described. A patient was treated for fractures of the eighth and ninth thoracic vertebra associated with traumatic paraplegia using Luque segmental spinal instrumentation. Ten years postoperatively, broken rods and sublaminar wires were found. One of the broken rods migrated caudad penetrating the sacrum and protruding into the pelvic cavity. The rod had projected into the rectum, and was extracted through the wall of the rectum and the anus. This case report emphasizes the importance of careful surgical technique and long-term follow up for patients who had undergone spinal instrumentation surgery. PMID:17414990

  14. Primary extradural hydatid cyst extended to paraspinal muscles

    PubMed Central

    Boulahroud, Omar; Dao, Ibrahim; El Asri, Cherif Abad; Boucetta, Mohammed

    2012-01-01

    Primary spinal epidural hydatid cyst without bony involvement is extremely rare. Authors report the case of a 44-year-old female brought to their attention for a rapidly progressive paraplegia. Magnetic resonance imaging (MRI) revealed extradural multiple cysts with “bunch of grapes” appearance extended to the paraspinal muscles through neural foramina without bony involvement on computed tomography (CT) scan. Histopathologic examination after a surgical approach confirmed the diagnosis of hydatid cyst. The early postoperative period showed a progressive improvement of her neurological deficit. The long-term follow-up under discontinued antihelminthic chemotherapy was uneventful. PMID:23188999

  15. Allan-Herndon-Dudley syndrome (AHDS) in two consecutive generations caused by a missense MCT8 gene mutation. Phenotypic variability with the presence of normal serum T3 levels.

    PubMed

    Boccone, Loredana; Dessì, Valentina; Meloni, Antonella; Loudianos, Georgios

    2013-04-01

    Allan-Herndon-Dudley syndrome (AHDS), an X linked condition, is characterized by severe intellectual disability, dysarthria, athetoid movements, muscle hypoplasia and spastic paraplegia in combination with altered TH levels, in particular, high serum T3 levels. Mutations in the MCT8 gene coding for the monocarboxylate thyroid hormone transporter 8 have been associated with AHDS. Here we describe a family with the presence of a MCT8 gene mutation, p.A224T, in three consecutive generations. In two generations its presence was detected in the hemizygous state in two males with neurological abnormalities including mental retardation, axial hypotonia, hypertonia of arms and legs and athetoid movements. One of them presented normal thyroid hormone levels. Mutation was also detected, although in the heterozygous state, in three females showing thyroid hormone levels in the normal range. Our results show the difficulty of distinguishing AHDS from patients with X-linked intellectual disability solely on the basis of clinical features and biochemical tests, and we advise screening for MCT8 mutations in either young or older patients with severe intellectual disability, axial hypotonia/dystonia, poor head control, spastic paraplegia, and athetoid movements even when they have normal thyroid hormone profiles. PMID:23419639

  16. Management of thoracolumbar spine fractures with neurologic disorder.

    PubMed

    Charles, Y P; Steib, J-P

    2015-02-01

    Thoracic and lumbar fractures represent approximately 50% of neurologic spinal trauma. They lead to paraplegia or cauda equina syndrome depending on the level injured. In the acute phase, the extension of spinal cord lesions should be limited by immediately treating secondary systemic injury factors. Quick recovery of hemodynamic stability, with mean arterial blood pressure>85 mm Hg, appears essential. There is no clinical evidence in favor of high-dose corticosteroid protocols. Their effect on neurologic recovery is unproven, whereas they lead to a higher rate of secondary septic and pulmonary complications. Incomplete deficits (ASIA B-D) require urgent surgery. There is no consensus with regard to complete paraplegia (ASIA A), but early surgery can enable neurologic recovery in some cases. The principle of surgical treatment is based on spinal cord decompression, instrumentation and fracture reduction. Early stabilization of the spine improves respiratory function and shortens the duration of mechanical ventilation and thus intensive care unit stay. Depending on the severity of associated lesions, early surgery within 48 hours is beneficial in polytrauma patients. Percutaneous instrumentation combined with mini-open posterior decompression stabilizes the spine, limiting approach-related morbidity. PMID:25577599

  17. Tropical myelopathies.

    PubMed

    Román, Gustavo C

    2014-01-01

    A large number of causal agents produce spinal cord lesions in the tropics. Most etiologies found in temperate regions also occur in the tropics including trauma, herniated discs, tumors, epidural abscess, and congenital malformations. However, infectious and nutritional disorders occur with higher prevalence in tropical regions. Among the most common infectious etiologies are tuberculous Pott's disease, brucellosis, and neuroborreliosis. Parasitic diseases such as schistosomiasis, neurocysticercosis, and eosinophilic meningitis are frequent causes of nontraumatic paraplegia. The retrovirus HTLV-1 is a cause of tropical spastic paraparesis. Nutritional causes of paraparesis include deficiencies of vitamin B12 and folate; endemic clusters of konzo and tropical ataxic myeloneuropathy are associated in Africa with malnutrition and excessive consumption of cyanide-containing bitter cassava. Other toxic etiologies of tropical paraplegia include lathyrism and fluorosis. Nutritional forms of myelopathy are associated often with optic and sensory neuropathy, hence the name tropical myeloneuropathies. Acute transverse myelopathy is seen in association with vaccination, infections, and fibrocartilaginous embolism of the nucleus pulposus. Multiple sclerosis and optic myelopathy occur in the tropics but with lesser prevalence than in temperate regions. The advent of modern imaging in the tropics, including computed tomography and magnetic resonance imaging, has allowed better diagnosis and treatment of these conditions that are a frequent cause of death and disability. PMID:24365434

  18. 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

  19. 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

  20. Protrudin binds atlastins and endoplasmic reticulum-shaping proteins and regulates network formation

    PubMed Central

    Chang, Jaerak; Lee, Seongju; Blackstone, Craig

    2013-01-01

    Hereditary spastic paraplegias are inherited neurological disorders characterized by progressive lower-limb spasticity and weakness. Although more than 50 genetic loci are known [spastic gait (SPG)1 to -57], over half of hereditary spastic paraplegia cases are caused by pathogenic mutations in four genes encoding proteins that function in tubular endoplasmic reticulum (ER) network formation: atlastin-1 (SPG3A), spastin (SPG4), reticulon 2 (SPG12), and receptor expression-enhancing protein 1 (SPG31). Here, we show that the SPG33 protein protrudin contains hydrophobic, intramembrane hairpin domains, interacts with tubular ER proteins, and functions in ER morphogenesis by regulating the sheet-to-tubule balance and possibly the density of tubule interconnections. Protrudin also interacts with KIF5 and harbors a Rab-binding domain, a noncanonical FYVE (Fab-1, YGL023, Vps27, and EEA1) domain, and a two phenylalanines in an acidic tract (FFAT) domain and, thus, may also function in the distribution of ER tubules via ER contacts with the plasma membrane or other organelles. PMID:23969831

  1. Pneumomediastinum, Subcutaneous Emphysema, and Tracheal Tear in the Early Postoperative Period of Spinal Surgery in a Paraplegic Achondroplastic Dwarf

    PubMed Central

    Kahraman, Sinan; Enercan, Meriç; Demirhan, Özkan; ?engül, Türker; Hamzao?lu, Azmi

    2013-01-01

    Achondroplasia was first described in 1878 and is the most common form of human skeletal dysplasia. Spinal manifestations include thoracolumbar kyphosis, foramen magnum, and spinal stenosis. Progressive kyphosis can result in spinal cord compression and paraplegia due to the reduced size of spinal canal. The deficits are typically progressive, presenting as an insidious onset of paresthesia, followed by the inability to walk and then by urinary incontinence. Paraplegia can be the result of direct pressure on the cord by bone or the injury to the anterior spinal vessels by a protruding bone. Surgical treatment consists of posterior instrumentation, fusion with total wide laminectomy at stenosis levels, and anterior interbody support. Pedicle screws are preferred for spinal instrumentation because wires and hooks may induce spinal cord injury due to the narrow spinal canal. Pedicle lengths are significantly shorter, and 20–25?mm long screws are appropriate for lower thoracic and lumbar pedicles in adult achondroplastic There is no information about the appropriate length of screws for the upper thoracic pedicles. Tracheal injury due to inappropriate pedicle screw length is a rare complication. We report an extremely rare case of tracheal tear due to posterior instrumentation and its management in the early postoperative period. PMID:24455372

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

    SciTech Connect

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

    2005-09-09

    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.

  3. Use of the BioMedicus centrifugal pump in traumatic tears of the thoracic aorta.

    PubMed

    Olivier, H F; Maher, T D; Liebler, G A; Park, S B; Burkholder, J A; Magovern, G J

    1984-12-01

    Traumatic blunt thoracic aortic injury is a clinical entity of increasing incidence. After the diagnosis of traumatic tear of the aorta is made, there is some controversy over whether the aorta should be repaired using cardiopulmonary bypass, a heparinized shunt, or cross-clamping and graft interposition without a shunt or bypass. At Allegheny General Hospital, 19 patients were treated for traumatic tears of the thoracic aorta between July 1, 1977, and June 30, 1983. They can be divided into two groups: Group 1 (July 1, 1977, through October 31, 1981), in which no shunt or bypass or only a heparinized shunt was used, and Group 2 (November 1, 1981, through June 30, 1983), in which left atrium-femoral artery bypass was performed using a BioMedicus heparinless pump and tubing. Among the 10 patients in Group 1, 4 died and 2 had paraplegia postoperatively. Among the 9 patients in Group 2, 1 died and none experienced paraplegia following operation. We believe that the BioMedicus centrifugal pump is a simple, safe means of perfusing the lower body, kidneys, and spinal column without necessitating heparinization in a patient with multiple injuries or the placement of a cumbersome heparinized shunt. Because of the simplicity and the reliability demonstrated, this pump should be considered for use in all patients with traumatic tears of the thoracic aorta. PMID:6508414

  4. PNPLA6 mutations cause Boucher-Neuhäuser and Gordon Holmes syndromes as part of a broad neurodegenerative spectrum

    PubMed Central

    Synofzik, Matthis; Gonzalez, Michael A.; Lourenco, Charles Marques; Coutelier, Marie; Haack, Tobias B.; Rebelo, Adriana; Hannequin, Didier; Strom, Tim M.; Prokisch, Holger; Kernstock, Christoph; Durr, Alexandra; Schöls, Ludger; Lima-Martínez, Marcos M.; Farooq, Amjad; Schüle, Rebecca; Stevanin, Giovanni; Marques, Wilson

    2014-01-01

    Boucher-Neuhäuser and Gordon Holmes syndromes are clinical syndromes defined by early-onset ataxia and hypogonadism plus chorioretinal dystrophy (Boucher-Neuhäuser syndrome) or brisk reflexes (Gordon Holmes syndrome). Here we uncover the genetic basis of these two syndromes, demonstrating that both clinically distinct entities are allelic for recessive mutations in the gene PNPLA6. In five of seven Boucher-Neuhäuser syndrome/Gordon Holmes syndrome families, we identified nine rare conserved and damaging mutations by applying whole exome sequencing. Further, by dissecting the complex clinical presentation of Boucher-Neuhäuser syndrome and Gordon Holmes syndrome into its neurological system components, we set out to analyse an additional 538 exomes from families with ataxia (with and without hypogonadism), pure and complex hereditary spastic paraplegia, and Charcot–Marie–Tooth disease type 2. We identified four additional PNPLA6 mutations in spastic ataxia and hereditary spastic paraplegia families, revealing that Boucher-Neuhäuser and Gordon Holmes syndromes in fact represent phenotypic clusters on a spectrum of neurodegenerative diseases caused by mutations in PNPLA6. Structural analysis indicates that the majority of mutations falls in the C-terminal phospholipid esterase domain and likely inhibits the catalytic activity of PNPLA6, which provides the precursor for biosynthesis of the neurotransmitter acetylcholine. Our findings show that PNPLA6 influences a manifold of neuronal systems, from the retina to the cerebellum, upper and lower motor neurons and the neuroendocrine system, with damage of this protein causing an extraordinarily broad continuous spectrum of associated neurodegenerative disease. PMID:24355708

  5. A Spinal Arteriovenous Fistula in a 3-Year Old Boy

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-05-01

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

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

    PubMed

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

    1998-05-01

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

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

    PubMed Central

    2014-01-01

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

  9. Endovascular versus open repair for descending thoracic aortic rupture: institutional experience and meta-analysis.

    PubMed

    Xenos, Eleftherios Sarantis; Minion, David J; Davenport, Daniel L; Hamdallah, Omar; Abedi, Nick N; Sorial, Ehab E; Endean, Eric D

    2009-02-01

    Rupture of thoracic aneurysm, acute type B dissection, blunt thoracic trauma, and penetrating aortic ulcer can present with a similar clinical profile of thoracic aortic rupture. We report a meta-analysis of comparative studies evaluating endoluminal graft versus open repair of these lesions as well as the early experience from our institution. We searched the following databases for reports of endovascular versus open repair of acute descending thoracic aortic rupture: Medline/PubMed, OVID, EMBASE, CINAHL, ClinicalTrials.gov, the Cochrane central register of controlled trials and the Cochrane database of systematic reviews. We used the random-effects model to calculate the odds ratio (OR) and 95% confidence intervals (CI) for mortality, paraplegia/paraparesis and stroke rates. Also, the medical records of the patients treated in our institution with this technique from 2000 to 2008 were reviewed. Demographics, comorbidities and operative procedure information were retrieved. Outcomes examined were mortality, paraplegia and stroke. Meta-analysis indicates that endoluminal graft repair is accompanied by lower procedure related mortality (OR 0.46, 95% CI 0.26-0.78, p=0.005) and paraplegia rates (OR 0.23, 95% CI 0.08-0.65, p=0.005), as compared to open repair. There was no difference in stroke rate between the two methods (OR 0.86, 95% CI 0.26-2.8, p=0.8). We have treated 13 patients with endoluminal stent-grafts. No conversion to open repair was necessary. Stroke rate was 15%, no patient died as a result of the stent-graft placement, one patient died as a result of massive head injury (overall 30-day mortality: 7.5%). There were no spinal cord ischemic complications. Our experience and meta-analysis indicate that thoracic endograft repair has low mortality and spinal cord complication rates for treatment of acute thoracic aortic rupture. If this method proves to be durable, it could replace open repair as the treatment of choice for these critically ill patients. PMID:19081731

  10. 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

  11. A 7-month-old male with Allan-Herndon-Dudley syndrome and the power of T3.

    PubMed

    Langley, Katherine G; Trau, Steven; Bean, Lora J H; Narravula, Alekhya; Schrier Vergano, Samantha A

    2015-05-01

    Allan-Herndon-Dudley syndrome (AHDS, MIM 300523) is an X-linked neurodegenerative disorder characterized by intellectual disability, severe hypotonia, diminished muscle mass, and progressive spastic paraplegia. All affected males have pathognomonic thyroid profiles with an elevated T3 , low-normal free T4 , and normal TSH. Mutations in the monocarboxylate transporter 8 (MCT8) gene, SLC16A2, have been found to be causative. Here, we describe a proband whose extensive evaluation and ultimate diagnosis of AHDS unmasked three previously undiagnosed generations of affected individuals in one family. This case illustrates the need for clinicians to consider obtaining full thyroid studies on individuals with the non-specific findings of severe hypotonia, failure to thrive, and gross motor delay. © 2015 Wiley Periodicals, Inc. PMID:25755011

  12. 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.

  13. 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.

  14. [Amyotrophic lateral sclerosis syndrome of syphilitic origin. 5 cases].

    PubMed

    el Alaoui-Faris, M; Medejel, A; al Zemmouri, K; Yahyaoui, M; Chkili, T

    1990-01-01

    We studied 5 cases of syphilitic lateral amyotrophic sclerosis. The diagnosis was based on the presence of a lymphocytic reaction in the CSF and positive VDRL and TPHA reactions in both blood and CSF. Clinically, the disease affected the arms in 3 cases and produced paraplegia in 2 cases. The gradual extension of amyotrophy over several months, the diffusion of electromyographic abnormalities and the finding of spinal cord atrophy at myelography and CT suggested a subacute ischemic mechanism with meningo-myelic arteritis involving the anterior horns. After treatment with penicillin G in high doses, the outcome was constantly favourable, with improvement of motor deficit in 4 cases and stabilisation in 1 case in a 5 to 13 years' follow-up. PMID:2408129

  15. Klebsiella pneumoniae liver abscess associated with septic spinal epidural abscess.

    PubMed

    Kuramochi, Gen; Takei, Shin-Ichi; Sato, Munehiro; Isokawa, Osamu; Takemae, Takashi; Takahashi, Akira

    2005-01-01

    A 56-year-old Japanese man with hypertension presented with a 10 days history of high fever, right and left upper quadrant tenderness. An abdominal ultrasonography and computerized tomographic scan revealed a large collection in the right lobe of the liver that was consistent with an abscess. A drainage catheter was placed and purulent fluid was drained. Cultures of the fluid and blood were positive for a strain of ampicillin-resistant Klebsiella pneumoniae. Six days after admission, paraplegia and urinary retention were found. On the neurological examination, deep tendon reflexes of the lower extremities were absent bilaterally. Magnetic resonance imaging scan detected thoracic spinal epidural abscess and paraspinal abscess. He received the emergent decompressive laminectomy. Culture of surgical specimen grew ampicillin-resistant K. pneumoniae. The patient was treated with biapenem intravenously. Thereafter, clinical symptoms improved gradually and he was removed to the professional hospital to continue rehabilitation for gait disturbance on hospital day 147. PMID:15652471

  16. Systematic enhancement of functioning as a therapeutic technique in conversion disorder

    PubMed Central

    Andrade, Chittaranjan; Bhakta, Savita G.; Singh, Nagendra M.

    2009-01-01

    To explicitly outline a therapeutic technique for symptom removal in conversion disorder. We describe one patient with conversion dumbness and another with conversion paraplegia. The first patient was successfully treated in a single session, and the second was successfully treated across two weeks, both using systematic enhancement of functioning as a technique for symptom removal. This technique encourages the patient to express the desired behavior to whatever extent possible; subsequently, the patient is encouraged to gradually amplify the response until normal levels of functioning are achieved. The technique outlined is simple and practical but nevertheless receives no mention in conversion disorder literature. The technique can be applied to any situation in which behavioral amplification is desired. PMID:19823633

  17. Systematic enhancement of functioning as a therapeutic technique in conversion disorder.

    PubMed

    Andrade, Chittaranjan; Bhakta, Savita G; Singh, Nagendra M

    2009-04-01

    To explicitly outline a therapeutic technique for symptom removal in conversion disorder. We describe one patient with conversion dumbness and another with conversion paraplegia. The first patient was successfully treated in a single session, and the second was successfully treated across two weeks, both using systematic enhancement of functioning as a technique for symptom removal. This technique encourages the patient to express the desired behavior to whatever extent possible; subsequently, the patient is encouraged to gradually amplify the response until normal levels of functioning are achieved. The technique outlined is simple and practical but nevertheless receives no mention in conversion disorder literature. The technique can be applied to any situation in which behavioral amplification is desired. PMID:19823633

  18. Management of Acute Aortic Syndrome and Chronic Aortic Dissection

    SciTech Connect

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

    2011-10-15

    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.

  19. Cervical Symmetric Dumbbell Ganglioneuromas Causing Severe Paresis

    PubMed Central

    Miyamoto, Kei; Hirose, Yoshinobu; Kito, Yusuke; Fushimi, Kazunari; Shimizu, Katsuji

    2014-01-01

    We report an extremely rare case with bilateral and symmetric dumbbell ganglioneuromas of the cervical spine in an elderly patient. A 72-year-old man came by ambulance to our hospital due to progressive incomplete paraplegia. Magnetic resonance imaging demonstrated bilateral symmetric dumbbell tumors at the C1/2 level. We performed total resection of the intracanalar tumor, aiming at complete decompression of the spinal cord, and partial and subtotal resection of foraminal outside portions. Histopathological examination of the surgical specimen indicated the tumor cells to be spindle cells with the presence of ganglion cells and no cellular pleomorphism, suggesting a diagnosis of ganglioneuroma. Although the surgery was not curative, the postoperative course was uneventful and provided a satisfactory outcome. This is the fourth known case of cervical ganglioneuromas of the bilateral symmetric dumbbell type. PMID:24596609

  20. Cervical symmetric dumbbell ganglioneuromas causing severe paresis.

    PubMed

    Hioki, Akira; Miyamoto, Kei; Hirose, Yoshinobu; Kito, Yusuke; Fushimi, Kazunari; Shimizu, Katsuji

    2014-02-01

    We report an extremely rare case with bilateral and symmetric dumbbell ganglioneuromas of the cervical spine in an elderly patient. A 72-year-old man came by ambulance to our hospital due to progressive incomplete paraplegia. Magnetic resonance imaging demonstrated bilateral symmetric dumbbell tumors at the C1/2 level. We performed total resection of the intracanalar tumor, aiming at complete decompression of the spinal cord, and partial and subtotal resection of foraminal outside portions. Histopathological examination of the surgical specimen indicated the tumor cells to be spindle cells with the presence of ganglion cells and no cellular pleomorphism, suggesting a diagnosis of ganglioneuroma. Although the surgery was not curative, the postoperative course was uneventful and provided a satisfactory outcome. This is the fourth known case of cervical ganglioneuromas of the bilateral symmetric dumbbell type. PMID:24596609

  1. "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

  2. Subcutaneous pellet testosterone replacement therapy: the "first steps" in treating men with spinal cord injuries.

    PubMed

    Gray, Kendra M; Derosa, Angela

    2013-12-01

    The authors describe the case of a 36-year-old man who presented with hormone level concerns 6 months after a rock climbing accident that resulted in paraplegia. Hypogonadism was diagnosed, and the patient received subcutaneous pellet testosterone replacement therapy. Within 6 months, the patient had substantial improvement in muscle function and was able to take several steps with the assistance of crutches or a walker. This case highlights the potential improvement in quality of life and overall prognosis resulting from the subcutaneous pellet form of testosterone when used as part of the overall treatment plan in such patients. Considering the overwhelming preponderance of hypogonadism in men with spinal cord injuries, the standard of care for such patients should include screening, laboratory hormone evaluation, and prompt treatment for testosterone deficiency. PMID:24285035

  3. [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

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

    PubMed Central

    Renvoisé, Benoît; Blackstone, Craig

    2010-01-01

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

  5. Crystal structure of the human spastin AAA domain

    PubMed Central

    Taylor, Jennifer L.; White, Susan Roehl; Lauring, Brett; Kull, F. Jon

    2012-01-01

    Hereditary spastic paraplegia (HSP) is a motor neuron disease caused by a progressive degeneration of the motor axons of the corticospinal tract. Point mutations or exon deletions in the microtubule-severing ATPase, spastin, are responsible for approximately 40% of cases of autosomal dominant HSP. Here, we report the 3.3 Å X-ray crystal structure of a hydrolysis- deficient mutant (E442Q) of the human spastin protein AAA domain. This structure is analyzed in the context of the existing Drosophila melanogaster spastin AAA domain structure and crystal structures of other closely related proteins in order to build a more unifying framework for understanding the structural features of this group of microtubule-severing ATPases. PMID:22446388

  6. Crystal structure of the human spastin AAA domain.

    PubMed

    Taylor, Jennifer L; White, Susan Roehl; Lauring, Brett; Kull, F Jon

    2012-08-01

    Hereditary spastic paraplegia (HSP) is a motor neuron disease caused by a progressive degeneration of the motor axons of the corticospinal tract. Point mutations or exon deletions in the microtubule-severing ATPase, spastin, are responsible for approximately 40% of cases of autosomal dominant HSP. Here, we report the 3.3 Å X-ray crystal structure of a hydrolysis-deficient mutant (E442Q) of the human spastin protein AAA domain. This structure is analyzed in the context of the existing Drosophila melanogaster spastin AAA domain structure and crystal structures of other closely related proteins in order to build a more unifying framework for understanding the structural features of this group of microtubule-severing ATPases. PMID:22446388

  7. VAMP1 Mutation Causes Dominant Hereditary Spastic Ataxia in Newfoundland Families

    PubMed Central

    Bourassa, Cynthia V.; Meijer, Inge A.; Merner, Nancy D.; Grewal, Kanwal K.; Stefanelli, Mark G.; Hodgkinson, Kathleen; Ives, Elizabeth J.; Pryse-Phillips, William; Jog, Mandar; Boycott, Kym; Grimes, David A.; Goobie, Sharan; Leckey, Richard; Dion, Patrick A.; Rouleau, Guy A.

    2012-01-01

    Our group previously described and mapped to chromosomal region 12p13 a form of dominantly inherited hereditary spastic ataxia (HSA) in three large Newfoundland (Canada) families. This report identifies vesicle-associated membrane protein 1 (VAMP1), which encodes a critical protein for synaptic exocytosis, as the responsible gene. In total, 50 affected individuals from these families and three independent probands from Ontario (Canada) share the disease phenotype together with a disruptive VAMP1 mutation that affects a critical donor site for the splicing of VAMP1 isoforms. This mutation leads to the loss of the only VAMP1 isoform (VAMP1A) expressed in the nervous system, thus highlighting an association between the well-studied VAMP1 and a neurological disorder. Given the variable phenotype seen in the affected individuals examined here, we believe that VAMP1 should be tested for mutations in patients with either ataxia or spastic paraplegia. PMID:22958904

  8. VAMP1 mutation causes dominant hereditary spastic ataxia in Newfoundland families.

    PubMed

    Bourassa, Cynthia V; Meijer, Inge A; Merner, Nancy D; Grewal, Kanwal K; Stefanelli, Mark G; Hodgkinson, Kathleen; Ives, Elizabeth J; Pryse-Phillips, William; Jog, Mandar; Boycott, Kym; Grimes, David A; Goobie, Sharan; Leckey, Richard; Dion, Patrick A; Rouleau, Guy A

    2012-09-01

    Our group previously described and mapped to chromosomal region 12p13 a form of dominantly inherited hereditary spastic ataxia (HSA) in three large Newfoundland (Canada) families. This report identifies vesicle-associated membrane protein 1 (VAMP1), which encodes a critical protein for synaptic exocytosis, as the responsible gene. In total, 50 affected individuals from these families and three independent probands from Ontario (Canada) share the disease phenotype together with a disruptive VAMP1 mutation that affects a critical donor site for the splicing of VAMP1 isoforms. This mutation leads to the loss of the only VAMP1 isoform (VAMP1A) expressed in the nervous system, thus highlighting an association between the well-studied VAMP1 and a neurological disorder. Given the variable phenotype seen in the affected individuals examined here, we believe that VAMP1 should be tested for mutations in patients with either ataxia or spastic paraplegia. PMID:22958904

  9. 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

  10. Cervical spine fracture in a patient with ankylosing spondylitis causing a C2-T9 spinal epidural hematoma- Treatment resulted in a rapid and complete recovery from tetraplegia: Case report and literature review

    PubMed Central

    Wong, Albert Sii Hieng; Yu, Denis Hee youg

    2015-01-01

    Full recovery from tetraplegia is uncommon in cervical spine injury. This has not being reported for cervical spine fracture in a patient with ankylosing spondylitis causing spinal epidural hematoma. We report on a case of cervical spine fracture in a patient with ankylosing spondylitis who came with tetraplegia. He underwent a two stage fixation and fusion. He had a complete recovery. Two hours after the operation he regained full strength in all the limbs while in the Intensive Care Unit. He went back to full employment. There are only two other reports in the literature where patients with ankylosing spondylitis and extradural hematoma who underwent treatment within 12 h and recovered completely from tetraparesis and paraplegia respectively. Patient with ankylosing spondylitis has a higher incidence of spinal fracture and extradural hematoma. Good outcome can be achieved by early diagnosis and treatment. This can ensure not only a stable spine, but also a rapid and complete recovery in a tetraplegic patient.

  11. Bridging Over the Troubled Heterogeneity of SPG-Related Pathologies: Mechanisms Unite What Genetics Divide.

    PubMed

    Tessa, A; Denora, P S; Racis, L; Storti, E; Orlacchio, A; Santorelli, F M

    2014-10-10

    The hereditary spastic paraplegias (HSP) are characterized by spastic gait with weakness in the legs and additional neurological or extra-neurological signs in "complicated" forms. The past two decades have witnessed major advances in our understanding of their molecular bases with the identification of a plethora of loci and the cloning of several SPG genes. Combined genetic and clinical information has permitted a modern, molecularly-driven classification and an improved diagnosis, with several new data on the possible disease mechanisms. Further heterogeneity will rapidly emerge with the diffusion of next-generation sequencing platforms and, under the shadow of common themes in the pathogenesis, new therapeutic options will likely emerge for a great number of patients. PMID:25323869

  12. Inversion duplication of the short arm of chromosome 8: Clinical data on seven patients and review of the literature

    SciTech Connect

    Die-Smulders, C.E.M. de; Engelen, J.J.M.; Schrander-Stumpel, C.T.R.M. [Univ. of Limburg, Maastricht (Netherlands)] [and others

    1995-11-20

    We report on clinical and cytogenetic data on 5 children and 2 adults with a de novo inverted duplication of the short arm of chromosome 8, and we give a review of 26 patients from the literature. The clinical picture in young children is characterized by minor facial anomalies, hypotonia, and severe developmental delay. In older patients the facial traits are less characteristic, spastic paraplegia develops, and severe orthopedic problems are frequent. Psychomotor retardation is always severe-to-profound. Duplication of 8p21-p22 results in a clinically recognizable multiple congenital anomalies/mental retardation (MCA/MR) syndrome. It is shown that in all patients examined, the duplication was accompanied by a deletion of the most terminal part of 8p. 16 refs., 4 figs., 2 tabs.

  13. Superimposed cocaine-induced rhabdomyolysis in a patient with aortic dissection rhabdomyolysis.

    PubMed

    Goldberg, Andrew

    2015-03-15

    A 52-year-old man presented with acute, sharp chest pain radiating to the back and abdomen after using cocaine 18 hours previously. Computed tomographic angiography revealed a type B aortic dissection that extended to the iliac arteries. The patient underwent balloon fenestration, placement of multiple aortic stents, and bilateral leg fasciotomy. He eventually went into hyperkalemic arrest but was successfully resuscitated, after which his serum lactate and creatine kinase levels peaked at 7.4 mmol/L and 990,400 U/L, respectively. The combination of aortic dissection and creatine kinase toxicity was extensive enough to cause permanent renal failure and paraplegia below T6. The severity of the patient's symptoms was attributed to concomitant cocaine-induced rhabdomyolysis and aortic dissection rhabdomyolysis. PMID:25774753

  14. [Histological evaluation of ischemic injury to the spinal cord. Experimental study in the rabbit].

    PubMed

    Vaquero, Carlos; Arce, Nuria; Agudo, Javier; Martinez, Rafael; Gutiérrez, Vicente; Diago, Maria Victoria

    2006-01-01

    Sometimes in clinical practice the spinal cord is subjected to a more or less prolonged period of ischemia, after which cellular lesions may occur, causing paraplegia. The purpose of this paper is to quantify morphologically the damage of the spinal cord after an induced ischemia. Seventy male adult rabbits were used. They were divided into three groups: one group was used for evaluation of spinal cord ischemia at 3 hours, the second at 12 hours and the third at 24 hours. The recovery periods ranged from 3, to 12 and 24 hours. At the end of this period, the animals were anesthetized and killed. A clinical evaluation was made using the Tarlov method and criteria. The spinal cord was subjected to a histological evaluation. The results revealed different changes according to the multiple groups of study. The authors discuss the data of the present study and compare to the reports published in the bibliography on the subject. PMID:17308628

  15. Adaptor protein complexes and intracellular transport

    PubMed Central

    Park, Sang Yoon; Guo, Xiaoli

    2014-01-01

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

  16. Mutations in PNPLA6 are linked to photoreceptor degeneration and various forms of childhood blindness.

    PubMed

    Kmoch, S; Majewski, J; Ramamurthy, V; Cao, S; Fahiminiya, S; Ren, H; MacDonald, I M; Lopez, I; Sun, V; Keser, V; Khan, A; Stránecký, V; Hartmannová, H; P?istoupilová, A; Hoda?ová, K; Piherová, L; Kucha?, L; Baxová, A; Chen, R; Barsottini, O G P; Pyle, A; Griffin, H; Splitt, M; Sallum, J; Tolmie, J L; Sampson, J R; Chinnery, P; Banin, E; Sharon, D; Dutta, S; Grebler, R; Helfrich-Foerster, C; Pedroso, J L; Kretzschmar, D; Cayouette, M; Koenekoop, R K

    2015-01-01

    Blindness due to retinal degeneration affects millions of people worldwide, but many disease-causing mutations remain unknown. PNPLA6 encodes the patatin-like phospholipase domain containing protein 6, also known as neuropathy target esterase (NTE), which is the target of toxic organophosphates that induce human paralysis due to severe axonopathy of large neurons. Mutations in PNPLA6 also cause human spastic paraplegia characterized by motor neuron degeneration. Here we identify PNPLA6 mutations in childhood blindness in seven families with retinal degeneration, including Leber congenital amaurosis and Oliver McFarlane syndrome. PNPLA6 localizes mostly at the inner segment plasma membrane in photoreceptors and mutations in Drosophila PNPLA6 lead to photoreceptor cell death. We also report that lysophosphatidylcholine and lysophosphatidic acid levels are elevated in mutant Drosophila. These findings show a role for PNPLA6 in photoreceptor survival and identify phospholipid metabolism as a potential therapeutic target for some forms of blindness. PMID:25574898

  17. 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

    2014-11-18

    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

  18. Clinical features and neurologic progression of hyperargininemia.

    PubMed

    Carvalho, Daniel R; Brum, Jaime M; Speck-Martins, Carlos E; Ventura, Fabrício D; Navarro, Mônica M M; Coelho, Kátia E F A; Portugal, Dalton; Pratesi, Riccardo

    2012-06-01

    Hyperargininemia is an autosomal recessive metabolic disorder caused by a deficiency of enzyme arginase I. It is a rare pan-ethnic disease with a clinical presentation distinct from that of other urea cycle disorders, and hyperammonemic encephalopathy is not usually observed. Hyperargininemia is one of the few treatable causes of pediatric spastic paraparesis, and can be confused with cerebral palsy. We retrospectively evaluated the clinical onset, neurologic manifestations, progression of abnormalities, electroencephalographic abnormalities, and laboratory findings of 16 Brazilian patients with hyperargininemia. Relevant data about the clinical spectrum and natural history of hyperargininemia are detailed. Progressive spastic diplegia constituted the key clinical abnormality in this group, but variability in clinical presentation and progression were evident in our series. Seizures in hyperargininemia may be more common than reported in previous studies. Features distinguishing hyperargininemia from cerebral palsy and hereditary spastic paraplegia are emphasized in this large series of patients. PMID:22633632

  19. The endoplasmic reticulum-based acetyltransferases, ATase1 and ATase2, associate with the oligosaccharyltransferase to acetylate correctly folded polypeptides.

    PubMed

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

    2014-11-14

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

  20. Severe aortic and arterial aneurysms associated with a TGFBR2 mutation

    PubMed Central

    LeMaire, Scott A; Pannu, Hariyadarshi; Tran-Fadulu, Van; Carter, Stacey A; Coselli, Joseph S; Milewicz, Dianna M

    2008-01-01

    Background A 24-year-old man presented with previously diagnosed Marfan’s syndrome. Since the age of 9 years, he had undergone eight cardiovascular procedures to treat rapidly progressive aneurysms, dissection and tortuous vascular disease involving the aortic root and arch, the thoracoabdominal aorta, and brachiocephalic, vertebral, internal thoracic and superior mesenteric arteries. Throughout this extensive series of cardiovascular surgical repairs, he recovered without stroke, paraplegia or renal impairment. Investigations CT scans, arteriogram, genetic mutation screening of transforming growth factor ? receptors 1 and 2. Diagnosis Diffuse and rapidly progressing vascular disease in a patient who met the diagnostic criteria for Marfan’s syndrome, but was later rediagnosed with Loeys–Dietz syndrome. Genetic testing also revealed a de novo mutation in transforming growth factor ? receptor 2. Management Regular cardiovascular surveillance for aneurysms and dissections, and aggressive surgical treatment of vascular disease. PMID:17330129

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

    PubMed

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

    2015-04-01

    Thoraco-abdominal aneurysms (TAAA) represents a particularly lethal vascular disease that without surgical repair carries a dismal prognosis. However, there is an inherent risk from surgical repair of spinal cord ischaemia that can result in paraplegia. One method of reducing this risk is cerebrospinal fluid (CSF) drainage. We believe that the CSF contains clinically significant biomarkers that can indicate impending spinal cord ischaemia. This work therefore presents a novel measurement method for proteins, namely albumin, as a precursor to further work in this area. The work uses an interdigitated electrode (IDE) sensor and shows that it is capable of detecting various concentrations of albumin (from 0 to 100 g/L) with a high degree of repeatability at 200 MHz (R(2)?=?0.991) and 4 GHz (R(2)?=?0.975). PMID:25686914

  2. 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

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

    PubMed Central

    Ha, Kee-Yong; Kim, Hyun-Woo

    2013-01-01

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

  4. Bilateral nonunion of the sacrum in a long-term paraplegic patient treated with trans-sacral bar and spinopelvic fixation.

    PubMed

    Kanezaki, Shozo; Rommens, Pol Maria

    2015-03-01

    The incidence of fragility fractures of the pelvis is sharply increasing in accordance with growing life expectancy in developed countries. Numerous conditions may compromise bone density and quality, and paraplegia due to spinal cord injury is one of them. As screw anchorage is often problematic in poor bone stock, spinopelvic dissociation demands a type of osteosynthesis, which is less dependent on the density of trabecular bone. We present a case of a paraplegic 45-year-old man, with non-displaced bilateral nonunion of the sacrum. The patient was treated with trans-sacral bar and spinopelvic fixation. Rapid relief from pain and functional recovery was achieved with complete bone healing 1 year after the operation. PMID:25559304

  5. Open fenestration for complicated acute aortic B dissection

    PubMed Central

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

    2014-01-01

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

  6. Pelizaeus-Merzbacher disease: Genetic and cellular pathogenesis.

    PubMed

    Garbern, J Y

    2007-01-01

    Pelizaeus-Merzbacher disease (PMD) and the allelic spastic paraplegia type 2 (SPG2) arise from mutations in the X-linked gene encoding myelin proteolipid protein (PLP). Analysis of mutations affecting PLP, the major protein in central nervous system myelin, has revealed previously unsuspected roles for myelinating glia in maintaining the integrity of the nervous system. The disease spectrum for PMD and SPG2 is extraordinarily broad and can be best understood by accounting not only for the wide range of mutations that can occur but also for the effects of PLP1 mutations on both cell autonomous and non-cell autonomous processes in myelinating cells. Appreciating the wide range of genetic and cellular effects of PLP1 mutations is important for patient and family counseling, understanding disease pathogenesis, and, ultimately, for developing future disease-specific therapies. PMID:17115121

  7. Ophthalmic manifestations of inherited neurodegenerative disorders.

    PubMed

    Kersten, Hannah M; Roxburgh, Richard H; Danesh-Meyer, Helen V

    2014-06-01

    Ophthalmic findings are common features of neurodegenerative disorders and, in addition to being clinically important, have emerged as potentially useful biomarkers of disease progression in several conditions. Clinically, these visual system abnormalities can be a clue to diagnosis, as well as being a prominent cause of disability in affected patients. In this Review, we describe the various afferent visual system and other ophthalmic features of inherited neurodegenerative disorders, including the muscular dystrophies, Friedreich ataxia, the spinocerebellar ataxias, hereditary spastic paraplegia, Charcot-Marie-Tooth disease, and other conditions. We focus on the expanding role of optical coherence tomography in diagnostic imaging of the retina and optic nerve head, and the possible use of ophthalmic findings as biomarkers of disease severity in hereditary neurodegenerative disorders. In addition, we discuss the ophthalmic manifestations and treatment implications of mitochondrial dysfunction, which is a feature of many inherited neurodegenerative diseases. PMID:24840976

  8. Friedreich's Ataxia (FRDA) is an extremely rare cause of autosomal recessive ataxia in Chinese Han population.

    PubMed

    Zeng, Junsheng; Wang, Junling; Zeng, Sheng; He, Miao; Zeng, Xianfeng; Zhou, Yao; Liu, Zhen; Jiang, Hong; Tang, Beisha

    2015-04-15

    Friedreich's Ataxia (FRDA) is a very common cause of hereditary autosomal recessive ataxia among western Europeans. We aim to define the frequency of FRDA in Chinese Han population due to the lack of reports of FRDA in China. The GAA trinucleotide repeats in the FXN gene were analyzed by triplet repeat-primed PCR (TP-PCR) in 122 unrelated hereditary ataxia (HA) and 114 unrelated hereditary spastic paraplegia (HSP) patients. The GAA copy numbers in the FXN gene of all the subjects ranged from 5 to 16. There were no FRDA patients that could be diagnosed base on the results of TP-PCR. It suggests that FRDA is a very rare cause of inheritance ataxia and FRDA genetic analysis should not be used as a routine genetic diagnosis test in China. PMID:25765228

  9. Acute spontaneous spinal subdural hematoma with vague symptoms.

    PubMed

    Chung, Jaehwan; Park, In Sung; Hwang, Soo-Hyun; Han, Jong-Woo

    2014-09-01

    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

  10. 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

  11. 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

  12. 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

  13. [2 cases of vertebral hydatidosis treated by the association of surgery and mebendazole].

    PubMed

    Cardona, J M; Giné, J; Flores, X; Algara, C; Ballester, J

    1983-01-01

    Two cases of vertebral hydatidosis were diagnosed only at the time of operation. The first one, a lumbar localisation treated as a tuberculosis, by posterior graft and chemotherapy went to a large vertebral destruction with paraplegia. An anterior approach revealed the hydatids. A large excision associated with graft and osteosynthesis gave only a temporary improvement, but the treatment by Mebendazol cured the neurological symptoms. The second case, with a large destruction of L5 and S1, was also treated as a tuberculosis even after a decompressive laminectomy and recognized at a second operation on the sacrum. A left paralysis, incompletely improved by a decompression, appeared as favourably influenced by Mebendazol. Epidemiologic conditions of hydatosis, difficulties of diagnosis of the rare bony localizations, are recalled. The great problem of treatment, especially in the most frequent vertebral lesions, where complete excision is impossible, appears as hopefully improved by Mebendazol. PMID:6222434

  14. Immunohistochemical localization of spatacsin in ?-synucleinopathies.

    PubMed

    Kuru, Satoshi; Yoshida, Mari; Tatsumi, Shinsui; Mimuro, Maya

    2014-04-01

    Spatacsin (SPG11) is a major mutated gene in autosomal recessive spastic paraplegia with thin corpus callosum (ARHSP-TCC) and is responsible for juvenile Parkinsonism. To elucidate the role of spatacsin in the pathogenesis of ?-synucleinopathies, an immunohistochemical investigation was performed on the brain of patients with Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA) using anti-spatacsin antibody. In PD, Lewy bodies (LBs) in the brain stem were positive for spatacsin. These LBs showed intense staining in their peripheral portions and occasionally in the central cores. Lewy neurites were also spatacsin-positive. In DLB, cortical LBs were immunolabeled by spatacsin. In MSA, glial cytoplasmic inclusions (GCI) and a small fraction of neuronal cytoplasmic inclusions (NCI) were positive for spatacsin. The widespread accumulation of spatacsin observed in pathologic ?-synuclein-containing inclusions suggests that spatacsin may be involved in the pathogenesis of ?-synucleinopathies. PMID:24112408

  15. Characterisation of Lafora-like bodies and other polyglucosan bodies in two aged dogs with neurological disease.

    PubMed

    Márquez, Merce; Pérez, Lola; Serafín, Anna; Teijeira, Susana; Navarro, Carmen; Pumarola, Martí

    2010-02-01

    Canine Lafora disease is a genetic disorder of carbohydrate metabolism characterised by neurological signs and accumulation of a type of polyglucosan body (PGB), the Lafora body (LB), in the brain and other organs. Normal canine ageing is associated with accumulation of PGBs in the brain, especially those corresponding to corpora amylacea (CA). In this study, two aged dogs that presented with progressive tremors, ataxia and paraplegia had abundant PGBs throughout the brain, mainly in the hypothalamus and molecular layer of the cerebellum. Hypothalamic and cerebellar PGBs from both cases had lower alcohol-resistant metachromasia than CA when stained with toluidine blue. Immunohistochemical studies of these PGBs against neurone-specific enolase (NSE), glial fibrillary acid protein (GFAP), 200 KDa neurofilaments, S-100, Tau, ubiquitin and heat shock proteins 25 and 70, showed some differences to CA. PMID:19010069

  16. Fusing a lasting relationship between ER tubules.

    PubMed

    Moss, Tyler J; Daga, Andrea; McNew, James A

    2011-07-01

    Atlastin is an integral membrane GTPase localized to the endoplasmic reticulum (ER). In vitro and in vivo analyses indicate that atlastin is a membrane fusogen capable of driving membrane fusion, suggesting a role in ER structure and maintenance. Interestingly, mutations in the human atlastin-1 gene, SPG3A, cause a form of autosomal dominant hereditary spastic paraplegia (HSP). The etiology of HSP is unclear, but two predominant forms of the disorder are caused by mutant proteins that affect ER structure, formation and maintenance in motor neurons. In this review, we describe the current knowledge about the molecular mechanism of atlastin function and its potential role in HSP. Greater understanding of the function of atlastin and associated proteins should provide important insight into normal ER biogenesis and maintenance, as well as the pathology of disease. PMID:21550242

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

    PubMed

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

    2011-07-01

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

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

    SciTech Connect

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

    2012-02-15

    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.

  19. An aggressive vertebral hemangioma in pregnancy: a case report

    PubMed Central

    2014-01-01

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

  20. 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.

  1. Physiological Responses to Exergaming After Spinal Cord Injury

    PubMed Central

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

    2012-01-01

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

  2. Genetic Analysis of Inherited Leukodystrophies

    PubMed Central

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

    2014-01-01

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

  3. Anterolateral radical debridement and interbody bone grafting combined with transpedicle fixation in the treatment of thoracolumbar spinal tuberculosis.

    PubMed

    Cheng, Zhaohui; Wang, Jian; Zheng, Qixin; Wu, Yongchao; Guo, Xiaodong

    2015-04-01

    This retrospective cohort study was conducted to evaluate the clinical outcomes of radical anterolateral debridement and autogenous ilium with rib or titanium cage interbody autografting with transpedicle fixation for the treatment of thoracolumbar tuberculosis.Spinal tuberculosis operation aims to remove the lesions and necrotic tissues, remove spinal cord compression, and reconstruct spinal stability. However, traditional operation methods cannot effectively correct cyrtosis or stabilize the spine. In addition, the patient needs to stay in bed for a long time and may have many complications. So far, the best surgical method and fixation method for spinal tuberculosis remain controversial.There were a total of 43 patients, 16 involving spinal cord injury, from January 2004 to January 2011. The patients were surgically treated for radical anterolateral debridement via posterolateral incision and autogenous ilium with rib or titanium cage interbody autografting and single-stage transpedicle fixation. All the patients were followed up to determine the stages of intervertebral bone fusion and the corrections of spinal kyphosis with the restoration of neurological deficit.The erythrocyte sedimentation rate (ESR) of these patients decreased to normal levels for a mean of 2.8 months. The function of feeling, motion, and sphincter in 16 paraplegia cases gradually recovered after 1 week to 3 months postoperatively, and the American Spinal Injury Association scores significantly increased at the final follow-up. Intervertebral bone fusions were all achieved postoperatively. No internal fixation devices were loose, extracted, or broken. There was no correction degree loss during the follow-up.The method of radical anterolateral debridement and autogenous ilium with rib or titanium cage interbody autografting and single-stage transpedicle fixation was effective for the treatment of thoracolumbar tuberculosis, correcting kyphotic deformity, and reconstructing spinal stability, obtaining successful intervertebral bony fusion and promoting the recovery of paraplegia. These results showed satisfactory clinical outcomes. PMID:25860219

  4. 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

  5. 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.

  6. 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.

  7. 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

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

    PubMed

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

    1998-03-01

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

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

    PubMed Central

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

    2012-01-01

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

  10. Operation of a brain-computer interface walking simulator for individuals with spinal cord injury

    PubMed Central

    2013-01-01

    Background Spinal cord injury (SCI) can leave the affected individuals with paraparesis or paraplegia, thus rendering them unable to ambulate. Since there are currently no restorative treatments for this population, novel approaches such as brain-controlled prostheses have been sought. Our recent studies show that a brain-computer interface (BCI) can be used to control ambulation within a virtual reality environment (VRE), suggesting that a BCI-controlled lower extremity prosthesis for ambulation may be feasible. However, the operability of our BCI has not yet been tested in a SCI population. Methods Five participants with paraplegia or tetraplegia due to SCI underwent a 10-min training session in which they alternated between kinesthetic motor imagery (KMI) of idling and walking while their electroencephalogram (EEG) were recorded. Participants then performed a goal-oriented online task, where they utilized KMI to control the linear ambulation of an avatar while making 10 sequential stops at designated points within the VRE. Multiple online trials were performed in a single day, and this procedure was repeated across 5 experimental days. Results Classification accuracy of idling and walking was estimated offline and ranged from 60.5% (p?=?0.0176) to 92.3% (p?=?1.36×10?20) across participants and days. Offline analysis revealed that the activation of mid-frontal areas mostly in the ? and low ? bands was the most consistent feature for differentiating between idling and walking KMI. In the online task, participants achieved an average performance of 7.4±2.3 successful stops in 273±51 sec. These performances were purposeful, i.e. significantly different from the random walk Monte Carlo simulations (p<0.01), and all but one participant achieved purposeful control within the first day of the experiments. Finally, all participants were able to maintain purposeful control throughout the study, and their online performances improved over time. Conclusions The results of this study demonstrate that SCI participants can purposefully operate a self-paced BCI walking simulator to complete a goal-oriented ambulation task. The operation of the proposed BCI system requires short training, is intuitive, and robust against participant-to-participant and day-to-day neurophysiological variations. These findings indicate that BCI-controlled lower extremity prostheses for gait rehabilitation or restoration after SCI may be feasible in the future. PMID:23866985

  11. 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

  12. 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

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

    PubMed Central

    2010-01-01

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

  14. Potential beneficial effects of granulocyte colony-stimulating factor therapy for spastic paraparesis in a patient with kyphoscoliosis: a case report.

    PubMed

    Sienkiewicz, Dorota; Ku?ak, Wojciech; Okurowska-Zawada, Bo?ena; Wojtkowski, Janusz; Paszko-Patej, Gra?yna; Dmitruk, El?bieta; Kalinowska, Anna; Okulczyk, Kamila

    2014-10-01

    Congenital kyphosis and kyphoscoliosis are much less common than congenital scoliosis and more serious because these curves can progress rapidly and can lead to spinal cord compression and paraplegia. A 15-year-old boy presented with congenital kyphoscoliosis along with spastic paraparesis (American Spinal Injury Association Impairment Scale grade C). We examined the safety and effectiveness of a low dose of analog granulocyte colony-stimulating factor (G-CSF) in this patient. G-CSF 5 µg/kg was given subcutaneously, daily for 5 days per month for 3 months. Laboratory tests, including blood, biochemical tests, and CD34+ cells (marker hematopoietic progenitor cells) were performed, in addition to clinical examination. Clinical examination revealed an increase of muscle strength in the upper limbs and decrease spasticity in the lower limbs between baseline and day 90 and day 180. We found no serious adverse event, drug-related platelet reduction, or splenomegaly. Leukocyte levels remained below 21,000/µL. CD34+ increased significantly at day 5 of G-CSF administration. Low-dose G-CSF was safe and well tolerated by the patient. A significant increase in muscle strength in this patient with spastic paraparesis after 3 months of treatment may indicate beneficial effects of G-CSF factor in this disorder. These results are inspiring and warrant further studies. PMID:24752769

  15. Primary liposarcoma of the thoracic spine: case report.

    PubMed

    Hamlat, Abderrahmane; Saikali, Stephan; Gueye, Edouard-Marcel; Le Strat, Anne; Carsin-Nicol, Beatrice; Brassier, Gilles

    2005-08-01

    Liposarcoma is a malignant tumor of soft tissue. The thoracic spine is an unusual location, even for metastasis, and to our knowledge, no case of primary pleomorphic liposarcoma of the vertebral body has been reported until now. A female patient presented with paraplegia. She had a previous medical history of mental depression, and complained of dorsal pain for three months following a road accident. Magnetic Resonance Imaging (MRI) revealed a collapse of T7-T8, and the diagnosis of plasmocytoma was made. She was treated with decompressive laminectomy and posterior instrumentation. Histological examination revealed a pleomorphic liposarcoma. She received a course of radiotherapy. At 13 months follow-up she developed pulmonary metastases and rib involvement. The spine is an unusual location for pleomorphic liposarcoma, even as metastasis. The differential diagnoses of this rare entity are discussed, as well as the criteria for diagnosing primary spinal liposarcoma. Although rare, our case demonstrates that liposarcoma should be considered in the differential diagnosis of spinal tumors. PMID:15864668

  16. Role of calf muscle stimulation in the prevention of DVT in Indian patients undergoing surgeries for fractures around the hip

    PubMed Central

    Goyal, Aman; Arora, Sumit; Batra, Sumit; Sharma, Rohit; Mittal, Mahesh Kumar; Sharma, Vinod K

    2012-01-01

    Background: The venous stasis of soleal vein during surgery may be an important factor in the development of deep vein thrombosis (DVT). The stimulation of calf muscle during surgery may help in preventing DVT. The present study is conducted to evaluate the role of peroperative calf muscle electrostimulation in prevention of DVT in patients undergoing surgeries around the hip joint. Materials and Methods: The study comprised 200 patients undergoing surgeries around the hip joint. The patients having risk factors (such as previous myocardial infarction, malignancies, paraplegia or lower limb monoplegia, previous history of DVT or varicose veins, etc.) for the development of DVT were excluded. They were randomized into two groups: 100 cases were given peroperative calf muscle electrostimulation for DVT prophylaxis (Group A) and the remaining 100 patients were taken as controls without any prophylaxis (Group B). The color Doppler ultrasound was performed to exclude pre-existing DVT and on 7th day postoperative to find out the incidence of DVT in both the groups. Results: Two patients among Group A and six patients among Group B demonstrated DVT on ultrasonography, but the difference was not found to be statistically significant (P=0.279). None of the patients had any clinical evidence of DVT. Conclusion: The role of peroperative calf muscle electrostimulation for DVT prophylaxis remains controversial. The risk of developing DVT in patients undergoing surgeries around the hip joint is very less in patients analysed in our series. PMID:23162147

  17. 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

  18. Acute onset intramedullary spinal cord abscess with spinal artery occlusion: a case report and review.

    PubMed

    Iwasaki, Motoyuki; Yano, Shunsuke; Aoyama, Takeshi; Hida, Kazutoshi; Iwasaki, Yoshinobu

    2011-07-01

    Intramedullary spinal cord abscess (ISCA) without meningitis is an extremely rare entity in the central nervous system, and it is often difficult to diagnose immediately, and no definitive imaging findings have been established. We experienced the case of a 61-year-old male who presented with a sudden onset back pain without fever following rapidly worsening paraparesis for 3 days, who subsequently become unable to walk. According to the initial MRI and 3D-CTA, the presumptive diagnosis was spinal infarction due to spinal artery embolism. However, his symptoms did not improve, despite the gradual changes in MRI following antiplatelet therapy. He underwent a biopsy in an attempt to prevent the lesion from progressing toward the upper spinal cord. The pathological examination revealed an intramedullary abscess, so we performed a midline myelotomy and drained the pus from the abscess. After surgery, MRI showed improvement, but the patient's paraplegia persisted. To the best of our knowledge, this is the first case report of spinal cord abscess with the confirmation of spinal artery occlusion on angiography, which could have been caused by a bacterial embolism. We herein discuss its possible etiology and also review recent reports on ISCA. PMID:21308472

  19. Spinal cord protection with selective spinal perfusion during descending thoracic and thoracoabdominal aortic surgery.

    PubMed

    Kawaharada, Nobuyoshi; Ito, Toshiro; Koyanagi, Tetsuya; Harada, Ryo; Hyodoh, Hideki; Kurimoto, Yoshihiko; Watanabe, Atsushi; Higami, Tetsuya

    2010-06-01

    Open repair of aortic aneurysm causes spinal cord perfusion pressure to decrease due to the steal phenomenon from the bleeding of intercostal arteries and cross-clamping of the aorta. We attempted to perfuse the intercostal arteries for preoperative detection of the artery of Adamkiewicz using newly developed catheters. Fifteen patients underwent selective spinal perfusion with our original catheter as spinal protection during the procedure of distal descending thoracic aneurysm (DTA) or thoracoabdominal aortic aneurysm (TAAA) repair. Seven patients had distal DTA and eight had TAAA. Monitoring of motor evoked potential (MEP) was performed in all patients throughout the operation. The perfusion flow was 30-40 ml/min for each intercostal artery and was adjusted to keep the proximal circuit pressure at 150-200 mmHg. The average number of perfused intercostal arteries was 2.3 per patient and the number of intercostal arteries reimplanted per patient was 2.5. Intercostal arteries were reimplanted using an interpositional graft. MEPs were still observable after graft replacement in all patients and there were no cases of paraparesis/paraplegia. All patients were discharged ambulatory. Selective spinal perfusion maintains the quantity of total blood flow in the spinal cord and is very useful for reducing the incidence of ischemic injury of the spinal cord during operation. PMID:20233810

  20. Chondrosarcoma apoplexy in thoracic spine.

    PubMed

    Kim, Sang Woo; Kim, Min Su; Jung, Young Jin

    2013-01-01

    Chondrosarcoma is a very uncommon malignant primary bone tumor, especially, it occurs extremely rare in the spine. A 52-year-old man was admitted to the emergency room with sudden paraplegia. Twelve hours prior to a paraplegic event, he visited an outpatient clinic with discomfort and tenderness around the medial border of the right scapular, and his neurologic status was absolutely intact. Magnetic resonance imaging showed a lobulated soft tissue mass from T3 to T5, which extended to the epidural space. Computed tomography scans showed soft tissue mass on the spinal posterior arch and osteolytic change of the adjacent bony structures. Emergent surgery was performed and the lesion was removed. Dark reddish blood and gel-like material were encountered around the dura and posterior arch during the operation. Multiple pulmonary nodules were found on a chest CT scan and a biopsy of one of them had been proven to be a metastasis of chondrosarcoma. The histologic examination showed dedifferentiated chondrosarcoma. The patient's neurologic deficit was improved slowly from ASIA A to ASIA D. Chondrosarcoma in the spine is extremely rare, even more with acute hemorrhage and sudden expansion into the epidural space. We named it chondrosarcoma apoplexy. We should consider the possibility of a hemorrhagic event when the patient's neurologic deficit worsens suddenly with spinal bone tumor. PMID:23441034

  1. Body mass index underestimates adiposity in women with spinal cord injury

    PubMed Central

    Yarar-Fisher, Ceren; Chen, Yuying; Jackson, Amie B.; Hunter, Gary R.

    2012-01-01

    Objective To assess the relationship between body mass index (BMI) and adiposity as well as the influence of injury level on this relationship in 24 women with spinal cord injury (SCI) and 23 able-bodied (AB) women with similar age, race, and BMI. Design and methods Body composition was measured by dual energy x-ray absorptiometry (DXA). Analysis of covariance was performed to compare total and regional soft tissue percent fat (PF) measures between groups. Results Women with SCI had a higher soft tissue PF than AB women at any given BMI. The BMI-adjusted soft tissue PF (mean ± SE) was 44.4 ± 1.8%, 37.8 ± 1.3%, and 35.9 ±1.1% for tetraplegic, paraplegic, and AB women, respectively. The BMI explained about equal amounts of the variance in soft tissue PF among paraplegic and AB women (65%), but only 28% in tetraplegic women. Conclusion This study confirms a limited use of BMI in measuring adiposity in women with SCI, particularly among those with tetraplegia. Our observation of lower BMI cutoff points for defining obesity (28 kg/m2 for paraplegia and 21 kg/m2 for tetraplegia) needs further confirmation. The underweight/malnutrition issue also deserves the consideration while proposing the ideal weight and BMI range for persons with SCI. PMID:23913734

  2. 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

  3. Artificial gait in complete spinal cord injured subjects: how to assess clinical performance.

    PubMed

    Pithon, Karla Rocha; Abreu, Daniela Cristina Carvalho de; Vasconcelos-Neto, Renata; Martins, Luiz Eduardo Barreto; Cliquet-Jr, Alberto

    2015-02-01

    Objective Adapt the 6 minutes walking test (6MWT) to artificial gait in complete spinal cord injured (SCI) patients aided by neuromuscular electrical stimulation. Method Nine male individuals with paraplegia (AIS A) participated in this study. Lesion levels varied between T4 and T12 and time post injured from 4 to 13 years. Patients performed 6MWT 1 and 6MWT 2. They used neuromuscular electrical stimulation, and were aided by a walker. The differences between two 6MWT were assessed by using a paired t test. Multiple r-squared was also calculated. Results The 6MWT 1 and 6MWT 2 were not statistically different for heart rate, distance, mean speed and blood pressure. Multiple r-squared (r2 = 0.96) explained 96% of the variation in the distance walked. Conclusion The use of 6MWT in artificial gait towards assessing exercise walking capacity is reproducible and easy to apply. It can be used to assess SCI artificial gait clinical performance. PMID:25742579

  4. Clinical mitochondrial genetics

    PubMed Central

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

    1999-01-01

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

  5. Spontaneous epidural hematoma of spine associated with clopidogrel: A case study and review of the literature.

    PubMed

    Bhat, Khalid Javid; Kapoor, Sidhart; Watali, Yamin Zahoor; Sharma, Jaggatar Ram

    2015-01-01

    Spontaneous spinal epidural hematoma (SSEH) is an uncommon neurological emergency which can present with the features ranging from simple back pain with radiculopathy to complete paraplegia or quadriplegia depending on the site and severity of the compression. Spinal hemorrhage associated with anti-platelet drugs is rarely seen. We report a case of SSEH in a 68-year-old hypertensive male who was on a low dose clopidogrel for secondary stroke prophylaxis and presented with bilateral lower limb paralysis, preceeded by severe back bain. A spinal magnetic resonance imaging scan was performed which revealed a posterior epidural hematoma of the thoraco-lumbar spine. To the best of our knowledge, not more than four cases of clopidogrel related spinal epidural hematoma have been reported. Emergent decompressive laminectomy was done within 4 hours of the presentation with excellent clinical outcome. Clinicians should, therefore, consider the remote risk of SSEH in hypertensive patients who are on anti-platelet drugs as early decompressive laminectomy and evacuation of the hematoma minimizes the permanent neurological damage. PMID:25767588

  6. Souffle/Spastizin Controls Secretory Vesicle Maturation during Zebrafish Oogenesis

    PubMed Central

    Riedel, Dietmar; Schomburg, Christoph; Cerdà, Joan; Vollack, Nadine; Dosch, Roland

    2014-01-01

    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

  7. Axonal degeneration in paraplegin-deficient mice is associated with abnormal mitochondria and impairment of axonal transport

    PubMed Central

    Ferreirinha, Fatima; Quattrini, Angelo; Pirozzi, Marinella; Valsecchi, Valentina; Dina, Giorgia; Broccoli, Vania; Auricchio, Alberto; Piemonte, Fiorella; Tozzi, Giulia; Gaeta, Laura; Casari, Giorgio; Ballabio, Andrea; Rugarli, Elena I.

    2004-01-01

    In several neurodegenerative diseases, axonal degeneration occurs before neuronal death and contributes significantly to patients’ disability. Hereditary spastic paraplegia (HSP) is a genetically heterogeneous condition characterized by selective degeneration of axons of the corticospinal tracts and fasciculus gracilis. HSP may therefore be considered an exemplary disease to study the local programs mediating axonal degeneration. We have developed a mouse model for autosomal recessive HSP due to mutations in the SPG7 gene encoding the mitochondrial ATPase paraplegin. Paraplegin-deficient mice are affected by a distal axonopathy of spinal and peripheral axons, characterized by axonal swelling and degeneration. We found that mitochondrial morphological abnormalities occurred in synaptic terminals and in distal regions of axons long before the first signs of swelling and degeneration and correlated with onset of motor impairment during a rotarod test. Axonal swellings occur through massive accumulation of organelles and neurofilaments, suggesting impairment of anterograde axonal transport. Retrograde axonal transport is delayed in symptomatic mice. We speculate that local failure of mitochondrial function may affect axonal transport and cause axonal degeneration. Our data suggest that a timely therapeutic intervention may prevent the loss of axons. PMID:14722615

  8. The effects of exercise on human articular cartilage

    PubMed Central

    Eckstein, F; Hudelmaier, M; Putz, R

    2006-01-01

    The effects of exercise on articular hyaline articular cartilage have traditionally been examined in animal models, but until recently little information has been available on human cartilage. Magnetic resonance imaging now permits cartilage morphology and composition to be analysed quantitatively in vivo. This review briefly describes the methodological background of quantitative cartilage imaging and summarizes work on short-term (deformational behaviour) and long-term (functional adaptation) effects of exercise on human articular cartilage. Current findings suggest that human cartilage deforms very little in vivo during physiological activities and recovers from deformation within 90 min after loading. Whereas cartilage deformation appears to become less with increasing age, sex and physical training status do not seem to affect in vivo deformational behaviour. There is now good evidence that cartilage undergoes some type of atrophy (thinning) under reduced loading conditions, such as with postoperative immobilization and paraplegia. However, increased loading (as encountered by elite athletes) does not appear to be associated with increased average cartilage thickness. Findings in twins, however, suggest a strong genetic contribution to cartilage morphology. Potential reasons for the inability of cartilage to adapt to mechanical stimuli include a lack of evolutionary pressure and a decoupling of mechanical competence and tissue mass. PMID:16637874

  9. Catastrophic injuries in pole-vaulters.

    PubMed

    Boden, B P; Pasquina, P; Johnson, J; Mueller, F O

    2001-01-01

    Pole vaulting is a unique sport in that athletes often land from heights ranging from 10 to 20 feet. We retrospectively reviewed 32 catastrophic pole-vault injuries that were reported to the National Center for Catastrophic Sports Injury Research between 1982 and 1998. The purpose of this study was to determine the mechanisms of injury so that preventive strategies can be implemented. Information was obtained by means of a telephone interview with someone familiar with the accident. All injuries occurred in male athletes at an average age of 17.5 years; 31 were catastrophic head injuries and 1 was a thoracic spine fracture that resulted in paraplegia. Three common mechanisms were identified: 17 (53%) athletes landed with their body on the landing pad and their head on the surrounding hard ground, 8 (25%) landed in the vault box after being stranded at the height of the jump, and 5 (16%) completely missed the landing pad. The mechanism of injury in the remaining two athletes was unknown. The accident resulted in death in 16 (50%) athletes and in permanent disability in 6 (19%). Increasing the minimum landing pad size and enforcing the rule requiring soft surfaces adjacent to the landing pads are the primary recommendations for preventing injuries. The authors discuss other rule and equipment changes that may help reduce the occurrence of future injuries. PMID:11206256

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

    PubMed Central

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

    2014-01-01

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

  11. Emergency Diagnosis of Giant Cell Tumour (GCT) of Spine by Image Guided Fine Needle Aspiration Cytology (FNAC)

    PubMed Central

    Chaudhry, Manish; Singh, Amitoj

    2014-01-01

    Giant cell tumour (GCT) of spine is an extremely rare neoplasm accounting 0.5% to 1.5% of all cases. The patient usually presents with weakness of lower limbs. We describe a case of 25-year-old male who presented with sudden onset of paraplegia. On plain radiograph there was an osteolytic lesion in T9 vertebra. Computed tomography (CT) scan revealed expansile lytic lesion in T9 vertebral body with involvement of posterior elements on right side with associated soft tissue mass in the extradural location extending into the spinal cord. Further Magnetic Resonance Imaging (MRI) scan (T1 contrast) showed the enhancing extradural mass involving spinal cord from D 8-10 levels. A provisional radiological diagnosis of GCT was made. A CT guided FNAC of the mass was performed which revealed typical cytological features of Giant cell tumour. Role of image guided Fine Needle Aspiration Cytology (FNAC) of vertebral mass and its role in emergency situations with clear emphasis on differential diagnosis is highlighted. PMID:25177571

  12. [Spinal ischemia after biiliac aneurysm surgery related to Behçet's disease diagnosed two years later].

    PubMed

    Alami, A; Haddani, J; Ouardi, F; Toumi, Y; Mehadji, B A

    2002-06-01

    A 26-year-old woman underwent bypass surgery for biiliac aneurysm of unknown origin. The aorta was cross clamped below the renal arteries to insert a tube graft between the infra-renal aorta and the external iliac arteries with implantation of the internal iliac arteries on the prosthesis. Due to leakage from the posterior area of the proximal anastomosis, the proximal suture was redone. Total cross clamping lasted 65 minutes. No blood pressure drop was noted during or after the procedure. Postoperatively, the neurological examination revealed paraplegia with mild sensorial deficit and fecal and urinary incontinence. The fecal and urinary deficit resolved three months later. Nearly complete motor recovery was noted at the 18(th) postoperative month. The patient then presented oral and genital ulceration at 22 months postop leading to the diagnosis of Behçet's disease. Several risk factors have been suggested to explain spinal ischemia after abnormal aortic surgery: anatomic variablility of spinal perfusion, duration of aortic cross clamping, and intra- or postoperative episodes of hypotension. Thrombotic damage to the arterial system due to Behçet's disease could also perturb spinal blood supply and reproduce one of the mechanisms incriminated in ischemic spinal lesions occurring during aortic surgery for atheromatous aneurysm. PMID:12232534

  13. The Mitochondrial K-ATP Channel Opener, Diazoxide, Prevents Ischemia-Reperfusion Injury in the Rabbit Spinal Cord

    PubMed Central

    Roseborough, Glen; Gao, Daqing; Chen, Lei; Trush, Michael A.; Zhou, Shaoyu; Williams, G. Melville; Wei, Chiming

    2006-01-01

    Paraplegia resulting from ischemia is a catastrophic complication of thoracoabdominal aortic surgery. The current study was designed to investigate the effects of diazoxide (DZ) on mitochondrial structure, neurological function, DNA damage-repair, and apoptosis in spinal cord ischemia-reperfusion injury. Rabbits were subjected to 30 minutes of spinal cord ischemia and reperfusion (1 hour) with or without diazoxide (n = 6 in each group) by clamping and releasing the infrarenal aorta. The neurological functional score was significantly improved in the DZ-treated ischemia-reperfusion injury group. Electron microscopic studies demonstrated that mitochondrial damage in the spinal cord after injury was significantly reduced by DZ. Mitochondrial superoxide and hydrogen peroxide levels were also markedly decreased in the DZ-treated injury group compared with the untreated group. DZ decreased levels of the oxidative DNA damage product 8-oxoG and increased levels of the DNA repair enzyme OGG-1. Furthermore, DZ inhibited apoptosis via caspase-dependent and -independent pathways. These studies indicate for the first time that the mitochondrial K-ATP channel opener diazoxide improves neurological function after spinal cord ischemia and reperfusion by diminishing levels of reactive oxygen species, decreasing DNA oxidative damage, and inhibiting caspase-dependent and -independent apoptotic pathways while preserving mitochondrial structure. PMID:16651612

  14. Spinal cord infarction remote from maximal compression in a patient with Morquio syndrome.

    PubMed

    Tong, Calvin K W; Chen, James C H; Cochrane, D Douglas

    2012-06-01

    Morquio syndrome, or mucopolysaccharidosis type IV, is a rare enzyme deficiency disorder and results in skeletal dysplasia. Odontoid dysplasia is common among affected patients, resulting in atlantoaxial instability and spinal cord compression. Surgical treatments include decompression and prophylactic fusion, during which intraoperative neuromonitoring is important to alert the surgical team to changes in cord function so that they can prevent or mitigate spinal cord injury. This report describes a 16-year-old girl with Morquio syndrome who developed paraplegia due to thoracic spinal cord infarction during foramen magnum and atlantal decompression. This tragic event demonstrates the following: 1) that patients with Morquio syndrome are at risk for ischemic spinal cord injury at levels remote from areas of maximal anatomical compression while under anesthesia in the prone position, possibly due to impaired cardiac output; 2) the significance of absent motor evoked potential responses in the lower limbs with preserved upper-limb responses in an ambulatory patient; 3) the importance of establishing intraoperative neuromonitoring baseline assessments prior to turning patients to the prone position following induction of anesthesia; and 4) the importance of monitoring cardiac output during prone positioning in patients with chest wall deformity. PMID:22656250

  15. 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.

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

    PubMed

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

    2014-03-01

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

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

    PubMed

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

    2012-01-01

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

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

    PubMed

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

    2014-01-01

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

  19. Increased spasticity from a fracture in the baclofen catheter caused by charcot spine: case report.

    PubMed

    Ravindra, Vijay M; Ray, Wilson Z; Sayama, Christina M; Dailey, Andrew T

    2015-04-01

    In patients with Charcot spine, a loss of normal feedback response from the insensate spine results in spinal neuropathy. Increasing deformity, which can manifest as sitting imbalance, crepitus, or increased back pain, can result. We present the case of a patient with a high-thoracic spinal cord injury (SCI) who subsequently developed a Charcot joint at the T10-11 level that resulted in a dramatic increase in previously controlled spasticity after fracture of an existing baclofen catheter. The 68-year-old man with T4 paraplegia presented with increasing baclofen requirements and radiographic evidence of fracture of the intrathecal baclofen catheter with an associated Charcot joint with extensive bony destruction. The neuropathic spinal arthropathy caused mechanical baclofen catheter malfunction and resulting increased spasticity. The patient was found to have transected both his spinal cord and the baclofen catheter. Treatment consisted of removal of the catheter and stabilization with long-segment instrumentation and fusion from T6 to L2. Follow-up radiographs obtained a year and a half after surgery showed no evidence of hardware failure or significant malalignment. The patient has experienced resolution of symptoms and does not require oral or intrathecal baclofen. This is the only reported case of a Charcot spine causing intrathecal catheter fracture, leading to increased spasticity. This noteworthy case suggests that late spinal instability should be considered in the setting of SCI and increased spasticity. PMID:25461826

  20. A rare presentation of subacute progressive ascending myelopathy secondary to cement leakage in percutaneous vertebroplasty.

    PubMed

    Bhide, Rohit Prakash; Barman, Apurba; Varghese, Shiela Mary; Chatterjee, Ahana; Mammen, Suraj; George, Jacob; Thomas, Raji

    2014-05-01

    Percutaneous vertebroplasty is used to manage osteoporotic vertebral body compression fractures. Although it is relatively safe, complications after vertebroplasty ranging from minor to devastatingly major ones have been described. Cement leakage into the spinal canal is one such complication. Subacute progressive ascending myelopathy is an infrequent neurologic complication after spinal cord injury, typically presenting as ascending neurologic deficit within weeks after the initial insult. The precise cause of subacute progressive ascending myelopathy still remains an enigma, considering the rarity of this disorder. The authors present the case of a 62-yr-old woman with osteoporotic vertebral fracture who underwent percutaneous vertebroplasty and developed T6 complete paraplegia because of cement leakage. A few weeks later, the neurologic level ascended to higher cervical level (C3). To date, no case of subacute progressive ascending myelopathy secondary to cement leakage after percutaneous vertebroplasty has been reported. Literature is reviewed regarding subacute progressive ascending myelopathy, and the rehabilitation challenges in the management of this patient are discussed. PMID:24322431

  1. 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

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

    PubMed

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

    2013-11-01

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

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

    PubMed Central

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

    2014-01-01

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

  4. 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

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

    PubMed Central

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

    2014-01-01

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

  6. 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

  7. 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

  8. Spontaneous epidural hematoma of spine associated with clopidogrel: A case study and review of the literature

    PubMed Central

    Bhat, Khalid Javid; Kapoor, Sidhart; Watali, Yamin Zahoor; Sharma, Jaggatar Ram

    2015-01-01

    Spontaneous spinal epidural hematoma (SSEH) is an uncommon neurological emergency which can present with the features ranging from simple back pain with radiculopathy to complete paraplegia or quadriplegia depending on the site and severity of the compression. Spinal hemorrhage associated with anti-platelet drugs is rarely seen. We report a case of SSEH in a 68-year-old hypertensive male who was on a low dose clopidogrel for secondary stroke prophylaxis and presented with bilateral lower limb paralysis, preceeded by severe back bain. A spinal magnetic resonance imaging scan was performed which revealed a posterior epidural hematoma of the thoraco-lumbar spine. To the best of our knowledge, not more than four cases of clopidogrel related spinal epidural hematoma have been reported. Emergent decompressive laminectomy was done within 4 hours of the presentation with excellent clinical outcome. Clinicians should, therefore, consider the remote risk of SSEH in hypertensive patients who are on anti-platelet drugs as early decompressive laminectomy and evacuation of the hematoma minimizes the permanent neurological damage.

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

    SciTech Connect

    Alexander, T.S.

    1987-01-01

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

  10. 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

  11. Fibromyalgia and arachnoiditis presented as an acute spinal disorder

    PubMed Central

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

    2014-01-01

    Background: Adhesive arachnoiditis is a chronic, insidious condition that causes debilitating intractable pain and a range of other neurological problems. Its pathophysiology is not well understood. This manuscript discusses its presentations, which can mimic an acute spinal disorder, its hypothetical pathophysiology, treatment, and its relationship with fibromyalgia. Case Description: The authors present a case of a 47-year-old female who presented with clinical features mimicking an acute spinal disorder but later found to have an adhesive arachnoiditis. She was admitted following a trauma with complaints of back pain and paraplegia. On examination, there was marked tenderness over thoracolumbar spine with lower limbs upper motor neuron weakness. An urgent magnetic resonance imaging (MRI) of the spine revealed multiple lesions at her thoracic and lumbar spinal canals, which did not compress the spinal cord. Therefore, conservative management was initiated. Despite on regular therapies, her back and body pain worsened and little improvement in her limbs power was noted. Laminectomy was pursued and found to have spinal cord arachnoiditis. Subsequently, she was operated by other team members for multiple pelvic masses, which later proved to be benign. After gathering all the clinical information obtained at surgery and after taking detailed history inclusive of cognitive functions, diagnosis of an adhesive arachnoiditis syndrome was made. Currently, she is managed by neuropsychologist and pain specialist. Conclusion: This case report highlights the importance of knowing an adhesive arachnoiditis syndrome – a rarely discussed pathology by the neurosurgeon, which discloses a significant relationship between immune and nervous systems. PMID:25396073

  12. Temporal and tissue specific gene expression patterns of the zebrafish kinesin-1 heavy chain family, kif5s, during development

    PubMed Central

    Campbell, Philip D.; Marlow, Florence L.

    2013-01-01

    Homo- and heterodimers of Kif5 proteins form the motor domain of Kinesin-1, a major plus-end directed microtubule motor. Kif5s have been implicated in the intracellular transport of organelles, vesicles, proteins, and RNAs in many cell types. There are three mammalian KIF5s. KIF5A and KIF5C proteins are strictly neural in mouse whereas, KIF5B is ubiquitously expressed. Mouse knockouts indicate crucial roles for KIF5 in development and human mutations in KIF5A lead to the neurodegenerative disease Hereditary Spastic Paraplegia. However, the developmental functions and the extent to which individual kif5 functions overlap have not been elucidated. Zebrafish possess five kif5 genes: kif5Aa, kif5Ab, kif5Ba, kif5Bb, and kif5C. Here we report their tissue specific expression patterns in embryonic and larval stages. Specifically, we find that kif5As are strictly zygotic and exhibit neural-specific expression. In contrast, kif5Bs exhibit strong maternal contribution and are ubiquitously expressed. Lastly, kif5C exhibits weak maternal expression followed by enrichment in neural populations. In addition, kif5s show distinct expression domains in the larval retina. PMID:23684767

  13. An ESCRT–spastin interaction promotes fission of recycling tubules from the endosome

    PubMed Central

    Allison, Rachel; Lumb, Jennifer H.; Fassier, Coralie; Connell, James W.; Ten Martin, Daniel; Seaman, Matthew N.J.; Hazan, Jamilé

    2013-01-01

    Mechanisms coordinating endosomal degradation and recycling are poorly understood, as are the cellular roles of microtubule (MT) severing. We show that cells lacking the MT-severing protein spastin had increased tubulation of and defective receptor sorting through endosomal tubular recycling compartments. Spastin required the ability to sever MTs and to interact with ESCRT-III (a complex controlling cargo degradation) proteins to regulate endosomal tubulation. Cells lacking IST1 (increased sodium tolerance 1), an endosomal sorting complex required for transport (ESCRT) component to which spastin binds, also had increased endosomal tubulation. Our results suggest that inclusion of IST1 into the ESCRT complex allows recruitment of spastin to promote fission of recycling tubules from the endosome. Thus, we reveal a novel cellular role for MT severing and identify a mechanism by which endosomal recycling can be coordinated with the degradative machinery. Spastin is mutated in the axonopathy hereditary spastic paraplegia. Zebrafish spinal motor axons depleted of spastin or IST1 also had abnormal endosomal tubulation, so we propose this phenotype is important for axonal degeneration. PMID:23897888

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

    Objectives: We present our experience of endovascular surgery for traumatic aortic injury and the results of our procedures. Materials and Methods: From January 2009 to December 2013, we performed endovascular repairs of traumatic thoracic aortic injury on 5 male patients 16–75 years old (mean, 50.8), two of whom were young. Three of the patients had multiple organ injuries. The mean interval time to the operation is 22.0 hours (range, 10–36). All patients underwent endovascular repair with heparinization. The isthmus regions were seen in three cases and all of them were needed left subclavian artery (LSA) coverage. In the two young patients, the deployed stent graft was 22 mm (22.2% oversizing for diameter of aorta) and 26 mm (36.8% oversizing), respectively. Results: The procedures were successful in all patients, with no early mortality, paraplegia or stroke. During 3–63 months (mean, 30.8) follow-up period, no one experienced stent graft-related complications. One patient with LSA coverage experienced arm ischemia but the symptom improved with time. Conclusion: Endovascular surgery for traumatic thoracic aortic injury can be performed safely with low mortality or morbidity even in young small aorta. Accumulation of clinical experience and evaluation of long-term outcomes are necessary. PMID:25298833

  16. A case of very long-term appearing drug tolerance to intrathecal baclofen.

    PubMed

    Dones, I; Broggi, G

    2010-06-01

    A 66-year-old man affected by familial spastic paraplegia since he was 22 developed drug tolerance to intrathecal baclofen after 16 years of treatment A stable dosage of 850 microg/day, achieved after the first two years, appeared to be progressively inadeguate to relief his spasticity. No other evidence of additional diseases or progression of his neurological disease were recognized. The daily dosage was then increased to 1200 microg/day without any decrease in spasticity or improvement in the patient's motor performance. Thus a slow and progressive decrease of the daily dosage was performer by 10% each 15 days while the patient's clinical condition was monitored. The patient reached a complete withdrawal of the baclofen administration experiencing the same spasticity and motor performance he experienced at the beginning of his therapy with intrathecal baclofen in 1991. The patient was then kept on drug holiday for three months without any variation in his clinical picture. A stabilized daily baclofen dosage of 250 microg was then reached to maintain the same improvement of motor performance that the patient had experienced before the onset of drug-tolerance signs. Some cases of drug tolerance to intrathecal baclofen were previously reported but this is an original case of very long-term onset of this phenomenon. PMID:21313959

  17. Acute disseminated encephalomyelitis after allogeneic bone marrow transplantation for pure red cell aplasia - a case report and review of the literature.

    PubMed

    Paisiou, Anna; Goussetis, Evgenios; Dimopoulou, Maria; Kitra, Vassiliki; Peristeri, Ioulia; Vessalas, Giorgos; Gavra, Maria; Theodorou, Virginia A; Graphakos, Stelios

    2013-03-01

    ADEM is a rare inflammatory demyelinating disease of the CNS, which usually presents after a viral infection or a vaccination. We report a 15-yr-old boy who was diagnosed with ADEM after an HLA-identical sibling allogeneic BMT for transfusion-dependent PRCA. His course was complicated with GVHD affecting the skin and lungs. Five months post-BMT, he developed neurological symptoms including sudden mental status alteration, dysarthria, facial nerve palsy, and acute paraplegia. The MRI revealed multifocal hyperintense lesions mainly in the subcortical white matter of the cerebrum, the brainstem, the basal ganglia, and the thalami. CSF examination was normal. There was no laboratory evidence of infection. The typical MRI findings and an acute monophasic clinical course were consistent with the diagnosis of ADEM. Clinical and radiological improvement was observed after treatment with high-dose steroids and IVIG. Complete neurologic recovery was achieved six months after the onset of symptoms. We present a rare case of ADEM post-BMT and review of the literature. PMID:23216973

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

    PubMed Central

    2012-01-01

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

  19. Clinical imaging and neuropathological correlations in an unusual case of cerebrotendinous xanthomatosis.

    PubMed

    Wallon, D; Guyant-Maréchal, L; Laquerrière, A; Wevers, R A; Martinaud, O; Kluijtmans, L A J; Yntema, H G; Saugier-Veber, P; Hannequin, D

    2010-01-01

    Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive lipid storage disorder due to a deficiency of the mitochondrial enzyme sterol 27-hydroxylase (CYP 27) with reduced or no chenodeoxycholic synthesis. This deficiency leads to an accumulation of cholestanol in different sites such as the eye lens, central nervous system or tendons. We report a 64-year-old female patient with a progressive gait disorder associated with cognitive decline since the age of 59. The patient had no mental retardation, cataract or chronic diarrhea. Her family reported increasing behavioral modifications 10 years previously. Clinical examination revealed a spastic paraplegia and bilateral xanthomas on the Achilles tendons. Cerebral magnetic resonance imaging (MRI) revealed diffuse hyperintense T2 abnormalities in the pyramidal tracts from the internal capsules to the cerebral peduncles also Technetium-99m-ECD brain SPECT showed a severe cerebellar hypoperfusion. Serum cholestanol analysis was 7 µmol/l (N). After 2 years, she was bedridden and died of aspiration pneumonia. The neuropathological study confirmed the CTX diagnosis and the sequencing analysis revealed that she was compound heterozygous for two mutations in the CYP27A1 gene: 1435 C > T (exon 7) on one allele and a new mutation, 1017 G > C (exon 5) on the other. The interest of the present case is to report neuropathology findings strongly correlated with the MRI and SPECT abnormalities. PMID:21073839

  20. Flexion-distraction injuries of the lumbar spine and associated abdominal trauma.

    PubMed

    LeGay, D A; Petrie, D P; Alexander, D I

    1990-04-01

    Recent experience with flexion-distraction injuries of the lumbar spine associated with blunt abdominal trauma and the use of a lap belt alone has caused us to review our experience over the last 7 years. Eighteen patients were identified, with an average age of 22 years, and an average followup of 34 months. Fifteen were involved in motor vehicle accidents, with 11 being single-vehicle accidents. Of note, 12 of the 15 were rear seat passengers with lap belts only. Twelve patients suffered abdominal injury, seven requiring operative intervention, mainly for hollow viscus injury. In three patients, a delay of 24 hours or more occurred before recognition of intra-abdominal pathology requiring surgical therapy. One patient had an unrecognized spinal fracture for 2 weeks after abdominal surgery for a perforated viscus. The spinal injury was carefully assessed and analyzed for prognostic factors. Six were graded excellent, five good, four fair, and one poor. One case of paraplegia associated with avulsion of the spinal cord from distraction is reported. Prognostic factors included the amount of facet joint involvement and the degree of initial kyphosis. Those having greater than 17 degrees of kyphosis had a poor prognosis. Early recognition of the constellation of injuries involving the spine and abdomen associated with the use of the lap belt is recommended with surgery to the spinal fracture as outlined. PMID:2325176

  1. Spinal cord injuries in children and adolescents.

    PubMed

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

    2012-01-01

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

  2. The mitochondrial K-ATP channel opener, diazoxide, prevents ischemia-reperfusion injury in the rabbit spinal cord.

    PubMed

    Roseborough, Glen; Gao, Daqing; Chen, Lei; Trush, Michael A; Zhou, Shaoyu; Williams, G Melville; Wei, Chiming

    2006-05-01

    Paraplegia resulting from ischemia is a catastrophic complication of thoracoabdominal aortic surgery. The current study was designed to investigate the effects of diazoxide (DZ) on mitochondrial structure, neurological function, DNA damage-repair, and apoptosis in spinal cord ischemia-reperfusion injury. Rabbits were subjected to 30 minutes of spinal cord ischemia and reperfusion (1 hour) with or without diazoxide (n = 6 in each group) by clamping and releasing the infrarenal aorta. The neurological functional score was significantly improved in the DZ-treated ischemia-reperfusion injury group. Electron microscopic studies demonstrated that mitochondrial damage in the spinal cord after injury was significantly reduced by DZ. Mitochondrial superoxide and hydrogen peroxide levels were also markedly decreased in the DZ-treated injury group compared with the untreated group. DZ decreased levels of the oxidative DNA damage product 8-oxoG and increased levels of the DNA repair enzyme OGG-1. Furthermore, DZ inhibited apoptosis via caspase-dependent and -independent pathways. These studies indicate for the first time that the mitochondrial K-ATP channel opener diazoxide improves neurological function after spinal cord ischemia and reperfusion by diminishing levels of reactive oxygen species, decreasing DNA oxidative damage, and inhibiting caspase-dependent and -independent apoptotic pathways while preserving mitochondrial structure. PMID:16651612

  3. Neuroprotective effect of curcumin on spinal cord in rabbit model with ischemia/reperfusion

    PubMed Central

    Liu, Zhi-Qiang; Xing, Shan-Shan; Zhang, Wei

    2013-01-01

    Background Ischemic/reperfusion (I/R) injury of the spinal cord is a serious complication that can result from thoracoabdominal aortic surgery. Objective To investigate the neuroprotective effect of curcumin against I/R injury in a rabbit model. Methods A total of 36 rabbits were randomly divided into three groups: sham, I/R, and curcumin-treated group. Rabbits were subject to 30-min aortic occlusion to induce transient spinal cord ischemia. Neurological function was observed after reperfusion and spinal cord segment (L3–L5) was collected for histopathological evaluation. Malondialdehyde (MDA) and total superoxide dismutase (SOD) activity were also assayed. Results Rabbits in I/R group were induced to paraplegia. While after 48-hour treatment, compared with I/R group, curcumin significantly improved neurological function, reduced cell apoptosis and MDA levels as well as increased SOD activity (P < 0.05). Conclusions The results suggest that curcumin, at least in an animal model, can attenuate transient spinal cord ischemic injury potentially via reducing oxidative damage, which may provide a novel approach in the treatment of spinal cord ischemic injury. PMID:23809530

  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. Risk factors for 90-day and 180-day mortality in hospitalised patients with pressure ulcers.

    PubMed

    Flattau, Anna; Blank, Arthur E

    2014-02-01

    An understanding of risk factors associated with mortality among pressure ulcer patients can inform prognostic counselling and treatment plans. This retrospective cohort study examined associations of comorbid illness, demographic characteristics and laboratory values with 90-day and 90- to 180-day mortality in adult hospitalised patients with pressure ulcers. Data were extracted from hospital databases at two academic urban hospitals. Covariates included mortality risk factors identified in other populations, including demographic and laboratory variables, DRG weight, 'systemic infection or fever' and comorbidity categories from the Charlson comorbidity index. In adjusted Cox proportional hazards models, diabetes, chronic renal failure, congestive heart failure and metastatic cancer were significantly associated with mortality in both time frames. There was no significant effect on mortality from dementia, hemiplegia/paraplegia, rheumatic disease, chronic pulmonary disease or peripheral vascular disease. Myocardial infarction, cerebrovascular disease, liver disease and human immunodeficiency virus/AIDS were associated with mortality in the 90-day time frame only. 'Systemic infection or fever' was associated with mortality in the 90-day time frame but did not show a confounding effect on other variables, and the only significant interaction term was with metastatic cancer. Albumin was the only studied laboratory value that was strongly associated with mortality. Understanding the context of comorbid illness in pressure ulcer patients sets the groundwork for more robust studies of patient- and population-level outcomes, as well as study of heterogeneity within this group. PMID:22738290

  6. Movement-related cortical potentials in paraplegic patients: abnormal patterns and considerations for BCI-rehabilitation

    PubMed Central

    Xu, Ren; Jiang, Ning; Vuckovic, Aleksandra; Hasan, Muhammad; Mrachacz-Kersting, Natalie; Allan, David; Fraser, Matthew; Nasseroleslami, Bahman; Conway, Bernie; Dremstrup, Kim; Farina, Dario

    2014-01-01

    Non-invasive EEG-based Brain-Computer Interfaces (BCI) can be promising for the motor neuro-rehabilitation of paraplegic patients. However, this shall require detailed knowledge of the abnormalities in the EEG signatures of paraplegic patients. The association of abnormalities in different subgroups of patients and their relation to the sensorimotor integration are relevant for the design, implementation and use of BCI systems in patient populations. This study explores the patterns of abnormalities of movement related cortical potentials (MRCP) during motor imagery tasks of feet and right hand in patients with paraplegia (including the subgroups with/without central neuropathic pain (CNP) and complete/incomplete injury patients) and the level of distinctiveness of abnormalities in these groups using pattern classification. The most notable observed abnormalities were the amplified execution negativity and its slower rebound in the patient group. The potential underlying mechanisms behind these changes and other minor dissimilarities in patients’ subgroups, as well as the relevance to BCI applications, are discussed. The findings are of interest from a neurological perspective as well as for BCI-assisted neuro-rehabilitation and therapy. PMID:25221505

  7. The synaptic cytoskeleton in development and disease.

    PubMed

    Goellner, Bernd; Aberle, Hermann

    2012-01-01

    The cytoskeleton forms the backbone of neuronal architecture, sustaining its form and size, subcellular compartments and cargo logistics. The synaptic cytoskeleton can be categorized in the microtubule-based core cytoskeleton and the cortical membrane skeleton. While central microtubules form the fundamental basis for the construction of elaborate neuronal processes, including axons and synapses, cortical actin filaments are generally considered to function as mediators of synapse dynamics and plasticity. More recently, the submembranous network of spectrin and ankyrin molecules has been involved in the regulation of synaptic stability and maintenance. Disruption of the synaptic cytoskeleton primarily affects the stability and maturation of synapses but also secondarily disturbs neuronal communication. Consequently, a variety of inherited diseases are accompanied by cytoskeletal malfunctions, including spastic paraplegias, spinocerebellar ataxias, and mental retardation. Since the primary reasons for many of these diseases are still unknown model organisms with a conserved repertoire of cytoskeletal elements help to understand the underlying biological mechanisms. The astonishing technical as well as genetic accessibility of synapses in Drosophila has shown that loss of the cytoskeletal architecture leads to axonal transport defects, synaptic maturation deficits, and retraction of synaptic boutons, before synaptic terminals finally detach from their target cells, suggesting that similar processes could be involved in human neuronal diseases. PMID:21509946

  8. 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

  9. Endovascular Management of Thoracic Aortic Aneurysms

    SciTech Connect

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

    2011-12-15

    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.

  10. Surgical extraction after thrombosis around the Avalon dual lumen cannula.

    PubMed

    Kalem, V; Buchwald, D; Strauch, J; Sidiropoulos, A; Meindl, R; Schildhauer, T A; Swol, J

    2014-01-01

    The use of a dual lumen cannula (DLC) for venovenous extracorporeal membrane oxygenation (ECMO) has several advantages and reports of complications are rare. We present a case of thrombosis around and inside the Avalon Elite™ bicaval DLC (Avalon Laboratories, Rancho Dominguez, CA, US), for which simple removal by retraction was impossible. A 30-year-old man had experienced an unstable C6/7 fracture with spinal contusion and haematoma in the spinal canal with incomplete neurological paraplegia and thoracic trauma. He developed acute respiratory failure due to posttraumatic systemic inflammatory response syndrome and venovenous extracorporeal membrane oxygenation (ECMO) support was indicated. The cannulation was performed with an Avalon Elite™ cannula (31Fr) in the right jugular vein under fluoroscopy. After 18 days of ECMO therapy, despite the continuous administration of heparin (400iu/h), ECMO was discontinued because of the formation of a massive thrombus in the oxygenator. At that time, the patient's haemodynamic and respiratory parameters were stable, and we were able to induce a rapid weaning from ECMO. The surgical removal of the cannula became necessary and was performed using a small neck incision without complications. We report this case to emphasise that any resistance encountered during an attempt to extract the Avalon Elite™ cannula may cause serious complications. In such cases, surgical removal must be considered. PMID:24417857

  11. A conserved amphipathic helix is required for membrane tubule formation by Yop1p

    PubMed Central

    Brady, Jacob P.; Claridge, Jolyon K.; Smith, Peter G.; Schnell, Jason R.

    2015-01-01

    The integral membrane proteins of the DP1 (deleted in polyposis) and reticulon families are responsible for maintaining the high membrane curvature required for both smooth endoplasmic reticulum (ER) tubules and the edges of ER sheets, and mutations in these proteins lead to motor neuron diseases, such as hereditary spastic paraplegia. Reticulon/DP1 proteins contain reticulon homology domains (RHDs) that have unusually long hydrophobic segments and are proposed to adopt intramembrane helical hairpins that stabilize membrane curvature. We have characterized the secondary structure and dynamics of the DP1 family protein produced from the YOP1 gene (Yop1p) and identified a C-terminal conserved amphipathic helix (APH) that, on its own, interacts strongly with negatively charged membranes and is necessary for membrane tubule formation. Analyses of DP1 and reticulon family members indicate that most, if not all, contain C-terminal sequences capable of forming APHs. Together, these results indicate that APHs play a previously unrecognized role in RHD membrane curvature stabilization. PMID:25646439

  12. Intracranial Extension of Spinal Subarachnoid Hematoma Causing Severe Cerebral Vasospasm

    PubMed Central

    Nam, Kyoung Hyup; Lee, Jae Il; Choi, Byung Kwan

    2014-01-01

    Spinal subarachnoid hemorrhages (SAH) can extend into the intracranial subarachnoid space, but, severe cerebral vasospasm is rare complication of the extension of intracranial SAH from a spinal subarachnoid hematoma. A 67-year-old woman started anticoagulant therapy for unstable angina. The next day, she developed severe back pain and paraplegia. MRI showed intradural and extramedullar low signal intensity at the T2-3, consistent with intradural hematoma. High signal intensity was also noted in the spinal cord from C5 to T4. We removed subarachnoid hematoma compressing the spinal cord. The following day, the patient complained of severe headache. Brain CT revealed SAH around both parietal lobes. Three days later, her consciousness decreased and left hemiplegia also developed. Brain MRI demonstrated multiple cerebral infarctions, mainly in the right posterior cerebral artery territory, left parietal lobe and right watershed area. Conventional cerebral angiography confirmed diffuse severe vasospasm of the cerebral arteries. After intensive care for a month, the patient was transferred to the rehabilitation department. After 6 months, neurologic deterioration improved partially. We speculate that surgeons should anticipate possible delayed neurological complications due to cerebral vasospasm if intracranial SAH is detected after spinal subarachnoid hematoma. PMID:25628817

  13. Spinal cord ischemia in open and endovascular thoracoabdominal aortic aneurysm repair: new concepts.

    PubMed

    Etz, D C; Luehr, M; Aspern, K V; Misfeld, M; Gudehus, S; Ender, J; Koelbel, T; Debus, E S; Mohr, F-W

    2014-04-01

    For more than half a century ischemic spinal cord injury (SCI) and consecutively permanent paraplegia remained the most devastating complication after open and endovascular thoracoabdominal aortic aneurysm (TAAA) repair. Various neuroprotective strategies (e.g., motor-/somatosensory evoked potential monitoring and cerebrospinal fluid drainage) used as adjuncts have lowered the SCI; maybe most importantly, the modern collateral network (CN) has begun to replace the classic understanding of spinal cord blood supply implying several consequences. Reliable non-invasive tools to monitor cord perfusion to detect imminent spinal cord malperfusion, ischemia and forthcoming neurologic injury (particularly early postoperatively) is not available, neither is a reliable strategy to prevent ischemic injury during distal circulatory arrest and after segmental artery occlusion. Currently, two promising new concepts--potentially advancing spinal protection in open and endovascular TAAA repair--address these issues: 1) non-invasive real-time monitoring of the paraspinous CN-oxygenation via near-infrared spectroscopy (NIRS) as an alternative to the demanding direct neuromonitoring; and 2) preconditioning of the CN as minimally invasive, endovascular "first stage" to increase the resilience of spinal cord perfusion prior to definite aortic repair. This article illustrates both concepts discussing: 1) the clinical application of thoracic and lumbar collateral NIRS monitoring to indirectly detect spinal cord hypoperfusion; and 2) minimally invasive selective segmental artery coil-embolization (MISACE) for (arteriogenic) preconditioning of the CN prior to extensive open or endovascular staged TAAA repair. PMID:24796909

  14. Real-time strap pressure sensor system for powered exoskeletons.

    PubMed

    Tamez-Duque, Jesús; Cobian-Ugalde, Rebeca; Kilicarslan, Atilla; Venkatakrishnan, Anusha; Soto, Rogelio; Contreras-Vidal, Jose Luis

    2015-01-01

    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

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

    SciTech Connect

    Ilarioshkin, S.N.; Ivanova-Smolenskaya, I.A.; Markova, E.D. [Research Institute of Neurology, Moscow (Russian Federation)

    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.

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

    PubMed Central

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

    2014-01-01

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

  17. Comparison of heart rate response to tennis activity between persons with and without spinal cord injuries: implications for a training threshold.

    PubMed

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

    2009-03-01

    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). Average HR was determined for time spent in practice (e.g, drills) and game (i.e., a competitive set), and the ability to surpass 50% peak HR (HRpeak) and 64% HRpeak in each condition was evaluated. Average exercise intensity (%HRpeak) was not significantly different between the groups during practice (M WCT = 68.18, SD = 7.53%, M ABT = 68.78, SD = 5.44%; t = .22, p = .83) or game (M WCT = 68.17, SD = .17%, M ABT = 71.55, SD = 4.75%; t = 1.12, p =.28). Allparticipants averaged an intensity > or = 50% HR-peak during practice and game, and the difference between group participants averaging an intensity > or = 64% HRpeak was not significant during practice (chi2 = .92, p = .34) or game (chi2 = 3.85, p = .05). In terms of reaching a health and fitness training threshold during tennis, individuals with low-level SCI are similar to matched controls. PMID:19408469

  18. [A case of spinal epidural abscess in a renal transplant recipient].

    PubMed

    Egashira, T; Nose, T; Maki, Y

    1984-05-01

    A 44-year-old male underwent a cadaveric renal transplantation at the university hospital of Tsukuba on March 3, 1979. On June 11, 1979, he was discharged this hospital. Immunosuppressive therapy with azathioprine and methylprednisolone was done. On November 1, 1979, he developed back pain associated with fever. On November 3, 1979, he was admitted to the university hospital of Tsukuba. Laboratory study revealed leucocytosis. CRP inserum was positive. But pneumonia, urinary tract infection and infectious skin lesion were ruled out by physical, radiological and laboratory examination. On November 16, 1979, he became paraparetic. On the next day, he consulted the neurosurgical unit. Neurological findings were as follows: paraplegia, and hypesthesia and hypalgesia below the level of T4, and bilateral hyperrefrexia of P.T.R. and A.T.R. Lumbar myelogram revealed a complete block at the level T7. On November 17, 1979, a laminectomy from T4 through T7 was performed. The epidural abscess containing yellow pus was found and totally removed. Gram-positive rods were isolated on bacteriologic culture. On the 7th postoperative day, the sensory level dropped to L4 bilaterally and the muscle strength in the lower extremity became fair. About 3 years after operation, he became to be able to walk without cane. Discussion was made about this case together with previously reported cases. PMID:6379492

  19. Microtubule-targeting drugs rescue axonal swellings in cortical neurons from spastin knockout mice

    PubMed Central

    Fassier, Coralie; Tarrade, Anne; Peris, Leticia; Courageot, Sabrina; Mailly, Philippe; Dalard, Cécile; Delga, Stéphanie; Roblot, Natacha; Lefèvre, Julien; Job, Didier; Hazan, Jamilé; Curmi, Patrick A.; Melki, Judith

    2013-01-01

    SUMMARY Mutations in SPG4, encoding the microtubule-severing protein spastin, are responsible for the most frequent form of hereditary spastic paraplegia (HSP), a heterogeneous group of genetic diseases characterized by degeneration of the corticospinal tracts. We previously reported that mice harboring a deletion in Spg4, generating a premature stop codon, develop progressive axonal degeneration characterized by focal axonal swellings associated with impaired axonal transport. To further characterize the molecular and cellular mechanisms underlying this mutant phenotype, we have assessed microtubule dynamics and axonal transport in primary cultures of cortical neurons from spastin-mutant mice. We show an early and marked impairment of microtubule dynamics all along the axons of spastin-deficient cortical neurons, which is likely to be responsible for the occurrence of axonal swellings and cargo stalling. Our analysis also reveals that a modulation of microtubule dynamics by microtubule-targeting drugs rescues the mutant phenotype of cortical neurons. Together, these results contribute to a better understanding of the pathogenesis of SPG4-linked HSP and ascertain the influence of microtubule-targeted drugs on the early axonal phenotype in a mouse model of the disease. PMID:22773755

  20. Aortic Replacement with Sutureless Intraluminal Grafts

    PubMed Central

    Lemole, Gerald M.

    1990-01-01

    To avoid the anastomotic complications and long cross-clamp times associated with standard suture repair of aortic lesions, we have implanted sutureless intraluminal grafts in 122 patients since 1976. Forty-nine patients had disorders of the ascending aorta, aortic arch, or both: their operative mortality was 14% (7 patients), and the group's 5-year actuarial survival rate has been 64%. There have been no instances of graft dislodgment, graft infection, aortic bleeding, or pseudoaneurysm formation. Forty-two patients had disorders of the descending aorta and thoracoabdominal aorta: their early mortality was 10% (4 patients), and the group's 5-year actuarial survival rate has been 56%. There was 1 early instance of graft dislodgment, but no pseudoaneurysm formation, graft erosion, aortic bleeding, intravascular hemolysis, or permanent deficits in neurologic, renal, or vascular function. Thirty-one patients had the sutureless intraluminal graft implanted in the abdominal aortic position: their early mortality was 6% (2 patients), and the 5-year actuarial survival rate for this group has been 79%. There were no instances of renal failure, ischemic complication, postoperative paraplegia, pseudoaneurysm, or anastomotic true aneurysm. Our recent efforts have been directed toward developing an adjustable spool that can adapt to the widest aorta or the narrowest aortic arch vessel; but in the meanwhile, the present sutureless graft yields shorter cross-clamp times, fewer intraoperative complications, and both early and late results as satisfactory as those afforded by traditional methods of aortic repair. (Texas Heart Institute Journal 1990; 17:302-9) Images PMID:15227522

  1. Adverse neurological outcomes in Nigerian children with sickle cell disease.

    PubMed

    Lagunju, I A; Brown, B J

    2012-12-01

    Sickle cell disease (SCD) is reported to be the most common genetic disorder affecting Nigerians. Children with SCD are at a high risk of neurological morbidity. The main objective of this study was to determine the pattern of adverse neurological outcomes among a cohort of Nigerian children with SCD. All children with SCD seen in the Department of Paediatrics, University College Hospital, Ibadan, Nigeria, over a period of 2 years were carefully evaluated for symptoms and signs of neurological complications, defined as clinical outcomes referable to the central nervous system. Of the 214 children evaluated, 187 were diagnosed with Hb SS disease and 27 with Hb SC disease. Neurological complications were identified in 78 (36.4 %) of the cases. The most common complications were headache (17.8 %), seizure (9.3 %) and stroke (8.4 %). Other less frequent complications included bacterial meningitis (2.8 %), spontaneous visual loss (1.4 %), paraplegia (0.9 %) and transient ischaemic attacks (0.9 %). Neurological complications occurred more frequently in children with sickle cell anaemia than in those with Hb SC disease (P = 0.002, 95 % CI 1.450-82.870). Adverse neurological events are common in Nigerian children with SCD, with a significantly higher risk in Hb SS than Hb SC disease. Stroke represents a major underlying cause of symptomatic epilepsy in SCD. Institution of primary preventive measures for stroke in SCD will significantly reduce the burden of stroke and epilepsy associated with SCD in Nigeria. PMID:23129067

  2. Spinal tuberculosis: A review

    PubMed Central

    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

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

    PubMed Central

    Chang, Jaerak; Blackstone, Craig

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  5. KIF1A mutation in a patient with progressive neurodegeneration.

    PubMed

    Okamoto, Nobuhiko; Miya, Fuyuki; Tsunoda, Tatsuhiko; Yanagihara, Keiko; Kato, Mitsuhiro; Saitoh, Shinji; Yamasaki, Mami; Kanemura, Yonehiro; Kosaki, Kenjiro

    2014-11-01

    Kinesins are a large superfamily of molecular motors. They move along microtubule filaments and are powered by the hydrolysis of ATP. This transport system is essential for neuronal function and survival. KIF1A belongs to the kinesin 3 family and involves in the anterograde transport of synaptic vesicle precursors along axons. Several studies confirmed that KIF1A mutations cause spastic paraplegia and sensory neuropathy in an autosomal-recessive fashion. A missense mutation in the KIF1A gene (p.Thr99Met) has been reported in a patient with intellectual disability (ID), axial hypotonia and peripheral spasticity. Mild atrophy of the cerebellar vermis was found on magnetic resonance imaging. The mutation was heterozygous and de novo. We identified the second patient with the p.T99M mutation in the KIF1A gene by whole-exome sequencing. He showed severe ID, spasticity, optic atrophy, neurogenic bladder, growth failure and progressive cerebellar atrophy. The p.T99M mutation may be a common recurrent mutation. We suppose that this specific mutation of KIF1A shows a novel neurodegenerative syndrome. PMID:25253658

  6. Prevalence of chronic pain after traumatic spinal cord injury: a systematic review.

    PubMed

    Dijkers, Marcel; Bryce, Thomas; Zanca, Jeanne

    2009-01-01

    Published studies have reported widely divergent estimates of the prevalence of chronic pain among individuals with (traumatic) spinal cord injury (SCI). To develop an estimate based on a synthesis of the research, we used searches of MEDLINE, CINAHL, PsycINFO, and other bibliographic databases and an ancestor search to identify articles published since 1966 in any language that reported a pain prevalence rate for at least 30 subjects with certain or likely traumatic SCI. Data on sample makeup, study quality indicators, and pain prevalence were abstracted independently by two researchers. A total of 42 studies reported pain prevalence rates that ranged from 26% to 96%, with a fairly even spread between these extremes. The reported rate did not appear to be related to study quality. Pain prevalence in the combined samples did not appreciably differ between males and females, those with complete versus incomplete SCI, and those with paraplegia versus tetraplegia. We conclude that too much heterogeneity was present in the reports to calculate a post-SCI pain prevalence rate using meta-analytic methods. Further research is needed to determine whether rates are related to sample makeup (e.g., average subject age), research methods used (e.g., telephone interview vs self-report instruments), or even the definition of "chronic" pain. PMID:19533517

  7. 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

  8. Protective effect of delta opioid agonist [D-Ala2, D-Leu5] enkephalin on spinal cord ischemia reperfusion injury by regional perfusion into abdominal aorta in rabbits.

    PubMed

    Liu, Haitong; Chen, Binbin; Zhang, Yi; Qiu, Yimin; Xia, Yunfei; Li, Shitong; Yao, Junyan

    2015-01-01

    [D-Ala(2), D-Leu(5)] enkephalin (DADLE) has been reported to exhibit protective effects against hypoxic or ischemic induced brain insult. However its efficacy on the spinal cord ischemia-reperfusion injury remains unclear. Here we investigate whether DADLE could attenuate ischemia and reperfusion induced neural injury in the rabbit spinal cord. New Zealand white rabbits were subjected to spinal cord ischemia by infrarenal aortic occlusion for 30 min. In the period of spinal cord ischemia, DADLE 0.5 mg/kg or NS were infused continuously into the distal clamped abdominal aorta. The heart rate, blood pressure, and core temperature were monitored continuously during the whole experimental procedure. Then the neurological behavioral function was assessed with Tarlov scale system at 1h, 6h, 24h, 48 h after reperfusion, and neuronal injury evaluation in the ventral horn of gray matter was measured by counting the normal motor neurons at 48 h after reperfusion. Comparing with the control group, the Tarlov scores were significantly higher and the incidences of paraplegia were significantly lower in the DADLE group at four time-point recorded. In addition, the normal neurons numbers in the DADLE group were significant more than those in the control group at 48 h after reperfusion. These results suggested that DADLE infused into the abdominal aorta during ischemia period could attenuate behavioral retardation and the loss of normal motor neuron induced by ischemia-reperfusion in rabbits. PMID:25283992

  9. 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

  10. Total vertebrectomy for stabilisation of chronic spinal lumbar luxation in a paraplegic dog without nociception.

    PubMed

    Tertuliano Marinho, P V; Zani, C C; De Biasi, F; Bahr Arias, M V

    2014-10-01

    An adult male crossbred dog was referred with a history of a road traffic accident that took place 1 month earlier. Neurological examination revealed paraplegia with absent nociception in the pelvic limbs. On epaxial palpation, significant curvature of the anatomical axis of the spine between the third and fourth lumbar vertebrae was observed, with the presence of a bone end almost piercing the dog's skin. Survey radiographs of the lumbar spine revealed severe dislocation between L3 and L4 vertebrae. During surgery, the spinal cord was not visible between the dislocated segments. Because of difficulties in reducing the lumbar luxation during surgery, vertebrectomy and vertebral shortening were performed. After alignment between vertebrae L3 and L5, eight cortical orthopaedic screws and bone cement were used for fixation. After 30 days, the dog started to use a wheelchair and was considered by its owner to have a good quality of life with no evidence of pain. To the authors' knowledge, this is the first case of severe luxation treated by total vertebrectomy and spine shortening in a dog. This surgery can be considered as an option in the management of severe spine luxation when the spinal cord is physically transected. PMID:24962201

  11. Selection of optimal muscle set for 16-channel standing neuroprosthesis

    PubMed Central

    Gartman, Steven J.; Audu, Musa L.; Kirsch, Robert F.; Triolo, Ronald J.

    2009-01-01

    The Case Western Reserve University/Department of Veterans Affairs 8-channel lower-limb neuroprosthesis can restore standing to selected individuals with paraplegia by application of functional electrical stimulation. The second generation of this system will include 16 channels of stimulation and a closed-loop control scheme to provide automatic postural corrections. This study used a musculoskeletal model of the legs and trunk to determine which muscles to target with the new system in order to maximize the range of postures that can be statically maintained, which should increase the system’s ability to provide adequate support to maintain standing when the user’s posture moves away from a neutral stance, either by an external disturbance or a volitional change in posture by the user. The results show that the prime muscle targets should be the medial gastrocnemius, tibialis anterior, vastus lateralis, semimembranosus, gluteus maximus, gluteus medius, adductor magnus, and erector spinae. This set of 16 muscles supports 42 percent of the standing postures that are attainable by the nondisabled model. Coactivation of the lateral gastrocnemius and peroneus longus with the medial gastrocnemius and of the peroneus tertius with the tibialis anterior increased the percentage of feasible postures to 71 percent. PMID:16847793

  12. 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

  13. CAG repeat expansion in autosomal dominant familial spastic paraparesis: novel expansion in a subset of patients.

    PubMed

    Benson, K F; Horwitz, M; Wolff, J; Friend, K; Thompson, E; White, S; Richards, R I; Raskind, W H; Bird, T D

    1998-10-01

    Autosomal dominant familial spastic paraplegia (FSP) is a genetically heterogeneous neurodegenerative disorder displaying anticipation for which three loci have been mapped to the chromosomal positions 14q11.2-q24.3 (SPG3), 2p21-p24 (SPG4) and 15q11.1 (SPG6). The repeat expansion detection (RED) method has been used to demonstrate expanded CAG repeats in some FSP families that map to SPG4. We analyzed 20 FSP families, including four for which there is evidence for linkage to SPG4, and found that in most cases the repeat expansion detected by RED is due to non-pathogenic expansions of the chromosome 18q21.1 SEF2-1 or 17q21.3 ERDA1 locus. Polymorphic expansions at SEF2-1 and ERDA1 appear frequent and may confound RED studies in the search for genes causing disorders demonstrating anticipation. In six FSP families, however, CAG repeat expansion was detected in a subset of affected and at-risk individuals that did not result from expansion of the SEF2-1 and ERDA1 loci. Overall, 11 of 37 (30%) of the FSP patients with a CAG/CTG repeat expansion are unaccounted for by the SEF2-1 and ERDA1 loci, compared with two of 23 (9%) of the unaffected at-risk individuals and none of 19 controls. In the majority of cases these novel expansions were shorter than those previously reported. PMID:9736780

  14. Zebrafish atlastin controls motility and spinal motor axon architecture via inhibition of the BMP pathway.

    PubMed

    Fassier, Coralie; Hutt, James A; Scholpp, Steffen; Lumsden, Andrew; Giros, Bruno; Nothias, Fatiha; Schneider-Maunoury, Sylvie; Houart, Corinne; Hazan, Jamilé

    2010-11-01

    To better understand hereditary spastic paraplegia (HSP), we characterized the function of atlastin, a protein that is frequently involved in juvenile forms of HSP, by analyzing loss- and gain-of-function phenotypes in the developing zebrafish. We found that knockdown of the gene for atlastin (atl1) caused a severe decrease in larval mobility that was preceded by abnormal architecture of spinal motor axons and was associated with a substantial upregulation of the bone morphogenetic protein (BMP) signaling pathway. Overexpression analyses confirmed that atlastin inhibits BMP signaling. In primary cultures of zebrafish spinal neurons, Atlastin partially colocalized with type I BMP receptors in late endosomes distributed along neurites, which suggests that atlastin may regulate BMP receptor trafficking. Finally, genetic or pharmacological inhibition of BMP signaling was sufficient to rescue the loss of mobility and spinal motor axon defects of atl1 morphants, emphasizing the importance of fine-tuning the balance of BMP signaling for vertebrate motor axon architecture and stability. PMID:20935645

  15. A network of genetic repression and derepression specifies projection fates in the developing neocortex

    PubMed Central

    Srinivasan, Karpagam; Leone, Dino P.; Bateson, Rosalie K.; Dobreva, Gergana; Kohwi, Yoshinori; Kohwi-Shigematsu, Terumi; Grosschedl, Rudolf; McConnell, Susan K.

    2012-01-01

    Neurons within each layer in the mammalian cortex have stereotypic projections. Four genes—Fezf2, Ctip2, Tbr1, and Satb2—regulate these projection identities. These genes also interact with each other, and it is unclear how these interactions shape the final projection identity. Here we show, by generating double mutants of Fezf2, Ctip2, and Satb2, that cortical neurons deploy a complex genetic switch that uses mutual repression to produce subcortical or callosal projections. We discovered that Tbr1, EphA4, and Unc5H3 are critical downstream targets of Satb2 in callosal fate specification. This represents a unique role for Tbr1, implicated previously in specifying corticothalamic projections. We further show that Tbr1 expression is dually regulated by Satb2 and Ctip2 in layers 2–5. Finally, we show that Satb2 and Fezf2 regulate two disease-related genes, Auts2 (Autistic Susceptibility Gene2) and Bhlhb5 (mutated in Hereditary Spastic Paraplegia), providing a molecular handle to investigate circuit disorders in neurodevelopmental diseases. PMID:23144223

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

    SciTech Connect

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

    2006-10-15

    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.

  17. A recurrent deletion syndrome at chromosome bands 2p11.2-2p12 flanked by segmental duplications at the breakpoints and including REEP1.

    PubMed

    Stevens, Servi J C; Blom, Eveline W; Siegelaer, Ingrid T J; Smeets, Eric E J G L

    2015-04-01

    We identified an identical and recurrent 9.4-Mbp deletion at chromosome bands 2p11.2-2p12, which occurred de novo in two unrelated patients. It is flanked at the distal and proximal breakpoints by two homologous segmental duplications consisting of low copy repeat (LCR) blocks in direct orientation, which have >99% sequence identity. Despite the fact that the deletion was almost 10?Mbp in size, the patients showed a relatively mild clinical phenotype, that is, mild-to-moderate intellectual disability, a happy disposition, speech delay and delayed motor development. Their phenotype matches with that of previously described patients. The 2p11.2-2p12 deletion includes the REEP1 gene that is associated with spastic paraplegia and phenotypic features related to this are apparent in most 2p11.2-2p12 deletion patients, but not in all. Other hemizygous genes that may contribute to the clinical phenotype include LRRTM1 and CTNNA2. We propose a recurrent but rare 2p11.2-2p12 deletion syndrome based on (1) the identical, non-random localisation of the de novo deletion breakpoints in two unrelated patients and a patient from literature, (2) the patients' phenotypic similarity and their phenotypic overlap with other 2p deletions and (3) the presence of highly identical LCR blocks flanking both breakpoints, consistent with a non-allelic homologous recombination (NAHR)-mediated rearrangement. PMID:24986827

  18. 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

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

    SciTech Connect

    Saratzis, N.; Saratzis, Athanasios, E-mail: a_saratzis@yahoo.gr; Melas, N.; Ginis, G.; Lioupis, A.; Lykopoulos, D.; Lazaridis, J.; Kiskinis, Dimitrios [Aristotle University of Thessaloniki Papageorgiou General Hospital, Department of Surgery (Greece)

    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.

  20. Detailed Shoulder MRI Findings in Manual Wheelchair Users with Shoulder Pain

    PubMed Central

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

    2014-01-01

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

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

    E-print Network

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

    2006-01-01

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

  2. Serotonin-induced activation of the network for locomotion in adult spinal rats.

    PubMed

    Feraboli-Lohnherr, D; Barthe, J Y; Orsal, D

    1999-01-01

    The biogenic amine serotonin has been described in the literature as a powerful modulator of the spinal central pattern generator for locomotion. In the present study, we tested whether administration of serotonin or its agonist quipazine could restore motor activity in a model of paraplegia. One to three weeks after a complete transection of the spinal cord at a low thoracic level, rats were given either intrathecal injections of serotonin (5 mM, 15 microL) or intraperitoneal injections of quipazine (400-600 microg/kg). Both treatments allowed recovery of locomotor activity on a treadmill in response to tail pinching. As compared with the activity elicited before treatment, the locomotor activity produced by spinal animals was characterised by longer locomotor sequences with a larger number of successive steps, better body support, better interlimb coordination, and a higher amplitude of electromyographic bursts. These results suggest that serotonergic drugs could be used for the recovery of motor functions after lesions of the spinal cord. PMID:9890437

  3. Spinal cord injury in the pediatric population: a systematic review of the literature.

    PubMed

    Parent, Stefan; Mac-Thiong, Jean-Marc; Roy-Beaudry, Marjolaine; Sosa, Jose Felix; Labelle, Hubert

    2011-08-01

    Spinal Cord Injury (SCI) in the pediatric population is relatively rare but carries significant psychological and physiological consequences. An interdisciplinary group of experts composed of medical and surgical specialists treating patients with SCI formulated the following questions: 1) What is the epidemiology of pediatric spinal cord injury and fractures?; 2) Are there unique features of pediatric SCI which distinguish the pediatric SCI population from adult SCI?; 3) Is there evidence to support the use of neuroprotective approaches, including hypothermia and steroids, in the treatment of pediatric SCI? A systematic review of the literature using multiple databases was undertaken to evaluate these three specific questions. A search strategy composed of specific search terms (Spinal Cord Injury, Paraplegia, Quadriplegia, tetraplegia, lapbelt injuries, seatbelt injuries, cervical spine injuries and Pediatrics) returned over 220 abstracts that were evaluated and by two observers. Relevant abstracts were then evaluated and papers were graded using the Downs and Black method. A table of evidence was then presented to a panel of experts using a modified Delphi approach and the following recommendation was then formulated using a consensus approach: Pediatric patients with traumatic SCI have different mechanisms of injury and have a better neurological recovery potential when compared to adults. Patients with SCI before their adolescent growth spurt have a high likelihood of developing scoliosis. Because of these differences, traumatic SCI should be highly suspected in the presence of abnormal neck or neurological exam, a high-risk mechanism of injury or a distracting injury even in the absence of radiological anomaly. PMID:21501096

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

    PubMed

    Hübner, Christian A; Kurth, Ingo

    2014-12-01

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

  5. Assessment of passive knee stiffness and viscosity in individuals with spinal cord injury using pendulum test.

    PubMed

    Joghtaei, Mahmoud; Arab, Amir Massoud; Hashemi-Nasl, Hamed; Joghataei, Mohammad Taghi; Tokhi, Mohammad Osman

    2015-03-01

    Objective Stiffness and viscosity represent passive resistances to joint motion related with the structural properties of the joint tissue and of the musculotendinous complex. Both parameters can be affected in patients with spinal cord injury (SCI). The purpose of this study was to measure passive knee stiffness and viscosity in patients with SCI with paraplegia and healthy subjects using Wartenberg pendulum test. Design Non-experimental, cross-sectional, case-control design. Setting An outpatient physical therapy clinic, University of social welfare and Rehabilitation Science, Iran. Patients A sample of convenience sample of 30 subjects participated in the study. Subjects were categorized into two groups: individuals with paraplegic SCI (n = 15, age: 34.60 ± 9.18 years) and 15 able-bodied individuals as control group (n = 15, age: 30.66 ± 11.13 years). Interventions Not applicable. Main measures Passive pendulum test of Wartenberg was used to measure passive viscous-elastic parameters of the knee (stiffness, viscosity) in all subjects. Results Statistical analysis (independent t-test) revealed significant difference in the joint stiffness between healthy subjects and those with paraplegic SCI (P = 0.01). However, no significant difference was found in the viscosity between two groups (P = 0.17). Except for first peak flexion angle, all other displacement kinematic parameters exhibited no statistically significant difference between normal subjects and subjects with SCI. Conclusions Patients with SCI have significantly greater joint stiffness compared to able-bodied subjects. PMID:25437824

  6. Moderately different NADPH-diaphorase positivity in the selected peripheral nerves after ischemia/ reperfusion injury of the spinal cord in rabbit.

    PubMed

    Lackova, Monika; Schreiberova, Andrea; Kolesar, Dalibor; Lukacova, Nadezda; Marsala, Jozef

    2006-01-01

    1. To vicariously investigate the nitric oxide synthase (NOS) production after spinal cord injury, NADPH-d histochemistry was performed on the selected peripheral nerves of adult rabbits 7 days after ischemia. The effect of transient spinal cord ischemia (15 min) on possible degenerative changes in the motor and mixed peripheral nerves of Chinchilla rabbits was evaluated. 2. The NADPH-diaphorase histochemistry was used to determine NADPH-diaphorase activity after ischemia/reperfusion injury in radial nerve and mediane nerve isolated from the fore-limb and femoral nerve, saphenous nerve and sciatic nerve separated from the hind-limb of rabbits. The qualitative analysis of the optical density of NADPH-diaphorase in selected peripheral nerves demonstrated different frequency of staining intensity (attained by UTHSCSA Image Tool 2 analysis for each determined nerve). 3. On the seventh postsurgery day, the ischemic spinal cord injury resulted in an extensive increase of NADPH-d positivity in isolated nerves. The transient ischemia caused neurological disorders related to the neurological injury--a partial paraplegia. The sciatic, femoral, and saphenous nerves of paraplegic animals presented the noticeable increase of NADPH-d activity. The mean of NADPH-diaphorase intensity staining per unit area ranged from 134.87 (+/-32.81) pixels to 141.65 (+/-35.06) pixels (using a 256-unit gray scale where 0 denotes black, 256 denotes white) depending on the determined nerve as the consequence of spinal cord ischemia. The obtained data were compared to the mean values of staining intensity in the same nerves in the limbs of control animals (163.69 (+/-25.66) pixels/unit area in the femoral nerve, 173.00 (+/-32.93) pixels/unit area in saphenous nerve, 186.01 (+/-29.65) pixels/unit area in sciatic nerve). Based on the statistical analysis of the data (two-way unpaired Mann-Whitney test), a significant increase (p< or =0.05) of NADPH-d activity in femoral and saphenous nerve, and also in sciatic nerve (p< or =0.001) has been found. On the other hand, there was no significant difference between the histochemically stained nerves of fore-limbs after ischemia/reperfusion injury and the same histochemically stained nerves of fore-limbs in control animals. 4. The neurodegenerative changes of the hind-limbs, characterized by damage of their motor function exhibiting a partial paraplegia after 15 min spinal cord ischemia and subsequent 7 days of reperfusions resulted in the different sensitivity of peripheral nerves to transient ischemia. Finally, we suppose that activation of NOS indirectly demonstrable through the NADPH-d study may contribute to the explanation of neurodegenerative processes and the production of nitric oxide could be involved in the pathophysiology of spinal cord injury by transient ischemia. PMID:16783526

  7. Physical strain of handcycling: An evaluation using training guidelines for a healthy lifestyle as defined by the American College of Sports Medicine

    PubMed Central

    Hettinga, Florentina J.; de Groot, Sonja; van Dijk, Frank; Kerkhof, Faes; Woldring, Ferry; van der Woude, Luc

    2013-01-01

    Objective Developments in assistive technology such as handcycling provide attractive possibilities to pursue a healthy lifestyle for patients with spinal cord injury. The objective of the study is to evaluate physical stress and strain of handcycling against training guidelines as defined by the American College of Sports Medicine (ACSM). Design Seven able-bodied males conducted an incremental peak exercise handcycling test on a treadmill. In addition, two indoor treadmill (1.3 m/second with an inclination of 0.7% and 1.0 m/second with an inclination of 4.8%) and three outdoor over ground exercise bouts were performed (1.7, 3.3, and 5.0 m/second). One individual handcycled a representative 8-km-distance outdoors. Outcome measures Physical stress and strain were described in terms of absolute and relative power output, oxygen uptake (VO2), gross efficiency (GE), and heart rate (HR). Also, local perceived discomfort (LPD) was determined. Results Relative handcycling exercise intensities varied between 23.3 ± 4.2 (below the ACSM lower limit of 46%VO2peak) and 72.5 ± 15.1%VO2peak (well above the ACSM lower limit), with GE ranging from 6.0 ± 1.5% at the lower to 13.0 ± 2.6% at the higher exercise intensities. Exercise intensities were performed at 49.8 ± 4.2 to 80.1 ± 10.5%HRpeak. LPD scores were low to moderate (<27 ± 7). Conclusion Handcycling is relatively efficient and exercise intensities > 46%VO2peak were elicited. However, exercise load seems to be underestimated using %HRpeak. LPD was not perceived as limiting. Physiological stress and strain in able-bodied individuals appear to be comparable to individuals with a paraplegia. To understand individualize and optimize upper-body training, different training programs must be evaluated. PMID:23820153

  8. 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

  9. Early onset (childhood) monogenic neuropathies.

    PubMed

    Landrieu, Pierre; Baets, Jonathan

    2013-01-01

    Hereditary neuropathies (HN) with onset in childhood are categorized according to clinical presentation, pathogenic mechanism based on electrophysiology, genetic transmission and, in selected cases, pathological findings. Especially relevant to pediatrics are the items "secondary" versus "primary" neuropathy, "syndromic versus nonsyndromic," and "period of life." Different combinations of these parameters frequently point toward specific monogenic disorders. Ruling out a neuropathy secondary to a generalized metabolic disorder remains the first concern in pediatrics. As a rule, metabolic diseases include additional, orienting symptoms or signs, and their biochemical diagnosis is based on logical algorithms. Primary, motor sensory are the most frequent HN and are dominated by demyelinating autosomal dominant (AD) forms (CMT1). Other forms include demyelinating autosomal recessive (AR) forms, axonal AD/AR forms, and forms with "intermediate" electrophysiological phenotype. Peripheral motor neuron disorders are dominated by AR SMN-linked spinal muscular atrophies. (Distal) hereditary motor neuropathies represent <10% of HN but exhibit large clinical and genetic heterogeneity. Sensory/dysautonomic HN involves five classic subtypes, each one related to specific genes. However, genetic heterogeneity is larger than initially suspected. Syndromic HN distinguish "purely neurological syndromes", which are multisystemic, such as spinocerebellar atrophies +, spastic paraplegias +, etc. Peripheral neuropathy is possibly the presenting feature, including in childhood. Autosomal recessive forms, on average, start more frequently in childhood. "Multiorgan syndromes", on the other hand, are more specific to Pediatrics. AR forms, which are clearly degenerative, prompt the investigation of a large set of pleiotropic genes. Other syndromes expressed in the perinatal period are mainly developmental disorders, and can sometimes be related to specific transcription factors. Systematic malformative workup and ethical considerations are necessary. Altogether, >40 genes with various biological functions have been found to be responsible for primary HN. Many are responsible for various phenotypes, including some without the polyneuropathic trait, and some for various types of transmission. PMID:23931819

  10. Low Magnitude and High Frequency Mechanical Loading Prevents Decreased Bone Formation Responses of 2T3 Preosteoblasts

    PubMed Central

    Patel, Mamta J.; Chang, Kyungh Hwa; Sykes, Michelle C.; Talish, Roger; Rubin, Clinton; Jo, Hanjoong

    2009-01-01

    Bone loss due 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 loading has been shown to normalize and prevent bone loss. However, the underlying molecular changes and the target cells by which LMHF mechanical loading alleviate bone loss are not known. Here, we hypothesized that direct application of LMHF mechanical loading to osteoblasts alters their cell responses, preventing decreased bone formation induced by disuse or microgravity conditions. To test our hypothesis, preosteoblast 2T3 cells were exposed to a disuse condition using the Random Positioning Machine (RPM) and intervened with an LMHF mechanical load (0.1-0.4g at 30Hz for 10-60 min/day). Exposure of 2T3 cells to the RPM decreased bone formation responses as determined by alkaline phosphatase (ALP) activity and mineralization even in the presence of a submaximal dose of BMP4 (20ng/ml). However, LMHF mechanical loading prevented the RPM-induced decrease in ALP activity and mineralization. Mineralization induced by LMHF mechanical loading was enhanced by treatment with bone morphogenic protein 4 (BMP4) and blocked by the BMP antagonist noggin, suggesting a role for BMPs in this response. In addition, LMHF mechanical loading rescued the RPM-induced decrease in gene expression of ALP, runx2, osteomodulin, parathyroid hormone receptor 1, and osteoglycin. These findings suggest that preosteoblasts may directly respond to LMHF mechanical loading to induce differentiation responses. The mechanosensitive genes identified here provide potential targets for pharmaceutical treatments that may be used in combination with low level mechanical loading to better treat osteoporosis or disuse-induced bone loss. PMID:19125415

  11. A new X linked recessive deafness syndrome with blindness, dystonia, fractures, and mental deficiency is linked to Xq22.

    PubMed Central

    Tranebjaerg, L; Schwartz, C; Eriksen, H; Andreasson, S; Ponjavic, V; Dahl, A; Stevenson, R E; May, M; Arena, F; Barker, D

    1995-01-01

    X linked recessive deafness accounts for only 1.7% of all childhood deafness. Only a few of the at least 28 different X linked syndromes associated with hearing impairment have been characterised at the molecular level. In 1960, a large Norwegian family was reported with early onset progressive sensorineural deafness, which was indexed in McKusick as DFN-1, McKusick 304700. No associated symptoms were described at that time. This family has been restudied clinically. Extensive neurological, neurophysiological, neuroradiological, and biochemical, as well as molecular techniques, have been applied to characterise the X linked recessive syndrome. The family history and extensive characterisation of 16 affected males in five generations confirmed the X linked recessive inheritance and the postlingual progressive nature of the sensorineural deafness. Some obligate carrier females showed signs of minor neuropathy and mild hearing impairment. Restudy of the original DFN-1 family showed that the deafness is part of a progressive X linked recessive syndrome, which includes visual disability leading to cortical blindness, dystonia, fractures, and mental deficiency. Linkage analysis indicated that the gene was linked to locus DXS101 in Xq22 with a lod score of 5.37 (zero recombination). Based on lod-1 support interval of the multipoint analysis, the gene is located in a region spanning from 5 cM proximal to 3 cM distal to this locus. As the proteolipid protein gene (PLP) is within this region and mutations have been shown to be associated with non-classical PMD (Pelizaeus-Merzbacher disease), such as complex X linked hereditary spastic paraplegia, PLP may represent a candidate gene for this disorder. This family represents a new syndrome (Mohr-Tranebjaerg syndrome, MTS) and provides significant new information about a new X linked recessive sydromic type of deafness which was previously thought to be isolated deafness. PMID:7643352

  12. StartReact restores reaction time in HSP: evidence for subcortical release of a motor program.

    PubMed

    Nonnekes, Jorik; Oude Nijhuis, Lars B; de Niet, Mark; de Bot, Susanne T; Pasman, Jacobus W; van de Warrenburg, Bart P C; Bloem, Bastiaan R; Weerdesteyn, Vivian; Geurts, Alexander C

    2014-01-01

    Startling acoustic stimuli (SAS) can accelerate reaction times ("StartReact" effect), but the underlying mechanism remains unclear. Both direct release of a subcortically stored motor program and a subcortically mediated trigger for a cortically stored motor program have been hypothesized. To distinguish between these hypotheses, we examined the StartReact effect in humans with pure hereditary spastic paraplegia (HSP). Delayed reaction times in HSP patients in trials both with and without a SAS would argue in favor of a cortically stored response. We instructed 12 HSP patients and 12 matched controls to respond as rapidly as possible to a visual imperative stimulus, in two different conditions: dorsiflexion of the dominant ankle; or flexion of the dominant wrist. In 25% of trials, a SAS was delivered simultaneously with the imperative stimulus. Before these tests, subjects received five SAS while standing to verify normal function of the reticulospinal tract in HSP. Latencies of startle responses in sternocleidomastoid and tibialis anterior muscles were comparable between patients and controls. During the ankle dorsiflexion task, HSP patients had an average 19 ms delay in reaction times compared with controls. Administration of a SAS accelerated ankle dorsiflexion in both groups, but more so in the patients, which completely normalized their latencies. The wrist flexion task yielded no differences in onset latencies between HSP patients and controls. The reticulospinal tract seems unaffected in HSP patients, because startle reflex onsets were normal. The corticospinal tract was affected, as reflected by delayed ankle dorsiflexion reaction times. These delayed onsets in HSP were normalized when the imperative stimulus was combined with a SAS, presumably through release of a subcortically stored motor program conveyed by the preserved reticulospinal tract. PMID:24381288

  13. 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

  14. ?-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

  15. Restoration of micturition using microelectric current in experimentally induced spastic urinary bladder in rabbits.

    PubMed

    Karoutas, G; Karacostas, D; Artemis, N; Liapis, J; Tzotzoras, T; Andreou, A; Tsitsopoulos, P

    1988-12-01

    The 29 rabbits used in this study were divided into three groups, A (A1 and A2), B, and C. In subgroup A1, 4 animals were used in order to verify whether the contact of an electrode to the sacral nerves results in some abnormality of voiding reflex. In subgroups A1 and A2 (4 animals each) we further studied the micturition function using three parameters: (i) urinary bladder fluoroscopy and radiography, (ii) cystomanometry, and (iii) electromyography of the pelvic floor muscles (external sphinter). In group B (9 rabbits) spastic paraplegia and micturition disturbances resulted from spinal cord compression that was induced by inserting a balloon catheter into the T11-T12 intervertebral foramen. In this group the parameters studied revealed a spastic urinary bladder in all animals. Finally, the 12 animals of group C were rendered paraplegic as described in group B, and microelectrodes were placed over the sacral nerves as in subgroup A1. By applying a specific sequence of sacral nerve stimulation we succeeded in satisfactory urinary bladder emptying as confirmed by the micturition parameters studied: The urinary bladder pressure decreased from 65 +/- 3 to 28 +/- 3 mm Hg. The pelvic floor muscle amplitude was lowered from 130 +/- 7 to 20 +/- 3 microV, and finally the radiological bladder size also decreased from 38 cm2 before voiding to 18 +/- 3 cm2 after voiding. These results indicate that microelectric current stimulation of the sacral nerves, when applied under a specific sequence, could rather satisfactorily restore micturition disturbances, at least in this experimental animal. PMID:3264248

  16. Untangling the web: Mechanisms underlying ER network formation

    PubMed Central

    Goyal, Uma; Blackstone, Craig

    2013-01-01

    The ER is a continuous membrane system consisting of the nuclear envelope, flat sheets often studded with ribosomes, and a polygonal network of highly-curved tubules extending throughout the cell. Although protein and lipid biosynthesis, protein modification, vesicular transport, Ca2+dynamics, and protein quality control have been investigated in great detail, mechanisms that generate the distinctive architecture of the ER have been uncovered only recently. Several protein families including the reticulons and REEPs/DP1/Yop1p harbor hydrophobic hairpin domains that shape high-curvature ER tubules and mediate intramembrane protein interactions. Members of the atlastin/RHD3/Sey1p family of dynamin-related GTPases interact with the ER-shaping proteins and mediate the formation of three-way junctions responsible for the polygonal structure of the tubular ER network, with Lunapark proteins acting antagonistically. Additional classes of tubular ER proteins including some REEPs and the M1 spastin ATPase interact with the microtubule cytoskeleton. Flat ER sheets possess a different complement of proteins such as p180, CLIMP-63 and kinectin implicated in shaping, cisternal stacking and cytoskeletal interactions. The ER is also in constant motion, and numerous signaling pathways as well as interactions among cytoskeletal elements, the plasma membrane, and organelles cooperate to position and shape the ER dynamically. Finally, many proteins involved in shaping the ER network are mutated in the most common forms of hereditary spastic paraplegia, indicating a particular importance for proper ER morphology and distribution in large, highly-polarized cells such as neurons. PMID:23602970

  17. Pathogenic Mutation of Spastin Has Gain-of-Function Effects on Microtubule Dynamics

    PubMed Central

    Solowska, Joanna M.; D'Rozario, Mitchell; Jean, Daphney C.; Davidson, Michael W.; Marenda, Daniel R.

    2014-01-01

    Mutations to the SPG4 gene encoding the microtubule-severing protein spastin are the most common cause of hereditary spastic paraplegia. Haploinsufficiency, the prevalent model for the disease, cannot readily explain many of its key aspects, such as its adult onset or its specificity for the corticospinal tracts. Treatment strategies based solely on haploinsufficiency are therefore likely to fail. Toward developing effective therapies, here we investigated potential gain-of-function effects of mutant spastins. The full-length human spastin isoform called M1 or a slightly shorter isoform called M87, both carrying the same pathogenic mutation C448Y, were expressed in three model systems: primary rat cortical neurons, fibroblasts, and transgenic Drosophila. Although both isoforms had ill effects on motor function in transgenic flies and decreased neurite outgrowth from primary cortical neurons, mutant M1 was notably more toxic than mutant M87. The observed phenotypes did not result from dominant-negative effects of mutated spastins. Studies in cultured cells revealed that microtubules can be heavily decorated by mutant M1 but not mutant M87. Microtubule-bound mutant M1 decreased microtubule dynamics, whereas unbound M1 or M87 mutant spastins increased microtubule dynamics. The alterations in microtubule dynamics observed in the presence of mutated spastins are not consistent with haploinsufficiency and are better explained by a gain-of-function mechanism. Our results fortify a model wherein toxicity of mutant spastin proteins, especially mutant M1, contributes to axonal degeneration in the corticospinal tracts. Furthermore, our results provide details on the mechanism of the toxicity that may chart a course toward more effective treatment regimens. PMID:24478365

  18. Pathogenic mutation of spastin has gain-of-function effects on microtubule dynamics.

    PubMed

    Solowska, Joanna M; D'Rozario, Mitchell; Jean, Daphney C; Davidson, Michael W; Marenda, Daniel R; Baas, Peter W

    2014-01-29

    Mutations to the SPG4 gene encoding the microtubule-severing protein spastin are the most common cause of hereditary spastic paraplegia. Haploinsufficiency, the prevalent model for the disease, cannot readily explain many of its key aspects, such as its adult onset or its specificity for the corticospinal tracts. Treatment strategies based solely on haploinsufficiency are therefore likely to fail. Toward developing effective therapies, here we investigated potential gain-of-function effects of mutant spastins. The full-length human spastin isoform called M1 or a slightly shorter isoform called M87, both carrying the same pathogenic mutation C448Y, were expressed in three model systems: primary rat cortical neurons, fibroblasts, and transgenic Drosophila. Although both isoforms had ill effects on motor function in transgenic flies and decreased neurite outgrowth from primary cortical neurons, mutant M1 was notably more toxic than mutant M87. The observed phenotypes did not result from dominant-negative effects of mutated spastins. Studies in cultured cells revealed that microtubules can be heavily decorated by mutant M1 but not mutant M87. Microtubule-bound mutant M1 decreased microtubule dynamics, whereas unbound M1 or M87 mutant spastins increased microtubule dynamics. The alterations in microtubule dynamics observed in the presence of mutated spastins are not consistent with haploinsufficiency and are better explained by a gain-of-function mechanism. Our results fortify a model wherein toxicity of mutant spastin proteins, especially mutant M1, contributes to axonal degeneration in the corticospinal tracts. Furthermore, our results provide details on the mechanism of the toxicity that may chart a course toward more effective treatment regimens. PMID:24478365

  19. SPG20 Protein Spartin Is Recruited to Midbodies by ESCRT-III Protein Ist1 and Participates in Cytokinesis

    PubMed Central

    Renvoisé, Benoît; Parker, Rell L.; Yang, Dong; Bakowska, Joanna C.; Hurley, James H.

    2010-01-01

    Hereditary spastic paraplegias (HSPs, SPG1-46) are inherited neurological disorders characterized by lower extremity spastic weakness. Loss-of-function SPG20 gene mutations cause an autosomal recessive HSP known as Troyer syndrome. The SPG20 protein spartin localizes to lipid droplets and endosomes, and it interacts with tail interacting protein 47 (TIP47) as well as the ubiquitin E3 ligases atrophin-1-interacting protein (AIP)4 and AIP5. Spartin harbors a domain contained within microtubule-interacting and trafficking molecules (MIT) at its N-terminus, and most proteins with MIT domains interact with specific ESCRT-III proteins. Using yeast two-hybrid and in vitro surface plasmon resonance assays, we demonstrate that the spartin MIT domain binds with micromolar affinity to the endosomal sorting complex required for transport (ESCRT)-III protein increased sodium tolerance (Ist)1 but not to ESCRT-III proteins charged multivesicular body proteins 1–7. Spartin colocalizes with Ist1 at the midbody, and depletion of Ist1 in cells by small interfering RNA significantly decreases the number of cells where spartin is present at midbodies. Depletion of spartin does not affect Ist1 localization to midbodies but markedly impairs cytokinesis. A structure-based amino acid substitution in the spartin MIT domain (F24D) blocks the spartin–Ist1 interaction. Spartin F24D does not localize to the midbody and acts in a dominant-negative manner to impair cytokinesis. These data suggest that Ist1 interaction is important for spartin recruitment to the midbody and that spartin participates in cytokinesis. PMID:20719964

  20. Zebrafish models of human motor neuron diseases: advantages and limitations.

    PubMed

    Babin, Patrick J; Goizet, Cyril; Raldúa, Demetrio

    2014-07-01

    Motor neuron diseases (MNDs) are an etiologically heterogeneous group of disorders of neurodegenerative origin, which result in degeneration of lower (LMNs) and/or upper motor neurons (UMNs). Neurodegenerative MNDs include pure hereditary spastic paraplegia (HSP), which involves specific degeneration of UMNs, leading to progressive spasticity of the lower limbs. In contrast, spinal muscular atrophy (SMA) involves the specific degeneration of LMNs, with symmetrical muscle weakness and atrophy. Amyotrophic lateral sclerosis (ALS), the most common adult-onset MND, is characterized by the degeneration of both UMNs and LMNs, leading to progressive muscle weakness, atrophy, and spasticity. A review of the comparative neuroanatomy of the human and zebrafish motor systems showed that, while the zebrafish was a homologous model for LMN disorders, such as SMA, it was only partially relevant in the case of UMN disorders, due to the absence of corticospinal and rubrospinal tracts in its central nervous system. Even considering the limitation of this model to fully reproduce the human UMN disorders, zebrafish offer an excellent alternative vertebrate model for the molecular and genetic dissection of MND mechanisms. Its advantages include the conservation of genome and physiological processes and applicable in vivo tools, including easy imaging, loss or gain of function methods, behavioral tests to examine changes in motor activity, and the ease of simultaneous chemical/drug testing on large numbers of animals. This facilitates the assessment of the environmental origin of MNDs, alone or in combination with genetic traits and putative modifier genes. Positive hits obtained by phenotype-based small-molecule screening using zebrafish may potentially be effective drugs for treatment of human MNDs. PMID:24705136

  1. Posterior approach to ventrally located spinal meningiomas

    PubMed Central

    Voulgaris, Spyridon; Mihos, Evaggelos; Karagiorgiadis, Dimitrios; Zigouris, Andreas; Fotakopoulos, George; Drosos, Dimitrios; Pahaturidis, Dimitrios

    2010-01-01

    For the resection of anteriorly located meningiomas, various approaches have been used. Posterior approach is less invasive and demanding; however, it has been associated with increased risk of spinal cord injury. We evaluated ten consecutive patients that underwent surgery for spinal meningiomas. All patients were preoperative assessed by neurological examination, computed tomography and magnetic resonance imaging. All tumors were ventrally located and removed via a posterior approach. Transcranial motor-evoked potentials (TcMEPs), somatosensory-evoked potential (SSEP) and free running electromyography (EMG) were monitored intraoperative. Postoperative all patients had regular follow-up examinations. There were four males and six females. The mean age was 68.2 years (range 39–82 years). In nine out of ten cases, the tumor was located in the thoracic spine. A case of a lumbar meningioma was recorded. The most common presenting symptom was motor and sensory deficits and unsteady gait, whereas no patient presented with paraplegia. All meningiomas were operated using a microsurgical technique via a posterior approach. During the operation, free running EMG monitoring prompted a surgical alert in case of irritation, whereas TcMEP and SSEP amplitudes remained unchanged. Histopathology revealed the presence of typical (World Health Organisation grade I) meningiomas. The mean Ki-67/MIB-1 index was 2.75% (range 0.5–7). None of our patients sustained a transient or permanent motor deficit. After a mean follow-up period of 26 months (range 56–16 months), no tumor recurrence and no instability were found. Posterior approach for anteriorly located meningiomas is a safe procedure with the use of intraoperative monitoring, less invasive and well-tolerated especially in older patients. Complete tumor excision can be performed with satisfactory results. PMID:20127494

  2. Depression and Anxiety in Adolescents With Pediatric-Onset Spinal Cord Injury

    PubMed Central

    Klaas, Sara J.

    2014-01-01

    Background: Little is known about depression and anxiety in adolescents with spinal cord injury (SCI). Objective: To examine how depression, anxiety, suicidal ideation, and usage of treatment differ by age and sex among adolescents with SCI. Method: Youth 12 to 18 years old who had acquired SCI at least 1 year prior were recruited from 3 specialty hospitals. They completed the Children’s Depression Inventory (ages 12-17 years) or Beck Depression Inventory-II (18 years), and Revised Children’s Manifest Anxiety Scale (12-18 years). Analyses assessed differences between younger and older adolescents and between males and females. Results: The 236 participants were an average age of 15.58 years (SD 1.98), 58% were male, and 60% Caucasian. Average age at injury was 10.57 years (SD 5.50), and 62% had paraplegia. For depression, 5.5% of adolescents ages 12 to 17 years exceeded the clinical cutoff and 12.7% of 18-year-old adolescents fell into a range of moderate or severe depression. For anxiety, 10.6% of adolescents ages 12 to 18 years exceeded the clinical cutoff. Univariate results revealed that older adolescents were more depressed than younger adolescents, and girls were more anxious than boys. An interaction between sex and age emerged, in that older adolescent girls were significantly more anxious than other youth. Older adolescents were also more likely to be taking medications for emotional, psychological, or behavioral reasons. Reports of suicidal ideation did not differ by adolescent age or sex. Conclusion: For these adolescents, depression differed with age, and anxiety differed based on age and sex. Implications for intervention include early identification and treatment for struggling adolescents. PMID:24574818

  3. 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

  4. Energy consumption of paraplegic locomotion using reciprocating gait orthosis.

    PubMed

    Beillot, J; Carré, F; Le Claire, G; Thoumie, P; Perruoin-Verbe, B; Cormerais, A; Courtillon, A; Tanguy, E; Nadeau, G; Rochcongar, P; Dassonville, J

    1996-01-01

    The energy cost of walking using a reciprocating gait orthosis (RGOII) with functional electrical stimulation (FES) was assessed in 14 patients with spastic complete paraplegia from six rehabilitation centres. Before and after training asing RGOII with FES, the subjects performed a progressive maximal test on an arm-crank ergometer to obtain their laboratory peak oxygen uptake (LVO2peak), heart rate (HR) and blood lactate concentration changes. At the end of the training session, oxygen uptake (VO2) was measured during a walking test with orthosis at different speeds (6 min steady state at 0.1 m.s-1, followed by 2-min stages at progressively increasing speeds up to exhaustion). Of the subjects 4 repeated this test using orthosis without FES. At a speed of 0.1 m.s-1, VO2 represented 47 (SD 23)% of LVO2peak, mean HR was 137 (SD 21) beats.min-1 and mean blood lactate concentration 2.4. (SD 1.4) mmol.l-1. Maximal speed ranged from 0.23 to 0.5 m.s-1. At maximal speed, VO2 was 91 (SD 18)% of LVO2peak, mean HR reached 96 (SD 7)% and mean blood lactate concentration only 52 (SD 19)% of the maximal values measured during the laboratory test. Walking without electrical stimulation induced an increase in HR but there was no difference in VO2 and blood lactate compared to walking with stimulation. The training period did not result in any improvement in maximal physiological data. We concluded that the free cadence walking speed with orthosis remains much lower than that of able-bodied people or wheelchair users. The metabolic cost at a given speed is much higher even if, using a stimulation device, the cardiovascular stress is reduced. PMID:8781872

  5. Free plasma catecholamines in spinal cord injured persons with different injury levels at rest and during exercise.

    PubMed

    Schmid, A; Huonker, M; Stahl, F; Barturen, J M; König, D; Heim, M; Lehmann, M; Keul, J

    1998-01-19

    Spinal cord lesion leads to an interruption of pathways from brain to the peripheral sympathetic nervous system, which results in pathological changes in sympathetic innervation. Free epinephrine (E), norepinephrine (NE) and dopamine (DA) were measured in 30 tetraplegics (TETRA), 15 high-lesion paraplegics (T1 and T4, HPARA), 15 paraplegics with injuries between T5 and T10 (MPARA), 15 low-lesion paraplegics (below T10, LPARA) and 16 non-handicapped control persons (C) at rest, at 60 and 100% of maximal oxygen consumption during graded wheelchair ergometry (WCE). The TETRA showed significant lower E and NE levels at rest and only slight increases during physical exercise. The E and NE concentrations of the paraplegics with a lesion below T5 were significantly higher than those of the high-lesion paraplegics, as well as those of the control persons at every point in the study. All paraplegics and the control persons showed, at submaximal and maximal exercise, a significant increase in NE. Only a slight increase in E in HAPRA was shown. No differences were found at rest and during exercise in E and NE levels in the MPARA and LPARA. No significant differences were found in the dopamine concentration at rest or during exercise for any of the groups. In summary, different levels of lesion and the resulting interruption to sympathetic pathways in the spinal cord are decisive factors in the degree of impairment of sympathetic innervation in SCI persons. Tetraplegics show less preganglionic resting activity because of interruption of impulses from central centers and no considerable stimulation of the sympathetic nervous system during maximal exercise. Individuals with high paraplegia have a partial impairment of catecholamine release, especially of epinephrine, at rest and during exercise. Paraplegics with a lesion level below T5 showed an augmented basal and exercise-induced upper spinal thoracic sympathetic activity in comparison to control persons. PMID:9531449

  6. 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

  7. Problems in early diagnosis of bladder cancer in a spinal cord injury patient: Report of a case of simultaneous production of granulocyte colony stimulating factor and parathyroid hormone-related protein by squamous cell carcinoma of urinary bladder

    PubMed Central

    Vaidyanathan, Subramanian; Mansour, Paul; Ueno, Munehisa; Yamazaki, Kazuto; Wadhwa, Meenu; Soni, Bakul M; Singh, Gurpreet; Hughes, Peter L; Watson, Ian D; Sett, Pradipkumar

    2002-01-01

    Background Typical symptoms and signs of a clinical condition may be absent in spinal cord injury (SCI) patients. Case presentation A male with paraplegia was passing urine through penile sheath for 35 years, when he developed urinary infections. There was no history of haematuria. Intravenous urography showed bilateral hydronephrosis. The significance of abnormal outline of bladder was not appreciated. As there was large residual urine, he was advised intermittent catheterisation. Serum urea: 3.5 mmol/L; creatinine: 77 umol/L. A year later, serum urea: 36.8 mmol/l; creatinine: 632 umol/l; white cell count: 22.2; neutrophils: 18.88. Ultrasound: bilateral hydronephrosis. Bilateral nephrostomy was performed. Subsequently, blood tests showed: Urea: 14.2 mmol/l; Creatinine: 251 umol/l; Adjusted Calcium: 3.28 mmol/l; Parathyroid hormone: < 0.7 pmol/l (1.1 – 6.9); Parathyroid hormone-related protein (PTHrP): 2.3 pmol/l (0.7 – 1.8). Ultrasound scan of urinary bladder showed mixed echogenicity, which was diagnosed as debris. CT of pelvis was interpreted as vesical abscess. Urine cytology: Transitional cells showing mild atypia. Bladder biopsy: Inflamed mucosa lined by normal urothelial cells. A repeat ultrasound scan demonstrated a tumour arising from right lateral wall; biopsy revealed squamous cell carcinoma. In view of persistently high white cell count and high calcium level, immunohistochemistry for G-CSF and PTHrP was performed. Dense staining of tumour cells for G-CSF and faintly positive staining for C-terminal PTHrP were observed. This patient expired about five months later. Conclusion This case demonstrates how delay in diagnosis of bladder cancer could occur in a SCI patient due to absence of characteristic symptoms and signs. PMID:12201902

  8. MRI as a tool to study brain structure from mouse models for mental retardation

    NASA Astrophysics Data System (ADS)

    Verhoye, Marleen; Sijbers, Jan; Kooy, R. F.; Reyniers, E.; Fransen, E.; Oostra, B. A.; Willems, Peter; Van der Linden, Anne-Marie

    1998-07-01

    Nowadays, transgenic mice are a common tool to study brain abnormalities in neurological disorders. These studies usually rely on neuropathological examinations, which have a number of drawbacks, including the risk of artefacts introduced by fixation and dehydration procedures. Here we present 3D Fast Spin Echo Magnetic Resonance Imaging (MRI) in combination with 2D and 3D segmentation techniques as a powerful tool to study brain anatomy. We set up MRI of the brain in mouse models for the fragile X syndrome (FMR1 knockout) and Corpus callosum hypoplasia, mental Retardation, Adducted thumbs, Spastic paraplegia and Hydrocephalus (CRASH) syndrome (L1CAM knockout). Our major goal was to determine qualitative and quantitative differences in specific brain structures. MRI of the brain of fragile X and CRASH patients has revealed alterations in the size of specific brain structures, including the cerebellar vermis and the ventricular system. In the present MRI study of the brain from fragile X knockout mice, we have measured the size of the brain, cerebellum and 4th ventricle, which were reported as abnormal in human fragile X patients, but found no evidence for altered brain regions in the mouse model. In CRASH syndrome, the most specific brain abnormalities are vermis hypoplasia and abnormalities of the ventricular system with some degree of hydrocephalus. With the MRI study of L1CAM knockout mice we found vermis hypoplasia, abnormalities of the ventricular system including dilatation of the lateral and the 4th ventricles. These subtle abnormalities were not detected upon standard neuropathological examination. Here we proved that this sensitive MRI technique allows to measure small differences which can not always be detected by means of pathology.

  9. Neuroprotective effects of PEP-1-Cu,Zn-SOD against ischemic neuronal damage in the rabbit spinal cord.

    PubMed

    Kim, Woosuk; Kim, Dae Won; Yoo, Dae Young; Chung, Jin Young; Hwang, In Koo; Won, Moo-Ho; Choi, Soo Young; Jeon, Sei Woong; Jeong, Je Hoon; Hwang, Hyung Sik; Moon, Seung Myung

    2012-02-01

    A rabbit model of spinal cord ischemia has been introduced as a good model to investigate the pathophysiology of ischemia-reperfusion (I-R)-induced paraplegia. In the present study, we observed the effects of Cu,Zn-superoxide dismutase (SOD1) against ischemic damage in the ventral horn of L(5-6) levels in the rabbit spinal cord. For this study, the expression vector PEP-1 was constructed, and this vector was fused with SOD1 to create a PEP-1-SOD1 fusion protein that easily penetrated the blood-brain barrier. Spinal cord ischemia was induced by transient occlusion of the abdominal aorta for 15 min. PEP-1-SOD1 (0.5 mg/kg) was intraperitoneally administered to rabbits 30 min before ischemic surgery. The administration of PEP-1-SOD1 significantly improved neurological scores compared to those in the PEP-1 (vehicle)-treated ischemia group. Also, in this group, the number of cresyl violet-positive cells at 72 h after I-R was much higher than that in the vehicle-treated ischemia group. Malondialdehyde levels were significantly decreased in the ischemic spinal cord of the PEP-1-SOD1-treated ischemia group compared to those in the vehicle-treated ischemia group. In contrast, the administration of PEP-1-SOD1 significantly ameliorated the ischemia-induced reduction of SOD and catalase levels in the ischemic spinal cord. These results suggest that PEP-1-SOD1 protects neurons from spinal ischemic damage by decreasing lipid peroxidation and maintaining SOD and catalase levels in the ischemic rabbit spinal cord. PMID:21964799

  10. Extract EGb 761 pretreatment limits ubiquitin positive aggregates in rabbit spinal cord neurons after ischemia-reperfusion.

    PubMed

    Mechírová, Eva; Feriková, Marianna; Domoráková, Iveta

    2006-01-01

    1. Ubiquitin immunohistochemistry was used for investigation of time dependent changes of ubiquitin in the nerve cells reacting to ischemic/reperfusion damage. In the rabbit spinal cord ischemia model a period of 30 min ischemia followed by 24 and 72 h of reperfusion caused neuronal degeneration selectively in the ventral horn motor neurons as well as interneurons of the intermediate zone. 2. Ubiquitin aggregates were accumulated in the neurons of lamina IX and the neurons of intermediate zone destined to die 72 h after 30 min of the spinal cord ischemia. 3. The activation of ubiquitin hydrolytic system is related to a defective homeostasis and could trigger different degenerative processes. Having in mind this, we used EGb 761 to rescue the motor neurons and interneurons against ischemia/reperfusion damage. Our results show that after 30 min of ischemia and 24 or 72 h of reperfusion with EGb 761 pre-treatment for 7 days the vulnerable neurons in the intermediate zone and lamina IX exhibit marked elevation of ubiquitin-positive granules in the cytoplasm, dendrites and nuclei. Abnormal protein aggregates have not been observed in these cells. 4. The rabbits were completely paraplegic after 30 min of ischemia and 24 or 72 h of reperfusion. However, after 7 days EGb 761 pre-treatment, 30 min of ischemia and 24 or 72 h of reperfusion the animals did not show paraplegia. 5. Evaluated ubiquitin-positive neurons of the L(5)-L(6) segments showed significant decrease in number and significant increase of density after 30 min of ischemia followed by 24 h and mainly 72 h of reperfusion. Ubiquitin immunohistochemistry confirmed the protective effect of EGb 761 against ischemia/reperfusion damage in the rabbit spinal cord. PMID:16670948

  11. Multi-system neurological disease is common in patients with OPA1 mutations

    PubMed Central

    Yu-Wai-Man, P.; Griffiths, P.G.; Gorman, G.S.; Lourenco, C.M.; Wright, A.F.; Auer-Grumbach, M.; Toscano, A.; Musumeci, O.; Valentino, M.L.; Caporali, L.; Lamperti, C.; Tallaksen, C.M.; Duffey, P.; Miller, J.; Whittaker, R.G.; Baker, M.R.; Jackson, M.J.; Clarke, M.P.; Dhillon, B.; Czermin, B.; Stewart, J.D.; Hudson, G.; Reynier, P.; Bonneau, D.; Marques, W.; Lenaers, G.; McFarland, R.; Taylor, R.W.; Turnbull, D.M.; Votruba, M.; Zeviani, M.; Carelli, V.; Bindoff, L.A.; Horvath, R.; Amati-Bonneau, P.

    2010-01-01

    Additional neurological features have recently been described in seven families transmitting pathogenic mutations in OPA1, the most common cause of autosomal dominant optic atrophy. However, the frequency of these syndromal ‘dominant optic atrophy plus’ variants and the extent of neurological involvement have not been established. In this large multi-centre study of 104 patients from 45 independent families, including 60 new cases, we show that extra-ocular neurological complications are common in OPA1 disease, and affect up to 20% of all mutational carriers. Bilateral sensorineural deafness beginning in late childhood and early adulthood was a prominent manifestation, followed by a combination of ataxia, myopathy, peripheral neuropathy and progressive external ophthalmoplegia from the third decade of life onwards. We also identified novel clinical presentations with spastic paraparesis mimicking hereditary spastic paraplegia, and a multiple sclerosis-like illness. In contrast to initial reports, multi-system neurological disease was associated with all mutational subtypes, although there was an increased risk with missense mutations [odds ratio = 3.06, 95% confidence interval = 1.44–6.49; P = 0.0027], and mutations located within the guanosine triphosphate-ase region (odds ratio = 2.29, 95% confidence interval = 1.08–4.82; P = 0.0271). Histochemical and molecular characterization of skeletal muscle biopsies revealed the presence of cytochrome c oxidase-deficient fibres and multiple mitochondrial DNA deletions in the majority of patients harbouring OPA1 mutations, even in those with isolated optic nerve involvement. However, the cytochrome c oxidase-deficient load was over four times higher in the dominant optic atrophy + group compared to the pure optic neuropathy group, implicating a causal role for these secondary mitochondrial DNA defects in disease pathophysiology. Individuals with dominant optic atrophy plus phenotypes also had significantly worse visual outcomes, and careful surveillance is therefore mandatory to optimize the detection and management of neurological disability in a group of patients who already have significant visual impairment. PMID:20157015

  12. 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

  13. Cytochrome P450s in the synthesis of cholesterol and bile acids--from mouse models to human diseases.

    PubMed

    Lorbek, Gregor; Lewinska, Monika; Rozman, Damjana

    2012-05-01

    The present review describes the transgenic mouse models that have been designed to evaluate the functions of the cytochrome P450s involved in cholesterol and bile acid synthesis, as well as their link with disease. The knockout of cholesterogenic Cyp51 is embrionally lethal, with symptoms of Antley-Bixler syndrome occurring in mice, whereas the evidence for this association is conflicting in humans. Disruption of Cyp7a1 from classic bile acid synthesis in mice leads to either increased postnatal death or a milder phenotype with elevated serum cholesterol. The latter is similar to the case in humans, where CYP7A1 mutations associate with high plasma low-density lipoprotein and hepatic cholesterol content, as well as deficient bile acid excretion. Disruption of Cyp8b1 from an alternative bile acid pathway results in the absence of cholic acid and a reduced absorption of dietary lipids; however, the human CYP8B1 polymorphism fails to explain differences in bile acid composition. Unexpectedly, apparently normal Cyp27a1(-/-) mice still synthesize bile acids that originate from the compensatory pathway. In humans, CYP27A1 mutations cause cerebrotendinous xanthomatosis, suggesting that only mice can compensate for the loss of alternative bile acid synthesis. In line with this, Cyp7b1 knockouts are also apparently normal, whereas human CYP7B1 mutations lead to a congenital bile acid synthesis defect in children or spastic paraplegia in adults. Mouse knockouts of the brain-specific Cyp46a1 have reduced brain cholesterol excretion, whereas, in humans, CYP46A1 polymorphisms associate with cognitive impairment. At present, cytochrome P450 family 39 is poorly characterized. Despite important physiological differences between humans and mice, mouse models prove to be an invaluable tool for understanding the multifactorial facets of cholesterol and bile acid-related disorders. PMID:22111624

  14. 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

  15. Whole-Exome Sequencing Identifies Homozygous AFG3L2 Mutations in a Spastic Ataxia-Neuropathy Syndrome Linked to Mitochondrial m-AAA Proteases

    PubMed Central

    Martinelli, Paola; Cherukuri, Praveen F.; Teer, Jamie K.; Hansen, Nancy F.; Cruz, Pedro; Mullikin for the NISC Comparative Sequencing Program, James C.; Blakesley, Robert W.; Golas, Gretchen; Kwan, Justin; Sandler, Anthony; Fuentes Fajardo, Karin; Markello, Thomas; Tifft, Cynthia; Blackstone, Craig; Rugarli, Elena I.; Langer, Thomas; Gahl, William A.; Toro, Camilo

    2011-01-01

    We report an early onset spastic ataxia-neuropathy syndrome in two brothers of a consanguineous family characterized clinically by lower extremity spasticity, peripheral neuropathy, ptosis, oculomotor apraxia, dystonia, cerebellar atrophy, and progressive myoclonic epilepsy. Whole-exome sequencing identified a homozygous missense mutation (c.1847G>A; p.Y616C) in AFG3L2, encoding a subunit of an m-AAA protease. m-AAA proteases reside in the mitochondrial inner membrane and are responsible for removal of damaged or misfolded proteins and proteolytic activation of essential mitochondrial proteins. AFG3L2 forms either a homo-oligomeric isoenzyme or a hetero-oligomeric complex with paraplegin, a homologous protein mutated in hereditary spastic paraplegia type 7 (SPG7). Heterozygous loss-of-function mutations in AFG3L2 cause autosomal-dominant spinocerebellar ataxia type 28 (SCA28), a disorder whose phenotype is strikingly different from that of our patients. As defined in yeast complementation assays, the AFG3L2Y616C gene product is a hypomorphic variant that exhibited oligomerization defects in yeast as well as in patient fibroblasts. Specifically, the formation of AFG3L2Y616C complexes was impaired, both with itself and to a greater extent with paraplegin. This produced an early-onset clinical syndrome that combines the severe phenotypes of SPG7 and SCA28, in additional to other “mitochondrial” features such as oculomotor apraxia, extrapyramidal dysfunction, and myoclonic epilepsy. These findings expand the phenotype associated with AFG3L2 mutations and suggest that AFG3L2-related disease should be considered in the differential diagnosis of spastic ataxias. PMID:22022284

  16. N-methyl-D-aspartate receptor antagonist MK-801 prevents apoptosis in rats that have undergone fetal spinal cord transplantation following spinal hemisection

    PubMed Central

    ZHANG, QIANG; SHAO, YANG; ZHAO, CHANGSONG; CAI, JUAN; SUN, SHENG

    2014-01-01

    Spinal cord injury is the main cause of paraplegia, but effective therapies for it are lacking. Embryonic spinal cord transplantation is able to repair spinal cord injury, albeit with a large amount of neuronal apoptosis remaining in the spinal cord. MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, is able to reduce cell death by decreasing the concentration of excitatory amino acids and preventing extracellular calcium ion influx. In this study, the effect of MK-801 on the apoptosis of spinal cord neurons in rats that have received a fetal spinal cord (FSC) transplant following spinal hemisection was investigated. Wistar rats were divided into three groups: Spinal cord hemisection injury with a combination of FSC transplantation and MK-801 treatment (group A); spinal cord hemisection injury with FSC transplantation (group B); and spinal cord injury with insertion of a Gelfoam pledget (group C). The rats were sacrificed 1, 3, 7 and 14 days after the surgery. Apoptosis in spinal slices from the injured spinal cord was examined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling reaction, and the expression of B-cell lymphoma-2 (Bcl-2) was measured by immunohistochemistry. The positive cells were quantitatively analyzed using a computer image analysis system. The rate of apoptosis and the positive expression of Bcl-2 protein in the spinal cord neurons in the three groups decreased in the following order: C>B>A (P<0.05) and A>B>C (P<0.05), respectively. This indicates that treatment with the NMDA receptor antagonist MK-801 prevents apoptosis in the spinal cord neurons of rats that have undergone FSC transplantation following spinal hemisection. PMID:25371724

  17. 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

  18. Clinical outcomes of hybrid repair for thoracoabdominal aortic aneurysms

    PubMed Central

    Tshomba, Yamume; Logaldo, Davide; Rinaldi, Enrico; Bertoglio, Luca; Civilini, Efrem; Psacharopulo, Daniele; Chiesa, Roberto

    2012-01-01

    Background Thoracoabdominal aortic aneurysm (TAAA) hybrid repair consists of aortic visceral branch rerouting followed by TAAA endograft exclusion. This technique has been shown to represent a technically feasible strategy in selected patients. Methods We analyzed 52 high-risk patients who underwent hybrid TAAA repair between 2001 and 2012 in our centre with a variety of visceral rerouting configurations and of commercially available thoracic endografts. Thirty-seven simultaneous (71.2%) and 15 staged procedures (21.8%) were performed with a four-vessel revascularization in 18 cases (34.6%), a three-vessel revascularization in 11 cases (21.2%) and a two-vessel revascularization in 23 cases (44.2%). Results No intraoperative deaths were observed. We recorded a perioperative mortality rate of 13.5% (n=7), including deaths from multiorgan failure (n=2), myocardial infarction (n=2), coagulopathy (n=1), pancreatitis (n=1) and bowel infarction (n=1). Perioperative morbidity rate was 28.8% (n=15), including 2 cases of transient paraparesis and 1 case of permanent paraplegia. Renal failure (n=5), pancreatitis (n=3), respiratory failure (n=3) and dysphagia (n=1) were also observed. At median follow-up of 23.9 months procedure-related mortality rate was 9.6%: two patients died from visceral graft occlusion and three from aortic rupture. There were three endoleaks and one endograft migration, none of which resulted in death. Five patients (9.6%) died as a consequence of unrelated events. Conclusions Typical complications of conventional TAAA open surgery have not been eliminated by hybrid repair, and significant mortality and morbidity rates have been recorded. Fate of visceral bypasses and incidence of endoleak and other endograft-related complications needs to be carefully assessed. Hybrid TAAA repair should currently be limited to high-risk surgical patients with unfit anatomy for endovascular repair. PMID:23977511

  19. 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

  20. Spinal Cord Injury in the Pediatric Population: A Systematic Review of the Literature

    PubMed Central

    Mac-Thiong, Jean-Marc; Roy-Beaudry, Marjolaine; Sosa, Jose Felix; Labelle, Hubert

    2011-01-01

    Abstract Spinal Cord Injury (SCI) in the pediatric population is relatively rare but carries significant psychological and physiological consequences. An interdisciplinary group of experts composed of medical and surgical specialists treating patients with SCI formulated the following questions: 1) What is the epidemiology of pediatric spinal cord injury and fractures?; 2) Are there unique features of pediatric SCI which distinguish the pediatric SCI population from adult SCI?; 3) Is there evidence to support the use of neuroprotective approaches, including hypothermia and steroids, in the treatment of pediatric SCI? A systematic review of the literature using multiple databases was undertaken to evaluate these three specific questions. A search strategy composed of specific search terms (Spinal Cord Injury, Paraplegia, Quadriplegia, tetraplegia, lapbelt injuries, seatbelt injuries, cervical spine injuries and Pediatrics) returned over 220 abstracts that were evaluated and by two observers. Relevant abstracts were then evaluated and papers were graded using the Downs and Black method. A table of evidence was then presented to a panel of experts using a modified Delphi approach and the following recommendation was then formulated using a consensus approach: Pediatric patients with traumatic SCI have different mechanisms of injury and have a better neurological recovery potential when compared to adults. Patients with SCI before their adolescent growth spurt have a high likelihood of developing scoliosis. Because of these differences, traumatic SCI should be highly suspected in the presence of abnormal neck or neurological exam, a high-risk mechanism of injury or a distracting injury even in the absence of radiological anomaly. PMID:21501096

  1. N-methyl-D-aspartate receptor antagonist MK-801 prevents apoptosis in rats that have undergone fetal spinal cord transplantation following spinal hemisection.

    PubMed

    Zhang, Qiang; Shao, Yang; Zhao, Changsong; Cai, Juan; Sun, Sheng

    2014-12-01

    Spinal cord injury is the main cause of paraplegia, but effective therapies for it are lacking. Embryonic spinal cord transplantation is able to repair spinal cord injury, albeit with a large amount of neuronal apoptosis remaining in the spinal cord. MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, is able to reduce cell death by decreasing the concentration of excitatory amino acids and preventing extracellular calcium ion influx. In this study, the effect of MK-801 on the apoptosis of spinal cord neurons in rats that have received a fetal spinal cord (FSC) transplant following spinal hemisection was investigated. Wistar rats were divided into three groups: Spinal cord hemisection injury with a combination of FSC transplantation and MK-801 treatment (group A); spinal cord hemisection injury with FSC transplantation (group B); and spinal cord injury with insertion of a Gelfoam pledget (group C). The rats were sacrificed 1, 3, 7 and 14 days after the surgery. Apoptosis in spinal slices from the injured spinal cord was examined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling reaction, and the expression of B-cell lymphoma-2 (Bcl-2) was measured by immunohistochemistry. The positive cells were quantitatively analyzed using a computer image analysis system. The rate of apoptosis and the positive expression of Bcl-2 protein in the spinal cord neurons in the three groups decreased in the following order: C>B>A (P<0.05) and A>B>C (P<0.05), respectively. This indicates that treatment with the NMDA receptor antagonist MK-801 prevents apoptosis in the spinal cord neurons of rats that have undergone FSC transplantation following spinal hemisection. PMID:25371724

  2. 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.

  3. Emergent Repair of Acute Thoracic Aortic Catastrophes

    PubMed Central

    Naughton, Peter A.; Park, Michael S.; Morasch, Mark D.; Rodriguez, Heron E.; Garcia-Toca, Manuel; Wang, C. Edward; Eskandari, Mark K.

    2014-01-01

    Objective To provide a contemporary institutional comparative analysis of expedient correction of acute catastrophes of the descending thoracic aorta (ACDTA) by traditional direct thoracic aortic repair (DTAR) or thoracic endovascular aortic repair (TEVAR). Design Single-center retrospective review (April 2001-January 2010). Setting Academic medical center. Patients One hundred patients with ACDTA treated with either TEVAR (n=76) or DTAR (n=24). Indications for repair included ruptured degenerative aneurysm (n = 41), traumatic transection (n = 27), complicated acute type B dissection (n=20), penetrating ulcer (n=4), intramural hematoma (n=3), penetrating injury (n=3), and embolizing lesion (n=2). Main Outcome Measures Demographics and 30-day and late outcomes were analyzed using multivariate analysis over a mean follow-up of 33.8 months. Results Among the 100 patients, mean (SD) age was 58.5 (17.3) years (range, 18–87 years). Demographics and comorbid conditions were similar between the 2 groups, except more patients in the DTAR group had prior aortic surgery (P=.02) and were older (P=.01). Overall 30-day mortality was significantly better among the TEVAR group (8% vs 29%; P=.007). Incidence of postoperative myocardial infarction, acute renal failure, stroke, and paraplegia/paresis was similar between the 2 treatment groups (TEVAR, 5%, 12%, 8%, and 8% vs DTAR, 13%, 13%, 9%, and 13%, respectively). Major respiratory complications were lower in the TEVAR group (16% vs 48%; P<.05). Mean length of hospital stay was also shorter after TEVAR (13.5 vs 16.3 days; P=.30). Independent predictors of patient mortality included age (P=.004) and DTAR (P=.001). Conclusion Patients presenting with ACDTA are best treated with TEVAR whenever feasible. PMID:22430904

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

    PubMed

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

    2014-10-01

    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

  5. Skeletal Manifestations of Hydatid Disease in Serbia: Demographic Distribution, Site Involvement, Radiological Findings, and Complications

    PubMed Central

    Bracanovic, Djurdja; Sopta, Jelena; Djonic, Danijela; Lujic, Nenad

    2013-01-01

    Although Serbia is recognized as an endemic country for echinococcosis, no information about precise incidence in humans has been available. The aim of this study was to investigate the skeletal manifestations of hydatid disease in Serbia. This retrospective study was conducted by reviewing the medical database of Institute for Pathology (Faculty of Medicine in Belgrade), a reference institution for bone pathology in Serbia. We reported a total of 41 patients with bone cystic echinococcosis (CE) during the study period. The mean age of 41 patients was 40.9±18.8 years. In 39% of patients, the fracture line was the only visible radiological sign, followed by cyst and tumefaction. The spine was the most commonly involved skeletal site (55.8%), followed by the femur (18.6%), pelvis (13.9%), humerus (7.0%), rib (2.3%), and tibia (2.3%). Pain was the symptom in 41.5% of patients, while some patients demonstrated complications such as paraplegia (22.0%), pathologic fracture (48.8%), and scoliosis (9.8%). The pathological fracture most frequently affected the spine (75.0%) followed by the femur (20.0%) and tibia (5.0%). However, 19.5% of patients didn't develop any complication or symptom. In this study, we showed that bone CE is not uncommon in Serbian population. As reported in the literature, therapy of bone CE is controversial and its results are poor. In order to improve the therapy outcome, early diagnosis, before symptoms and complications occur, can be contributive. PMID:24039289

  6. Outcomes of Open Surgical Repair of Descending Thoracic Aortic Disease

    PubMed Central

    Lee, Won-Young; Yoo, Jae Suk; Kim, Joon Bum; Jung, Sung-Ho; Choo, Suk Jung; Chung, Cheol Hyun; Lee, Jae Won

    2014-01-01

    Background To determine the predictors of clinical outcomes following surgical descending thoracic aortic (DTA) repair. Methods We identified 103 patients (23 females; mean age, 64.1±12.3 years) who underwent DTA replacement from 1999 to 2011 using either deep hypothermic circulatory arrest (44%) or partial cardiopulmonary bypass (CPB, 56%). Results The early mortality rate was 4.9% (n=5). Early major complications occurred in 21 patients (20.3%), which included newly required hemodialysis (9.7%), low cardiac output syndrome (6.8%), pneumonia (7.8%), stroke (6.8%), and multi-organ failure (3.9%). None experienced paraplegia. During a median follow-up of 56.3 months (inter-quartile range, 23.1 to 85.1 months), there were 17 late deaths and one aortic reoperation. Overall survival at 5 and 10 years was 80.9%±4.3% and 71.7%±5.9%, respectively. Reoperation-free survival at 5 and 10 years was 77.3%±4.8% and 70.2%±5.8%. Multivariable analysis revealed that age (hazard ratio [HR], 1.10; 95% confidence interval [CI], 1.05 to 1.15; p<0.001) and left ventricle (LV) function (HR, 0.88; 95% CI, 0.82 to 0.96; p<0.003) were significant and independent predictors of long-term mortality. CPB strategy, however, was not significantly related to mortality (p=0.49). Conclusion Surgical DTA repair was practicable in terms of acceptable perioperative mortality/morbidity as well as favorable long-term survival. Age and LV function were risk factors for long-term mortality, irrespective of the CPB strategy. PMID:25207223

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

    SciTech Connect

    Thompson, Matt, E-mail: matt.thompson@stgeorges.nhs.uk; Ivaz, Stella [4th Floor St James Wing, St George's Hospital NHS Trust, St George's Vascular Institute (United Kingdom); Cheshire, Nicholas [St Mary's Regional Vascular Unit (United Kingdom); Fattori, Rosella [University Hospital, Department of Cardiovascular Radiology (Italy); Rousseau, Herve [Centre Hospitalier Universitaire, Department of Radiology (France); Heijmen, Robin [St Antonius Hospital, Department of Cardiothoracic Surgery (Netherlands); Beregi, Jean-Paul [Hopital Cardiologique, Department of Vascular Radiology (France); Thony, Frederic [Hospitalier Universitaire de Grenoble, Service de Radiologie Centre (France); Horne, Gillian; Morgan, Robert; Loftus, Ian [4th Floor St James Wing, St George's Hospital NHS Trust, St George's Vascular Institute (United Kingdom)

    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.

  8. Effect of sports activity on bone mineral density in wheelchair athletes.

    PubMed

    Miyahara, Kimiko; Wang, Da-Hong; Mori, Keiko; Takahashi, Kayo; Miyatake, Nobuyuki; Wang, Bing-Ling; Takigawa, Tomoko; Takaki, Jiro; Ogino, Keiki

    2008-01-01

    The present study carried out a measurement of body composition and a nutrition survey, targeting 28 male wheelchair athletes and comparing them with 25 male physically able healthy athletes as the controls. The DXA method was used to measure bone mineral density (BMD), percentage of body fat (% body fat), and lean body mass (LBM). Possible factors affecting the BMD of the wheelchair athletes with spinal injuries were analyzed including age, body part, type of sport, area of injury, length of injury, and the length of time it took before restarting sports activity after injury. BMD in the arms, body trunk, legs, and entire body was measured. There were no significant differences in the BMD of the wheelchair athletes by age group (from 20 to 29, from 30 to 39, and 40 years and older), by sports (basketball, track and field, and tennis), and by area of injury (high and low paraplegia). BMD in the legs (r = -0.549, P < 0.01), body trunk (r = -0.414, P < 0.05), and entire body (r = -0.452, P < 0.05) of the wheelchair athletes was negatively correlated with the period since injury; however, no such a relationship was observed in the arms. In addition, the multiple regression analysis for BMD of each body region showed that the earlier the wheelchair athletes restarted sports after injury, the higher values the BMD of legs (r = -0.467, P < 0.05), body trunk (r = -0.469, P < 0.05), and entire body (r = -0.488, P < 0.05), independent of age and sports. The leg BMD of the wheelchair athletes was lower than that of the physically able athletes, with a BMD 76.5% of the controls. The present study suggests that restarting sports activity in a timely manner after treatment and rehabilitation for the injury is useful in preventing loss of BMD in wheelchair athletes and ultimately improving their quality of life. PMID:18095071

  9. Skin thickness on bony prominences measured by ultrasonography in patients with spinal cord injury

    PubMed Central

    Yalcin, Elif; Akyuz, Mufit; Onder, Burcu; Unalan, Halil; Degirmenci, Ibrahim

    2013-01-01

    Objective The detailed assessment of soft tissues over bony prominences and identification of methods of predicting pressure sores would improve the quality of care for patients with spinal cord injury (SCI). Comparing skin thicknesses on bony prominences in patients with SCI to those in healthy individuals will represent, to our knowledge, the first study aimed at determining whether differences in skin thicknesses between these groups can be detected by ultrasound. Design In both patients and controls, skin thicknesses on the sites at risk for pressure ulcers – sacrum, greater trochanter, and ischium – were evaluated using high-frequency ultrasound. The waist was also evaluated by the same method for control as it was considered to be a pressure-free region. Participants Thirty-two patients with complete thoracic SCI and 34 able-bodied individuals. Results The skin was significantly thinner over the sacrum and ischial tuberosity in individuals with SCI compared with healthy individuals. No significant differences were observed in skin thicknesses over the greater trochanter or the waist between the two groups. Conclusions Protecting skin integrity in patients with paraplegia is challenging due to many contributing factors, such as prolonged pressure, frictional/shearing forces, and poor nutrition. Thinning of the skin can increase the risk of soft tissue damage, leading to pressure ulcers. The significant differences in skin thickness at the sacrum and ischium provide the basis for establishing the early signs of pressure damage. Measuring skin thickness by ultrasound is a reliable non-invasive method that could be a promising tool for predicting pressure ulcers. PMID:23809593

  10. Neuropathy Target Esterase Gene Mutations Cause Motor Neuron Disease

    PubMed Central

    Rainier, Shirley; Bui, Melanie; Mark, Erin; Thomas, Donald; Tokarz, Debra; Ming, Lei; Delaney, Colin; Richardson, Rudy J.; Albers, James W.; Matsunami, Nori; Stevens, Jeff; Coon, Hilary; Leppert, Mark; Fink, John K.

    2008-01-01

    The possibility that organophosphorus (OP) compounds contribute to motor neuron disease (MND) is supported by association of paraoxonase 1 polymorphisms with amyotrophic lateral sclerosis (ALS) and the occurrence of MND in OP compound-induced delayed neuropathy (OPIDN), in which neuropathy target esterase (NTE) is inhibited by organophosphorylation. We evaluated a consanguineous kindred and a genetically unrelated nonconsanguineous kindred in which affected subjects exhibited progressive spastic paraplegia and distal muscle wasting. Affected subjects resembled those with OPIDN and those with Troyer Syndrome due to SPG20/spartin gene mutation (excluded by genetic linkage and SPG20/spartin sequence analysis). Genome-wide analysis suggested linkage to a 22 cM homozygous locus (D19S565 to D19S884, maximum multipoint LOD score 3.28) on chromosome 19p13 to which NTE had been mapped (GenBank AJ004832). NTE was a candidate because of its role in OPIDN and the similarity of our patients to those with OPIDN. Affected subjects in the consanguineous kindred were homozygous for disease-specific NTE mutation c.3034A?G that disrupted an interspecies conserved residue (M1012V) in NTE's catalytic domain. Affected subjects in the nonconsanguineous family were compound heterozygotes: one allele had c.2669G?A mutation, which disrupts an interspecies conserved residue in NTE's catalytic domain (R890H), and the other allele had an insertion (c.2946_2947insCAGC) causing frameshift and protein truncation (p.S982fs1019). Disease-specific, nonconserved NTE mutations in unrelated MND patients indicates NTE's importance in maintaining axonal integrity, raises the possibility that NTE pathway disturbances contribute to other MNDs including ALS, and supports the role of NTE abnormalities in axonopathy produced by neuropathic OP compounds. PMID:18313024

  11. 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., E-mail: shamim.lotfi@kcl.ac.uk; Clough, R. E.; Ali, T. [Guy's and St. Thomas' NHS Trust, Vascular Surgery (United Kingdom)] [Guy's and St. Thomas' NHS Trust, Vascular Surgery (United Kingdom); Salter, R. [Guy's and St. Thomas' NHS Trust, Interventional Radiology (United Kingdom)] [Guy's and St. Thomas' NHS Trust, Interventional Radiology (United Kingdom); Young, C. P. [Guy's and St. Thomas' NHS Trust, Cardiac Surgery (United Kingdom)] [Guy's and St. Thomas' NHS Trust, Cardiac Surgery (United Kingdom); Bell, R.; Modarai, B.; Taylor, P., E-mail: peter.taylor@gstt.nhs.uk [Guy's and St. Thomas' NHS Trust, Vascular Surgery (United Kingdom)

    2013-02-15

    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.

  12. Altered behavioral performance and live imaging of circuit-specific neural deficiencies in a zebrafish model for psychomotor retardation.

    PubMed

    Zada, David; Tovin, Adi; Lerer-Goldshtein, Tali; Vatine, Gad David; Appelbaum, Lior

    2014-09-01

    The mechanisms and treatment of psychomotor retardation, which includes motor and cognitive impairment, are indefinite. The Allan-Herndon-Dudley syndrome (AHDS) is an X-linked psychomotor retardation characterized by delayed development, severe intellectual disability, muscle hypotonia, and spastic paraplegia, in combination with disturbed thyroid hormone (TH) parameters. AHDS has been associated with mutations in the monocarboxylate transporter 8 (mct8/slc16a2) gene, which is a TH transporter. In order to determine the pathophysiological mechanisms of AHDS, MCT8 knockout mice were intensively studied. Although these mice faithfully replicated the abnormal serum TH levels, they failed to exhibit the neurological and behavioral symptoms of AHDS patients. Here, we generated an mct8 mutant (mct8-/-) zebrafish using zinc-finger nuclease (ZFN)-mediated targeted gene editing system. The elimination of MCT8 decreased the expression levels of TH receptors; however, it did not affect the expression of other TH-related genes. Similar to human patients, mct8-/- larvae exhibited neurological and behavioral deficiencies. High-throughput behavioral assays demonstrated that mct8-/- larvae exhibited reduced locomotor activity, altered response to external light and dark transitions and an increase in sleep time. These deficiencies in behavioral performance were associated with altered expression of myelin-related genes and neuron-specific deficiencies in circuit formation. Time-lapse imaging of single-axon arbors and synapses in live mct8-/- larvae revealed a reduction in filopodia dynamics and axon branching in sensory neurons and decreased synaptic density in motor neurons. These phenotypes enable assessment of the therapeutic potential of three TH analogs that can enter the cells in the absence of MCT8. The TH analogs restored the myelin and axon outgrowth deficiencies in mct8-/- larvae. These findings suggest a mechanism by which MCT8 regulates neural circuit assembly, ultimately mediating sensory and motor control of behavioral performance. We also propose that the administration of TH analogs early during embryo development can specifically reduce neurological damage in AHDS patients. PMID:25255244

  13. Altered Behavioral Performance and Live Imaging of Circuit-Specific Neural Deficiencies in a Zebrafish Model for Psychomotor Retardation

    PubMed Central

    Lerer-Goldshtein, Tali; Vatine, Gad David; Appelbaum, Lior

    2014-01-01

    The mechanisms and treatment of psychomotor retardation, which includes motor and cognitive impairment, are indefinite. The Allan-Herndon-Dudley syndrome (AHDS) is an X-linked psychomotor retardation characterized by delayed development, severe intellectual disability, muscle hypotonia, and spastic paraplegia, in combination with disturbed thyroid hormone (TH) parameters. AHDS has been associated with mutations in the monocarboxylate transporter 8 (mct8/slc16a2) gene, which is a TH transporter. In order to determine the pathophysiological mechanisms of AHDS, MCT8 knockout mice were intensively studied. Although these mice faithfully replicated the abnormal serum TH levels, they failed to exhibit the neurological and behavioral symptoms of AHDS patients. Here, we generated an mct8 mutant (mct8?/?) zebrafish using zinc-finger nuclease (ZFN)-mediated targeted gene editing system. The elimination of MCT8 decreased the expression levels of TH receptors; however, it did not affect the expression of other TH-related genes. Similar to human patients, mct8?/? larvae exhibited neurological and behavioral deficiencies. High-throughput behavioral assays demonstrated that mct8?/? larvae exhibited reduced locomotor activity, altered response to external light and dark transitions and an increase in sleep time. These deficiencies in behavioral performance were associated with altered expression of myelin-related genes and neuron-specific deficiencies in circuit formation. Time-lapse imaging of single-axon arbors and synapses in live mct8?/? larvae revealed a reduction in filopodia dynamics and axon branching in sensory neurons and decreased synaptic density in motor neurons. These phenotypes enable assessment of the therapeutic potential of three TH analogs that can enter the cells in the absence of MCT8. The TH analogs restored the myelin and axon outgrowth deficiencies in mct8?/? larvae. These findings suggest a mechanism by which MCT8 regulates neural circuit assembly, ultimately mediating sensory and motor control of behavioral performance. We also propose that the administration of TH analogs early during embryo development can specifically reduce neurological damage in AHDS patients. PMID:25255244

  14. 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

  15. 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.

  16. 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

  17. Transverse myelitis secondary to Melioidosis; A case report

    PubMed Central

    2012-01-01

    Background Melioidosis has become an emerging infection in Sri Lanka; a country which is considered non endemic for it. Paraplegia due to Burkholderia pseudomallei is a very rare entity encountered even in countries where the disease is endemic. There are no reported cases of transverse myelitis due to melioidosis in Sri Lankan population thus we report the first case. Case presentation A 21?year old farmer presented with sudden onset bi lateral lower limb weakness, numbness and urine retention. Examination revealed flaccid areflexic lower limbs with a sensory loss of all modalities and a sensory level at T10 together with sphincter involvement. MRI of the thoracolumbar spine showed extensive myelitis of the thoracic spine complicating left psoas abscess without definite extension to the spinal cord or cord compression. Burkholderia pseudomallei was isolated from the psoas abscess pus cultures and the diagnosis of melioidosis was confirmed with high titers of Burkholderia pseudomallei antibodies and positive PCR. He was treated with high doses of IV ceftazidime and oral cotrimoxazole for one month with a plan to continue cotrimoxazole and doxycycline till one year. Patient’s general condition improved but the residual neurological problems persisted. Conclusion The exact pathogenesis of spinal cord melioidosis is not quite certain except in the cases where there is direct microbial invasion, which does not appear to be the case in our patient. We postulate our patient’s presentation could be due to ischemia of the spinal cord following septic embolisation or thrombosis of spinal artery due to the abscess nearby. A neurotrophic exotoxin causing myelitis or post infectious immunological demyelination is yet another possibility. This emphasizes the necessity of further studies to elucidate the exact pathogenesis in this type of presentations. Health care professionals in Sri Lanka, where this is an emerging infection, need to improve their knowledge regarding this disease and should have high degree of suspicion to make a correct and a timely diagnosis to reduce the morbidity and mortality due to Burkholderia pseudomallei infection. It is highly likely that this infection is under diagnosed in developing countries where diagnostic facilities are minimal. Therefore strategies to improve the awareness and upgrade the diagnostic facilities need to be implemented in near future. PMID:23020820

  18. Neurology and the kidney

    PubMed Central

    Burn, D; Bates, D

    1998-01-01

    Renal failure is relatively common, but except in association with spina bifida or paraplegia it is unlikely to occur as a result of disease of the CNS. Renal failure, however, commonly affects the nervous system. The effects of kidney failure on the nervous system are more pronounced when failure is acute. In addition to the important problems related to renal failure there are both acquired and genetically determined diseases which may affect the kidney and the brain. Those acquired diseases include the vasculitides, the paraproteinaemias, and various granulomatous conditions (considered in other chapters of Neurology and Medicine). In two of the most commonly encountered genetically determined diseases, Von Hippel-Lindau disease and polycystic kidney disease, location of pathogenic mutations will provide improved screening programmes and, possibly, allow therapeutic intervention. Uraemia may affect both the central and peripheral nervous systems. Whereas the clinical features of uraemia are well documented, the pathophysiology is less well understood and probably multifactorial. Uraemic encephalopathy, which classically fluctuates, is associated with problems in cognition and memory and may progress to delirium, convulsions, and coma. The encephalopathy may initially worsen with periods of dialysis and almost certainly relates to altered metabolic states in association with ionic changes and possibly impaired synaptic function. Renal failure may affect the peripheral nervous system, resulting in a neuropathy which shows a predilection for large diameter axons. This may be reversed by dialysis and transplantation. The myopathy seen in renal failure, often associated with bone pain and tenderness, is similar to that encountered in primary hyperparathyroidism and osteomalacia.? Dialysis itself is associated with neurological syndromes including the dysequilibrium syndrome, subdural haematoma, and Wernicke's encephalopathy. Dialysis dementia, which was prevalent during the 1970s, has reduced in frequency with the use of aluminium free dialysate. With the introduction of transplantation and the concomitant use of powerful immunosuppressive drugs, the pattern of neurological problems encountered in renal replacement therapy has shifted. Five per cent of patients develop nerve injuries during renal transplantation, and up to 40% of patients experience neurological side effects from cyclosporine. Furthermore, CNS infections, often fungal in type, have been reported in up to 45% of transplant patients coming to postmortem. The nature of the involvement of neurologists with their nephrology colleagues is therefore evolving.?? PMID:9854955

  19. Providers' Perceptions of Spinal Cord Injury Pressure Ulcer Guidelines

    PubMed Central

    Thomason, Susan S; Evitt, Celinda P; Harrow, Jeffrey J; Love, Linda; Moore, D. Helen; Mullins, Maria A; Powell-Cope, Gail; Nelson, Audrey L

    2007-01-01

    Background/Objective: Pressure ulcers are a serious complication for people with spinal cord injury (SCI). The Consortium for Spinal Cord Medicine (CSCM) published clinical practice guidelines (CPGs) that provided guidance for pressure ulcer prevention and treatment after SCI. The aim of this study was to assess providers' perceptions for each of the 32 CPG recommendations regarding their agreement with CPGs, degree of CPG implementation, and CPG implementation barriers and facilitators. Methods: This descriptive mixed-methods study included both qualitative (focus groups) and quantitative (survey) data collection approaches. The sample (n = 60) included 24 physicians and 36 nurses who attended the 2004 annual national conferences of the American Paraplegia Society or American Association of Spinal Cord Injury Nurses. This sample drew from two sources: a purposive sample from a list of preregistered participants and a convenience sample of conference attendee volunteers. We analyzed quantitative data using descriptive statistics and qualitative data using a coding scheme to capture barriers and facilitators. Results: The focus groups agreed unanimously on the substance of 6 of the 32 recommendations. Nurse and physician focus groups disagreed on the degree of CGP implementation at their sites, with nurses as a group perceiving less progress in implementation of the guideline recommendations. The focus groups identified only one recommendation, complications of surgery, as being fully implemented at their sites. Categories of barriers and facilitators for implementation of CPGs that emerged from the qualitative analysis included (a) characteristics of CPGs: need for research/evidence, (b) characteristics of CPGs: complexity of design and wording, (c) organizational factors, (d) lack of knowledge, and (e) lack of resources. Conclusions: Although generally SCI physicians and nurses agreed with the CPG recommendations as written, they did not feel these recommendations were fully implemented in their respective clinical settings. The focus groups identified multiple barriers to the implementation of the CPGs and suggested several facilitators/solutions to improve implementation of these guidelines in SCI. Participants identified organizational factors and the lack of knowledge as the most substantial systems/issues that created barriers to CPG implementation. PMID:17591223

  20. Optic neuromyelitis syndrome in Brazilian patients

    PubMed Central

    Papais-Alvarenga, R; Miranda-Santos, C; Puccioni-Sohler, M; de Almeida, A M V; Oliveira, S; De Oliveira, C A B.; Alvarenga, H; Poser, C

    2002-01-01

    Objectives: To report the clinical features and outcome of 24 Brazilian patients with optic neuromyelitis syndrome (ONM); discuss the underlying pathological events associated with the ONM syndrome; review the nosological situation of ONM in the group of inflammatory and demyelinating diseases of the central nervous system. Patients and Methods: Patients with ONM treated at the Hospital da Lagoa, Rio de Janeiro were studied. Demographic, clinical, magnetic resonance imaging, cerebrospinal fluid, and pathological data were analysed. Results: The study consisted of 20 women, four men of whom 10 were white and 14 Afro-Brazilians. Clinical course was recurrent in 22 cases and monophasic in two. Neurological manifestations at inclusion were: sensory impairment (66%), bilateral (41.6%) or unilateral blindness (20.8%), paraplegia or quadriplegia (37.5%). The EDSS was moderate/severe in 70.8%. The underlying pathological events were respectively pulmonary tuberculosis and upper respiratory infection in the two monophasic cases; in the 22 recurrent ONM patients: pulmonary tuberculosis (3), neurocysticercosis (1), polyarteritis nodosa (1), antinuclear antibody and rheumatoid factor (1), antiphospholipid antibody primary syndrome (1), diabetes mellitus (1), hypothyroidism (1), and amenorrhea-galactorrhea (4). Normal cerebrospinal fluid was found in 52% and an inflammatory profile in 48%. Only four recurrent ONM white patients had brain and spinal cord magnetic resonance imaging and cerebrospinal fluid findings compatible with the diagnosis of multiple sclerosis. Large lesions were seen in 62% of spinal magnetic resonance images. Six of 12 recurrent ONM Afro-Brazilian died. There were no statistical differences in the demographic data of the two ethnic groups. Afro-Brazilians were significantly more severely impaired and had a higher mortality rate than the white patients. Conclusion: These cases were classified as follows: two monophasic acute disseminated encephalomyelitis; one recurrent disseminated encephalomyelitis; three recurrent ONM associated with Hughes syndrome, autoantibodies and polyarteritis nodosa; six recurrent ONM with endocrinopathies; and finally, four muliple sclerosis cases. The remaining cases were not associated with any other condition. It would seem clear that ONM is a syndrome rather than a single disease. PMID:12235313

  1. 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

  2. TEVAR for Symptomatic Stanford B Dissection: A Systematic Review of 30-Day Mortality and Morbidity.

    PubMed

    Ramdass, Michael

    2015-03-01

    Background?The aim of this study was to determine morbidity and 30-day mortality rates of thoracic endovascular aortic repair (TEVAR) for Stanford B dissection over a 16-year period and determine if these rates have improved with better stent-graft technology and surgical technique. Methods?Electronic databases were searched in all languages and a systematic review conducted. A comparison of the early (1998-2007?=?787 patients) and later (2007-2013?=?787 patients) halves of the patient population was done. Studies were chosen based on availability of details regarding morbidity and mortality. Ambiguous studies were excluded. Results?A total of 69 suitable studies published between 1998 and 2013 (1,574 patients) were examined including 1 randomized control trial, 55 retrospective studies, 3 prospective, 1 mixed, and 9 case reports. Overall mortality and morbidity rates for TEVAR was 8.07% (n?=?127) and 30.8% (n?=?485), respectively. The stent-graft-related death rate was 6.20% (97 cases excluding medically related deaths). The endoleak rate was 5.9% of which most were type I. Major complications include stroke (2.7%), paraplegia (1.9%), partial thrombosis of false lumen (2.5%), retrograde type A dissection (3.1%), visceral malperfusion (2.0%), conversion to open intervention (1.9%), and secondary intervention (4.1%). The stent-graft-related mortality rate increased in the 2007 to 2013 group compared with the 1998 to 2007 group (56.2 vs. 24% of patients who died; p??0.05. Conclusion?Mortality and morbidity rates for TEVAR seemed to have increased over the past 16 years despite improved technology and surgical technique. This may be explained by the increasing liberal use of TEVAR intervention and quite possibly better reporting. The current data are highly heterogenous making it difficult for solid conclusions to be drawn. The only way forward is through better data registries and well-designed clinical trials. PMID:24752872

  3. Endovascular Repair of Descending Thoracic Aneurysms: Results With “On-Label” Application in the Post Food and Drug Administration Approval Era

    PubMed Central

    Hughes, G. Chad; Lee, Sean M.; Daneshmand, Mani A.; Bhattacharya, Syamal D.; Williams, Judson B.; Tucker, Sonny W.; McCann, Richard L.

    2013-01-01

    Background Most studies of thoracic endovascular aortic repair (TEVAR) published since the technology gained US Food and Drug Administration (FDA) approval in March 2005 have included multiple applications including dissection, trauma, and “hybrid” approaches, all of which are currently “off-label.” However, little post-approval data exist for the only FDA-approved application, namely descending thoracic aneurysm (DTA). The purpose of this study was to examine our experience with TEVAR for aneurysms limited to the descending thoracic aorta. Methods Between March 23, 2005 (date of initial FDA approval) and April 6, 2009, 210 TEVAR procedures were performed at our institution. Of these, 79 (38%) were for saccular (n = 31) or fusiform (n = 48) DTA and form the basis of this report. Patients requiring “hybrid” approaches other than carotid-subclavian bypass were excluded. Devices utilized were Gore TAG (W. L. Gore Associates, Flagstaff, AZ) (n = 67; 85%), Zenith TX2 (Cook Medical Incorporated, Bloomington, IN) (n = 10; 13%), and Medtronic Talent (Medtronic, Inc, Santa Rosa, CA) (n = 5; 6%); 3 (4%) patients received more than one type of device. Results Median patient age was 73 ± 4 years; 35 (44%) were female. Mean aortic diameter was 5.8 ± 1.8 cm. Twenty-four (30%) procedures were urgent-emergent. Thirty-day inhospital rates of death, stroke, and permanent paraplegia-paresis were 5.1% (n =4; 1.9% elective mortality), 2.5% (n = 2), and 1.3% (n =1), respectively. The median postoperative length of stay was 3.0 days (25th and 75th percentiles = 2 and 6, respectively). At a mean follow-up of 23 ±17 months (range, 6 to 55), there were 2 (2.5%) late aortic deaths from graft infection (n = 1) and aneurysm rupture (n = 1). Overall actuarial midterm survival is 73% at 55 months, with an aorta-specific actuarial survival of 86% during this same time interval. Five patients (6.3%) required late (>30 days) secondary endovascular re-intervention for type I (n = 4) or type II (n = 1) endoleak; re-intervention was successful in 4 of 5. Conclusions Despite the advanced age, comorbid conditions, and significant incidence of urgent-emergent status of patients presenting with DTA, on-label application of TEVAR yields excellent 30-day and midterm outcomes, especially when compared with historic rates of morbidity and mortality with open repair. However, “on-label” applications represent a minority of current TEVAR use, likely due to the relative scarcity of DTA. These data appear to support the increasing utilization of TEVAR as a treatment strategy for this pathology. PMID:20609753

  4. Mild-to-moderate hypothermia in aortic arch surgery using circulatory arrest: a change of paradigm?†

    PubMed Central

    Urbanski, Paul P.; Lenos, Aristidis; Bougioukakis, Petros; Neophytou, Ioannis; Zacher, Michael; Diegeler, Anno

    2012-01-01

    OBJECTIVES Antegrade cerebral perfusion makes deep hypothermia non-essential for neuroprotection; therefore, there is a growing tendency to increase the body temperature during circulatory arrest with selective brain perfusion. However, very little is known about the clinical efficacy of mild-to-moderate hypothermia for ischemic organ protection during circulatory arrest. The aim of this study was to evaluate the safety and efficiency of mild-to-moderate hypothermia for lower-body protection during aortic arch surgery with circulatory arrest and antegrade cerebral perfusion. METHODS Between January 2005 and December 2009, a total of 347 patients underwent non-emergent arch surgery. In all patients, the systematic cooling was adapted to the expected time of circulatory arrest, and cerebral perfusion was performed at a constant blood temperature of 28 °C. There were 40 cardiac or aortic re-operations, 312 patients had concomitant aortic valve or root surgery, and 10 patients had replacement of the descending aorta. All examined data were collected prospectively. RESULTS The duration of circulatory arrest and the deepest rectal temperature were 18 ± 11 min (range, 6–70 min) and 31.5 ± 1.6 °C (range, 26.0–35.0 °C) for all 347 patients, and 34 ± 12 min (range, 17–70 min) and 29.9 ± 1.7 °C (range, 26.0–34.6 °C) for 77 patients having total/subtotal arch replacement. The maximum serum lactate level on the first postoperative day was, on average, 2.3 ± 1.2 mmol l?1. In the statistical analysis, no association between the duration of temperature-adapted circulatory arrest and lactate, creatinine, or lactate dehydrogenase levels after surgery could be demonstrated. The 30-day mortality was 0.9%. Permanent neurological deficit or temporary dysfunction occurred in three (0.9%) and eight (2.3%) patients, respectively. No paraplegia and no hepatic failure were reported; however, mesenteric ischemia occurred in one patient with severe stenosis of the celiac and upper mesenteric arteries. Temporary dialysis was necessary primarily after surgery in five patients. All of them underwent hemiarch replacement only, and four patients had an increased creatinine level before surgery. CONCLUSION Systemic mild-to-moderate hypothermia that is adapted to the duration of circulatory arrest is a simple, safe, and effective method of organ protection and can be recommended in routine aortic arch surgery with circulatory arrest and cerebral perfusion. PMID:21616675

  5. Synostosis between pubic bones due to neurogenic, heterotopic ossification.

    PubMed

    Vaidyanathan, Subramanian; Hughes, Peter L; Soni, Bakul M

    2006-01-01

    Neurogenic, heterotopic ossification is characterised by the formation of new, extraosseous (ectopic) bone in soft tissue in patients with neurological disorders. A 33-year-old female, who was born with spina bifida, paraplegia, and diastasis of symphysis pubis, had indwelling urethral catheter drainage and was using oxybutynin bladder instillations. She was prescribed diuretic for swelling of feet, which aggravated bypassing of catheter. Hence, suprapubic cystostomy was performed. Despite anticholinergic therapy, there was chronic urine leak around the suprapubic catheter and per urethra. Therefore, the urethra was mobilised and closed. After closure of the urethra, there was no urine leak from the urethra, but urine leak persisted around the suprapubic catheter. Cystogram confirmed the presence of a Foley balloon inside the bladder; there was no urinary fistula. The Foley balloon ruptured frequently, leading to extrusion of the Foley catheter. X-ray of abdomen showed heterotopic bone formation bridging the gap across diastasis of symphysis pubis. CT of pelvis revealed heterotopic bone lying in close proximity to the balloon of the Foley catheter; the sharp edge of heterotopic bone probably acted like a saw and led to frequent rupture of the balloon of the Foley catheter. Unique features of this case are: (1) temporal relationship of heterotopic bone formation to suprapubic cystostomy and chronic urine leak; (2) occurrence of heterotopic ossification in pubic region; (3) complications of heterotopic bone formation viz. frequent rupture of the balloon of the Foley catheter by the irregular margin of heterotopic bone and difficulty in insertion of suprapubic catheter because the heterotopic bone encroached on the suprapubic track; (4) synostosis between pubic bones as a result of heterotopic ossification.. Common aetiological factors for neurogenic, heterotopic ossification, such as forceful manipulation, trauma, or spasticity, were absent in this patient. Since heterotopic bone formation was observed in the pubic region after suprapubic cystostomy and chronic urine leak, it is possible that risk factors related to the urinary tract might have played a role in heterotopic bone formation, which resulted in synostosis between pubic bones. PMID:17619722

  6. Spinal tuberculosis in children: Retrospective analysis of 124 patients

    PubMed Central

    Moon, Myung-Sang; Kim, Sung-Soo; Lee, Bong-Jin; Moon, Jeong-Lim

    2012-01-01

    Background: There is a paucity of report on spinal tuberculosis in children. We report a retrospective analysis of 124 children with TB spine treated over 30 years. Materials and Methods: We retrospectively reviewed 124 children; of cervical (n=36), cervicothoracic (n=4), thoracic (n=53), and lumbar and lumbosacral tuberculosis (n=31) with no skip or multifocal lesions treated between 1971-2004. The age ranged from 2 to 15 years of age with 28 children less than 5 years of age, 58 were between 6 and 10 years, and 38 were over 10 years, 18 had paraplegia of various degrees. Ninety-one children were treated conservatively, while 33 children were subjected to surgery for focal debridement (n=23), posterior interspinous wiring and cementation (n=4), and posterior instrumentation with rods and segmental wiring (n=14). Triple chemotherapy (isoniazid, streptomycin, and PAS) was given for 18 months (3HSPa, 15Hpa) between 1971 and 1975, and triple or quadruple chemotherapy (isoniazid, rifampicin, ethambutol, or pyrazinamide) after 1976 to 2004 for 12 months (12RHZ or 12 RHZE). Some of the children in the current series belonged to the British MRC conservative study patients. The average duration of followup was 5 years and 8 months (range 1.6-20 years). Results: All children attained healed status and showed neural recovery (n=18). The patients attained healed status at 18 months in the first series and at 12 months in the second series after chemotherapy. Spontaneous intercorporal fusion occurred only in 10 (8.06%) of 124 children. Sagittal curve during growth showed three different patterns: Unchanged, decreased, and increased curves. The residual kyphosis was unavoidable in cases with growth plate damage. Kyphosis increased in cases with wedged monovertebra and fused wedged block vertebra, though it was different at different level. Conclusion: The vertebral reformation and curve correction were possible only through the growth plates. The posterior instrumented stabilization alone could correct and/or prevent progress of the kyphosis. However, for active tuberculosis, posterior instrumented stabilization combined with anterior radical surgery should be reserved only for the advanced tuberculosis with instability, rapid progress of kyphosis, and/or unacceptable pre-existing kyphosis, though there is a new trend of prophylactic posterior instrumentation even for the early tuberculosis. PMID:22448052

  7. Continuous improvement after multiple mesenchymal stem cell transplantations in a patient with complete spinal cord injury.

    PubMed

    Jarocha, Danuta; Milczarek, Olga; Wedrychowicz, Anna; Kwiatkowski, Stanislaw; Majka, Marcin

    2015-01-01

    Interruption of spinal cord (SC) continuity leads to functional loss below the lesion level. The purpose of this study was to evaluate the safety and efficacy of bone marrow nucleated cell (BMNC) and multiple mesenchymal stem cell (MSC) transplantations in spinal cord injury (SCI). A patient with total SC interruption at the Th2-3 level underwent experimental therapy with BMNC and MSC transplantations followed with intensive neurorehabilitation treatment. At admission, 6 h after SCI, the patient was scored ASIA A, had a Th1 sensation level, paraplegia with sphincter palsy, and was without the ability to control trunk movement. Neurophysiology examination showed bilateral axonal damage to the motor and sensory neural fibers with no motor unit potentials or peripheral motor nerve conduction in the lower extremities. The standard therapy had been applied and had not produced any positive results. The patient was treated with autologous BMNCs injected intravenously (3.2?×?10(9)) and intrathecally (0.5?×?10(9)) 10 weeks after the SCI and with five rounds of MSCs every 3-4 months (1.3-3.65?×?10(7)) administered via lumbar puncture. Total number of transplanted MSC cells during the course of treatment was 1.54?×?10(8). There were no complications related to transplantations and no side effects related to the therapy during 2 years of treatment. The ASIA score improved from A to C/D (from 112 to 231 points). The sensation level expanded from Th1 to L3-4, and the patient's ability to control the body trunk was fully restored. Bladder filling sensation, bladder control, and anal sensation were also restored. Muscle strength in the left lower extremities improved from plegia to deep paresis (1 on the Lovett scale). The patient's ability to move lower extremities against gravity supported by the movements in quadriceps was restored. The patient gained the ability to stand in a standing frame and was able to walk with the support of hip and knee ortheses. Magnetic resonance imaging (MRI) revealed that at the Th2/Th3 level, where the hemorrhagic necrosis was initially observed, small tissue structures appeared. Our results suggest that repeated intrathecal infusions of MSCs might have the potential to produce clinically meaningful improvements for SCI patients. PMID:25807231

  8. Cooling athletes with a spinal cord injury.

    PubMed

    Griggs, Katy E; Price, Michael J; Goosey-Tolfrey, Victoria L

    2015-01-01

    Cooling strategies that help prevent a reduction in exercise capacity whilst exercising in the heat have received considerable research interest over the past 3 decades, especially in the lead up to a relatively hot Olympic and Paralympic Games. Progressing into the next Olympic/Paralympic cycle, the host, Rio de Janeiro, could again present an environmental challenge for competing athletes. Despite the interest and vast array of research into cooling strategies for the able-bodied athlete, less is known regarding the application of these cooling strategies in the thermoregulatory impaired spinal cord injured (SCI) athletic population. Individuals with a spinal cord injury (SCI) have a reduced afferent input to the thermoregulatory centre and a loss of both sweating capacity and vasomotor control below the level of the spinal cord lesion. The magnitude of this thermoregulatory impairment is proportional to the level of the lesion. For instance, individuals with high-level lesions (tetraplegia) are at a greater risk of heat illness than individuals with lower-level lesions (paraplegia) at a given exercise intensity. Therefore, cooling strategies may be highly beneficial in this population group, even in moderate ambient conditions (~21 °C). This review was undertaken to examine the scientific literature that addresses the application of cooling strategies in individuals with an SCI. Each method is discussed in regards to the practical issues associated with the method and the potential underlying mechanism. For instance, site-specific cooling would be more suitable for an athlete with an SCI than whole body water immersion, due to the practical difficulties of administering this method in this population group. From the studies reviewed, wearing an ice vest during intermittent sprint exercise has been shown to decrease thermal strain and improve performance. These garments have also been shown to be effective during exercise in the able-bodied. Drawing on additional findings from the able-bodied literature, the combination of methods used prior to and during exercise and/or during rest periods/half-time may increase the effectiveness of a strategy. However, due to the paucity of research involving athletes with an SCI, it is difficult to establish an optimal cooling strategy. Future studies are needed to ensure that research outcomes can be translated into meaningful performance enhancements by investigating cooling strategies under the constraints of actual competition. Cooling strategies that meet the demands of intermittent wheelchair sports need to be identified, with particular attention to the logistics of the sport. PMID:25119157

  9. 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

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

    SciTech Connect

    Pitton, Michael B., E-mail: pitton@radiologie.klinik.uni-mainz.de; Scheschkowski, Tobias; Ring, Markus; Herber, Sascha; Oberholzer, Katja; Leicher-Dueber, Annegret [University Hospital of Mainz, Johannes Gutenberg University of Mainz, Department of Diagnostic and Interventional Radiology (Germany); Neufang, Achim; Schmiedt, Walther [University Hospital of Mainz, Johannes Gutenberg University of Mainz, Department of Cardiovascular and Thoracic Surgery (Germany); Dueber, Christoph [University Hospital of Mainz, Johannes Gutenberg University of Mainz, Department of Diagnostic and Interventional Radiology (Germany)

    2009-09-15

    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.

  11. 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

  12. 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

  13. Pulmonary epithelioid hemangioendothelioma presenting with vertebral metastases: a case report

    PubMed Central

    2014-01-01

    Introduction Epithelioid hemangioendothelioma is a rare vascular tumor that has an epithelioid and histiocytoid appearance, originates from vascular endothelial or pre-endothelial cells and comprises less than 1% of all vascular tumors. It was described for the first time in 1975 as pulmonary epithelioid hemangioendothelioma, because initially it was believed to be an aggressive form of bronchoalveolar cell carcinoma with a remarkable propensity to invade adjacent blood vessels and small airways. Only a few cases have been reported in the literature to date. Tumor cells expressing Fli-1 and CD31 have been identified as relatively specific endothelial markers. Epithelioid hemangioendothelioma may affect multiple organs and may vary considerably in its clinical and radiological presentation. More than 50% to 76% of pulmonary epithelioid hemangioendothelioma patients are asymptomatic. They are usually incidentally diagnosed on the basis of abnormal chest radiography during routine physical examinations. Hematologic and gastrointestinal disorders and weakness or numbness may also be observed, in addition to respiratory symptoms, in cases of disseminated pulmonary epithelioid hemangioendothelioma. Pain and swelling, pathological fractures, spine compression or paresthesia, loss of muscular strength and paraplegia may be present when bone metastases occur. Because of the rarity of this disease, there is no standard for treatment. Case presentation A 46-year-old Caucasian woman presented to our institution in November 2009 with metastases of pulmonary epithelioid hemangioendothelioma from the L3 and L4 vertebrae. A course of radiotherapy at a dosage of 3,000cGy delivered in individual doses of 200cGy/day for 5 days/wk to the L3 and L4 vertebrae led to the disappearance of the patient’s lumbar pain without any detectable side effects. Percussion of the patient’s vertebral spine was negative, and no radiological progression of bone disease was found at her 1-year follow-up examination. Conclusion Since epithelioid hemangioendothelioma was first correctly defined, several research groups have reported their experiences with epithelioid hemangioendothelioma irradiation. Further studies are needed to establish a standard radiation dose to be used for such a complex and extremely rare disease. In our present case, a radiotherapy dosage of 3,000cGy delivered in individual doses 200cGy/day for 5 days/wk allowed us to reach our goals: local pain control with good tolerance and better quality of life by the 1-year follow-up examination. PMID:24942542

  14. [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

  15. Long-Term Follow-Up After Endovascular Treatment of Acute Aortic Emergencies

    SciTech Connect

    Pitton, M. B., E-mail: pitton@radiologie.klinik.uni-mainz.de; Herber, S. [University Hospital of Mainz, Johannes Gutenberg University of Mainz, Department of Diagnostic and Interventional Radiology (Germany); Schmiedt, W.; Neufang, A.; Dorweiler, B. [University Hospital of Mainz, Johannes Gutenberg University of Mainz, Department of Cardiovascular Surgery (Germany); Dueber, C. [University Hospital of Mainz, Johannes Gutenberg University of Mainz, Department of Diagnostic and Interventional Radiology (Germany)

    2008-01-15

    Purpose. To investigate the long-term outcome and efficacy of emergency treatment of acute aortic diseases with endovascular stent-grafts. Methods. From September 1995 to April 2007, 37 patients (21 men, 16 women; age 53.9 {+-} 19.2 years, range 18-85 years) with acute complications of diseases of the descending thoracic aorta were treated by endovascular stent-grafts: traumatic aortic ruptures (n = 9), aortobronchial fistulas due to penetrating ulcer or hematothorax (n = 6), acute type B dissections with aortic wall hematoma, penetration, or ischemia (n = 13), and symptomatic aneurysm of the thoracic aorta (n = 9) with pain, penetration, or rupture. Diagnosis was confirmed by contrast-enhanced CT. Multiplanar reformations were used for measurement of the landing zones of the stent-grafts. Stent-grafts were inserted via femoral or iliac cut-down. Two procedures required aortofemoral bypass grafting prior to stent-grafting due to extensive arteriosclerotic stenosis of the iliac arteries. In this case the bypass graft was used for introduction of the stent-graft. Results. A total of 46 stent-grafts were implanted: Vanguard/Stentor (n = 4), Talent (n = 31), and Valiant (n = 11). Stent-graft extension was necessary in 7 cases. In 3 cases primary graft extension was done during the initial procedure (in 1 case due to distal migration of the graft during stent release, in 2 cases due to the total length of the aortic aneurysm). In 4 cases secondary graft extensions were performed-for new aortic ulcers at the proximal stent struts (after 5 days) and distal to the graft (after 8 months) and recurrent aortobronchial fistulas 5 months and 9 years after the initial procedure-resulting in a total of 41 endovascular procedures. The 30-day mortality rate was 8% (3 of 37) and the overall follow-up was 29.9 {+-} 36.6 months (range 0-139 months). All patients with traumatic ruptures demonstrated an immediate sealing of bleeding. Patients with aortobronchial fistulas also demonstrated a satisfactory follow-up despite the necessity for reintervention and graft extension in 3 of 6 cases (50%). Two patients with type B dissection died due to mesenteric ischemia despite sufficient mesenteric blood flow being restored (but too late). Two suffered from neurologic complications, 1 from paraplegia and 1 from cerebral ischemia (probably embolic), 1 from penetrating ulcer, and 1 from persistent ischemia of the kidney. Five of 9 (56%) patients with symptomatic thoracic aneurysm demonstrated endoleaks during follow-up and there was an increase in the aneurysm in 1. Conclusion. Endovascular treatment is safe and effective for emergency treatment of life-threatening acute thoracic aortic syndromes. Results are encouraging, particularly for traumatic aortic ruptures. However, regular follow-up is mandatory, particularly in the other pathologies, to identify late complications of the stent-graft and to perform appropriate additional corrections as required.