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Sample records for paraplegia

  1. Hysterical paraplegia.

    PubMed Central

    Baker, J H; Silver, J R

    1987-01-01

    Between 1944 and 1984 20 patients were admitted to a spinal injuries centre with a diagnosis of traumatic paraplegia. They subsequently walked out and the diagnosis was revised to hysterical paraplegia. A further 23 patients with incomplete traumatic injuries, who also walked from the centre, have been compared with them as controls. The features that enabled a diagnosis of hysterical paraplegia to be arrived at were: They were predominantly paraplegic, There was a high incidence of previous psychiatric illness and employment in the Health Service or allied professions, Many were actively seeking compensation. The physical findings were a disproportionate motor paralysis, non anatomical sensory loss, the presence of downgoing plantar responses, normal tone and reflexes. They made a rapid total recovery. In contrast, the control traumatic cases showed an incomplete recovery and a persistent residual neurological deficit. Investigations apart from plain radiographs of the spinal column were not warranted, and the diagnosis should be possible on clinical grounds alone. PMID:3585346

  2. Hereditary Spastic Paraplegia

    MedlinePlus

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  3. Fluorosis... causing paraplegia... mutilating life...

    PubMed

    Ahsan, Tasnim; Jabeen, Rakhshanda; Hashim, Saba; Bano, Zeenat; Ghafoor, Subheen

    2016-02-01

    Fluorosis is thought to be rare in Pakistan but endemic in various parts of the world, especially in India and China. In Pakistan only a few cases have been reported from Thar, Sibbi and Manga Mandi, with probability of fluorosis on MRI findings, supported by high drinking waterfluoride content. Neurological manifestations of skeletal fluorosis may vary from radiculo-myelopathy to neuropathy. A case of 26 years old female from Thul, Sindh, who presented with paraplegia, is reported here. Her MRI showed extensive classical degenerative changes throughout the spine, consistent with fluorosis, leading to cord compression at multiple levels. No such case with confirmed fluorosis has been previously reported from Pakistan. PMID:26819172

  4. Genetics Home Reference: spastic paraplegia type 11

    MedlinePlus

    ... with mental impairment and thin corpus callosum HSP-TCC SPG11-related hereditary spastic paraplegia with thin corpus ... A, Stevanin G, Santorelli FM. Screening of ARHSP-TCC patients expands the spectrum of SPG11 mutations and ...

  5. Acute Aortic Occlusion Presenting as Flaccid Paraplegia

    PubMed Central

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

    2015-01-01

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

  6. Acute aortic occlusion presenting as flaccid paraplegia.

    PubMed

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

    2015-01-01

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

  7. 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.

  8. 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

  9. Acute Paraplegia due to Thoracic Hematomyelia

    PubMed Central

    Celik, Bahattin; Canbek, Ihsan; Karavelioğlu, Ergun

    2016-01-01

    Spontaneous intraspinal intramedullary hemorrhage is a rare entity with the acute onset of neurologic symptoms. The etiology of idiopathic spontaneous hematomyelia (ISH) is unknown, and there are few published case reports. Hematomyelia is mostly associated with trauma, but the other nontraumatic etiologies are vascular malformations, tumors, bleeding disorders, syphilis, syrinx, and myelitis. MRI is a good choice for early diagnosis. Hematomyelia usually causes acute spinal cord syndrome due to the compression and destruction of the spinal cord. A high-dose steroid treatment and surgical decompression and evacuation of hematoma are the urgent solution methods. We present idiopathic spontaneous hematomyelia of a previously healthy 80-year-old male with a sudden onset of back pain and paraplegia. PMID:27478663

  10. Acute Paraplegia due to Thoracic Hematomyelia.

    PubMed

    Akpınar, Aykut; Celik, Bahattin; Canbek, Ihsan; Karavelioğlu, Ergun

    2016-01-01

    Spontaneous intraspinal intramedullary hemorrhage is a rare entity with the acute onset of neurologic symptoms. The etiology of idiopathic spontaneous hematomyelia (ISH) is unknown, and there are few published case reports. Hematomyelia is mostly associated with trauma, but the other nontraumatic etiologies are vascular malformations, tumors, bleeding disorders, syphilis, syrinx, and myelitis. MRI is a good choice for early diagnosis. Hematomyelia usually causes acute spinal cord syndrome due to the compression and destruction of the spinal cord. A high-dose steroid treatment and surgical decompression and evacuation of hematoma are the urgent solution methods. We present idiopathic spontaneous hematomyelia of a previously healthy 80-year-old male with a sudden onset of back pain and paraplegia. PMID:27478663

  11. Paraplegia due to Spinal Epidermoid Cyst Rupture at Asthma Attack

    PubMed Central

    Kim, Kweon Young; Kang, Jung Hun; Choi, Dae Woo; Lee, Min Hong

    2013-01-01

    Spinal epidermoid cyst is less than 1% of the entire spinal cord tumor and a rare tumor. It is a slowly proliferating benign tumor and can be a result of either congenital or acquired factors. In particular, reports of acute paraplegia due to spinal epidermoid cyst rupture are very rare. Since authors experienced paraplegia resulting from congenital spinal epidermoid cyst rupture during an asthma attack, it is reported with a review of literature. PMID:23705125

  12. Collecting duct carcinoma of the renal medulla presenting with paraplegia.

    PubMed

    Ockrim, J; Tsiriopoulos, I; Rees, H; Mendoza, N; Christmas, T J

    2005-01-01

    We report an interesting case of a patient with collecting duct carcinoma arising from the left kidney who presented with paraplegia secondary to metastases. The diagnosis was based on CT and histology. To our knowledge this is the first case of collecting duct carcinoma to present with paraplegia. The literature review also highlights the rarity of this disease with less than a hundred cases reported to date and the aggressive nature and poor prognosis despite prompt interventions.

  13. Genetic and phenotypic characterization of complex hereditary spastic paraplegia

    PubMed Central

    Kara, Eleanna; Tucci, Arianna; Manzoni, Claudia; Lynch, David S.; Elpidorou, Marilena; Bettencourt, Conceicao; Chelban, Viorica; Manole, Andreea; Hamed, Sherifa A.; Haridy, Nourelhoda A.; Federoff, Monica; Preza, Elisavet; Hughes, Deborah; Pittman, Alan; Jaunmuktane, Zane; Brandner, Sebastian; Xiromerisiou, Georgia; Wiethoff, Sarah; Schottlaender, Lucia; Proukakis, Christos; Morris, Huw; Warner, Tom; Bhatia, Kailash P.; Korlipara, L.V. Prasad; Singleton, Andrew B.; Hardy, John; Wood, Nicholas W.; Lewis, Patrick A.

    2016-01-01

    The hereditary spastic paraplegias are a heterogeneous group of degenerative disorders that are clinically classified as either pure with predominant lower limb spasticity, or complex where spastic paraplegia is complicated with additional neurological features, and are inherited in autosomal dominant, autosomal recessive or X-linked patterns. Genetic defects have been identified in over 40 different genes, with more than 70 loci in total. Complex recessive spastic paraplegias have in the past been frequently associated with mutations in SPG11 (spatacsin), ZFYVE26/SPG15, SPG7 (paraplegin) and a handful of other rare genes, but many cases remain genetically undefined. The overlap with other neurodegenerative disorders has been implied in a small number of reports, but not in larger disease series. This deficiency has been largely due to the lack of suitable high throughput techniques to investigate the genetic basis of disease, but the recent availability of next generation sequencing can facilitate the identification of disease-causing mutations even in extremely heterogeneous disorders. We investigated a series of 97 index cases with complex spastic paraplegia referred to a tertiary referral neurology centre in London for diagnosis or management. The mean age of onset was 16 years (range 3 to 39). The SPG11 gene was first analysed, revealing homozygous or compound heterozygous mutations in 30/97 (30.9%) of probands, the largest SPG11 series reported to date, and by far the most common cause of complex spastic paraplegia in the UK, with severe and progressive clinical features and other neurological manifestations, linked with magnetic resonance imaging defects. Given the high frequency of SPG11 mutations, we studied the autophagic response to starvation in eight affected SPG11 cases and control fibroblast cell lines, but in our restricted study we did not observe correlations between disease status and autophagic or lysosomal markers. In the remaining cases, next

  14. Strümpell's familial spastic paraplegia: genetics and neuropathology

    PubMed Central

    Behan, Wilhelmina M. H.; Maia, Maria

    1974-01-01

    Uncomplicated Strümpell's disease (Strümpell's familial spastic paraplegia) with a dominant mode of inheritance is recorded in six families. The neuropathological findings in two cases from these families are given, bringing the total of similar histologically documented reports in the literature to 11. It is concluded that, although exact classification and identification of the many different hereditary neurological degenerative diseases is not yet practicable, cases conforming to the picture described by Strümpell can be separated from larger general group of familial spastic paraplegias, show a consistent clinical picture, and have a standard pathology. It is suggested that, since the lesions are confined to the longest fibre tracts in the central nervous system, the pathological process may be different from that found in the `system' degenerations. Images PMID:4813430

  15. 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.

  16. [Transient delayed paraplegia after repair of thoracic and thoracoabdominal aneurysms].

    PubMed

    Martín Torrijos, M; Aguilar Lloret, C; Ariño Irujo, J J; Serrano Hernando, F J; López Timoneda, F

    2013-11-01

    Thoracoabdominal aneurysm requires multidisciplinary management due to its complexity both in surgical technique and anesthetic considerations. One of the most feared postoperative complication is spinal cord ischemia. It can be presented as different clinical patterns, and its recovery may be partial or complete. The postoperative management of spinal cord ischemia is mainly based on techniques to increase spinal cord perfusion, above all, hemodynamic stability and cerebrospinal fluid drainage. We present two cases of delayed paraplegia after an open repair of a thoracoabdominal aneurysm and a descending thoracic aortic aneurysm repair using an endovascular stent graft. They both had a complete neurological recovery after cerebrospinal fluid drainage.

  17. Rehabilitation for patients with paraplegia and lower extremity amputation

    PubMed Central

    Wang, Fangyong; Hong, Yi

    2015-01-01

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

  18. Rehabilitation for patients with paraplegia and lower extremity amputation.

    PubMed

    Wang, Fangyong; Hong, Yi

    2015-10-01

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

  19. Paraplegia following cervical epidural catheterization using loss of resistance technique with air: a case report.

    PubMed

    Chae, Yun Jeong; Han, Kyung Ream; Park, Hyung Bae; Kim, Chan; Nam, Si Gweon

    2016-02-01

    We report a case of paraplegia without neurologic deficit of upper extremities following cervical epidural catheterization using air during the loss of resistance technique. A 41-year-old woman diagnosed with complex regional pain syndrome had upper and lower extremity pain. A thoracic epidural lead was inserted for a trial spinal cord stimulation for treating lower extremity pain and cervical epidural catheterization was performed for treating upper extremity pain. Rapidly progressive paraplegia developed six hours after cervical epidural catheterization. Spine CT revealed air entrapment in multiple thoracic intervertebral foraminal spaces and surrounding epidural space without obvious spinal cord compression before the decompressive operation, which disappeared one day after the decompressive operation. Her paraplegia symptoms were normalized immediately after the operation. The presumed cause of paraplegia was transient interruption of blood supply to the spinal cord through the segmental radiculomedullary arteries feeding the spinal cord at the thoracic level of the intervertebral foramen caused by the air.

  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. Paraplegia caused by aortic coarctation complicated with spinal epidural hemorrhage.

    PubMed

    Tsai, Yi-Da; Hsu, Chin-Wang; Hsu, Chia-Ching; Liao, Wen-I; Chen, Sy-Jou

    2016-03-01

    Aortic coarctation complicated with spinal artery aneurysm rupture is exceptionally rare and can be source of intraspinal hemorrhage with markedly poor prognosis. A 21-year-old man visited the emergency department because of chest and back pain along with immobility of bilateral lower limbs immediately after he woke up in the morning. Complete flaccid paraplegia and hypoesthesia in dermatome below bilateral T3 level and pain over axial region from neck to lumbar region were noted. A computed tomography excluded aortic dissection. Magnetic resonance imaging revealed a fusiform lesion involving the anterior epidural space from C7 to T2 level suspected of epidural hemorrhage, causing compression of spinal cord. He started intravenous corticosteroid but refused operation concerning the surgical benefits. Severe chest pain occurred with newly onset right bundle branch block that developed the other day. Coronary artery angiography revealed myocardial bridge of left anterior descending coronary artery at middle third and coarctation of aorta. He underwent thoracic endovascular aortic repair uneventfully. The patient was hemodynamically stable but with slow improvement in neurologic recovery of lower limbs. Aortic coarcation can cause paralysis by ruptured vascular aneurysms with spinal hemorrhage and chest pain that mimics acute aortic dissection. A history of hypertension at young age and aortic regurgitated murmurs may serve as clues for further diagnostic studies. Cautious and prudent evaluation and cross disciplines cares are essential for diagnosis and successful management of the disease.

  2. Paraplegia caused by aortic coarctation complicated with spinal epidural hemorrhage.

    PubMed

    Tsai, Yi-Da; Hsu, Chin-Wang; Hsu, Chia-Ching; Liao, Wen-I; Chen, Sy-Jou

    2016-03-01

    Aortic coarctation complicated with spinal artery aneurysm rupture is exceptionally rare and can be source of intraspinal hemorrhage with markedly poor prognosis. A 21-year-old man visited the emergency department because of chest and back pain along with immobility of bilateral lower limbs immediately after he woke up in the morning. Complete flaccid paraplegia and hypoesthesia in dermatome below bilateral T3 level and pain over axial region from neck to lumbar region were noted. A computed tomography excluded aortic dissection. Magnetic resonance imaging revealed a fusiform lesion involving the anterior epidural space from C7 to T2 level suspected of epidural hemorrhage, causing compression of spinal cord. He started intravenous corticosteroid but refused operation concerning the surgical benefits. Severe chest pain occurred with newly onset right bundle branch block that developed the other day. Coronary artery angiography revealed myocardial bridge of left anterior descending coronary artery at middle third and coarctation of aorta. He underwent thoracic endovascular aortic repair uneventfully. The patient was hemodynamically stable but with slow improvement in neurologic recovery of lower limbs. Aortic coarcation can cause paralysis by ruptured vascular aneurysms with spinal hemorrhage and chest pain that mimics acute aortic dissection. A history of hypertension at young age and aortic regurgitated murmurs may serve as clues for further diagnostic studies. Cautious and prudent evaluation and cross disciplines cares are essential for diagnosis and successful management of the disease. PMID:26275629

  3. 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.

  4. 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

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

    SciTech Connect

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

    1994-09-01

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

  6. Prognosis of conservatively treated patients with Pott's paraplegia: logistic regression analysis

    PubMed Central

    Kalita, J; Misra, U; Mandal, S; Srivastava, M

    2005-01-01

    Methods: The study included 43 patients with Pott's paraplegia, managed conservatively. The diagnosis of Pott's spine was based on clinical, magnetic resonance imaging, and computed tomography or ultrasound guided aspiration biopsy. All patients were examined clinically, and motor evoked potentials (MEPs) to lower limbs and tibial somatosensory evoked potentials (SEP) were recorded. Outcome at six months was defined as good or poor. For evaluating predictors of outcome, 15 clinical, investigative, and evoked potential variables were analysed, using multiple logistic regression analysis. Results: The age range of the patients was 16–70 years, and 22 were female. Mild spasticity with hyperreflexia only was seen in 13 patients. In the remaining, weakness was severe in eight, and moderate and mild in 11 patients each. Twenty patients had loss of joint position sensation. MEP and SEP were abnormal in 19 and 18 patients, respectively. On multiple regression analysis, the best model predicting six month outcome included power, paraplegia score, SEP, and MEP. Conclusion: Patients with Pott's paraplegia are likely to recover completely by six months if they have mild weakness, lower paraplegia score and normal SEPs and MEPs. PMID:15897514

  7. 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"…

  8. 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 ...

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

    PubMed Central

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

    2015-01-01

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

  10. 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

  11. X-linked recessive type of pure spastic paraplegia in a large pedigree: absence of detectable linkage with Xg.

    PubMed Central

    Zatz, M; Penha-Serrano, C; Otto, P A

    1976-01-01

    A family with 24 males affected by an X-linked type of spastic paraplegia is reported. Twelve affected members were personally examined showing the pure form of the disease. Half of the affected males had many descendants, all normal. Linkage studies strongly suggest that this X-linked form of spastic paraplegia and Xg loci are not at a measurable distance on the X chromosome. PMID:1084423

  12. Paraplegia after thoracotomy for division and suture Patent Ductus Arteriosus (PDA).

    PubMed

    Sayasathid, Jarun; Somboonna, Naraporn; Numchaisiri, Chun

    2006-12-01

    A Thai women, aged 22 years old, came to hospital with Patent Ductus Arteriosis (PDA). Left thoracotomy, with division and suturing PDA, was performed. The second day after operation, she developed paraplegia below umbilical level. The CT-scan detected an extradural hematoma in the spinal cavity from T3-T6. To remove the blood clot, the T spine laminectomy was performed. 6 months after the laminectomy, the patient was able to perform her regular exercise. PMID:17214069

  13. 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

  14. REEPing the benefits of an animal model of hereditary spastic paraplegia

    PubMed Central

    Deutch, Ariel Y.; Hedera, Peter; Colbran, Roger J.

    2013-01-01

    The hereditary spastic paraplegias (HSPs) are characterized by spasticity of the leg muscles due to axonal degeneration of corticospinal neurons. Beetz et al. report that the core motor phenotype and axonal pathology of HSPs are recapitulated in mice lacking the HSP-associated gene Reep1. REEP1 is shown to regulate ER structure in motor cortex neurons. The Reep1 knockout mouse should be a very useful model in which to study the mechanisms of progressive axon loss in HSPs and other disorders. PMID:24051371

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

    PubMed Central

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

    2015-01-01

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

  16. A nullimorphic ERLIN2 mutation defines a complicated hereditary spastic paraplegia locus (SPG18).

    PubMed

    Alazami, Anas M; Adly, Nouran; Al Dhalaan, Hisham; Alkuraya, Fowzan S

    2011-11-01

    Hereditary Spastic Paraplegia (HSP) is a clinically and genetically heterogeneous group of neurological disorders that are characterized by progressive spasticity of the lower extremities. We describe an extended consanguineous Saudi family in which HSP is linked to SPG18, a previously reported autosomal recessive locus, and show that it is associated with a nullimorphic deletion of ERLIN2, a component of endoplasmic reticulum associated degradation. This finding adds to the growing diversity of cellular functions that are now known to be involved in the maintenance of the corticospinal tract neurons.

  17. Complicated hereditary spastic paraplegia with peripheral neuropathy, optic atrophy and mental retardation.

    PubMed

    Miyama, S; Arimoto, K; Kimiya, S; Tomi, H

    2000-08-01

    An 8-year old girl with a not previously described type of complicated hereditary spastic paraplegia (HSP) is presented. Spasticity in her lower limbs had already been recognized during infancy and worsened progressively. Severe delay in mental development was observed. Peripheral neuropathy and optic atrophy developed at 5 years of age. On brain magnetic resonance imaging, an abnormally thin corpus callosum was observed. Involvement of the fasciculus gracilis was suggested by somatosensory evoked potentials. To our knowledge, there has been no reported case of complicated HSP with peripheral neuropathy, optic atrophy and mental retardation so far. We postulate that our patient is a sporadic case of not previously described complicated HSP. PMID:11071149

  18. 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

  19. 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.

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

    PubMed

    Benfield, Jon; Maknojia, Asif; Epstein, Franklin

    2016-03-01

    Ten years after placement of a spinal cord stimulator (SCS) and resolution of pain, this patient presented with progressive paraplegia, worsening thoracic radicular pain at the same dermatome level of the electrodes, and bowel and bladder incontinence. Computed tomographic myelogram confirmed thoracic spinal cord central canal stenosis at the level of electrodes. After removal of the fibrotic tissue and electrodes, the patient had resolution of his thoracic radicular pain and a return of his pre-SCS pain and minimal neurologic and functional return. To the authors' knowledge, no studies have been identified with thoracic SCS lead fibrosis in the United States causing permanent paraplegia. Only one other case has been reported in Madrid, Spain. Patients with SCS presenting with loss of pain relief, new-onset radicular or neuropathic pain in same dermatome(s) as SCS electrodes, worsening neuromuscular examination, or new bladder or bowel incontinence need to be evaluated for complications regarding SCS implantation causing spinal stenosis and subsequent cord compression to avoid permanent neurologic deficits. PMID:26495817

  1. Sudden onset of paraplegia caused by hemorrhagic spinal epidural angiolipoma. A case report.

    PubMed

    Akhaddar, Ali; Albouzidi, Abderrahmane; Elmostarchid, Brahim; Gazzaz, Miloudi; Boucetta, Mohamed

    2008-09-01

    Spinal epidural angiolipoma is a rare benign tumor containing vascular and mature adipose elements. A slow progressive clinical course was mostly presented and rarely a fluctuating course during pregnancy. The authors report the original case of spontaneous spinal epidural bleeding resulting from thoracic epidural angiolipoma who presented with hyperacute onset of paraplegia, simulating an extradural hematoma. The patient was admitted with sudden non-traumatic hyperacute paraplegia during a prolonged walk. Neurologic examination showed sensory loss below T6 and bladder disturbances. Spinal MRI revealed a non-enhanced heterogeneous thoracic epidural lesion, extending from T2 to T3. A bilateral T2-T4 laminectomy was performed to achieve resection of a lipomatous tumor containing area of spontaneous hemorrhage. The postoperative course was uneventful with complete neurologic recovery. Histologic examination revealed the tumor as an angiolipoma. Because the prognosis after rapid surgical management of this lesion is favorable, the diagnosis of spinal angiolipoma with bleeding should be considered in the differential diagnosis of hyperacute spinal cord compression.

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

    PubMed

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

    2013-11-01

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

  3. A new locus for autosomal recessive hereditary spastic paraplegia maps to chromosome 16q24.3.

    PubMed Central

    De Michele, G; De Fusco, M; Cavalcanti, F; Filla, A; Marconi, R; Volpe, G; Monticelli, A; Ballabio, A; Casari, G; Cocozza, S

    1998-01-01

    Hereditary spastic paraplegia is a genetically and phenotypically heterogeneous disorder. Both pure and complicated forms have been described, with autosomal dominant, autosomal recessive, and X-linked inheritance. Various loci (SPG1-SPG6) associated with this disorder have been mapped. Here, we report linkage analysis of a large consanguineous family affected with autosomal recessive spastic paraplegia with age at onset of 25-42 years. Linkage analysis of this family excluded all previously described spastic paraplegia loci. A genomewide linkage analysis showed evidence of linkage to chromosome 16q24.3, with markers D16S413 (maximum LOD score 3.37 at recombination fraction [theta] of .00) and D16S303 (maximum LOD score 3.74 at straight theta=.00). Multipoint analysis localized the disease gene in the most telomeric region, with a LOD score of 4.2. These data indicate the presence of a new locus linked to pure recessive spastic paraplegia, on chromosome 16q24.3, within a candidate region of 6 cM. PMID:9634528

  4. 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…

  5. Paraparesis (paraplegia), tetraparesis (tetraplegia), urinary/fecal incontinence. Spinal cord diseases.

    PubMed

    Kornegay, J N

    1991-09-01

    Paraparesis (paraplegia) refers to partial (-paresis) or complete (-plegia) loss of voluntary motor function in the pelvic limbs. Similar involvement of all four limbs is termed tetraparesis (tetraplegia). Paraparesis generally results from spinal cord lesions caudad to the second thoracic spinal cord segment, whereas tetraparesis occurs because of lesions craniad to this segment (see discussion of spinal cord lesion localization in The Neurologic Examination and Lesion Localization, on page 328). The limbs may be affected equally; however, asymmetric lesions cause greater clinical involvement on the ipsilateral side. Strictly unilateral lesions at C1-T2 result in clinical involvement on only the affected side of the body (hemiparesis, hemiplegia). Monoparesis (monoplegia) occurs subsequent to unilateral T2-S1 lesions. Trauma and neoplasia are the most common spinal cord diseases affecting cats. Urinary and fecal incontinence often occur concomitant with paresis. General concepts relating to disorders of micturition are discussed at the conclusion of this chapter. PMID:1802259

  6. Targeted NGS meets expert clinical characterization: Efficient diagnosis of spastic paraplegia type 11.

    PubMed

    Castro-Fernández, Cristina; Arias, Manuel; Blanco-Arias, Patricia; Santomé-Collazo, Luis; Amigo, Jorge; Carracedo, Ángel; Sobrido, Maria-Jesús

    2015-06-01

    Next generation sequencing (NGS) is transforming the diagnostic approach for neurological disorders, since it allows simultaneous analysis of hundreds of genes, even based on just a broad, syndromic patient categorization. However, such an approach bears a high risk of incidental and uncertain genetic findings. We report a patient with spastic paraplegia whose comprehensive neurological and imaging examination raised a high clinical suspicion of SPG11. Thus, although our NGS pipeline for this group of disorders includes gene panel and exome sequencing, in this sample only the spatacsin gene region was captured and subsequently searched for mutations. Two probably pathogenic variants were quickly and clearly identified, confirming the diagnosis of SPG11. This case illustrates how combination of expert clinical characterization with highly oriented NGS protocols leads to a fast, cost-efficient diagnosis, minimizing the risk of findings with unclear significance.

  7. A novel mutation in PLP1 causes severe hereditary spastic paraplegia type 2.

    PubMed

    Noetzli, Leila; Sanz, Pablo G; Brodsky, Gary L; Hinckley, Jesse D; Giugni, Juan C; Giannaula, Rolando J; Gonzalez-Alegre, Pedro; Di Paola, Jorge

    2014-01-01

    Hereditary spastic paraplegia (HSP) type 2 is a proteolipid protein (PLP1)-related genetic disorder that is characterized by dysmyelination of the central nervous system resulting primarily in limb spasticity, cognitive impairment, nystagmus, and spastic urinary bladder of varying severity. Previously reported PLP1 mutations include duplications, point mutations, or whole gene deletions with a continuum of phenotypes ranging from severe Pelizaeus-Merzbacher disease (PMD) to uncomplicated HSP type 2. In this manuscript we report a novel PLP1 missense mutation (c.88G>C) in a family from Argentina. This mutation is in a highly conserved transmembrane domain of PLP1 and the mutant protein was found to be retained in the endoplasmic reticulum when expressed in vitro. Due to the variable expressivity that characterizes these disorders our report contributes to the knowledge of genotype-phenotype correlations of PLP1-related disorders. PMID:24103481

  8. A recurrent mutation in KCNA2 as a novel cause of hereditary spastic paraplegia and ataxia.

    PubMed

    Helbig, Katherine L; Hedrich, Ulrike B S; Shinde, Deepali N; Krey, Ilona; Teichmann, Anne-Christin; Hentschel, Julia; Schubert, Julian; Chamberlin, Adam C; Huether, Robert; Lu, Hsiao-Mei; Alcaraz, Wendy A; Tang, Sha; Jungbluth, Chelsy; Dugan, Sarah L; Vainionpää, Leena; Karle, Kathrin N; Synofzik, Matthis; Schöls, Ludger; Schüle, Rebecca; Lehesjoki, Anna-Elina; Helbig, Ingo; Lerche, Holger; Lemke, Johannes R

    2016-10-01

    The hereditary spastic paraplegias (HSPs) are heterogeneous neurodegenerative disorders with over 50 known causative genes. We identified a recurrent mutation in KCNA2 (c.881G>A, p.R294H), encoding the voltage-gated K(+) -channel, KV 1.2, in two unrelated families with HSP, intellectual disability (ID), and ataxia. Follow-up analysis of > 2,000 patients with various neurological phenotypes identified a de novo p.R294H mutation in a proband with ataxia and ID. Two-electrode voltage-clamp recordings of Xenopus laevis oocytes expressing mutant KV 1.2 channels showed loss of function with a dominant-negative effect. Our findings highlight the phenotypic spectrum of a recurrent KCNA2 mutation, implicating ion channel dysfunction as a novel HSP disease mechanism. Ann Neurol 2016. PMID:27543892

  9. Central motor conduction in hereditary motor and sensory neuropathy and hereditary spastic paraplegia.

    PubMed

    Cruz Martínez, A; Tejada, J

    1999-09-01

    Conduction of the central motor pathways (CMCT) by magnetic stimulation of the motor cortex (TMS) was performed in 17 patients with hereditary motor sensory neuropathy (HMSN) and 2 siblings with hereditary spastic paraplegia (HSP). CMCT was prolonged in two patients with HMSN I with associated pyramidal features and in two subjects with HMSN II without clinical pyramidal signs. CMCT may be abnormal in HMSN due to central motor pathways involvement or altered spinal excitability with increased synaptic delay. CMCT was normal in the upper limbs in patients with HSP but increased in the legs. Diagnostic yield of TMS increased in less disabled cases with HSP when selective conduction at the spinal level (C7-S1) was calculated. Abnormal spinal conduction in HSP is consistent with degeneration of the crossed corticospinal tracts at the thoracic level found in neuropathologic observations.

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

    PubMed

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

    2015-11-01

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

  11. A recurrent mutation in KCNA2 as a novel cause of hereditary spastic paraplegia and ataxia.

    PubMed

    Helbig, Katherine L; Hedrich, Ulrike B S; Shinde, Deepali N; Krey, Ilona; Teichmann, Anne-Christin; Hentschel, Julia; Schubert, Julian; Chamberlin, Adam C; Huether, Robert; Lu, Hsiao-Mei; Alcaraz, Wendy A; Tang, Sha; Jungbluth, Chelsy; Dugan, Sarah L; Vainionpää, Leena; Karle, Kathrin N; Synofzik, Matthis; Schöls, Ludger; Schüle, Rebecca; Lehesjoki, Anna-Elina; Helbig, Ingo; Lerche, Holger; Lemke, Johannes R

    2016-10-01

    The hereditary spastic paraplegias (HSPs) are heterogeneous neurodegenerative disorders with over 50 known causative genes. We identified a recurrent mutation in KCNA2 (c.881G>A, p.R294H), encoding the voltage-gated K(+) -channel, KV 1.2, in two unrelated families with HSP, intellectual disability (ID), and ataxia. Follow-up analysis of > 2,000 patients with various neurological phenotypes identified a de novo p.R294H mutation in a proband with ataxia and ID. Two-electrode voltage-clamp recordings of Xenopus laevis oocytes expressing mutant KV 1.2 channels showed loss of function with a dominant-negative effect. Our findings highlight the phenotypic spectrum of a recurrent KCNA2 mutation, implicating ion channel dysfunction as a novel HSP disease mechanism. Ann Neurol 2016.

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

    PubMed Central

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

    2014-01-01

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

  13. Clinical and Paraclinical Indicators of Motor System Impairment in Hereditary Spastic Paraplegia: A Pilot Study

    PubMed Central

    Martinuzzi, Andrea; Montanaro, Domenico; Vavla, Marinela; Paparella, Gabriella; Bonanni, Paolo; Musumeci, Olimpia; Brighina, Erika; Hlavata, Hana; Rossi, Giuseppe; Aghakhanyan, Gayane; Martino, Nicola; Baratto, Alessandra; D’Angelo, Maria Grazia; Peruch, Francesca; Fantin, Marianna; Arnoldi, Alessia; Citterio, Andrea; Vantaggiato, Chiara; Rizzo, Vincenzo; Toscano, Antonio; Bresolin, Nereo; Bassi, Maria Teresa

    2016-01-01

    Background Hereditary spastic paraplegias (HSP) are a composite and genetically heterogeneous group of conditions mainly expressed by the impairment of the central motor system (“pure” forms). The involvement of other components of the central nervous system or of other systems is described in the “complicate” forms. The definition of an investigation protocol capable, by assembling clinical and paraclinical indicators to fully represent the extent of the motor system impairment, would help both the clinical handling of these conditions and contribute to our understanding of their pathogenesis. Methods We applied a clinical and paraclinical protocol which included tools exploring motor and non motor functioning, neurophysiology and MRI to a composite cohort of 70 molecularly defined HSP patients aged 3 to 65, to define for each indicator its significance in detailing the presence and the severity of the pathology. Results Clinically increased deep tendon reflexes and lower limb (LL) weakness are constant findings in all patients. The “complicated” forms are characterized by peripheral motor impairment, cognitive and cerebellar involvement. The Spastic Paraplegia Rating Scale efficiently reflects the severity of functional problems and correlates with disease duration. Neurophysiology consistently documents the impairment of the central motor pathway to the LLs. Nevertheless, the upper extremities and sensory system involvement is a frequent finding. MRI diffusion tensor imaging (DTI) highlighted a significant alteration of FA and MD. Combining the sampling of the various portion of the cortico-spinal tract (CST) DTI consistently discriminated patients from controls. Conclusion We propose a graded clinical and paraclinical protocol for HSP phenotype definition, indicating for each tool the discriminative and descriptive capacity. Our protocol applied to 9 different forms of HSP showed that the functional impairment often extends beyond the CST. The novel

  14. Car Transfer and Wheelchair Loading Techniques in Independent Drivers with Paraplegia

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-08-27

    Paraplegia following complex aortic intervention relies on crude evaluation of lower extremity strength such as whether the patient can lift their legs or flex the ankle. Little attention has been given to the possible long-term neurologic sequelae following these procedures in patients appearing functionally normal. We hypothesize that mice subjected to minimal ischemic time will have functional and histological changes despite the gross appearance of normal function. Male mice underwent 3 min of aortic occlusion (n=14) or sham surgery (n=4) via a median sternotomy. Neurologic function was graded by Basso Motor Score (BMS) preoperatively and at 24h intervals after reperfusion. Mice appearing functionally normal and sham mice were placed on a walking beam and recorded on high-definition, for single-frame motion analysis. After 96 hrs, spinal cords were removed for histological analysis. Following 3 min of ischemia, functional outcomes were split evenly with either mice displaying almost normal function n=7 or near complete paraplegia n=7. Additionally, single-frame motion analysis revealed significant changes in gait. Histologically, there was a significant stepwise reduction of neuronal viability, with even the normal function ischemic group demonstrating significant loss of neurons. Despite the appearance of normal function, temporary ischemia induced marked cyto-architectural changes and neuronal degeneration. Furthermore high-definition gait analysis revealed significant changes in gait and activity following thoracic aortic occlusion. These data suggest that all patients undergoing procedures, even with short ischemic times, may have spinal cord injury that is not evident clinically. PMID:26005132

  16. A novel frameshift mutation of DDHD1 in a Japanese patient with autosomal recessive spastic paraplegia.

    PubMed

    Miura, Shiroh; Morikawa, Takuya; Fujioka, Ryuta; Kosaka, Kengo; Yamada, Kohei; Hattori, Gohsuke; Motomura, Manabu; Taniwaki, Takayuki; Shibata, Hiroki

    2016-08-01

    Spastic paraplegia (SPG) type 28 is an autosomal recessive SPG caused by mutations in the DDHD1 gene. We examined a Japanese 54-years-old male patient with autosomal recessive SPG. His parents were consanguineous. He needed a wheelchair for transfer due to spastic paraplegia. There was a history of operations for bilateral hallux valgus, thoracic ossification of the yellow ligament, bilateral carpal tunnel syndrome, bilateral ankle contracture, and lumbar spinal canal stenosis. He noticed gait disturbance at age 14. He used a cane for walking in his 40s. On neurological examination, he showed hyperreflexia, spasticity, and weakness in the lower extremities and bilateral Babinski reflexes. Urinary dysfunctions and impaired vibration sense in the lower limbs were observed. By exome sequencing analysis using Agilent SureSelect and Illumina MiSeq, we identified 17,248 homozygous nucleotide variants in the patient. Through the examination of 48 candidate genes known to be responsible for autosomal recessive SPG, we identified a novel homozygous 4-bp deletion, c.914_917delGTAA, p.Ser305Ilefs*2 in exon2 of the DDHD1 gene encoding phosphatidic acid-preferring phospholipase A1 (PA-PLA1). The mutation is expected to cause a frameshift generating a premature stop codon 3-bp downstream from the deletion. In consequence, the DDHD domain that is known to be critical for PLA1 activity is completely depleted in the mutated DDHD1 protein, predicted to be a functionally null mutation of the DDHD1 gene. By Sanger sequencing, we confirmed that both parents are heterozygous for the mutation. This variation was not detected in 474 Japanese control subjects as well as the data of the 1,000G Project. We conclude that the novel mutation in DDHD1 is the causative variant for the SPG28 patient that is the first record of the disease in Japanese population. PMID:27216551

  17. Progressive paraplegia caused by recurrence of mantle-cell lymphoma with atypical spinal magnetic resonance imaging features.

    PubMed

    Yamane, Hiromichi; Ochi, Nobuaki; Yamagishi, Tomoko; Takigawa, Nagio; Maeda, Yoshinobu

    2015-01-01

    We describe a case of paraplegia, which had progressed rapidly in a 60-year-old Japanese man with mantle-cell lymphoma. (MCL). He admitted to our hospital due to lumbago and progressive muscle weakness of bilateral lower thighs lasting for 1. month, while he had the history of the systemic chemotherapy for MCL since 10 months. Magnetic resonance imaging. (MRI) revealed a wide-spreading intradural tumor situated in the spinal canal from L1 to L5 with an intervertebral slipped disk as the only site of recurrence. Laminectomy followed by salvage chemotherapy led disappearance of lumbago and paraplegia of the bilateral lower extremities. Although wide-spreading tumor formation in spinal canal without other involvement sites is very rare in MCL, physicians should be aware of such patterns of central nervous system. (CNS) relapse for the early diagnosis and adequate selection of treatment modality. PMID:26881642

  18. Enhancing stance phase propulsion during level walking by combining FES with a powered exoskeleton for persons with paraplegia.

    PubMed

    Ha, Kevin H; Quintero, Hugo A; Farris, Ryan J; Goldfarb, Michael

    2012-01-01

    This paper describes the design and implementation of a cooperative controller that combines functional electrical stimulation (FES) with a powered lower limb exoskeleton to provide enhanced hip extension during the stance phase of walking in persons with paraplegia. The controller utilizes two sources of actuation: the electric motors of the powered exoskeleton and the user's machine (FSM), a set of FES. It consists of a finite-state machine (FSM), a set of proportional-derivative (PD) controllers for the exoskeleton and a cycle-to-cycle adaptive controller for muscle stimulation. Level ground walking is conducted on a single subject with complete T10 paraplegia. Results show a 34% reduction in electrical power requirements at the hip joints during the stance phase of the gait cycle with the cooperative controller compared to using electric motors alone. PMID:23365900

  19. Ultrasound guided block of the saphenous neuroma following use of an AFO in a patient with paraplegia. A case report.

    PubMed

    Kesikburun, S; Köroğlu Omaç, Ö; Yaşar, E; Yilmaz, B; Kenan Tan, A

    2014-04-01

    The saphenous nerve is the terminal branch of the femoral nerve and a pure sensory nerve that provide sensation to medial leg. Injury to saphanous nerve following trauma or surgery of the knee can result in formation of a painful neuroma along its distribution. We present a case of saphenous neuroma following use of an ankle-foot orthosis (AFO) in a patient with paraplegia. A 36-year-old patient with paraplegia who was capable of walking independently with his AFO presented to our department with a 3-month history of pain in his left calf. Examination revealed tenderness, paresthesias and positive Tinel sign over the anteromedial aspect of the calf. Ultrasonographic examination of the painful area showed a mass with heterogenous echogenity which was consistent with a saphenous neuroma at the site where fastener band of AFO compressed to skin. We performed a nerve block with steroid and local anesthetic injection under ultrasound guidance to the neuroma. The patient reported pain relief following injection. The use of the AFO may cause a painful saphenous neuroma which is an unusual cause of extremity pain in patients with paraplegia. Ultrasound may be a beneficial diagnostic tool and a guidance for the therapeutic interventions in this condition.

  20. 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

  1. 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

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

    PubMed

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

    2014-10-14

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

  3. Motor neuron degeneration in spastic paraplegia 11 mimics amyotrophic lateral sclerosis lesions.

    PubMed

    Denora, Paola S; Smets, Katrien; Zolfanelli, Federica; Ceuterick-de Groote, Chantal; Casali, Carlo; Deconinck, Tine; Sieben, Anne; Gonzales, Michael; Zuchner, Stephan; Darios, Frédéric; Peeters, Dirk; Brice, Alexis; Malandrini, Alessandro; De Jonghe, Peter; Santorelli, Filippo M; Stevanin, Giovanni; Martin, Jean-Jacques; El Hachimi, Khalid H

    2016-06-01

    The most common form of autosomal recessive hereditary spastic paraplegia is caused by mutations in the SPG11/KIAA1840 gene on chromosome 15q. The nature of the vast majority of SPG11 mutations found to date suggests a loss-of-function mechanism of the encoded protein, spatacsin. The SPG11 phenotype is, in most cases, characterized by a progressive spasticity with neuropathy, cognitive impairment and a thin corpus callosum on brain MRI. Full neuropathological characterization has not been reported to date despite the description of >100 SPG11 mutations. We describe here the clinical and pathological features observed in two unrelated females, members of genetically ascertained SPG11 families originating from Belgium and Italy, respectively. We confirm the presence of lesions of motor tracts in medulla oblongata and spinal cord associated with other lesions of the central nervous system. Interestingly, we report for the first time pathological hallmarks of SPG11 in neurons that include intracytoplasmic granular lysosome-like structures mainly in supratentorial areas, and others in subtentorial areas that are partially reminiscent of those observed in amyotrophic lateral sclerosis, such as ubiquitin and p62 aggregates, except that they are never labelled with anti-TDP-43 or anti-cystatin C. The neuropathological overlap with amyotrophic lateral sclerosis, associated with some shared clinical manifestations, opens up new fields of investigation in the physiopathological continuum of motor neuron degeneration. PMID:27016404

  4. 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

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

    PubMed

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

    2016-03-15

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

  6. Complicated spastic paraplegia in patients with AP5Z1 mutations (SPG48)

    PubMed Central

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

    2016-01-01

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

  7. 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.

  8. Paraplegia following intrathecal methotrexate: report of a case and review of the literature.

    PubMed

    Gagliano, R G; Costanzi, J J

    1976-04-01

    A patient who developed paraplegia following the intrathecal instillation of methotrexate is discribed. The ten previously reported cases of this unusual complication are reviewed. The following factors appear to predispose to the development of this complication: abnormal cerebrospinal dynamics related to the presence of central nervous system leukemia, and epidural cerebrospinal leakage; elevated cerebrospinal fluid methothexate concentration related to abnormal cerebrospinal fluid dynamics and to inappropriately high methotrexate doses based on body surface area calculations in older children and adults; the presence of neurotoxic preservatives in commercially available methotrexate preparations and diluents; and the use of methotrexate diluents of unphysiologic pH, ionic content and osmolarity. The role of methotrexate contaminants, local folate deficiency, and cranial irradiation in the pathogenesis of intrathecal methotrexate toxicity is unclear. The incidence of neurotoxicity may be reduced by employing lower doses of methotrexate in the presence of central nervous system leukemia, in older children and adults, and in the presence of epidural leakage. Only preservative-free methotrexate in Elliott's B Solution at a concentration of not more than 1 mg/ml should be used for intrathecal administration. Periodic monitoring of cerebruspinal fluid methotrexate levels may be predictive of the development of serious neurotoxicity. PMID:946593

  9. Intragenic modifiers of hereditary spastic paraplegia due to spastin gene mutations.

    PubMed

    Svenson, Ingrid K; Kloos, Mark T; Gaskell, P Craig; Nance, Martha A; Garbern, James Y; Hisanaga, Shin-ichi; Pericak-Vance, Margaret A; Ashley-Koch, Allison E; Marchuk, Douglas A

    2004-09-01

    Hereditary spastic paraplegia (HSP) is a genetically heterogeneous neurodegenerative disease characterized by wide variability in phenotypic expression, both within and among families. The most-common cause of autosomal dominant HSP is mutation of the gene encoding spastin, a protein of uncertain function. We report the existence of intragenic polymorphisms of spastin that modify the HSP phenotype. One (S44L) is a previously described recessively acting allele and the second is a novel allele affecting the adjacent amino acid residue (P45Q). In 4 HSP families in which either L44 or Q45 segregates independently of a missense or splicing mutation in the AAA domain of spastin, L44 and Q45 are each associated with a striking decrease in age at onset in the presence of the AAA domain mutations. Using a bioinformatics approach, we found that the highly conserved S44 is predicted to be phosphorylated by a number of family members of the proline-directed serine/threonine cyclin-dependent kinases (Cdks). Cdk1 and Cdk5 showed no kinase activity toward synthetic spastin peptide in an in vitro kinase assay, suggesting that this serine residue may be phosphorylated by a different Cdk. Our identification of S44L and P45Q as modifiers of the HSP phenotype suggests a role for spastin phosphorylation by Cdks in the neurodegeneration of the most-common form of HSP. PMID:15248095

  10. Complicated spastic paraplegia in patients with AP5Z1 mutations (SPG48)

    PubMed Central

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

    2016-01-01

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

  11. SPG11 mutations cause Kjellin syndrome, a hereditary spastic paraplegia with thin corpus callosum and central retinal degeneration.

    PubMed

    Orlén, Hanna; Melberg, Atle; Raininko, Raili; Kumlien, Eva; Entesarian, Miriam; Söderberg, Per; Påhlman, Magnus; Darin, Niklas; Kyllerman, Mårten; Holmberg, Eva; Engler, Henry; Eriksson, Urban; Dahl, Niklas

    2009-10-01

    Autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC) is genetically heterogenous and approximately 35% of patients carry mutations in either of the SPG11 or SPG15 genes. Disease onset is during the first three decades of life with spastic paraplegia and mental impairment. Peripheral neuropathy and amyotrophy may occur. Kjellin syndrome is characterized by central retinal degeneration in addition to ARHSP-TCC and the disease is associated with mutations in the SPG15 gene. We identified five patients in four unrelated kindreds with spastic paraplegia and mental impairment. Magnetic resonance imaging revealed TCC, atrophy elsewhere in the brain and increased T2 signal intensity in the periventricular white matter. Probands from the four kindreds were screened for mutations in the SPG11 gene. All patients were found homozygous or compound heterozygous for truncating SPG11 mutations of which four are reported for the first time. Ophthalmological investigations revealed that the four index cases have central retinal degeneration consistent with Kjellin syndrome. PET examinations with N-[11C-methyl]-L-deuterodeprenyl (DED) and fluor-18 2-fluorodeoxyglucose (FDG) were performed in two patients with Kjellin syndrome. We observed a reduced glucose uptake in the thalami, anterior cingulum, and sensorimotor cortex indicating neuronal loss, and an increased DED binding in the thalami and pons which suggests astrogliosis. From our results we extend the SPG11 associated phenotype to comprise also Kjellin syndrome, previously found to be associated with mutations in the SPG15 gene. We anticipate that degeneration of the central retina is a common and previously unrecognized feature in SPG11 related disease.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-08-01

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

  14. 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.

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

    PubMed

    Raymond, J; Davis, G M; Clarke, J; Bryant, G

    2001-07-01

    In this study the cardiorespiratory responses during arm crank ergometry (ACE) performed at two submaximal intensities (30% and 50% of heart rate reserve) and moderate orthostatic challenge were investigated in individuals with paraplegia (PARA). The effect of concurrent electrical stimulation (ES)-induced leg muscle contractions on the responses to ACE during orthostatic challenge was also investigated. Eight PARA (T5-T12) and eight able-bodied (AB) individuals participated in this study, however only seven subjects from each group completed all tests and were used in subsequent data analyses. Oxygen uptake (VO2), heart rate (fc), stroke volume (SV) and cardiac output (Qc) were assessed during (1) ACE alone, (2) ACE and lower body negative pressure (ACE + LBNP), and, in PARA only, (3) ACE + LBNP with ES (ACE + LBNP+ ES). In both PARA and AB, ACE + LBNP decreased SV (by 13-18% and 20-23%, respectively) and increased fc (by 13-15% and 16%, respectively) compared to ACE alone. The decrease in SV was greater in AB than in PARA (significant group x trial interaction; both ACE intensities pooled), but there was no difference in the magnitude of increase in fc between groups. ES-induced leg muscle contractions increased SV (up to 16%) but did not change VO2 or Qc. The smaller reduction in SV from ACE to ACE + LBNP in PARA may indicate a mechanism by which adequate central blood volume can be maintained in the face of orthostatic challenge, despite the absence of supraspinal control below the spinal cord lesion. With ES-induced leg muscle contractions, the decrease in SV, which occurred during ACE + LBNP, was reversed via reactivation of the lower limb muscle pump and augmented venous return.

  16. [Familial spastic paraplegia with syndrome of continuous muscle fiber activity (Isaacs)].

    PubMed

    Yokota, T; Matsunaga, T; Furukawa, T; Tsukagoshi, H

    1989-06-01

    A woman aged fifty-three developed paraparesis at the age of 4, which progressed slowly and required crutches by the age of 30. At the age of 51, muscle stiffness involved bilateral hands and arms gradually. At the age of 53, she suffered from painful spasms in right deltoid muscle. Her two brothers had spastic paraplegia without other neurological deficits. Her paternal grandfather and maternal grandmother were cousins. Slight dementia was noted (WAIS: IQ, 79). Her posture was stiff and muscles of upper limbs were in a persistent contraction; Subcutaneous tissue was thin, and muscles were well-defined and firm. There was moderate muscle weakness of legs and hands. Continuous fasciculations and myokymias were recognized in muscles of the arms and the limb girdles. Muscle tone was considerably increased especially in the bilateral arms. The deep tendon reflexes were exaggerated with extensor plantar responses. Profuse sweating affected palms, soles and backs. No sensory disturbance was appreciated. There was no myotonic responses to percussion of muscles. Following laboratory data were normal; thyroid functions, CSF studies, anti HTLV-I antibody and long chain fatty acid in red blood cells, myelography and brain CT except for increased basal metabolic rate (53%). Electromyographic study in the arms and hands revealed spontaneous motor unit activities including doublets at rest and increased proportion of polyphasic potentials and high amplitude potentials in voluntary contraction. Biopsy of right quadriceps femoris muscle showed hypertrophy of type I fibers and angulated atrophy of type II fibers. Continuous muscle activities in upper limbs did not change at sleep or with intravenous administration of 7 mg diazepam.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2803825

  17. Total knee arthroplasty in patient with paraplegia after spinal cord injury.

    PubMed

    Zietek, P; Dobiecki, K

    2015-01-01

    The clinical management of paraplegic patients is more complex than in able-bodied subjects. Spinal cord injury (SCI) affects younger, active people more often than the elderly during high-energy fall or traffic accidents. In order to return to work after suffering an SCI, patients need to regain their functional independence, especially their ability to drive. The literature lacks strong evidence addressing the surgical solutions in severe knee arthrosis in paralyzed patients after SCI. We present a favourable outcome of total knee arthroplasty (TKA) of a stiff knee in extension in a man with T12 grade C paraplegia after SCI. We describe an effective rehabilitation protocol after knee arthroplasty in patient with damage to the spinal cord. Several factors should be taken into account before performing surgery: 1. ability of regaining some of spinal cord locomotor function through intensive gait rehabilitation in SCI patients, 2. presence of muscle imbalance and knee contractures combined with a risk of bone fracture resulting from intensive postoperative rehabilitation, 3. the impaired microvasculature of the skin and subcutaneous tissues and increased risk of occlusion occurrence of the capillaries and small vessels of the leg, 4. higher prevalence of secondary infections via urinary entry sites in patients after SCI, 5. patient's strong determination and willingness to undergo the arthroplasty procedure. TKA might be considered in selected paralyzed patients after SCI, especially in those with severe arthrosis as well as significant knee contractures. Our study reveals the advantage of performing TKA in improving functional state in patients with cord injury. PMID:25748667

  18. Cycling with Functional Electrical Stimulation Before and After a Distal Femur Fracture in a Man with Paraplegia

    PubMed Central

    Marino, Ralph J.; Oleson, Christina V.; Schmidt-Read, Mary; Modlesky, Christopher M.

    2015-01-01

    Case Presentation: A man with chronic paraplegia sustained a distal femur fracture following an unrelated fall while enrolled in a study examining musculoskeletal changes after 6 months of cycling with functional electrical stimulation (FES). After healing, he restarted and completed the study. Management and Outcome: Study measures included areal bone mineral density, trabecular bone microarchitecture, cortical bone macroarchitecture, serum bone formation/resorption markers, and muscle volume. The patient made small gains in bone- and muscle-related measures. Bone markers had not returned to baseline prior to restarting cycling, which may have impacted results. Discussion: This case shows that cycling with FES may be safely resumed after distal femur fracture. PMID:26689692

  19. Acute Paraplegia as a Result of Hemorrhagic Spinal Ependymoma Masked by Spinal Anesthesia: Case Report and Review of Literature.

    PubMed

    Lee, Sang-Hyo; Park, David Jaehyun; Jeun, Sin-Soo

    2016-04-01

    Ependymomas are the most common intramedullary spinal cord tumors in adults. Although a hemorrhage within spinal ependymoma on imaging studies is not uncommon, it has rarely been reported to bea cause of acute neurological deficit. In the present report, we describe a case of a 24-year-old female patient who developed acute paraplegia as a result of hemorrhagic spinal ependymoma immediately after a cesarean delivery under spinal regional anesthesia. We review the literature of hemorrhagic spinal ependymomas presenting with acute neurological deficit and discuss the most appropriate treatment for a good neurological recovery. PMID:27195260

  20. Acute Paraplegia as a Result of Hemorrhagic Spinal Ependymoma Masked by Spinal Anesthesia: Case Report and Review of Literature

    PubMed Central

    Lee, Sang-Hyo; Jeun, Sin-Soo

    2016-01-01

    Ependymomas are the most common intramedullary spinal cord tumors in adults. Although a hemorrhage within spinal ependymoma on imaging studies is not uncommon, it has rarely been reported to bea cause of acute neurological deficit. In the present report, we describe a case of a 24-year-old female patient who developed acute paraplegia as a result of hemorrhagic spinal ependymoma immediately after a cesarean delivery under spinal regional anesthesia. We review the literature of hemorrhagic spinal ependymomas presenting with acute neurological deficit and discuss the most appropriate treatment for a good neurological recovery. PMID:27195260

  1. Effect of choice of recovery patterns on handrim kinetics in manual wheelchair users with paraplegia and tetraplegia

    PubMed Central

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

    2012-01-01

    Background Impact forces experienced by the upper limb at the beginning of each wheelchair propulsion (WCP) cycle are among the highest forces experienced by wheelchair users. Objective To determine whether the magnitude of hand/forearm velocity prior to impact and effectiveness of rim impact force are dependent on the type of hand trajectory pattern chosen by the user during WCP. Avoiding patterns that inherently cause higher impact force and have lower effectiveness can be another step towards preserving upper limb function in wheelchair users. Methods Kinematic (50 Hz) and kinetic (2500 Hz) data were collected on 34 wheelchair users (16 with paraplegia and 18 with tetraplegia); all participants had motor complete spinal cord injuries ASIA A or B. The four-hand trajectory patterns were analyzed based on velocity prior to contact, peak impact force and the effectiveness of force at impact. Results A high correlation was found between the impact force and the relative velocity of the hand with respect to the wheel (P < 0.05). The wheelchair users with paraplegia were found to have higher effectiveness of force at impact as compared to the users with tetraplegia (P < 0.05). No significant differences in the impact force magnitudes were found between the four observed hand trajectory patterns. Conclusion The overall force effectiveness tended to be associated with the injury level of the user and was found to be independent of the hand trajectory patterns. PMID:22507024

  2. 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

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

    PubMed

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

    2015-11-15

    Spastic paraplegia type 10 (SPG10) is a rare form of autosomal dominant hereditary spastic paraplegia (AD-HSP) due to mutations in KIF5A, a gene encoding the neuronal kinesin heavy-chain involved in axonal transport. KIF5A mutations have been associated with a wide clinical spectrum, ranging from pure HSP to isolated peripheral nerve involvement or complicated HSP phenotypes. Most KIF5A mutations are clustered in the motor domain of the protein that is necessary for microtubule interaction. Here we describe two Spanish families with an adult onset complicated AD-HSP in which neurological studies revealed a mild sensory neuropathy. Intention tremor was also present in both families. Molecular genetic analysis identified two novel mutations c.773 C>T and c.833 C>T in the KIF5A gene resulting in the P258L and P278L substitutions respectively. Both were located in the highly conserved kinesin motor domain of the protein which has previously been identified as a hot spot for KIF5A mutations. This study adds to the evidence associating the known occurrence of mild peripheral neuropathy in the adult onset SPG10 type of AD-HSP. PMID:26403765

  4. Autosomal recessive spastic paraplegia (SPG45) with mental retardation maps to 10q24.3-q25.1.

    PubMed

    Dursun, Umut; Koroglu, Cigdem; Kocasoy Orhan, Elif; Ugur, Sibel Aylin; Tolun, Aslihan

    2009-10-01

    Hereditary spastic paraplegias (HSPs) are characterized by progressive spasticity in the lower limbs. They are clinically heterogeneous, and pure forms as well as complicated forms with other accompanying clinical findings are known. HSPs are also genetically heterogeneous. We performed clinical and genetic studies in a consanguineous family with five affected members. A genome scan using 405 microsatellite markers for eight members of the family identified candidate gene loci, and subsequent fine mapping in 16 members identified the gene locus responsible for the HSP. The clinical manifestations were very early onset spastic paraplegia (SPG) accompanied by mental retardation and ocular signs. The gene locus was identified as the interval 102.05-106.64 Mbp on chromosome 10. Gene MRPL43 was analyzed in the patients. No mutation but high levels of mRNA were detected. We have mapped a novel autosomal recessive complicated form of HSP (SPG45) to a 4.6-Mbp region at 10q24.3-q25.1 with multipoint logarithm of odds scores >4.5.

  5. Clinical and genetic heterogeneity in hereditary spastic paraplegias: from SPG1 to SPG72 and still counting.

    PubMed

    Klebe, S; Stevanin, G; Depienne, C

    2015-01-01

    Hereditary spastic paraplegias (HSPs) are genetically determined neurodegenerative disorders characterized by progressive weakness and spasticity of lower limbs, and are among the most clinically and genetically heterogeneous human diseases. All modes of inheritance have been described, and the recent technological revolution in molecular genetics has led to the identification of 76 different spastic gait disease-loci with 59 corresponding spastic paraplegia genes. Autosomal recessive HSP are usually associated with diverse additional features (referred to as complicated forms), contrary to autosomal dominant HSP, which are mostly pure. However, the identification of additional mutations and families has considerably enlarged the clinical spectra, and has revealed a huge clinical variability for almost all HSP; complicated forms have also been described for primary pure HSP subtypes, adding further complexity to the genotype-phenotype correlations. In addition, the introduction of next generation sequencing in clinical practice has revealed a genetic and phenotypic overlap with other neurodegenerative disorders (amyotrophic lateral sclerosis, neuropathies, cerebellar ataxias, etc.) and neurodevelopmental disorders, including intellectual disability. This review aims to describe the most recent advances in the field and to provide genotype-phenotype correlations that could help clinical diagnoses of this heterogeneous group of disorders.

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

    PubMed

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

    2015-12-15

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

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

    PubMed

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

    2015-11-15

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

  8. 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

  9. Expanding the Clinical Spectrum of SPG11 Gene Mutations in Recessive Hereditary Spastic Paraplegia with Thin Corpus Callosum

    PubMed Central

    Aleem, Alice Abdel; Abu-Shahba, Nourhan; Swistun, Dominika; Silhavy, Jennifer; Bielas, Stephanie L.; Sattar, Shifteh; Gleeson, Joseph G.; Zaki, Maha

    2011-01-01

    Hereditary spastic paraplegia (HSP) represents a large group of neurological disorders characterized by progressive spasticity of the lower limbs. One subtype of HSP shows an autosomal recessive form of inheritance with this corpus callosum (ARHSP-TCC), and displays genetic heterogeneity with four known loci. We identified a consanguineous Egyptian family with five affected individuals with ARHSP-TCC. We found linkage to the SPG11 locus and identified a novel homozygous p.Q498X stop codon mutation in exon 7 in the SPG11 gene encoding Spatacsin. Cognitive impairment and polyneuropathy, reported as frequent in SPG11, were not evident. This family supports the importance of SPG11 as a frequent cause for ARHSP-TCC, and expands the clinic SPG11 spectrum. PMID:20971220

  10. 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.

  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. [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.

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

    SciTech Connect

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

    1995-05-22

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

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

    PubMed Central

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

    2015-01-01

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

  15. PMCA4 (ATP2B4) mutation in familial spastic paraplegia causes delay in intracellular calcium extrusion

    PubMed Central

    Ho, Philip Wing-Lok; Pang, Shirley Yin-Yu; Li, Miaoxin; Tse, Zero Ho-Man; Kung, Michelle Hiu-Wai; Sham, Pak-Chung; Ho, Shu-Leong

    2015-01-01

    Background 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. Recently, we described 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. Further to this finding, here we describe the functional effect of this mutation. Methods As PMCA4 removes cytosolic calcium, we measured transient changes and the time-dependent decay of cytosolic calcium level as visualized by using fura-2 fluorescent dye with confocal microscopy in human SH-SY5Y neuroblastoma cells overexpressing either wild-type or R268Q mutant PMCA4. Results Overexpressing both wild-type and R268Q PMCA4 significantly reduced maximum calcium surge after KCl-induced depolarization as compared with vector control cells. However, cells overexpressing mutant PMCA4 protein demonstrated significantly higher level of calcium surge when compared with wild-type. Furthermore, the steady-state cytosolic calcium concentration in these mutant cells remained markedly higher than the wild-type after SERCA inhibition by thapsigargin. Conclusion Our result showed that p.R268Q mutation in PMCA4 resulted in functional changes in calcium homeostasis in human neuronal cells. This suggests that calcium dysregulation may be associated with the pathogenesis of FSP. PMID:25798335

  16. Familial spastic paraplegia with distal muscle wasting in the Old Order Amish; atypical Troyer syndrome or "new" syndrome.

    PubMed

    Neuhäuser, G; Wiffler, C; Opitz, J M

    1976-03-01

    The Troyer syndrome was found by Cross & McKusick (1967) in 20 members of 12 Old Order Amish families in Holmes County, Ohio; it is a form of hereditary spastic paraplegia combined with distal muscle wasting, i.e. signs of involvement of lower motor neurons. The condition usually begins at 1 to 2 years and progresses at variable rates. Further manifestations include growth retardation, delayed speech development with dysarthria and drooling, and cerebellar signs; mental functions are usually not affected but severe emotional lability is a common finding. Brothers in a Wisconsin Old Order Amish family are reported with spastic diplegia, mental retardation, behavioral disorder and shortness of stature; the condition apparently is not progressive, and may be a "new" syndrome but could also represent a variant of the Troyer syndrome. Autosomal recessive inheritance is most likely, although consanguinity of the parents could not be proven. Another child in this family suffers from focal scleroderma (morphea) which is not related to the neurological syndrome. PMID:1261070

  17. Towards fully automated genotyping: use of an X linked recessive spastic paraplegia family to test alternative analysis methods.

    PubMed

    Kobayashi, H; Matise, T C; Perlin, M W; Marks, H G; Hoffman, E P

    1995-05-01

    Advances in dinucleotide-based genetic maps open possibilities for large scale genotyping at high resolution. The current rate-limiting steps in use of these dense maps is data interpretation (allele definition), data entry, and statistical calculations. We have recently reported automated allele identification methods. Here we show that a 10-cM framework map of the human X chromosome can be analyzed on two lanes of an automated sequencer per individual (10-12 loci per lane). We use this map and analysis strategy to generate allele data for an X-linked recessive spastic paraplegia family with a known PLP mutation. We analyzed 198 genotypes in a single gel and used the data to test three methods of data analysis: manual meiotic breakpoint mapping, automated concordance analysis, and whole chromosome multipoint linkage analysis. All methods pinpointed the correct location of the gene. We propose that multipoint exclusion mapping may permit valid inflation of LOD scores using the equation max LOD-(next best LOD). PMID:7759066

  18. An Approach for the Cooperative Control of FES With a Powered Exoskeleton During Level Walking for Persons With Paraplegia.

    PubMed

    Ha, Kevin H; Murray, Spencer A; Goldfarb, Michael

    2016-04-01

    This paper describes a hybrid system that combines a powered lower limb exoskeleton with functional electrical stimulation (FES) for gait restoration in persons with paraplegia. The general control structure consists of two control loops: a motor control loop, which utilizes joint angle feedback control to control the output of the joint motor to track the desired joint trajectories, and a muscle control loop, which utilizes joint torque profiles from previous steps to shape the muscle stimulation profile for the subsequent step in order to minimize the motor torque contribution required for joint angle trajectory tracking. The implementation described here incorporates stimulation of the hamstrings and quadriceps muscles, such that the hip joints are actuated by the combination of hip motors and the hamstrings, and the knee joints are actuated by the combination of knee motors and the quadriceps. In order to demonstrate efficacy, the control approach was implemented on three paraplegic subjects with motor complete spinal cord injuries ranging from levels T6 to T10. Experimental data indicates that the cooperative control system provided consistent and repeatable gait motions and reduced the torque and power output required from the hip and knee motors of the exoskeleton compared to walking without FES. PMID:25915961

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

    PubMed

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

    2016-01-01

    SPG11 belongs to the autosomal recessive hereditary spastic paraplegias (HSP) and presents during childhood or puberty with a complex clinical phenotype encompassing learning difficulties, ataxia, peripheral neuropathy, amyotrophy, and mental retardation. We hereby present the case of a 30-year-old female patient with complex autosomal recessive HSP with thinning of the corpus callosum (TCC) and dementia that was compound heterozygous with two novel mutations in the SPG11 gene. Sequence analysis of the SPG11 gene revealed two novel mutations in a compound heterozygous state in the index patient (c.2431C>T/p.Gln811Ter and c.6755_6756insT/p.Glu2252Aspfs*88). MRI showed abnormal TCC, white matter (WM) hyperintensities periventricularly, and the 'ears of the lynx' sign. Diffusion tensor imaging showed a mild-to-moderate decrease in fractional anisotropy and an increase in mean diffusivity in WM compared to age-matched controls, while magnetic resonance spectroscopy showed abnormal findings in affected WM with a decrease in N-acetyl-aspartate in WM regions of interest. This is the first SPG11 kindred from the Greek population to be reported in the medical literature. PMID:27318863

  20. An Approach for the Cooperative Control of FES With a Powered Exoskeleton During Level Walking for Persons With Paraplegia.

    PubMed

    Ha, Kevin H; Murray, Spencer A; Goldfarb, Michael

    2016-04-01

    This paper describes a hybrid system that combines a powered lower limb exoskeleton with functional electrical stimulation (FES) for gait restoration in persons with paraplegia. The general control structure consists of two control loops: a motor control loop, which utilizes joint angle feedback control to control the output of the joint motor to track the desired joint trajectories, and a muscle control loop, which utilizes joint torque profiles from previous steps to shape the muscle stimulation profile for the subsequent step in order to minimize the motor torque contribution required for joint angle trajectory tracking. The implementation described here incorporates stimulation of the hamstrings and quadriceps muscles, such that the hip joints are actuated by the combination of hip motors and the hamstrings, and the knee joints are actuated by the combination of knee motors and the quadriceps. In order to demonstrate efficacy, the control approach was implemented on three paraplegic subjects with motor complete spinal cord injuries ranging from levels T6 to T10. Experimental data indicates that the cooperative control system provided consistent and repeatable gait motions and reduced the torque and power output required from the hip and knee motors of the exoskeleton compared to walking without FES.

  1. Molecular epidemiology and clinical spectrum of hereditary spastic paraplegia in the Japanese population based on comprehensive mutational analyses.

    PubMed

    Ishiura, Hiroyuki; Takahashi, Yuji; Hayashi, Toshihiro; Saito, Kayoko; Furuya, Hirokazu; Watanabe, Mitsunori; Murata, Miho; Suzuki, Mikiya; Sugiura, Akira; Sawai, Setsu; Shibuya, Kazumoto; Ueda, Naohisa; Ichikawa, Yaeko; Kanazawa, Ichiro; Goto, Jun; Tsuji, Shoji

    2014-03-01

    Hereditary spastic paraplegia (HSP) is one of the most genetically heterogeneous neurodegenerative disorders characterized by progressive spasticity and pyramidal weakness of lower limbs. Because >30 causative genes have been identified, screening of multiple genes is required for establishing molecular diagnosis of individual patients with HSP. To elucidate molecular epidemiology of HSP in the Japanese population, we have conducted mutational analyses of 16 causative genes of HSP (L1CAM, PLP1, ATL1, SPAST, CYP7B1, NIPA1, SPG7, KIAA0196, KIF5A, HSPD1, BSCL2, SPG11, SPG20, SPG21, REEP1 and ZFYVE27) using resequencing microarrays, array-based comparative genomic hybridization and Sanger sequencing. The mutational analysis of 129 Japanese patients revealed 49 mutations in 46 patients, 32 of which were novel. Molecular diagnosis was accomplished for 67.3% (33/49) of autosomal dominant HSP patients. Even among sporadic HSP patients, mutations were identified in 11.1% (7/63) of them. The present study elucidated the molecular epidemiology of HSP in the Japanese population and further broadened the mutational and clinical spectra of HSP. PMID:24451228

  2. CYP2U1 mutations in two Iranian patients with activity induced dystonia, motor regression and spastic paraplegia

    PubMed Central

    Kariminejad, A.; Schöls, L.; Schüle, R.; Tonekaboni, S.H.; Abolhassani, A.; Fadaee, M.; Rosti, R.O.; Gleeson, J.G.

    2016-01-01

    Hereditary spastic paraplegia (HSP) is a heterogeneous condition characterized by progressive spasticity and weakness in the lower limbs. It is divided into two major groups, complicated and uncomplicated, based on the presence of additional features such as intellectual disability, ataxia, seizures, peripheral neuropathy and visual problems. SPG56 is an autosomal recessive form of HSP with complicated and uncomplicated manifestations, complicated being more common. CYP2U1 gene mutations have been identified as responsible for SPG56. Intellectual disability, dystonia, subclinical sensory motor neuropathy, pigmentary degenerative maculopathy, thin corpus callosum and periventricular white-matter hyperintensities were additional features noted in previous cases of SPG56. Here we identified two novel mutations in CYP2U1 in two unrelated patients by whole exome sequencing. Both patients had complicated HSP with activity-induced dystonia, suggesting dystonia as an additional finding in SPG56. Two out of 14 previously reported patients had dystonia, and the addition of our patients suggests dystonia in a quarter of SPG56 patients. Developmental regression has not been reported in SPG56 patients so far but both of our patients developed motor regression in infancy. PMID:27292318

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

    PubMed

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

    2015-09-11

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

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

    PubMed

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

    2011-06-10

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

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

    PubMed

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

    2014-08-01

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

  6. Clinical exome sequencing for cerebellar ataxia and spastic paraplegia uncovers novel gene–disease associations and unanticipated rare disorders

    PubMed Central

    van de Warrenburg, Bart P; Schouten, Meyke I; de Bot, Susanne T; Vermeer, Sascha; Meijer, Rowdy; Pennings, Maartje; Gilissen, Christian; Willemsen, Michèl AAP; Scheffer, Hans; Kamsteeg, Erik-Jan

    2016-01-01

    Cerebellar ataxia (CA) and hereditary spastic paraplegia (HSP) are two of the most prevalent motor disorders with extensive locus and allelic heterogeneity. We implemented clinical exome sequencing, followed by filtering data for a ‘movement disorders' gene panel, as a generic test to increase variant detection in 76 patients with these disorders. Segregation analysis or phenotypic re-evaluation was utilized to substantiate findings. Disease-causing variants were identified in 9 of 28 CA patients, and 8 of 48 HSP patients. In addition, possibly disease-causing variants were identified in 1 and 8 of the remaining CA and HSP patients, respectively. In 10 patients with CA, the total disease-causing or possibly disease-causing variants were detected in 8 different genes, whereas 16 HSP patients had such variants in 12 different genes. In the majority of cases, the identified variants were compatible with the patient phenotype. Interestingly, in some patients variants were identified in genes hitherto related to other movement disorders, such as TH variants in two siblings with HSP. In addition, rare disorders were uncovered, for example, a second case of HSP caused by a VCP variant. For some patients, exome sequencing results had implications for treatment, exemplified by the favorable L-DOPA treatment in a patient with HSP due to ATP13A2 variants (Parkinson type 9). Thus, clinical exome sequencing in this cohort of CA and HSP patients suggests broadening of disease spectra, revealed novel gene–disease associations, and uncovered unanticipated rare disorders. In addition, clinical exome sequencing results have shown their value in guiding practical patient management. PMID:27165006

  7. Autosomal dominant familial spastic paraplegia: reduction of the FSP1 candidate region on chromosome 14q to 7 cM and locus heterogeneity.

    PubMed Central

    Gispert, S; Santos, N; Damen, R; Voit, T; Schulz, J; Klockgether, T; Orozco, G; Kreuz, F; Weissenbach, J; Auburger, G

    1995-01-01

    Three large pedigrees of German descent with autosomal dominant "pure" familial spastic paraplegia (FSP) were characterized clinically and genetically. Haplotype and linkage analyses, with microsatellites covering the FSP region on chromosome 14q (locus FSP1), were performed. In pedigree W, we found a haplotype that cosegregates with the disease and observed three crossing-over events, reducing the FSP1 candidate region to 7 cM; in addition, the observation of apparent anticipation in this family suggests a trinucleotide repeat expansion as the mutation. In pedigrees D and S, the gene locus could be excluded from the whole FSP1 region, confirming the locus heterogeneity of autosomal dominant FSP. PMID:7825576

  8. Palmo-Plantar hyperkeratosis, intellectual disability, and spastic paraplegia in two maternal half brothers: further evidence for an X-linked inheritance.

    PubMed

    Isidor, Bertrand; Lefebvre, Tiphaine; Barbarot, Sébastien; Perrier, Julie; Mercier, Sandra; Péréon, Yann; Le Caignec, Cédric; David, Albert

    2013-06-01

    In 1983, Fitzsimmons et al. reported four brothers with an unrecognized disorder characterized by intellectual disability, spastic paraplegia, and palmo-plantar hyperkeratosis (OMIM 309500). In this report, we describe a family in which two males, maternal half-brothers, had learning disabilities. Both patients also showed spasticity in the lower limbs and palmo-plantar hyperkeratosis. The mother of the affected boys had learning difficulties but did not show any dermatological symptoms. This report confirms that the association of features reported by Fitzsimmons et al. is a distinct entity and further suggests an X-linked mode of inheritance.

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

    PubMed

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

    2013-02-01

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

  10. A novel homozygous p.R1105X mutation of the AP4E1 gene in twins with hereditary spastic paraplegia and mycobacterial disease.

    PubMed

    Kong, Xiao-Fei; Bousfiha, Aziz; Rouissi, Abdelfettah; Itan, Yuval; Abhyankar, Avinash; Bryant, Vanessa; Okada, Satoshi; Ailal, Fatima; Bustamante, Jacinta; Casanova, Jean-Laurent; Hirst, Jennifer; Boisson-Dupuis, Stéphanie

    2013-01-01

    We report identical twins with intellectual disability, progressive spastic paraplegia and short stature, born to a consanguineous family. Intriguingly, both children presented with lymphadenitis caused by the live Bacillus Calmette-Guérin (BCG) vaccine. Two syndromes - hereditary spastic paraplegia (HSP) and mycobacterial disease - thus occurred simultaneously. Whole-exome sequencing (WES) revealed a homozygous nonsense mutation (p.R1105X) of the AP4E1 gene, which was confirmed by Sanger sequencing. The p.R1105X mutation has no effect on AP4E1 mRNA levels, but results in lower levels of AP-4ε protein and of the other components of the AP-4 complex, as shown by western blotting, immunoprecipitation and immunofluorescence. Thus, the C-terminal part of the AP-4ε subunit plays an important role in maintaining the integrity of the AP-4 complex. No abnormalities of the IL-12/IFN-γ axis or oxidative burst pathways were identified. In conclusion, we identified twins with autosomal recessive AP-4 deficiency associated with HSP and mycobacterial disease, suggesting that AP-4 may play important role in the neurological and immunological systems. PMID:23472171

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

    PubMed

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

    2016-06-01

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

  12. 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

  13. Mechanism of impaired microtubule-dependent peroxisome trafficking and oxidative stress in SPAST-mutated cells from patients with Hereditary Spastic Paraplegia

    PubMed Central

    Wali, Gautam; Sutharsan, Ratneswary; Fan, Yongjun; Stewart, Romal; Tello Velasquez, Johana; Sue, Carolyn M; Crane, Denis I.; Mackay-Sim, Alan

    2016-01-01

    Hereditary spastic paraplegia (HSP) is an inherited neurological condition that leads to progressive spasticity and gait abnormalities. Adult-onset HSP is most commonly caused by mutations in SPAST, which encodes spastin a microtubule severing protein. In olfactory stem cell lines derived from patients carrying different SPAST mutations, we investigated microtubule-dependent peroxisome movement with time-lapse imaging and automated image analysis. The average speed of peroxisomes in patient-cells was slower, with fewer fast moving peroxisomes than in cells from healthy controls. This was not because of impairment of peroxisome-microtubule interactions because the time-dependent saltatory dynamics of movement of individual peroxisomes was unaffected in patient-cells. Our observations indicate that average peroxisome speeds are less in patient-cells because of the lower probability of individual peroxisome interactions with the reduced numbers of stable microtubules: peroxisome speeds in patient cells are restored by epothilone D, a tubulin-binding drug that increases the number of stable microtubules to control levels. Patient-cells were under increased oxidative stress and were more sensitive than control-cells to hydrogen peroxide, which is primarily metabolised by peroxisomal catalase. Epothilone D also ameliorated patient-cell sensitivity to hydrogen-peroxide. Our findings suggest a mechanism for neurodegeneration whereby SPAST mutations indirectly lead to impaired peroxisome transport and oxidative stress. PMID:27229699

  14. An autopsy case of adult-onset hereditary spastic paraplegia type 2 with a novel mutation in exon 7 of the proteolipid protein 1 gene.

    PubMed

    Suzuki, Satoshi O; Iwaki, Toru; Arakawa, Kenji; Furuya, Hirokazu; Fujii, Naoki; Iwaki, Akiko

    2011-12-01

    We report an autopsy case of rare adult-onset spastic paraplegia type 2 (SPG2) with a novel missense mutation in exon 7 of the proteolipid protein 1 gene (PLP1). The patient was a 67-year-old man whose elder brother had died of a similar disease with onset in his 40s. Thirty-three years before death at the age of 35, he noticed difficulty in walking. He gradually became abasic over a period of 6 years. He also developed progressive dementia and eventually became bed-ridden by 28 years after onset. At autopsy, gross inspection revealed diffuse, moderate atrophy of the cerebrum with a dilated ventricular system and softening of the white matter throughout the central nervous system (CNS). Histopathologically, the CNS showed widespread myelin pallor in the white matter. By contrast, the gray matter and peripheral nerves were well preserved. Some white matter tracts, including the corticospinal tracts, were preferentially affected, and severe axonal degeneration was observed in these tracts. Genetic analysis revealed a novel mutation, p.Tyr263Cys, in exon 7 of PLP1. This case represents an adult-onset SPG2 patient with one of the oldest ages of onset reported to date. The late onset and long clinical course suggest that this novel mutation does not affect the maturation of oligodendrocytes, but is related to insufficient maintenance of myelin.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

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

    PubMed

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

    2010-10-01

    Hereditary spastic paraplegia (HSP) with thin corpus callosum (TCC) and mental impairment is a frequent subtype of complicated HSP, often inherited as an autosomal recessive (AR) trait. It is clear from molecular genetic analyses that there are several underlying causes of this syndrome, with at least six genetic loci identified to date. However, SPG11 and SPG15 are the two major genes for this entity. To map the responsible gene in a large AR-HSP-TCC family of Tunisian origin, we investigated a consanguineous family with a diagnosis of AR-HSP-TCC excluded for linkage to the SPG7, SPG11, SPG15, SPG18, SPG21, and SPG32 loci. A genome-wide scan was undertaken using 6,090 SNP markers covering all chromosomes. The phenotypic presentation in five patients was suggestive of a complex HSP that associated an early-onset spastic paraplegia with mild handicap, mental deterioration, congenital cataract, cerebellar signs, and TCC. The genome-wide search identified a single candidate region on chromosome 9, exceeding the LOD score threshold of +3. Fine mapping using additional markers narrowed the candidate region to a 45.1-Mb interval (15.4 cM). Mutations in three candidate genes were excluded. The mapping of a novel AR-HSP-TCC locus further demonstrates the extensive genetic heterogeneity of this condition. We propose that testing for this locus should be performed, after exclusion of mutations in SPG11 and SPG15 genes, in AR-HSP-TCC families, especially when cerebellar ataxia and cataract are present.

  19. Genetics Home Reference: spastic paraplegia type 15

    MedlinePlus

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

  20. Genetics Home Reference: spastic paraplegia type 31

    MedlinePlus

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

  1. 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 ...

  2. [Unconventional treatment procedures of the bladder in paraplegia and myelomeningocele].

    PubMed

    Sievert, K-D; Kessler, T M; Amend, B; Kiss, G; Pannek, J

    2012-12-01

    The established treatment of neurogenic lower urinary tract dysfunction (NLUTD) in patients with spinal cord injury (SCI) or meningomyelocele (MMC) is mainly conservative and is aimed at the lower urinary tract. For example, oral antimuscarinic medication is the standard treatment of neurogenic detrusor overactivity. Recently, however, treatment aiming directly or indirectly at the innervation of the urinary tract has gained increasing attention. Current evidence does not justify the use of nerve rerouting but the existing preliminary data are more promising for MMC patients than for those with SCI. Sacral neuromodulation is already a therapeutic option for incomplete SCI patients. Initial data from a pilot study indicate that in patients with complete SCI implementation in the spinal shock phase may prevent the development of NLUTD. Licensing of onabotulinum toxin A (Botox®) facilitated its clinical use for treating NLUTD but it is limited to the indication of neurogenic detrusor overactivity incontinence with a dosage of 200 IU. The mentioned unconventional treatments, although discussed controversially, are promising future treatment options for NLUTD. PMID:23160608

  3. Spinal cord infarction: a rare cause of paraplegia

    PubMed Central

    Patel, Sonali; Naidoo, Khimara; Thomas, Peter

    2014-01-01

    Spinal cord infarction is rare and represents a diagnostic challenge for many physicians. There are few reported cases worldwide with a prevalence of 1.2% of all strokes. Circulation to the spinal cord is supplied by a rich anastomosis. The anterior spinal artery supplies the anterior two thirds of the spinal cord and infarction to this area is marked by paralysis, spinothalamic sensory deficit and loss of sphincter control depending on where the lesion is. Treatment of spinal cord infarction focuses on rehabilitation with diverse outcomes. This report presents a case of acute spinal cord infarction with acquisition of MRI to aid diagnosis. PMID:24966260

  4. [Spinal sonography of a newborn infant with postpartal paraplegia].

    PubMed

    Sauter, R; Klemm, T

    1988-01-01

    Cranial ultrasonography is a well established diagnostic procedure. In contrast ultrasonography of the spine and the spinal cord is less frequently used. It is indicated in infants with spinal dysraphism and may help to diagnose patients with meningomyelocele, spinal lipoma or cord tethering. We present a newborn with parplectic symptoms as a result of an epidural hematoma, which could be demonstrated exclusively by ultrasonography. We want to stress that spinal ultrasonography is a method of high clinical value.

  5. Spinal cord infarction: a rare cause of paraplegia.

    PubMed

    Patel, Sonali; Naidoo, Khimara; Thomas, Peter

    2014-06-25

    Spinal cord infarction is rare and represents a diagnostic challenge for many physicians. There are few reported cases worldwide with a prevalence of 1.2% of all strokes. Circulation to the spinal cord is supplied by a rich anastomosis. The anterior spinal artery supplies the anterior two thirds of the spinal cord and infarction to this area is marked by paralysis, spinothalamic sensory deficit and loss of sphincter control depending on where the lesion is. Treatment of spinal cord infarction focuses on rehabilitation with diverse outcomes. This report presents a case of acute spinal cord infarction with acquisition of MRI to aid diagnosis.

  6. [Scuba diving as a rehabilitation approach in paraplegia].

    PubMed

    Novak, H F; Ladurner, G

    1999-08-01

    In a group of nine paraplegics a significant increase of pulmonary vital capacity could be shown after participating in a two weeks Scuba (self containing underwater breathing apparatus) diving training. During dives and for a certain time afterwards, a satisfyingly sensed reduction of painful muscle spasms occurred. A comparable group of sailing paraplegics did not show any significant changes within the same time. Because of strict ability criteria combined with an enormous effort of care to meet all security precautions this approach to neurorehabilitation can be offered to a limited number of patients only.

  7. Genetics Home Reference: spastic paraplegia type 3A

    MedlinePlus

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

  8. [Squamous cell carcinoma of the bladder in a patient with HIV and paraplegia].

    PubMed

    Bartel, P; Göcking, K; Janzen, J; Pannek, J

    2013-09-01

    In patients with spinal cord injury (SCI) the rate of squamous cell carcinomas (SCC) among bladder tumors is increased compared to the general population. An increased life expectancy is achieved by modern HIV treatment so that more AIDS-unrelated malignomas, e.g. bladder tumors, occur in these patients. Therefore, the risk for SCC in this group of patients is increased in patients with SCI and HIV but the combination of these two diseases is rare. We report the first case of SCC in a patient with SCI and HIV. Initial symptoms of bladder tumors in patients with SCI are often unspecific; therefore, in cases with new onset hematuria, recurrent urinary tract infections and changes in bladder function, cystoscopy and computed tomography (CT) scanning should be considered. PMID:23949540

  9. Cognitive Impairment Involving Social Cognition in SPG4 Hereditary Spastic Paraplegia

    PubMed Central

    Chamard, Ludivine; Ferreira, Sabrina; Pijoff, Alexa; Silvestre, Manon; Berger, Eric

    2016-01-01

    Objectives. To describe cognitive assessment including social cognition in SPG4 patients. Methods. We reported a series of nine patients with SPG4 mutation with an extensive neuropsychological examination including social cognition assessment. Results. None of our patients presented with mental retardation or dementia. All presented with mild cognitive impairment with a high frequency of attention deficit (100%), executive disorders (89%), and social cognition impairment (78%). An asymptomatic patient for motor skills presented with the same cognitive profile. No correlation was found in this small sample between cognitive impairment and motor impairment, age at disease onset, or disease duration. Conclusions. SPG4 phenotypes share some cognitive features of frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Cognitive disorders including executive disorders and social cognition impairment are frequent in SPG4 patients and might sometimes occur before motor disorders. Therefore, cognitive functions including social cognition should be systematically assessed in order to improve the clinical management of this population.

  10. Corticospinal reorganization after locomotor training in a person with motor incomplete paraplegia.

    PubMed

    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.

  11. An implantable neuroprosthesis for standing and walking in paraplegia: 5-year patient follow-up.

    PubMed

    Guiraud, David; Stieglitz, Thomas; Koch, Klaus Peter; Divoux, Jean-Louis; Rabischong, Pierre

    2006-12-01

    We present the results of a 5-year patient follow-up after implantation of an original neuroprosthesis. The system is able to stimulate both epimysial and neural electrodes in such a way that the complete flexor-extensor chain of the lower limb can be activated without using the withdrawal reflex. We demonstrate that standing and assisted walking are possible, and the results have remained stable for 5 years. Nevertheless, some problems were noted, particularly regarding the muscle response on the epimysial channels. Analysis of the electrical behaviour and thresholds indicated that the surgical phase is crucial because of the sensitivity of the functional responses to electrode placement. Neural stimulation proved to be more efficient and more stable over time. This mode requires less energy and provides more selective stimulation. This FES system can be improved to enable balanced standing and less fatiguing gait, but this will require feedback on event detection to trigger transitions between stimulation sequences, as well as feedback to the patient about the state of his lower limbs.

  12. An implantable neuroprosthesis for standing and walking in paraplegia: 5-year patient follow-up

    NASA Astrophysics Data System (ADS)

    Guiraud, David; Stieglitz, Thomas; Koch, Klaus Peter; Divoux, Jean-Louis; Rabischong, Pierre

    2006-12-01

    We present the results of a 5-year patient follow-up after implantation of an original neuroprosthesis. The system is able to stimulate both epimysial and neural electrodes in such a way that the complete flexor-extensor chain of the lower limb can be activated without using the withdrawal reflex. We demonstrate that standing and assisted walking are possible, and the results have remained stable for 5 years. Nevertheless, some problems were noted, particularly regarding the muscle response on the epimysial channels. Analysis of the electrical behaviour and thresholds indicated that the surgical phase is crucial because of the sensitivity of the functional responses to electrode placement. Neural stimulation proved to be more efficient and more stable over time. This mode requires less energy and provides more selective stimulation. This FES system can be improved to enable balanced standing and less fatiguing gait, but this will require feedback on event detection to trigger transitions between stimulation sequences, as well as feedback to the patient about the state of his lower limbs.

  13. 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.

  14. 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.

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

    PubMed

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

    2014-06-01

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

  16. Performance evaluation of a lower limb exoskeleton for stair ascent and descent with paraplegia.

    PubMed

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

    2012-01-01

    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

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

    PubMed Central

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

    1986-01-01

    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. Images PMID:3491180

  18. Cognitive Impairment Involving Social Cognition in SPG4 Hereditary Spastic Paraplegia

    PubMed Central

    Chamard, Ludivine; Ferreira, Sabrina; Pijoff, Alexa; Silvestre, Manon; Berger, Eric

    2016-01-01

    Objectives. To describe cognitive assessment including social cognition in SPG4 patients. Methods. We reported a series of nine patients with SPG4 mutation with an extensive neuropsychological examination including social cognition assessment. Results. None of our patients presented with mental retardation or dementia. All presented with mild cognitive impairment with a high frequency of attention deficit (100%), executive disorders (89%), and social cognition impairment (78%). An asymptomatic patient for motor skills presented with the same cognitive profile. No correlation was found in this small sample between cognitive impairment and motor impairment, age at disease onset, or disease duration. Conclusions. SPG4 phenotypes share some cognitive features of frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Cognitive disorders including executive disorders and social cognition impairment are frequent in SPG4 patients and might sometimes occur before motor disorders. Therefore, cognitive functions including social cognition should be systematically assessed in order to improve the clinical management of this population. PMID:27688599

  19. An implantable neuroprosthesis for standing and walking in paraplegia: 5-year patient follow-up.

    PubMed

    Guiraud, David; Stieglitz, Thomas; Koch, Klaus Peter; Divoux, Jean-Louis; Rabischong, Pierre

    2006-12-01

    We present the results of a 5-year patient follow-up after implantation of an original neuroprosthesis. The system is able to stimulate both epimysial and neural electrodes in such a way that the complete flexor-extensor chain of the lower limb can be activated without using the withdrawal reflex. We demonstrate that standing and assisted walking are possible, and the results have remained stable for 5 years. Nevertheless, some problems were noted, particularly regarding the muscle response on the epimysial channels. Analysis of the electrical behaviour and thresholds indicated that the surgical phase is crucial because of the sensitivity of the functional responses to electrode placement. Neural stimulation proved to be more efficient and more stable over time. This mode requires less energy and provides more selective stimulation. This FES system can be improved to enable balanced standing and less fatiguing gait, but this will require feedback on event detection to trigger transitions between stimulation sequences, as well as feedback to the patient about the state of his lower limbs. PMID:17124330

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

    PubMed Central

    Ganesh, Shankar; Mishra, Chittaranjan

    2016-01-01

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

  1. Treadmill step training-induced adaptive muscular plasticity in a chronic paraplegia model.

    PubMed

    Ilha, Jocemar; da Cunha, Núbia B; Jaeger, Mariane; de Souza, Daniela F; Nascimento, Patrícia S do; Marcuzzo, Simone; Figueiró, Micheli; Gottfried, Carmem; Achaval, Matilde

    2011-04-01

    The purpose of this study was to provide evidence that treadmill step training is capable of attenuating muscle atrophy and may regulate brain derived neurotrophic factor (BDNF) in soleus muscle after complete spinal cord transection (SCT) at T8-T9 in rats. Five days after SCT, spinal animals started a 9-week step-training program on a treadmill with partial body weight support and manual step help. The muscular trophism was studied by analyzing muscle weight and myofiber cross-sectional area of the soleus, while Western blot analysis was used to detect BDNF expression in the same muscle. Step training, initiated immediately after SCT in rats, may partially impede/revert muscular atrophy in chronic paralyzed soleus muscle. Moreover, treadmill step training promoted upregulation of the BDNF in soleus muscle, which was positively correlated with muscle weight and myofiber cross-sectional size. These findings have important implications for the comprehension of the neurobiological substrate that promotes exercise-induced effects on paralyzed skeletal muscle and suggests treadmill training is a viable therapeutic approach in spinal cord injuries.

  2. The Presynaptic Microtubule Cytoskeleton in Physiological and Pathological Conditions: Lessons from Drosophila Fragile X Syndrome and Hereditary Spastic Paraplegias.

    PubMed

    Bodaleo, Felipe J; Gonzalez-Billault, Christian

    2016-01-01

    The capacity of the nervous system to generate neuronal networks relies on the establishment and maintenance of synaptic contacts. Synapses are composed of functionally different presynaptic and postsynaptic compartments. An appropriate synaptic architecture is required to provide the structural basis that supports synaptic transmission, a process involving changes in cytoskeletal dynamics. Actin microfilaments are the main cytoskeletal components present at both presynaptic and postsynaptic terminals in glutamatergic synapses. However, in the last few years it has been demonstrated that microtubules (MTs) transiently invade dendritic spines, promoting their maturation. Nevertheless, the presence and functions of MTs at the presynaptic site are still a matter of debate. Early electron microscopy (EM) studies revealed that MTs are present in the presynaptic terminals of the central nervous system (CNS) where they interact with synaptic vesicles (SVs) and reach the active zone. These observations have been reproduced by several EM protocols; however, there is empirical heterogeneity in detecting presynaptic MTs, since they appear to be both labile and unstable. Moreover, increasing evidence derived from studies in the fruit fly neuromuscular junction proposes different roles for MTs in regulating presynaptic function in physiological and pathological conditions. In this review, we summarize the main findings that support the presence and roles of MTs at presynaptic terminals, integrating descriptive and biochemical analyses, and studies performed in invertebrate genetic models. PMID:27504085

  3. Experiencing Functional Electrical Stimulation Roots on Education, and Clinical Developments in Paraplegia and Tetraplegia With Technological Innovation.

    PubMed

    Varoto, Renato; Cliquet, Alberto

    2015-10-01

    Cybernetics-based concepts can allow for complete independence for paralyzed individuals, including sensory motor recovery. Spinal cord injuries are responsible for a huge stress on health and a financial burden to society. This article focuses on novel procedures such as functional diagnosis for paraplegics and tetraplegics, cybertherapies toward lessening comorbidities such as cardiovascular diseases, osteoporosis, etc., and the production of new technology for upper and lower limb control. Functional electrical stimulation reflects a unique opportunity for bipedal gait to be achieved by paraplegics and tetraplegics. Education and training of undergraduates and postgraduates in engineering and life sciences have also been a major aim of this work. PMID:26437800

  4. Experiencing Functional Electrical Stimulation Roots on Education, and Clinical Developments in Paraplegia and Tetraplegia With Technological Innovation.

    PubMed

    Varoto, Renato; Cliquet, Alberto

    2015-10-01

    Cybernetics-based concepts can allow for complete independence for paralyzed individuals, including sensory motor recovery. Spinal cord injuries are responsible for a huge stress on health and a financial burden to society. This article focuses on novel procedures such as functional diagnosis for paraplegics and tetraplegics, cybertherapies toward lessening comorbidities such as cardiovascular diseases, osteoporosis, etc., and the production of new technology for upper and lower limb control. Functional electrical stimulation reflects a unique opportunity for bipedal gait to be achieved by paraplegics and tetraplegics. Education and training of undergraduates and postgraduates in engineering and life sciences have also been a major aim of this work.

  5. Preliminary assessment of variable geometry stair ascent and descent with a powered lower limb orthosis for individuals with paraplegia.

    PubMed

    Ekelem, Andrew; Murray, Spencer; Goldfarb, Michael

    2015-08-01

    This paper describes a controller for a lower-limb exoskeleton that enables variable-geometry stair ascent and descent for persons with lower limb paralysis. The controller was evaluated on a subject with T10 complete spinal cord injury (SCI) on two staircases, one with a riser height and tread depth of 18.4 × 27.9 cm (7.25 × 11 in) and the other 17.8 × 29.8 cm (7 × 11.75 in). The controller enabled ascent and descent of both staircases without explicit tuning for each, and with an average step rate of 12.9 step/min during ascent and 14.6 step/min during descent. PMID:26737336

  6. 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…

  7. Physical therapy in the management of pelvic floor muscles hypertonia in a woman with hereditary spastic paraplegia.

    PubMed

    Ribeiro, Aline Moreira; Ferreira, Cristine Homsi Jorge; Cristine Lemes Mateus-Vasconcelos, Elaine; Moroni, Rafael Mendes; Brito, Luciane Maria Oliveira; Brito, Luiz Gustavo Oliveira

    2014-01-01

    Background. Pelvic floor (PF) hypertonic disorders are a group of conditions that present with muscular hypertonia or spasticity, resulting in a diminished capacity to isolate, contract, and relax the PF. Their presentation includes voiding and sexual dysfunctions, pelvic pain, and constipation. Various factors are associated, such as complicated vaginal birth, muscular injury, scar tissue formation, and neuropathies. Study Design. The case of a single patient will be presented, together with the management strategies employed. Case Description. A woman with hereditary spastic paraparesis and a history of muscle spasticity and urinary and fecal complaints since childhood. She presented to this institution seeking treatment for pelvic pain, pain during intercourse, constipation, and micturition problems. A physical therapy protocol was developed, with the trial of several treatment modalities. Outcome. After some failed attempts, perineal and pelvic floor stretching proved to be very efficacious therapies for this patient's complaint, leading to improved pain during intercourse, constipation, pelvic pain, and urinary stream. Discussion. PF spasticity can lead to severe disability and interfere with daily basic functions, such as micturition and evacuation. Physical therapy plays an essential role in the management of these patients and can lead to significant improvement in quality of life.

  8. Physical Therapy in the Management of Pelvic Floor Muscles Hypertonia in a Woman with Hereditary Spastic Paraplegia

    PubMed Central

    Ribeiro, Aline Moreira; Ferreira, Cristine Homsi Jorge; Cristine Lemes Mateus-Vasconcelos, Elaine; Moroni, Rafael Mendes; Brito, Luciane Maria Oliveira; Brito, Luiz Gustavo Oliveira

    2014-01-01

    Background. Pelvic floor (PF) hypertonic disorders are a group of conditions that present with muscular hypertonia or spasticity, resulting in a diminished capacity to isolate, contract, and relax the PF. Their presentation includes voiding and sexual dysfunctions, pelvic pain, and constipation. Various factors are associated, such as complicated vaginal birth, muscular injury, scar tissue formation, and neuropathies. Study Design. The case of a single patient will be presented, together with the management strategies employed. Case Description. A woman with hereditary spastic paraparesis and a history of muscle spasticity and urinary and fecal complaints since childhood. She presented to this institution seeking treatment for pelvic pain, pain during intercourse, constipation, and micturition problems. A physical therapy protocol was developed, with the trial of several treatment modalities. Outcome. After some failed attempts, perineal and pelvic floor stretching proved to be very efficacious therapies for this patient's complaint, leading to improved pain during intercourse, constipation, pelvic pain, and urinary stream. Discussion. PF spasticity can lead to severe disability and interfere with daily basic functions, such as micturition and evacuation. Physical therapy plays an essential role in the management of these patients and can lead to significant improvement in quality of life. PMID:25478261

  9. The Presynaptic Microtubule Cytoskeleton in Physiological and Pathological Conditions: Lessons from Drosophila Fragile X Syndrome and Hereditary Spastic Paraplegias

    PubMed Central

    Bodaleo, Felipe J.; Gonzalez-Billault, Christian

    2016-01-01

    The capacity of the nervous system to generate neuronal networks relies on the establishment and maintenance of synaptic contacts. Synapses are composed of functionally different presynaptic and postsynaptic compartments. An appropriate synaptic architecture is required to provide the structural basis that supports synaptic transmission, a process involving changes in cytoskeletal dynamics. Actin microfilaments are the main cytoskeletal components present at both presynaptic and postsynaptic terminals in glutamatergic synapses. However, in the last few years it has been demonstrated that microtubules (MTs) transiently invade dendritic spines, promoting their maturation. Nevertheless, the presence and functions of MTs at the presynaptic site are still a matter of debate. Early electron microscopy (EM) studies revealed that MTs are present in the presynaptic terminals of the central nervous system (CNS) where they interact with synaptic vesicles (SVs) and reach the active zone. These observations have been reproduced by several EM protocols; however, there is empirical heterogeneity in detecting presynaptic MTs, since they appear to be both labile and unstable. Moreover, increasing evidence derived from studies in the fruit fly neuromuscular junction proposes different roles for MTs in regulating presynaptic function in physiological and pathological conditions. In this review, we summarize the main findings that support the presence and roles of MTs at presynaptic terminals, integrating descriptive and biochemical analyses, and studies performed in invertebrate genetic models. PMID:27504085

  10. Elongation of the active anterior wall of the uro-genital pelvic diaphragm, a late unusual complication of paraplegia.

    PubMed

    Jurascheck, F; Dollfus, P; Jacob-Chia, D

    1980-08-01

    The situation of the usual bladder, prostate, membranous urethra channel, can vary, according to the morphology of the perineum which can be overstretched. A case of a young man with a T10 complete upper motor neurone lesion is presented. The normal anterior angulation at the prostate and membranous urethra junction was reduced anteriorly and pushed backwards, thus causing an added indirect factor of dysuria. The mechanism is discussed in comparison with other such late, but often overlooked consequences of alterations of the pelvic floor during micturition. PMID:7422341

  11. 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. PMID:25883834

  12. [X-linked hereditary spastic paraplegia due to mutation in the L1CAM gene: three cases reports of CRASH syndrome].

    PubMed

    Muñoz, Abián; Cabrera-López, José C; Santana-Rodríguez, Alfredo; Toledo-Bravo de Laguna, Laura; Santana-Artiles, Alexandre; Sebastián-García, Irma

    2016-03-01

    Introduccion. La paraplejia espastica hereditaria (PEH) representa un conjunto de cuadros clinicos neurodegenerativos que se caracteriza por perdida progresiva de fuerza en los miembros inferiores con espasticidad. Esto se debe a una lesion axonal en los haces corticoespinales. La de tipo 1, conocida como SPG1, es la forma mas comun de PEH ligada al cromosoma X. Esta se produce por una mutacion en el gen de la molecula de adhesion celular L1 (L1CAM). La SPG1 se manifiesta con el sindrome CRASH (corpus callosum hypoplasia, retardation, adducted thumbs, spasticity and hydrocephalus). Casos clinicos. Tres varones, dos hermanos y un primo (materno), con un cuadro clinico de discapacidad intelectual, paraparesia espastica, piramidalismo, dismorfias faciales y pulgares en aduccion. La neuroimagen mostro agenesia del cuerpo calloso y ventriculomegalia en los tres. Los estudios neurofisiologico y metabolico fueron normales. El estudio genetico evidencio en todos ellos una mutacion concreta en el gen L1CAM (Xq28). Conclusion. Se describen los hallazgos clinicorradiologicos de tres varones afectos de sindrome CRASH por mutacion c.516G>A en el exon 5 del gen L1CAM. Estos parecen ser los primeros casos descritos en España segun la bibliografia actual. Recomendamos sospechar este sindrome cuando se asocian paraparesia espastica, discapacidad intelectual y pulgares aductos.

  13. [Spinal epidural angiolipoma: a case report].

    PubMed

    Dufrenot, Leïla; Pelé, Eric; Cursolle, Jean-Christophe; Coindre, Jean-Michel; Lepreux, Sébastien

    2010-02-01

    Spinal epidural angiolipoma is a rare tumor revealed by a slowly progressive paraplegia. We reported a case of a 44-year-old female and point out the peculiar pattern of this lesion characterized by the prominence of the vascular component over the lipomatous component. Recognition of this entity is important because this is a benign and curable cause of paraplegia.

  14. XY sex reversal and a nonprogressive neurologic disorder: a new syndrome?

    PubMed

    Mahbubul Huq, A H; Nigro, M A

    2000-10-01

    We report a patient with a unique combination of clinical findings: XY sex reversal, spastic paraplegia, mental retardation, dysmorphism, and infantile-onset olivopontocerebellar hypoplasia. The phenotype of our patient did not coincide with any of the described forms of XY reversal syndromes, hereditary or sporadic spastic paraplegias, or congenital or infantile-onset cerebellar or olivopontocerebellar atrophies or hypoplasias. The disorder of this patient likely represents a genetic condition with pleiotropic effects on brain development and sex determination and adds further evidence for the heterogeneity of spastic paraplegia/infantile olivopontocerebellar hypoplasia syndromes and sex reversal syndromes. PMID:11068172

  15. Genetics Home Reference: infantile-onset ascending hereditary spastic paralysis

    MedlinePlus

    ... and paraplegia result from degeneration (atrophy) of motor neurons , which are specialized nerve cells in the brain ... highest amounts in the brain, particularly in motor neurons. Alsin turns on (activates) multiple proteins called GTPases ...

  16. Spinal angiolipoma manifesting with apoplexy.

    PubMed

    Ramdasi, Raghvendra Vijayrao; Avinasha, K M; Mahore, Amit; Kawale, Juhi

    2014-05-19

    We report a 58-year-old man presenting with acute paraplegia. MRI showed a haematoma within a well-defined epidural lesion at C7-D1. Intraoperatively, organised epidural haematoma surrounded by tumour tissue was found. The final histopathology report was angiolipoma. The patient had dramatic recovery. Angiolipomas should be considered in the differential diagnosis of acute paraplegia when imaging shows well-circumscribed haematoma.

  17. Neurological Complications Following Endoluminal Repair of Thoracic Aortic Disease

    SciTech Connect

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

    2007-09-15

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

  18. Comparison of neck and upper-limb muscle activities between able-bodied and paraplegic individuals during wheelchair propulsion on the ground.

    PubMed

    Kim, Sang Jin; Park, So Hyun; Lee, Chang-Ryeol

    2015-05-01

    [Purpose] This study compared the muscle activities of the neck and upper-limb muscles between able-bodied individuals and persons with paraplegia during wheelchair propulsion on the ground. [Subjects and Methods] The muscle activities of the neck and upper-limb muscles of 8 normal individuals and 8 individuals with paraplegia were analyzed during wheelchair propulsion. The activities of the latissimus dorsi, pectoralis major, anterior/posterior deltoids, triceps brachii, extensor carpi radialis, and sternocleidomastoid muscles were assessed. [Results] The paraplegic group showed significantly higher sternocleidomastoid activity than the normal group. Latissimus dorsi activity was also higher in the paraplegia group than in the normal group, but the difference was not significant. There were no significant differences in the other muscle activities between groups. [Conclusion] Paraplegic patients tend to use the sternocleidomastoid and latissimus dorsi muscles with greater degrees of activity. Therefore, physiotherapists should not overlook the treatment of these muscles for paraplegic patients who are long-term wheelchair users.

  19. Multimodal MRI-based study in patients with SPG4 mutations.

    PubMed

    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

  20. A Rare Complication of Spinal Cord Ischemia Following Endovascular Aneurysm Repair of an Infrarenal Abdominal Aortic Aneurysm with Arteriosclerosis Obliterans: Report of a Case

    PubMed Central

    Matsumoto, Takuya; Matsubara, Yutaka; Inoue, Kentaro; Aoyagi, Yukihiko; Matsuda, Daisuke; Tanaka, Shinichi; Okadome, Jun; Maehara, Yoshihiko

    2016-01-01

    We herein report a case of a rare complication of spinal cord ischemia (SCI) following endovascular aneurysm repair (EVAR). Computed tomography showed stenosis and calcification of bilateral iliac arteries and a saccular aneurysm of the terminal aorta. Paraplegia occurred soon after balloon angioplasty of iliac arteries and EVAR. Cerebrospinal fluid drainage was not performed because the patient was on dual antiplatelet drugs. The patient was treated with intravenous methylpredonisolone and naloxone; however, this did not improve his paraplegia. SCI after EVAR is extremely rare and unpredictable complication, however, physicians should be aware of SCI after EVAR in patients with atherosclerosis. PMID:27738476

  1. [Spontaneous spinal epidural hematoma during pregnancy: report of a case].

    PubMed

    Hack, I; Cademartori, M S; Mamani, R S; Beltrame, C M; Cademartori, C G

    1984-03-01

    A case of spontaneous dorso- lumbar spinal epidural hematoma during pregnancy is reported. The hematoma was removed 8 hours after the onset of paraplegia, and there was no evidence of vascular malformation. The motor deficit remained unchanged post-operatively. The etiology, clinical findings and the value of early laminectomy are discussed.

  2. 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).…

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

    PubMed

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

    1995-01-01

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

  4. 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,…

  5. Cerebrospinal fluid may mediate CNS ischemic injury

    PubMed Central

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

    2005-01-01

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

  6. Pigmentary degenerative maculopathy as prominent phenotype in an Italian SPG56/CYP2U1 family.

    PubMed

    Leonardi, Luca; Ziccardi, Lucia; Marcotulli, Christian; Rubegni, Anna; Longobardi, Antonino; Serrao, Mariano; Storti, Eugenia; Pierelli, Francesco; Tessa, Alessandra; Parisi, Vincenzo; Santorelli, Filippo M; Carlo, Casali

    2016-04-01

    SPG56 is an autosomal recessive form of hereditary spastic paraplegia (HSP) associated with mutations in CYP2U1. There is no clear documentation of visual impairment in the few reported cases of SPG56, although this form is complex on clinical ground and visual deficit are extremely frequent in complicated HSP. We report three patients in a consanguineous family harboring the novel homozygous c.1168C>T (p.R390*) in SPG56/CYP2U1, and showing a pigmentary degenerative maculopathy associated with progressive spastic paraplegia. Furthermore, we characterized precisely the ophthalmologic phenotype through indirect ophthalmoscopy, retinal optical coherence tomography and visual evoked potentials. This is the first formal report of pigmentary degenerative maculopathy associated with a CYP2U1 homozygous mutation. PMID:26914923

  7. Spinal cord infarction in giant cell arteritis associated with scalp necrosis.

    PubMed

    Mustafa, Khader N; Hadidy, Azmy; Joudeh, Anwar; Obeidat, Fatima Nouri; Abdulfattah, Khalid W

    2015-02-01

    Spinal cord infarction is extremely rare in patients with giant cell arteritis (GCA). There are only four case reports in the literature. We describe a 65-year-old man who presented with sudden paraplegia and back pain of 4-days duration with sensory loss below the umbilicus and bilateral scalp necrosis. Magnetic resonance imaging finding was consistent with dorsal spinal cord infarction. Biopsy of the temporal artery confirmed the diagnosis of GCA. The patient was treated with high dose of corticosteroids, which resulted in healing of the scalp ulcerations in 3 weeks, but the paraplegia was irreversible. To our knowledge, this is the first report of spinal cord infarction and simultaneous occurrence of bilateral scalp necrosis in a histopathologically proven GCA. Although literature about spinal cord involvement in GCA is very limited, cord infarction is associated with high mortality and therapeutic challenges since little is understood regarding the pathogenesis that leads to infarction.

  8. Scuba diving: taking the wheelchair out of wheelchair sports.

    PubMed

    Madorsky, J G; Madorsky, A G

    1988-03-01

    In the past, physicians prohibited patients with neuromuscular disease or disability from participating in scuba diving. This report highlights the opportunities that self-contained underwater breathing apparatus (scuba) affords to physically handicapped individuals, to move without assistive devices in a gravity-free environment. The experience of a person with T10 paraplegia is used to illustrate the applicability of a new system of evaluation, training, and certification for scuba diving to patients with a wide variety of disabilities, such as paraplegia, quadriplegia, amputation, cerebral palsy, and poliomyelitis. This review also discusses equipment needs, potential risks, and safety precautions. Physicians are encouraged to support those handicapped individuals who choose to explore the submerged two thirds of our planet for its recreational as well as its potential vocational opportunities.

  9. [Endovascular repair for an acute traumatic aortic transection: a case report].

    PubMed

    Sanioğlu, Soner; Sahin, Sinan; Aydoğan, Hakki; Barutça, Hakan; Eren, Ergin

    2012-03-01

    A thirty-eight-year-old male patient who suffered from 10th and 11th thoracal vertebrae fractures, paraplegia and acute traumatic aortic transection because of accidental fall was referred to our hospital. Open surgical repair carried a very high risk due to severe coexisting injuries. Transection was treated with 30x100 mm Valiant thoracic endograft, which was deployed just distal to the ostium of the left carotid artery. The patient was transferred to the neurosurgery clinic for treatment of paraplegia after an uneventful recovery. Endovascular repair of acute transection confers substantial advantages in mortality and morbidity compared to surgical repair. However, the long-term durability of thoracic endografts remains unknown. If the long-term results are as satisfactory as the promising mid-term results, this technique may become the gold standard approach for the treatment of acute transection. PMID:22792827

  10. Spinal angiolipoma in a pregnant woman presenting with acute epidural hemorrhage.

    PubMed

    Tsutsumi, Satoshi; Nonaka, Yasuomi; Abe, Yusuke; Yasumoto, Yukimasa; Ito, Masanori

    2011-06-01

    A 26-year-old woman in week 31 of pregnancy presented to the emergency room with acute onset of paraplegia. Her medical history was unremarkable. Neurological examination revealed complete paraplegia, total sensory loss below the T7 dermatome, and significant vesicorectal dysfunction. MRI revealed an intraspinal mass from T3 to T4, which was hyperintense on both T1-weighted and T2-weighted images. Blood examination found no abnormality. She underwent emergent hemilaminectomy and removal of the hematoma. Intraoperatively, unusually ectatic venous vessels were found adhered to the lower surface of the epidural clot. No concurrent vascular malformations were identified and the dura mater was intact. The histological diagnosis was angiolipoma. Postoperatively her neurological deficits showed remarkable improvement, and she gave birth to a healthy baby. Spinal angiolipoma in a pregnant woman may be complicated with acute epidural hemorrhage. Emergent surgical evacuation can be performed safely with a good functional prognosis.

  11. Cerebral folate deficiency: life-changing supplementation with folinic acid.

    PubMed

    Hansen, Flemming Juul; Blau, Nenad

    2005-04-01

    Cerebral folate deficiency is characterized by low cerebrospinal fluid (CSF) concentrations of 5-methyltetrahydrofolate and a broad spectrum of clinical signs and symptoms. A patient with progressive spasticity, gait disturbance, speech difficulties, initially diagnosed as a recessive spastic paraplegia recovered on folinic acid (15-30 mg/day) and her 5-methyltetrahydrofolate in CSF normalized. This report demonstrates the importance of CSF investigation in the diagnosis of cerebral folate deficiency and efficiency of folinic acid (5-formyltetrahydrofolate) supplementation. PMID:15781200

  12. Endovascular intervention in thoracic arterial trauma.

    PubMed

    Hoffer, Eric K

    2008-11-01

    The management of thoracic vascular injury has improved dramatically over the past two decades. The availability of multi-row detector CT has facilitated early diagnosis and incorporation of minimally invasive endograft repair for traumatic aortic injury has improved mortality and paraplegia rates. This review evaluates the available data on stent-graft repair of acute blunt traumatic aortic injury and traumatic great vessel injury with regard to safety and efficacy in comparison with conventional open surgical repair. PMID:18842261

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

    PubMed

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

    2006-07-01

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

  14. 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

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

    PubMed

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

    2013-05-01

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

  16. Mobility Outcomes Following Five Training Sessions with a Powered Exoskeleton

    PubMed Central

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

    2015-01-01

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

  17. Heliox treatment for spinal decompression sickness following air dives.

    PubMed

    Douglas, J D; Robinson, C

    1988-07-01

    Enforced delay in treatment of spinal decompression sickness following scuba diving can result in paraplegia. Poor response from initial recompression to 18 m presents the clinician with a difficult management problem. Theoretical objections have been raised to the use of He-O2 as treatment regimen. We report 3 cases that show He-O2 to be an excellent method of treatment in spinal decompression sickness after air diving.

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

    PubMed Central

    Cruz–Arámbulo, Robert; Nykamp, Stephanie

    2012-01-01

    A 9-year-old spayed female Bengal Red cat was evaluated for high-rise syndrome. The cat had paraplegia of the hind limbs, intact reflexes and pain perception, and hyperesthesia in the caudal thoracic area. Mentation, cranial nerve function, forelimb proprioceptive responses, and spinal reflexes were normal. There were no abnormalities on radiographs or computed tomography scan, but magnetic resonance imaging revealed a hyperintense intraparenchymal spinal cord lesion on T2-weighted and T2 fat saturation images. PMID:22942443

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

    PubMed

    Preussner, P R

    1991-11-01

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

  20. The surgical management and treatment of metastatic lesions in the proximal femur

    PubMed Central

    Feng, Helin; Wang, Jin; Xu, Jianfa; Chen, Wei; Zhang, Yingze

    2016-01-01

    Abstract Review current treatments of metastatic lesions in the proximal femur. We reviewed published literature related to diagnosis and surgical treatments and summarized current treatment options. Surgical management mainly consist of internal fixation, hip replacement, and percutaneous femoroplasty (PFP) which has been newly applied in clinical practice. An appropriate series of treatments is necessary for patients to avoid the occurrence of paraplegia and prolong survival time. PMID:27428183

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

    Hereditary spastic paraplegias are a clinically and genetically heterogeneous group of gait disorders. Their pathological hallmark is a length-dependent distal axonopathy of nerve fibers in the corticospinal tract. Involvement of other neurons can cause additional neurological symptoms, which define a diverse set of complex hereditary spastic paraplegias. We present two siblings who have the unusual combination of early-onset spastic paraplegia, optic atrophy, and neuropathy. Genome-wide SNP-typing, linkage analysis, and exome sequencing revealed a homozygous c.316C>T (p.R106C) variant in the Trk-fused gene (TFG) as the only plausible mutation. Biochemical characterization of the mutant protein demonstrated a defect in its ability to self-assemble into an oligomeric complex, which is critical for normal TFG function. In cell lines, TFG inhibition slows protein secretion from the endoplasmic reticulum (ER) and alters ER morphology, disrupting organization of peripheral ER tubules and causing collapse of the ER network onto the underlying microtubule cytoskeleton. The present study provides a unique link between altered ER architecture and neurodegeneration. PMID:23479643

  3. Misregulation of a DDHD Domain-containing Lipase Causes Mitochondrial Dysfunction in Yeast.

    PubMed

    Yadav, Pradeep Kumar; Rajasekharan, Ram

    2016-08-26

    The DDHD domain-containing proteins, which belong to the intracellular phospholipase A1 (iPLA1) family, have been predicted to be involved in phospholipid metabolism, lipid trafficking, membrane turnover, and signaling. Defective cardiolipin (CL), phosphatidylethanolamine, and phosphatidylglycerol remodeling cause Barth syndrome and mitochondrial dysfunction. Here, we report that Yor022c is a Ddl1 (DDHD domain-containing lipase 1) that hydrolyzes CL, phosphatidylethanolamine, and phosphatidylglycerol. Ddl1 has been implicated in the remodeling of mitochondrial phospholipids and CL degradation. Our data also suggested that the accumulation of monolysocardiolipin is deleterious to the cells. We show that Aft1 and Aft2 transcription factors antagonistically regulate the DDL1 gene. This study reveals that the misregulation of DDL1 by Aft1/2 transcription factors alters CL metabolism and causes mitochondrial dysfunction in the cells. In humans, mutations in the DDHD1 and DDHD2 genes cause specific types of hereditary spastic paraplegia (SPG28 and SPG54, respectively), and the yeast DDL1-defective strain produces similar phenotypes of hereditary spastic paraplegia (mitochondrial dysfunction and defects in lipid metabolism). Therefore, the DDL1-defective strain could be a good model system for understanding hereditary spastic paraplegia.

  4. Management of Traumatic Aortic Rupture: A 30-Year Experience

    PubMed Central

    Cardarelli, Marcelo G.; McLaughlin, Joseph S.; Downing, Stephen W.; Brown, James M.; Attar, Safuh; Griffith, Bartley P.

    2002-01-01

    Objective To present the authors’ 30-year experience with traumatic aortic rupture (TAR). Summary Background Data TAR is a highly lethal injury. Most institutions manage a small number of cases, and most surgeons receive only modest exposure during training. Methods Between 1971 and 2001, the authors operated on 219 patients with a diagnosis of TAR. Diagnosis of TAR since 1994 has been based exclusively on the use of contrast-enhanced spiral computed tomography, with angiography reserved for equivocal cases (periaortic mediastinal hematoma without aortic wall abnormalities). Patients were divided according to surgical technique. Eighty-two patients (group A) were operated on with a clamp-and-sew technique. Sixty-four patients (group B) underwent surgery with the use of a passive shunt, and 73 patients (group C) were treated using heparin-less partial cardiopulmonary bypass. Results Mortality was 18 patients for group A (21.9%), 23 patients for group B (35.9%), and 13 patients for group C (17.8%) (P = .03). Paraplegia occurred in 15 of 64 survivors in group A (23.4%), 7 of 41 survivors in group B (17%), and 0 of 60 survivors in group C (P = .0005). Aortic occlusion without lower body perfusion for longer than 30 minutes (P = .004) and surgical technique without lower body bypass support (P = .0005) were associated with paraplegia. Conclusions Surgery for TAR based on spiral computed tomography screening and diagnosis is reliable. The use of heparin-less distal cardiopulmonary bypass in the authors’ hands is safe and is associated with a reduced incidence of paraplegia. PMID:12368675

  5. 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

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

    PubMed Central

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

    2008-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2006-10-01

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

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

    PubMed Central

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

    2016-01-01

    Introduction: Diffusion tensor imaging (DTI) has been used in cervical trauma and spondylotic myelopathy, and it has been found to correlate with neural deficit and prognosticate neural recovery. Such a correlation has not been studied in Pott’s spine with paraplegia. Hence, this prospective study has been used to find correlation of DTI parameters with neural deficit in these patients. Methods: Thirty-four patients of spinal TB were enrolled and DTI was performed before the start of treatment and after six months. Fractional anisotropy (FA), Mean diffusivity (MD), and Tractography were studied. Neurological deficit was graded by the Jain and Sinha scoring. Changes in FA and MD at and below the site of lesion (SOL) were compared to above the SOL (control) using the unpaired t-test. Pre-treatment and post-treatment values were also compared using the paired t-test. Correlation of DTI parameters with neurological score was done by Pearson’s correlation. Subjective assessment of Tractography images was done. Results: Mean average FA was not significantly decreased at the SOL in patients with paraplegia as compared to control. After six months of treatment, a significant decrease (p = 0.02) in mean average FA at the SOL compared to pre-treatment was seen. Moderate positive correlation (r = 0.49) between mean average FA and neural score after six months of treatment was found. Tractography images were not consistent with severity of paraplegia. Conclusion: Unlike spondylotic myelopathy and trauma, epidural collection and its organized inflammatory tissue in Pott’s spine precludes accurate assessment of diffusion characteristics of the compressed cord. PMID:27163110

  9. [Botulinum neurotoxin type A in neurogenic detrusor overactivity: consensus paper of the Working Group Neuro-Urology of the DMGP].

    PubMed

    Böthig, R; Kaufmann, A; Bremer, J; Pannek, J; Domurath, B

    2014-04-01

    The use of botulinum neurotoxin (BoNT-A) for suppression of neurogenic detrusor overactivity was first reported in 2000. Since that time, this method has gained widespread use. A number of recommendations and consensus statements have already been published. The current practice-oriented consensus paper takes into account recent developments and the over 10-year experience of most members of the Working Group Neuro-Urology of the German-speaking Medical Society for Paraplegia (DMGP) with a focus on the use of BoNT-A in paraplegic patients and in patients with multiple sclerosis. PMID:24604016

  10. Telangiectatic osteosarcoma of the spine: a case report

    PubMed Central

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

    2008-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-11-01

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

  13. The challenge of spinal cord injury care in the developing world

    PubMed Central

    Burns, Anthony S.; O'Connell, Colleen

    2012-01-01

    Great strides have been made in reducing morbidity and mortality following spinal cord injury (SCI), and improving long-term health and community participation; however, this progress has not been uniform across the globe. This review highlights differences in global epidemiology of SCI and the ongoing challenges in meeting the needs of individuals with SCI in the developing world, including post-disaster. Significant disparities persist, with life expectancies of 2 years or less not uncommon for persons living with paraplegia in many developing countries. The international community has an important role in improving access to appropriate care following SCI worldwide. PMID:22330185

  14. [The electrical stimulation bicycle: a neuroprosthesis for the everyday use of paraplegic patients].

    PubMed

    Szecsi, J; Fiegel, M; Krafczyk, S; Straube, A; Quintern, J; Brandt, Th

    2004-06-24

    Until recently, few patients with complete paraplegia could walk or stand with the help of functional electrical stimulation (FES) of the leg muscles regularly at home. In comparison, FES cycling with an adapted tricycle is easy to put into practice because the legs remain connected to the pedals and through the use of a tricycle or stationary bicycle, the balancing problems of the patient recedes into the background. In the first German feasibility studies for paraplegic cycling, eleven completely paraplegic patients have been tested so far. The goal is to make FES cycling a daily activity in the lives of as many patients as possible.

  15. A very rare neurocutaneous disorder in 2 siblings: Sjögren-Larsson syndrome.

    PubMed

    Caglayan, Ahmet Okay; Gumus, Hakan

    2010-08-01

    Sjögren-Larsson syndrome is an autosomal-recessive hereditary disorder involving congenital ichthyosis, mental retardation, and spastic diplegia or tetraplegia. It is caused by the deficient activity of fatty aldehyde dehydrogenase. In this report, the authors describe 2 siblings with Sjögren-Larsson syndrome. Both the patients had generalized ichthyosis, and the older one had spastic paraplegia and mental retardation, and the fundus examination revealed foveal and parafoveal glistening dots. The authors report the large kinship with Sjögren-Larsson syndrome, which is a rare and most probably underdiagnosed syndrome.

  16. [State of local immunity in patients with inflammatory diseases of the spine].

    PubMed

    Shenderova, R I; Oleĭnik, V V; Iakunova, O A

    2001-01-01

    The paper presents the results of examination of spinal fluid in tuberculous spondylitis (n = 83), its sequelae (n = 58), spinal osteomyelitis (n = 25) for the levels of tuberculosis antibodies (TAb) by applying the routine enzyme immunoassay, specially adapted to this biological object, and immunoglobulins. A relationship was found between TAb detection and the rate of the process and the severity of a spinal cord lesion. Forty one patients had severe spinal cord disorders (paraplegia and deep paraparesis). To detect TAb in CF is shown to be of differential diagnostic value. There is new evidence for impaired blood-brain and immunological barriers in active tuberculosis in the spine with spinal cord compression.

  17. 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

  18. Spinal ischemia following abdominal aortic surgery.

    PubMed

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

    1975-03-01

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

  19. Conus medullaris metastasis in breast cancer: report of a case and a review of the literature.

    PubMed

    Hsu, Kao-Chih; Li, Tsung-Ying; Chu, Heng-Yi; Chen, Liang-Cheng; Chang, Shin-Tsu; Wu, Yung-Tsan

    2013-08-01

    Intramedullary spinal cord metastasis is quite rare. This report presents the case of a female patient with metastasis of the conus medullaris from breast cancer, presenting with paraplegia and sphincter dysfunction. Bladder dysfunction improved after removal of the conus mass. This report is the seventh case of conus medullaris metastasis from breast cancer and the first review of clinical outcome, survival time and other data of all these 7 cases. This study also reviewed cases of intramedullary spinal cord metastasis arising from breast cancer in regions other than the conus medullaris in the literature. Longer survival time resulted from surgery in contrast to those without surgery in the latter group.

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

    PubMed

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

    2016-04-01

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

  1. Perioperative spinal cord infarction in nonaortic surgery: report of three cases and review of the literature.

    PubMed

    Hobai, Ion A; Bittner, Edward A; Grecu, Loreta

    2008-06-01

    Paraplegia caused by a spinal cord infarction (SCI) is a devastating perioperative complication, most often associated with aortic and spine surgery. We present two other clinical scenarios in which perioperative SCI may occur. They happened during surgical procedures performed with epidural anesthesia, in the presence of several specific risk factors such as spinal stenosis, vascular disease, intraoperative hypotension, or the use of epinephrine in the local anesthetic solution. Second, SCI may occur during episodes of postoperative hypotension in patients with a history of aortic aneurysms.

  2. 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.

  3. [Pre-hospital care management of acute spinal cord injury].

    PubMed

    Hess, Thorsten; Hirschfeld, Sven; Thietje, Roland; Lönnecker, Stefan; Kerner, Thoralf; Stuhr, Markus

    2016-04-01

    Acute injury to the spine and spinal cord can occur both in isolation as also in the context of multiple injuries. Whereas a few decades ago, the cause of paraplegia was almost exclusively traumatic, the ratio of traumatic to non-traumatic causes in Germany is currently almost equivalent. In acute treatment of spinal cord injury, restoration and maintenance of vital functions, selective control of circulation parameters, and avoidance of positioning or transport-related additional damage are in the foreground. This article provides information on the guideline for emergency treatment of patients with acute injury of the spine and spinal cord in the preclinical phase. PMID:27070515

  4. Intradural Intramedullary Mixed Type Hemangioma: Optimizing the Surgical Management through Intraoperative Neurophysiological Monitoring

    PubMed Central

    Rahyussalim, Ahmad Jabir; Situmeang, Adrian; Safri, Ahmad Yanuar; Fadhly, Zulfa Indah K.

    2015-01-01

    Intradural intramedullary mixed type hemangioma is a rare histotype of primary spinal cord tumors, though it can carry a severe clinical burden leading to limb dysfunction or motor and sensory disturbances. Timely intervention with radical resection is the hallmark of treatment but achieving it is not an easy task even for experienced neurosurgeons. We herein present an exemplificative case presenting with sudden paraplegia in which total resection was achieved under intraoperative neurophysiology monitoring. A thorough discussion on the operative technique and the role of neuromonitoring in allowing a safe surgical management of primary spinal cord tumors is presented. PMID:26839729

  5. Analysis of 139 spinal cord injuries due to accidents in water sports.

    PubMed

    Steinbrück, K; Paeslack, V

    1980-04-01

    Between 1967 and 1978, a total of 2587 patients received primary treatment in the Spinal Cord Injury Centre at the University of Heidelberg. In 212 cases the paralysis was caused by sports or diving accidents. Injuries resulting from accidents in water sports totalled 139, 131(61.7 per cent) of which could be classified as actual diving accidents. These 131 cases consisted of 129 tetraplegias and only 2 paraplegias. In 5 cases, the tetraplegia resulted from high diving and in 3 cases from scuba-diving. The subjects of the analysis are causes of accidents, segmental diagnosis of neurological deficiency symptoms and prognosis.

  6. 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

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

    SciTech Connect

    Fransen, E.; Vits, L.; Van Camp, G.; Willems, P.J.

    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.

  8. Pyogenic spinal osteomyelitis: a review of 61 cases.

    PubMed

    Silverthorn, K G; Gillespie, W J

    1986-02-12

    The presentation and outcome of 61 cases of nontuberculous spinal osteomyelitis were reviewed. Although the commonest presentation was subacute, with back pain predominating, 10% had septicaemia and 7% paraperesis or paraplegia. Most infections were caudal to the fourth thoracic vertebra. One third were associated with preceding urinary, respiratory, dental or abdominal sepsis. Staphylococcus aureus was the infecting organism in 85% of isolates. Delay in diagnosis was frequent. There were four deaths, and seven individuals remained severely disabled: outcome was otherwise satisfactory. An algorithm for the investigation and management of this uncommon but serious condition is proposed.

  9. Severe compression of a bailout self-expanding chimney stent for rescuing the miscoverage of left common carotid artery during TEVAR of a type B aortic dissection.

    PubMed

    Wang, Lixin; Guo, Daqiao; Jiang, Junhao; Shi, Zhenyu; Fu, Weiguo; Wang, Yuqi

    2014-04-01

    A 54-year-old man who suffered from paraplegia due to type B aortic dissection was treated with a Valiant stent-graft. However, attempts to gain secure proximal sealing resulted in an inadvertent coverage of the left common carotid artery by the endograft. The blood flow in the left common carotid artery was restored by a transcarotid Smart Control stent in a chimney fashion. At 6- and 18-month follow-up, computed tomography scan showed that the chimney stent was severely compressed by the stent graft, although the patient remained neurologically asymptomatic. PMID:24309751

  10. Engineering evaluation of the energy-storing orthosis FES gait system.

    PubMed

    Kangude, Abhijit; Burgstahler, Brett; Durfee, William

    2010-01-01

    A system to restore walking in the vicinity of a wheelchair for people with paraplegia resulting from spinal cord injury is under development. The approach combines single channel surface electrical stimulation with an orthosis. The orthosis is spring loaded and contains a pneumatic system that stores energy during knee extension caused by quadriceps stimulation and transfers it to hip joint for hip extension. A laboratory version of the prototype of the gait system has been fabricated and engineering bench tests were performed. The paper presents the design of the wearable prototype and results of bench testing. PMID:21096941

  11. Spinal angiolipoma--case report.

    PubMed

    Chotai, Silky; Hur, Jun Seok; Moon, Hong Joo; Kwon, Taek-Hyun; Park, Youn Kwan; Kim, Joo Han

    2011-01-01

    A 69-year-old male presented with a rare spinal angiolipoma manifesting as history of back pain, and numbness in both lower limbs, which progressed over a period of 5 years. Total T10-T12 laminectomy was performed and the tumor was removed en bloc. The symptoms gradually improved postoperatively. Spinal angiolipoma is an uncommon benign extradural tumor of spine, which accounts for 0.14-1.2% of all spinal tumors and is a rare cause of spinal cord compression. Recognition of this entity is crucial as a benign and curable cause of paraplegia and back pain.

  12. [The electrical stimulation bicycle: a neuroprosthesis for the everyday use of paraplegic patients].

    PubMed

    Szecsi, J; Fiegel, M; Krafczyk, S; Straube, A; Quintern, J; Brandt, Th

    2004-06-24

    Until recently, few patients with complete paraplegia could walk or stand with the help of functional electrical stimulation (FES) of the leg muscles regularly at home. In comparison, FES cycling with an adapted tricycle is easy to put into practice because the legs remain connected to the pedals and through the use of a tricycle or stationary bicycle, the balancing problems of the patient recedes into the background. In the first German feasibility studies for paraplegic cycling, eleven completely paraplegic patients have been tested so far. The goal is to make FES cycling a daily activity in the lives of as many patients as possible. PMID:15529690

  13. Reviewing the genetic causes of spastic-ataxias.

    PubMed

    de Bot, Susanne T; Willemsen, Michel A A P; Vermeer, Sascha; Kremer, Hubertus P H; van de Warrenburg, Bart P C

    2012-10-01

    Although the combined presence of ataxia and pyramidal features has a long differential, the presence of a true spastic-ataxia as the predominant clinical syndrome has a rather limited differential diagnosis. Autosomal recessive ataxia of Charlevoix-Saguenay, late-onset Friedreich ataxia, and hereditary spastic paraplegia type 7 are examples of genetic diseases with such a prominent spastic-ataxic syndrome as the clinical hallmark. We review the various causes of spastic-ataxic syndromes with a focus on the genetic disorders, and provide a clinical framework, based on age at onset, mode of inheritance, and additional clinical features and neuroimaging signs, that could serve the diagnostic workup. PMID:23033504

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

    PubMed Central

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

    2016-01-01

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

  15. Centrifugal pump support for distal aortic perfusion during repair of traumatic thoracic aortic injury.

    PubMed

    Walls, Joseph T; Curtis, Jack J; McKenney-Knox, Charlotte A; Schmaltz, Richard A

    2002-11-01

    Paraplegia from ischemic injury of the spinal cord and renal failure from inadequate perfusion of the kidneys may occur from aortic cross-clamping during repair of traumatic thoracic aortic injuries. After Institutional Review Board approval, we retrospectively reviewed the charts of 26 patients surgically treated for traumatic transection of the descending thoracic aorta during a 14 year period (1987-2001), using centrifugal pump (Sarns) support for distal aortic perfusion. The study group comprised 19 males and 7 females, whose ages ranged from 15 to 69 years. For all but 1 patient, who fell from a flagpole, the injuries were incurred in motor vehicle accidents. Aortic cross-clamp time lasted between 5 to 78 min (median = 40 min). Mean arterial pressure ranged from 50 to 80 mm Hg (median = 70 mm Hg). All patients survived operation without developing paraplegia or renal failure. Distal centrifugal pump perfusion during repair of traumatic injury of the descending thoracic aorta is a valuable adjunct during surgical treatment and aids in preservation of spinal cord and renal function.

  16. [Debranch Thoracic Endovascular Aortic Therapy for Extending Aneurysms].

    PubMed

    Miyamoto, Shinji

    2016-07-01

    To apply endovascular aortic repair for arch or thoracoabdominal pathology, it is essential to reconstruct the branches originating in the treatment area. In cases that a stentgraft has to reach ascending aorta we perform "in situ fenestration with squid capture technique".During the procedure cerebral circulation is maintained by percutaneous cardiopulmonary bypass. After deploying the stentgraft we stab it by a needle while squeezed by snare wire and stick a covered stentgraft eventually. Unlike chimney technique which also can be applied for zone 0 thoracic endovascular aortic therapy( TEVAR),this method has no risk of gutter leak. For now there are no fenestrated nor branched grafts in Japan so that we should perform hybrid TEVAR for throacoabdominal aneurysms if patients' conditions cannot allow graft replacement. In such a case we make bypasses between the common iliac artery( or left leg of bifurcated graft) and visceral arteries using a quadrated graft. All anastomosis can be done in a retroperitoneal single plane. TEVAR shouldn't be performed simultaneously with bypass because unstable hemodynamic increase risk of paraplegia. We have never experienced paraplegia among 50 cases except for 1 case in which TEVAR had to be done urgently under critical hypotension. PMID:27440024

  17. Television programming and disability: a ten year span.

    PubMed

    Byrd, E K; McDaniel, R S; Rhoden, R B

    1980-01-01

    Television programming covering disability over a ten year span, 1967-68 and 1977-78, was studied to determine similarities and differences. Variables identified for comparisons included network, program type, disability, time slot, and length of programming. The largest frequency of programs occurred on NBC in 1968. However, in 1978 the largest frequency occurred on the Public Broadcasting System. This can be partially explained by the increased numbers of programs on PBS overall and their traditional concern with public interest and service programming. The commercial networks historically have been in the business of entertaining and portray disability more so in that fashion. Movies head the list in 1968. However, in 1978, dramatic series and children's programming head the list followed by news documentaries and telethon. Paraplegia was the most frequent disability portrayed in 1968 followed by mental illness, drug addiction and emotional disability. In 1978 mental illness headed the list followed by alcoholism, emotional disability and physically handicapped. Paraplegia in 1968 can be accounted for by the program "Ironside" that featured a paraplegic detective. Mental illness and emotional disturbance seem to be consistent targets over the decade for popular programming in prime time. PMID:6450185

  18. Long-Term Results of Open Stent-Grafting Using a Matsui-Kitamura Stent to Treat Thoracic Aortic Aneurysm

    PubMed Central

    Kanno, Megumu; Takano, Takashi; Watanabe, Kouyu; Ueno, Kyohei; Ono, Takashi; Satou, Kouichi

    2014-01-01

    Purpose: We describe a retrospective study of initial and long-term outcomes with an open stent grafting (OSG) with a Matsui-Kitamura stent for treating thoracic aortic aneurysm. Methods: Between August 2005 and September 2013, 50 patients with aortic arch disease extending to the descending aorta underwent OSG. Circulatory arrest with total cardiopulmonary bypass and selective cerebral perfusion were used, and the aorta was transected between the brachiocephalic and left subclavian artery. The stent-graft was inserted, sutured to a transected aortic edge, and anastomosed to a four-branched arch graft. Preoperative, operative, and short- and long-term postoperative data were obtained from the patients’ medical records. Results: The perioperative (within 30 days) mortality rate was 8%. Two patients (4%) had a stroke and 5 patients (10%) had a spinal cord injury resulting in paraplegia or paraparesis (1 patient each) or transient paraplegia (3 patients). Actuarial survival rates at 1, 3, 5, and 7 years postoperatively were 87.8%, 78.3%, 70.7%, and 65.3%, respectively; the rates of freedom from an aortic event were 100%, 89.1%, 82.2%, and 74.7%. There were no complications related to use of the stent-graft. Conclusion: Our OSG method provided durable results in patients treated for thoracic aortic aneurysm, with few adverse events. PMID:24899135

  19. [Spinal cord ischemia following subrenal aortic clamping].

    PubMed

    Battisti, G; Marigliani, M; Stio, F; Iavarone, C

    1990-01-01

    The paraplegia caused by an aortic clamping just below the Renal artery is a rare but very complication in aortic surgery. Such a complication is even rarer if we consider the few cases reported in literature following a reconstructive surgery for occlusive chronic diseases of aortiliac axes. The authors have studied the case of a patient bearing the syndrome of Leriche; this one had an aortic clamping below the kidney and soon after developed an acute ischaemic syndrome below the spinal medulla with flaccid paraparesis, anal and vesical sphincteric diseases and persistence of deep tactile sensibility. After a reconstruction of vascular anatomy of the medulla they emphasize the importance, in such a disease, of the "arteria radicularis magna" of Adamkievicz and its place of origin. After they discuss the severe physioopathologic moments that are connected: with the direct ischaemia following aortic clamping in the cases where the arteria radicularis magna rises at a level lower than the clamping itself; with the embolism or thrombosis caused by surgical manipulation peroperatively (it might be the cause of paraplegia more frequent in aneurysmectomia surgery); with the severe hypotension per- and post operatively for the existence of arteriosclerotic disease of the lumbar arteries. Finally they analyses preoperatively diagnostic possibilities and per operatively methods used in preventing this sort of complication.

  20. 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

  1. Measurement Properties of the Spinal Cord Injury-Functional Index (SCI-FI) Short Forms

    PubMed Central

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

    2015-01-01

    Objective To evaluate the psychometric properties of the Spinal Cord Injury Functional Index (SCI-FI) short forms (Basic Mobility, Self-Care, Fine Motor, Ambulation, Manual Wheelchair, and Power Wheelchair) based on internal consistency, correlations between short- and full item bank forms, and a 10-item compute adaptive test version, magnitude of ceiling and floor effects, and test information functions. Design Cross-sectional cohort study. Participants 855 individuals with traumatic spinal cord injury recruited from 6 National Spinal Cord Injury Model Systems facilities. Interventions Not applicable. Main outcome measures SCI-FI full item bank, 10-item computer adaptive test, and parallel short form scores. Results The SCI-FI short forms (with separate versions for individuals with paraplegia and tetraplegia) demonstrate very good internal consistency, group-level reliability, excellent correlations between short forms and scores based on the total item bank, minimal ceiling and floor effects (except ceiling effects for persons with paraplegia on Self-Care, Fine Motor and Power Wheelchair ability, and floor effects for persons with tetraplegia on Self-Care, Fine Motor and Manual Wheelchair ability). The test information functions are acceptable across the range of scores where most persons in the sample performed. Conclusions clinicians and researchers should consider the SCI-FI short forms when computer adaptive testing is not feasible. PMID:24602551

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

    PubMed Central

    Haley, Stephen M.

    2013-01-01

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

  3. Evidence for autosomal recessive inheritance in SPG3A caused by homozygosity for a novel ATL1 missense mutation

    PubMed Central

    Khan, Tahir Naeem; Klar, Joakim; Tariq, Muhammad; Anjum Baig, Shehla; Malik, Naveed Altaf; Yousaf, Raja; Baig, Shahid Mahmood; Dahl, Niklas

    2014-01-01

    Hereditary spastic paraplegias (HSPs) comprise a heterogeneous group of disorders characterized by progressive spasticity and weakness of the lower limbs. Autosomal dominant and ‘pure' forms of HSP account for ∼80% of cases in Western societies of whom 10% carry atlastin-1 (ATL1) gene mutations. We report on a large consanguineous family segregating six members with early onset HSP. The pedigree was compatible with both autosomal dominant and autosomal recessive inheritance. Whole-exome sequencing and segregation analysis revealed a homozygous novel missense variant c.353G>A, p.(Arg118Gln) in ATL1 in all six affected family members. Seven heterozygous carriers, five females and two males, showed no clinical signs of HSP with the exception of sub-clinically reduced vibration sensation in one adult female. Our combined findings show that homozygosity for the ATL1 missense variant remains the only plausible cause of HSP, whereas heterozygous carriers are asymptomatic. This apparent autosomal recessive inheritance adds to the clinical complexity of spastic paraplegia 3A and calls for caution using directed genetic screening in HSP. PMID:24473461

  4. 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.

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

    PubMed

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

    2016-01-01

    A 28-year-old man was hospitalized with advancing paraplegia. Under the diagnosis of Guillain-Barre syndrome, steroid pulse therapy was administered and plasmapheresis was performed. However, the paraplegia gradually progressed. Subsequently, a spinal cord tumor was revealed by magnetic resonance imaging (MRI). The pathological diagnosis, obtained by open biopsy, confirmed a mixed germ cell tumor in the spinal cord. Multiple lung and lymph nodes metastases were also detected upon computed tomography, along with increased serum alpha-fetoprotein (33.9 ng/mL) and human chorionic gonadotropin (182.5 mIU/mL) levels. Consequently, he received chemotherapy comprising three courses of BEP (bleomycin, etoposide, and cisplatin) as first-line therapy, followed by four courses of TGN (paclitaxel, gemcitabine, and nedaplatin) as second-line treatment. As a result, the spinal cord lesion area was significantly decreased and the alpha-fetoprotein and human chorionic gonadotropin levels were normalized. Four years after chemotherapy, MRI revealed pituitary gland and pineal organ recurrence of the germ cell tumor and additional TGN chemotherapy was performed. PMID:27628608

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

    PubMed

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

    2015-02-01

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

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

    PubMed Central

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

    2015-01-01

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

  8. Successful pregnancy achieved by intracytoplasmic sperm injection using cryopreserved electroejaculate sperm in a couple both with spinal cord injury: a case report.

    PubMed

    Chen, Shee-Uan; Shieh, Jen-Yi; Wang, Yen-Ho; Lu, Thomas; Ho, Hong-Nerng; Yang, Yu-Shih

    2005-09-01

    Anejaculation and poor semen quality are 2 major causes of infertility in men with spinal cord injury (SCI). The low motility of retrieved sperm often results in use of intracytoplasmic sperm injection (ICSI) to achieve fertilization. Pregnancy is a challenging event for women with SCI. Herein we report a pregnancy after ICSI with cryopreserved electroejaculate sperm for a couple both with SCI. The husband had T10 paraplegia with a neurogenic bladder. He underwent 2 electroejaculations. The concentration of sperm was 0.1 x 10(6)/mL to 0.3 x 10(6)/mL, with a motility of 5% to 20%. ICSI was considered the best choice for the couple. His wife had L2 paraplegia with cauda equina syndrome. She underwent controlled ovarian hyperstimulation, and 10 oocytes were retrieved. Eight mature oocytes were injected using thawed sperm, which resulted in 5 normal zygotes. Conception was achieved by the transfer of 4 embryos into the uterus. A healthy female baby was delivered vaginally at 39 weeks of gestation. This woman had never undergone any other assisted reproductive technology (ART) procedures. With the advancement of ART and prenatal care, this couple achieved a successful pregnancy. The use of cryopreserved electroejaculated sperm for ICSI can avoid the inconvenience or cost to the patient of repeated electroejaculations.

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

    SciTech Connect

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

    2005-09-09

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

  10. 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.

  11. Quantitative Gait Analysis Using a Motorized Treadmill System Sensitively Detects Motor Abnormalities in Mice Expressing ATPase Defective Spastin.

    PubMed

    Connell, James W; Allison, Rachel; Reid, Evan

    2016-01-01

    The hereditary spastic paraplegias (HSPs) are genetic conditions in which there is progressive axonal degeneration in the corticospinal tract. Autosomal dominant mutations, including nonsense, frameshift and missense changes, in the gene encoding the microtubule severing ATPase spastin are the most common cause of HSP in North America and northern Europe. In this study we report quantitative gait analysis using a motorized treadmill system, carried out on mice knocked-in for a disease-associated mutation affecting a critical residue in the Walker A motif of the spastin ATPase domain. At 4 months and at one year of age homozygous mutant mice had a number of abnormal gait parameters, including in stride length and stride duration, compared to heterozygous and wild-type littermates. Gait parameters in heterozygous animals did not differ from wild-type littermates. We conclude that quantitative gait analysis using the DigiGait system sensitively detects motor abnormalities in a hereditary spastic paraplegia model, and would be a useful method for analyzing the effects of pharmacological treatments for HSP.

  12. Health Condition and Quality of Life in Persons with Spinal Cord Injury

    PubMed Central

    TRGOVCEVIC, Sanja; MILICEVIC, Milena; NEDOVIC, Goran; JOVANIC, Goran

    2014-01-01

    Abstract Background During the last few decades, focus of rehabilitation outcome has been redirected to the lifetime monitoring of quality of life. The purpose of this study was to investigate the differences in quality of life perceptions between participants with spinal cord injury and participants of typical population. Methods This cross-sectional controlled study of 100 adults aged 18-65 years was based on two questionnaires, Short Form-36 Health Survey (SF-36) and Spinal Cord Injury Quality of Life Questionnaire (QL-23), completed by 23 participants with paraplegia, 21 participants with tetraplegia, and 56 participants of typical population. Mann-Whitney U-test for planned comparison between groups and χ2 test were used to analyze the differences between research groups. Results Participants from control group perceived their general quality of life at higher level in comparison to participants with spinal cord injury (U=415.000, z=-5.804, P<0.000). Negative influence of spinal cord injury was detected in six domains (physical functioning, physical role, bodily pain, vitality, social functioning, mental health). Statistical differences between participants with paraplegia and participants with tetraplegia only in domain of functional limitations (U=103.000, z=-3.256, P<0.005). Conclusion The participants with spinal cord injury perceived both health-related and general quality of life at a lower level in comparison to controls. However, the injury level only partially determined the estimated quality of life. PMID:26175977

  13. Multiple malignant lesions involving the orofacial region: a case report.

    PubMed

    Arotiba, J T; Akadiri, O A; Okeke, L I; Obimakinde, O S; Fasola, A O; Okoje, V N; Kolude, B

    2006-09-01

    We describe a rare finding in a 38 year old patient with previously undiagnosed prostate cancer who presented with multiple facial swellings, mental nerve neuropathy and paraplegia. While the co-existence of paraplegia and mental nerve neuropathy is a possible feature of metastatic prostate cancer involving the spine and mandible, the concomitant occurrence of multiple facial swellings involving the anterior mandible with its related gingival and lip mucosa, frontal bone and parotid glands is a rare finding. This raised a suspicion of two histologically different malignancies co-existing in this patient. Fine needle aspiration cytology (FNAC) of the parotid lesion and incisional biopsy of the gingival lesion were reported as Lymphoblastic lymphoma and Non Hodgkin's Lymphoma respectively. A Transrectal biopsy of the prostate gland confirmed adenocarcinoma of the prostate gland. The patient however died due to a number of intercurrent illnesses and rapid deterioration consequent on his disease condition. Unfortunately, all efforts to carry out an autopsy were unsuccessful due to strong objection of the relatives on religious grounds. Problem associated with the diagnosis and management of such a rare case in a developing economy was highlighted. PMID:17312748

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

    PubMed Central

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

    2014-01-01

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

  15. Salmonella prostatitis in a man with spinal cord injury

    PubMed Central

    Krebs, Jörg; Göcking, Konrad; Pannek, Jürgen

    2014-01-01

    Context Prostatitis is a very unusual manifestation of Salmonella urinary tract infection and has not been reported in men with spinal cord injury (SCI). Findings A 57-year-old man with paraplegia and a history of recurrent symptomatic urinary tract infections presented with Salmonella typhimurium prostatitis. Clinical and sonographic examination of the urinary tract, as well as urinalysis including microbiologic examination, revealed no relevant abnormalities. The microbiologic analysis of the ejaculate revealed growth of monophasic Salmonella enterica ssp. enterica serotype 4,12:i:-. A 6-week course of antibiotic treatment was initiated. There were no recurrent symptomatic urinary tract infections during follow-up. Conclusion Salmonellosis is a reportable disease and carriers have to refrain from activities in the food sector. Therefore, Salmonella prostatitis should be considered and excluded in men with SCI and a history of recurrent urinary tract infection who use intermittent catheterization for bladder management. PMID:24090046

  16. 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

  17. Three cases of Troyer syndrome in two families of Filipino descent.

    PubMed

    Butler, Shauna; Helbig, Katherine L; Alcaraz, Wendy; Seaver, Laurie H; Hsieh, David T; Rohena, Luis

    2016-07-01

    Troyer syndrome is a complex hereditary spastic paraplegia (HSP) due to a mutation in SPG20 first reported in the Old Amish population. A genetic mutation in SPG20 is responsible for a loss of function of the protein spartin in this disease. Since its initial report, this syndrome has also been reported in Turkish and Omani families. Here we report the case of three patients of Filipino descent with Troyer syndrome. Whole exome sequencing (WES) identified a homozygous mutation c.364_365delAT which predicts p.Met122Valfs*2 in SPG20. This is the same mutation identified in affected patients from the Omani and Turkish families, and is the first report of this syndrome in the Filipino population. Although Troyer syndrome has characteristic phenotypic manifestations it is likely underdiagnosed due to its rarity and we expect that WES will lead to identifying this disease in other individuals. © 2016 Wiley Periodicals, Inc.

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

    SciTech Connect

    Jouet, M.; Kenwick, S.; Moncla, A.

    1995-06-01

    The neural cell-adhesion molecule L1 is involved in intercellular recognition and neuronal migration in the CNS. Recently, we have shown that mutations in the gene encoding L1 are responsible for three related disorders; X-linked hydrocephalus, MASA (mental retardation, aphasia, shuffling gait, and adducted thumbs) syndrome, and spastic paraplegia type I (SPG1). These three disorders represent a clinical spectrum that varies not only between families but sometimes also within families. To date, 14 independent L1 mutations have been reported and shown to be disease causing. Here we report nine novel L1 mutations in X-linked hydrocephalus and MASA-syndrome families, including the first examples of mutations affecting the fibronectin type III domains of the molecule. They are discussed in relation both to phenotypes and to the insights that they provide into L1 function. 39 refs., 5 figs., 3 tabs.

  19. Prognostic value of cortical magnetic stimulation in spinal cord injury.

    PubMed

    Clarke, C E; Modarres-Sadeghi, H; Twomey, J A; Burt, A A

    1994-08-01

    Cortical magnetic stimulation was performed in a consecutive series of 10 patients presenting within 15 days of traumatic spinal cord injury. In those patients with complete paraplegia or quadriplegia, motor evoked potentials at presentation were absent below the level of the lesion. Six months after the injury, potentials had returned in the biceps brachii and abductor pollicis brevis muscles in some quadriplegic cases, but remained absent from the tibialis anterior in all of this group. None of those with a complete lesion made a significant functional recovery. Of the three patients with incomplete quadriplegia, two showed a significant recovery after 6 months. Motor evoked potentials were recordable below the level of the lesion at presentation in these cases, although the latencies were prolonged. In the remaining patient who failed to improve, potentials were unrecordable throughout the study. This small pilot study suggests that cortical magnetic stimulation may be useful in refining the prognosis in patients with an incomplete spinal cord injury. PMID:7970860

  20. Cryptococcal meningitis in a goat – a case report

    PubMed Central

    2014-01-01

    Background Cryptococcus spp. are saprophytic and opportunistic fungal pathogens that are known to cause severe disease in immunocompromised animals. In goats there are reports of clinical cryptococcal pneumonia and mastitis but not of meningitis. Case presentation The following report describes a case of a five year old buck showing severe neurological signs, including paraplegia and strong pain reaction to touch of the hindquarters region. Treatment with antibiotics was unsuccessful and the animal was euthanized for humanitarian reasons. Postmortem examination revealed lumbar meningitis, lung nodules and caseous lymphadenitis lesions. Encapsulated Cryptococcus neoformans were identified from the lungs and meninges, showing that cryptococcal meningitis should be included in the differential diagnosis of goats showing paresis and hyperesthesia. The possibility of concurrent immunosuppression due to Corynebacterium pseudotuberculosis infection is raised. Conclusions Cryptoccocal meningitis should be included in the differential diagnosis list of goat diseases with ataxia and hyperesthesia. PMID:24708822

  1. Graded Control of Microtubule Severing by Tubulin Glutamylation.

    PubMed

    Valenstein, Max L; Roll-Mecak, Antonina

    2016-02-25

    Microtubule-severing enzymes are critical for the biogenesis and maintenance of complex microtubule arrays in axons, spindles, and cilia where tubulin detyrosination, acetylation, and glutamylation are abundant. These modifications exhibit stereotyped patterns suggesting spatial and temporal control of microtubule functions. Using human-engineered and differentially modified microtubules we find that glutamylation is the main regulator of the hereditary spastic paraplegia microtubule severing enzyme spastin. Glutamylation acts as a rheostat and tunes microtubule severing as a function of glutamate number added per tubulin. Unexpectedly, glutamylation is a non-linear biphasic tuner and becomes inhibitory beyond a threshold. Furthermore, the inhibitory effect of localized glutamylation propagates across neighboring microtubules, modulating severing in trans. Our work provides the first quantitative evidence for a graded response to a tubulin posttranslational modification and a biochemical link between tubulin glutamylation and complex architectures of microtubule arrays such as those in neurons where spastin deficiency causes disease.

  2. Coexistence of Spinal Intramedullary Tuberculoma and Multiple Intracranial Tuberculomas.

    PubMed

    Lee, Dong-Yoon; Kim, Sang-Pyo; Kim, In-Soo

    2015-06-01

    Spinal intramedullary tuberculoma remains a very rare entity of central nervous system tuberculosis. This is the same with the coexistence of spinal intramedullary and intracranial tuberculomas that remains extremely rare with less than 20 cases reported at present. Authors describe this uncommon case by analyzing a 65-year-old female patient who had past history of kidney transplantation due to stage 5 chronic kidney disease and pulmonary tuberculosis on medication. The patient experiences progressive paraplegia and numbness on both lower extremities. Magnetic resonance imaging demonstrated an intramedullary mass at T9-10 level and multiple intracranial enhancing nodules. Microsurgical resection of spinal intramedullary mass was performed and the lesion was histopathologically confirmed as Mycobacterium tuberculosis. Efficient diagnosis and management of this rare disease are reviewed along with previously reported cases.

  3. Hyperargininemia due to arginase I deficiency: the original patients and their natural history, and a review of the literature.

    PubMed

    Schlune, A; Vom Dahl, S; Häussinger, D; Ensenauer, R; Mayatepek, E

    2015-09-01

    Hyperargininemia is caused by deficiency of arginase 1, which catalyzes the hydrolysis of L-arginine to urea as the final enzyme in the urea cycle. In contrast to other urea cycle defects, arginase 1 deficiency usually does not cause catastrophic neonatal hyperammonemia but rather presents with progressive neurological symptoms including seizures and spastic paraplegia in the first years of life and hepatic pathology, such as neonatal cholestasis, acute liver failure, or liver fibrosis. Some patients have developed hepatocellular carcinoma. A usually mild or moderate hyperammonemia may occur at any age. The pathogenesis of arginase I deficiency is yet not fully understood. However, the accumulation of L-arginine and the resulting abnormalities in the metabolism of guanidine compounds and nitric oxide have been proposed to play a major pathophysiological role. This article provides an update on the first patients ever described, gives an overview of the distinct clinical characteristics, biochemical as well as genetical background and discusses treatment options. PMID:26123990

  4. Metastatic squamous cell carcinoma in a cat.

    PubMed

    Dhaliwal, Ravinder S; Kufuor-Mensah, Eric

    2007-02-01

    A 7-year-old, spayed female Persian cat was referred for evaluation of progressive paraplegia. The cat was thin, cachectic and paraplegic on presentation. The survey radiographs showed a left caudal pulmonary lesion and lytic skeletal lesions at the right iliac crest and left distal scapula. Due to a poor prognosis for complete recovery, the owner opted for euthanasia. Post-mortem examination revealed bilaterally small and irregular kidneys, lysis of the left iliac crest and left distal scapula and a dilated left ventricular lumen with a thin interventricular septum. Histologically, all the lesions were determined to be squamous cell carcinoma. It appears that the origin or the primary site of the malignancy in this case is pulmonary as cardiac and skeletal tissues are primarily mesenchymal in origin and are less likely to develop a primary epithelial malignancy. To the best of our knowledge, there is no description of cardiac or skeletal metastatic squamous cell carcinoma in a cat. PMID:16859943

  5. Spinal cord protection in aortic endovascular surgery.

    PubMed

    Scott, D A; Denton, M J

    2016-09-01

    A persistent neurological deficit, such as paraplegia or paraparesis, secondary to spinal cord injury remains one of the most feared complications of surgery on the descending thoracic or abdominal aorta. This is despite sophisticated advances in imaging and the use of less invasive endovascular procedures. Extensive fenestrated endovascular aortic graft prostheses still carry a risk of spinal cord injury of up to 10%; thus, this risk should be identified and strategies implemented to protect the spinal cord and maintain perfusion. The patients at highest risk are those undergoing extensive thoracic aortic stenting including thoracic, abdominal, and pelvic vessels. Although many techniques are available, lumbar cerebrospinal fluid drainage remains the most frequent intervention, along with maintenance of perfusion pressure and possibly staged procedures to allow collateral vessel stabilization. Many questions remain regarding other technical aspects, spinal cord monitoring and cooling, pharmacological protection, and the optimal duration of interventions into the postoperative period. PMID:27566805

  6. 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

  7. Enhancing physical activity guidelines: a needs survey of adults with spinal cord injury and health care professionals.

    PubMed

    Foulon, Brianne L; Lemay, Valérie; Ainsworth, Victoria; Martin Ginis, Kathleen A

    2012-10-01

    The purpose of this study was to determine preferences of people with spinal cord injury (SCI) and health care professionals (HCP) regarding the content and format of a SCI physical activity guide to support recently released SCI physical activity guidelines. Seventy-eight people with SCI and 80 HCP completed a survey questionnaire. Participants with SCI identified desired content items and their preferences for format. HCP rated the helpfulness of content items to prescribe physical activity. All content items were rated favorably by participants with SCI and useful by HCP. The risks and benefits of activity and inactivity, and strategies for becoming more active, were rated high by both samples. Photographs and separate information for those with paraplegia versus tetraplegia were strongly endorsed. These data were used to guide the development of an SCI physical activity guide to enhance the uptake of physical activity guidelines for people with SCI. The guide was publically released November 11, 2011.

  8. Intrathecal application of cyproheptadine impairs locomotion in intact rats.

    PubMed

    Majczyński, Henryk; Cabaj, Anna; Górska, Teresa

    In intact adult rats, cyproheptadine, a 5-HT2 antagonist, administered intrathecally at the midlumbar segments was found to impair hindlimb locomotor movements during overground locomotion. These effects were dose-dependent; they varied from transient complete hindlimb paraplegia seen at doses of 300 microg/20 microl, to short-lasting trunk instability at doses of 100 microg/20 microl. After the return of overground locomotion, transient abduction of one of the hindlimbs was observed in some animals. These findings demonstrate that the blockade of 5-HT2 receptors affects locomotion in intact rats. Our results provide support for the hypothesis of serotonergic involvement in rat locomotion, which, so far, has been based mainly on the effects of 5-HT2 agonists on the recovery of locomotion in spinal rats.

  9. Oral considerations in the management of sickle cell disease: a case report.

    PubMed

    Mello, Sandra M F; Paulo C Araujo, Roberto; Alves, Cresio

    2012-09-01

    The phenomenon of erythrocyte sickling observed in sickle cell anaemia is responsible for ischaemia and tissue infarction compromising several organs and systems including the mouth and face. This brief paper reports the case of a 17- year-old female with a complicated sickle cell anaemia, hypertension and paraplegia (after an ischaemic stroke at the age of six years). Oral examination revealed the absence of tooth 12, fractures of teeth 11, 21 and 22 (from trauma), active caries lesions in the enamel of teeth 36, 37 and 46, mucosal pallor, and a smooth tongue. Oral radiographs revealed bone rarefaction and trabecular bone coarsening. Dental surgeons and physicians should be aware of the general and oral abnormalities that can be present in individuals with sickle cell anaemia to allow for preventive measures and implementation of effective treatment options.

  10. Intradural Extramedullary Tuberculoma of the Spinal Cord Following Tuberculous Meningitis.

    PubMed

    Jeong, Deok-Ki; Kwon, Young-Min

    2015-06-01

    Intradural extramedullary tuberculoma of the spinal cord (IETSC) is an uncommon disease which can occurs secondary to tuberculous meningitis. A 31-year-old woman was diagnosed as tuberculous meningitis after mental disorientation. Her mentality was recovered after antituberculous therapy. After 7 months of antituberculous therapy, paraplegia has developed. Magnetic resonance imaging (MRI) revealed a mass lesion between the T1 and T12 spinal levels with arachnoid thickening which results in the development of tuberculoma. She received surgical resection of IETSC followed by antituberculous therapy and neurological function has been improved. The two years after surgical treatment, spinal MRI showed syringomyelia between T1 to L1. But, her neurological outcome was not aggravated. PMID:26217394

  11. Is Modulation of Oxidative Stress an Answer? The State of the Art of Redox Therapeutic Actions in Neurodegenerative Diseases

    PubMed Central

    Chiurchiù, Valerio

    2016-01-01

    The central nervous system is particularly sensitive to oxidative stress due to many reasons, including its high oxygen consumption even under basal conditions, high production of reactive oxygen and nitrogen species from specific neurochemical reactions, and the increased deposition of metal ions in the brain with aging. For this reason, along with inflammation, oxidative stress seems to be one of the main inducers of neurodegeneration, causing excitotoxicity, neuronal loss, and axonal damage, ultimately being now considered a key element in the onset and progression of several neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and hereditary spastic paraplegia. Thus, the present paper reviews the role of oxidative stress and of its mechanistic insights underlying the pathogenesis of these neurodegenerative diseases, with particular focus on current studies on its modulation as a potential and promising therapeutic strategy. PMID:26881039

  12. Do not forget the distal lower limb veins in screening patients with spinal cord injuries for deep venous thromboses.

    PubMed

    Germing, Alfried; Schakrouf, Mahmud; Lindstaedt, Michael; Grewe, Peter; Meindl, Renate; Mügge, Andreas

    2010-01-01

    In this prospective study, we aimed to document the rate and localization of deep venous thromboses in patients with spinal cord injuries. Patients with paraplegia or tetraplegia were screened by a serial color duplex sonography protocol for deep venous thrombosis within the first 36 hours after admission, at day 7, and at day 21. Sonography was performed by a complete scan including the veins below the knee. A total of 139 patients were included (19-90 years, 63.5% male). Cumulative rate of deep venous thrombosis after 3 duplex scans was 45.3% (n = 63). In 71.4% (n = 45), thromboses were localized below the knee. Because of the relevant number of distal vein thromboses, inclusion of the calf veins during screening scans is suggested. Further studies are needed to analyze the clinical benefit of diagnosing and treating distal vein thromboses.

  13. Thoracic spinal cord compression by a tophus.

    PubMed

    Ntsiba, Honoré; Makosso, Edouard; Moyikoua, Armand

    2010-03-01

    We report a case of thoracic (T10) spinal cord compression by a tophus in a patient with known chronic gout. Spastic paraplegia developed gradually over 6 months in this 43-year-old man with hypertension, alcohol abuse, and chronic gouty arthritis with tophi. Magnetic resonance imaging and computed tomography visualized an intradural nodule measuring 1.5cm in diameter at the level of T10, as well as geodes in the left T10 lamina and left T9-T10 articular processes. The nodule was removed surgically and shown by histological examination to be a tophus. The neurological impairments resolved rapidly and completely. We found about 60 similar cases in the literature. Spinal cord compression in a patient with chronic gout can be caused by a tophus.

  14. [Myeloradiculitis due to Schistosoma haematobium: about an observation in Dakar (Senegal)].

    PubMed

    Boubacar, S; Diagne, N S; Ben Adji, D W; Diop, A M; Seydi, M; Maiga, Y; Toure, K; Ndiaye, M; Diop, A G; Ndiaye, M M

    2016-05-01

    Nervous localisations of schistosomiasis are rare. We report the case of a 25 year-old Senegalese patient admitted for a progressive myeloradiculitis onset, over a one week period. The diagnosis of Schistosoma haematobium myeloradiculitis was made in front of a positive serum serology for S. haematobium, presence of S. haematobium eggs in urine, hyperproteinorachia, endemicity of S. haematobium in the region where the patient was originating and a past medical history of macroscopic hematuria in a context of river bathing. There was also no arguments for another cause to these neurological manifestations. Our patient was treated with praziquantel, prednisone and physiotherapy. Evolution was marked 6 weeks after the beginning of treatment by a significant improvement of motor deficit, enabling the patient to walk again. There was also a regression of genitosphincter dysfunction. Work-up for patients presenting with paraplegia in tropical countries, should also include search for S. heamatobium infection. PMID:26936766

  15. Endocytic membrane trafficking and neurodegenerative disease.

    PubMed

    Schreij, Andrea M A; Fon, Edward A; McPherson, Peter S

    2016-04-01

    Neurodegenerative diseases are amongst the most devastating of human disorders. New technologies have led to a rapid increase in the identification of disease-related genes with an enhanced appreciation of the key roles played by genetics in the etiology of these disorders. Importantly, pinpointing the normal function of disease gene proteins leads to new understanding of the cellular machineries and pathways that are altered in the disease process. One such emerging pathway is membrane trafficking in the endosomal system. This key cellular process controls the localization and levels of a myriad of proteins and is thus critical for normal cell function. In this review we will focus on three neurodegenerative diseases; Parkinson disease, amyotrophic lateral sclerosis, and hereditary spastic paraplegias, for which a large number of newly discovered disease genes encode proteins that function in endosomal membrane trafficking. We will describe how alterations in these proteins affect endosomal function and speculate on the contributions of these disruptions to disease pathophysiology. PMID:26721251

  16. Bacterial β-Glucosidase Reveals the Structural and Functional Basis of Genetic Defects in Human Glucocerebrosidase 2 (GBA2)

    PubMed Central

    2016-01-01

    Human glucosylcerebrosidase 2 (GBA2) of the CAZy family GH116 is responsible for the breakdown of glycosphingolipids on the cytoplasmic face of the endoplasmic reticulum and Golgi apparatus. Genetic defects in GBA2 result in spastic paraplegia and cerebellar ataxia, while cross-talk between GBA2 and GBA1 glucosylceramidases may affect Gaucher disease. Here, we report the first three-dimensional structure for any GH116 enzyme, Thermoanaerobacterium xylanolyticum TxGH116 β-glucosidase, alone and in complex with diverse ligands. These structures allow identification of the glucoside binding and active site residues, which are shown to be conserved with GBA2. Mutagenic analysis of TxGH116 and structural modeling of GBA2 provide a detailed structural and functional rationale for pathogenic missense mutations of GBA2. PMID:27115290

  17. Tuberculosis of spine

    PubMed Central

    Agrawal, Vinod; Patgaonkar, P. R.; Nagariya, S. P.

    2010-01-01

    Tuberculosis of the spine is one of the most common spine pathology in India. Over last 4 decades a lot has changed in the diagnosis, medical treatment and surgical procedures to treat this disorder. Further developments in diagnosis using molecular genetic techniques, more effective antibiotics and more aggressive surgical protocols have become essential with emergence of multidrug resistant TB. Surgical procedures such as single stage anterior and posterior stabilization, extrapleral dorsal spine anterior stabilization and endoscopic thoracoscopic surgeries have reduced the mortality and morbidity of the surgical procedures. is rapidly progressing. It is a challenge to treat MDR-TB Spine with late onset paraplegia and progressive deformity. Physicians must treat tuberculosis of spine on the basis of Culture and sensitivity. PMID:21572628

  18. [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.

  19. Novel mutations in the PNPLA6 gene in Boucher-Neuhäuser syndrome.

    PubMed

    Koh, Kishin; Kobayashi, Fumikazu; Miwa, Michiaki; Shindo, Kazumasa; Isozaki, Eiji; Ishiura, Hiroyuki; Tsuji, Shoji; Takiyama, Yoshihisa

    2015-04-01

    On whole-exome sequencing, a novel compound heterozygous mutation (c.2923A>G/c.3523_3524insTGTCCG, p.T975A/p.1175_1176insVS) and a novel homozygous one (c.3534G>C, p.W1178C) in the PNPLA6 gene were identified in sporadic and familial Japanese patients with Boucher-Neuhäuser syndrome (BNS), respectively. However, we did not find any mutations in the PNPLA6 gene in 88 patients with autosomal recessive hereditary spastic paraplegia (ARHSP). Our study confirmed the earlier report that a PNPLA6 mutation causes BNS. This is the first report on PNPLA6 mutations in non-Caucasian patients. Meanwhile, PNPLA6 mutations might be extremely rare in Japanese ARHSP patients. Moreover, we first found hypersegmented neutrophils in two BNS patients with PNPLA6 mutations.

  20. Loss of strumpellin in the melanocytic lineage impairs the WASH Complex but does not affect coat colour.

    PubMed

    Tyrrell, Benjamin J; Woodham, Emma F; Spence, Heather J; Strathdee, Douglas; Insall, Robert H; Machesky, Laura M

    2016-09-01

    The five-subunit WASH complex generates actin networks that participate in endocytic trafficking, migration and invasion in various cell types. Loss of one of the two subunits WASH or strumpellin in mice is lethal, but little is known about their role in mammals in vivo. We explored the role of strumpellin, which has previously been linked to hereditary spastic paraplegia, in the mouse melanocytic lineage. Strumpellin knockout in melanocytes revealed abnormal endocytic vesicle morphology but no impairment of migration in vitro or in vivo and no change in coat colour. Unexpectedly, WASH and filamentous actin could still localize to vesicles in the absence of strumpellin, although the shape and size of vesicles was altered. Blue native PAGE revealed the presence of two distinct WASH complexes, even in strumpellin knockout cells, revealing that the WASH complex can assemble and localize to endocytic compartments in cells in the absence of strumpellin. PMID:27390154

  1. Exclusion of serine palmitoyltransferase long chain base subunit 2 (SPTLC2) as a common cause for hereditary sensory neuropathy.

    PubMed

    Dawkins, Jennifer L; Brahmbhatt, Sonal; Auer-Grumbach, Michaela; Wagner, Klaus; Hartung, Hans-Peter; Verhoeven, Kristien; Timmerman, Vincent; De Jonghe, Peter; Kennerson, Marina; LeGuern, Eric; Nicholson, Garth A

    2002-10-01

    Recently point mutations in the SPTLC1 subunit of serine palmitoyltransferase have been shown to cause the common form of dominant hereditary sensory neuropathy (HSN1). Serine palmitoyltransferase (SPT) is a heterodimeric molecule made up of two subunits, SPTLC1 and SPTLC2. Twelve index patients from families with presumed genetic sensory neuropathies were screened for SPTLC2 mutations. These families comprised six multigenerational families, including two previously reported families not linked to the SPTLC1 locus on chromosome 9 and one multigenerational family with a complicated hereditary sensory neuropathy syndrome with associated palmar plantar keratosis, ataxia and spastic paraplegia. The remaining families included one consanguineous family with presumed recessive HSN with two affected siblings, one case of congenital sensory neuropathy and four sporadic cases with adult onset sensory neuropathy. No mutations in the SPTLC2 gene were found in any family. These results suggest that SPTLC2 mutations are not a common cause for genetic sensory neuropathies. PMID:12207934

  2. Management of Acute Aortic Syndrome and Chronic Aortic Dissection

    SciTech Connect

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

    2011-10-15

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

  3. Refining the genetic location of the gene for X linked hydrocephalus within Xq28.

    PubMed Central

    Jouet, M; Feldman, E; Yates, J; Donnai, D; Paterson, J; Siggers, D; Kenwrick, S

    1993-01-01

    The most common inherited form of hydrocephalus, X linked hydrocephalus (HSAS), is characterised by mental retardation, adducted thumbs, and spastic paraplegia. Genetic analysis has mapped the locus for HSAS to subchromosomal band Xq28 within a region of approximately 2 megabases of DNA. In order to refine the location of the disease gene we have conducted genetic linkage analysis with Xq28 marker loci in four additional HSAS families. A lod score of 4.26 with polymorphic marker DXS52 (St14) confirms the linkage of HSAS to Xq28. Identification of a recombination event between the HSAS gene and Xq28 loci F8C and DXS605 (2-19) reduces the size of the interval likely to contain the disease locus to about 1.5 megabases, the distance between DXS605 and DXS52. The locus for neural cell adhesion molecule, L1CAM, maps within this interval and therefore represents a candidate gene for HSAS. PMID:8474107

  4. Clinical Features of Spinal Cord Hemangioblastoma in a Dog.

    PubMed

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

    2015-01-01

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

  5. Clinical Features of Spinal Cord Hemangioblastoma in a Dog

    PubMed Central

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

    2015-01-01

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

  6. Spinal Muscular Atrophy

    PubMed Central

    Kolb, Stephen J.; Kissel, John T.

    2015-01-01

    Incidence The incidence of SMA is 1:11,000 live births [1]. Prevalence The prevalence of the carrier state is approximately 1 in 54 [1]. Severity The clinical severity of SMA correlates inversely with SMN2 gene copy number and varies from an extreme weakness and paraplegia of infancy to a mild proximal weakness of adulthood. Natural History The natural history of SMA is complex and variable. For this reason, clinical subgroups have been defined based upon best motor function attainment during development. Type 1 SMA infants never sit independently. Type 2 SMA children sit at some point during their childhood, but never walk independently. And Type 3 SMA children and adults are able to walk independently at some point in their childhood. PMID:26515624

  7. Spinal Intradural Schwannoma with Acute Intratumoural Haemorrhage: Case Report and Review

    PubMed Central

    Kongwad, Lakshman I.; Valiathan, Manna G.

    2016-01-01

    Schwannomas account for around half of all intradural spinal tumours, with chronic progressive symptoms as the most common presenting features. Intratumoural haemorrhage as a presenting feature of spinal schwannoma is very rare and only 11 cases have been reported till date. Authors here report a previously asymptomatic 40-year-old male who presented with acute onset paraplegia 12 hours after a minor trauma. MR imaging revealed a C7-D3 intradural-extramedullary lesion with features of acute blood and showing no enhancement. Emergency laminectomy and complete removal of the mass was performed and histopathology revealed features of schwannoma with haemorrhage. Patient had modest improvement of his neurological deficits at a follow-up of 6 months. Pertinent literature is reviewed in brief. PMID:26894121

  8. 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.

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

    PubMed Central

    Kmoch, S.; Majewski, J.; Ramamurthy, V.; Cao, S.; Fahiminiya, S.; Ren, H.; MacDonald, I.M.; Lopez, I.; Sun, V.; Keser, V.; Khan, A.; Stránecký, V.; Hartmannová, H.; Přistoupilová, A.; Hodaňová, K.; Piherová, L.; Kuchař, L.; Baxová, A.; Chen, R.; Barsottini, O.G.P.; Pyle, A.; Griffin, H.; Splitt, M.; Sallum, J.; Tolmie, J.L.; Sampson, J.R.; Chinnery, P.; Canada, Care4Rare; Banin, E.; Sharon, D.; Dutta, S.; Grebler, R.; Helfrich-Foerster, C.; Pedroso, J.L.; Kretzschmar, D.; Cayouette, M.; Koenekoop, R.K.

    2015-01-01

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

  10. Right-sided aortic arch: surgical treatment of an aneurysm arising from a Kommerell's diverticulum and extending to the descending thoracic aorta with an aberrant left subclavian artery.

    PubMed

    Caus, T; Gaubert, J Y; Monties, J R; Moulin, G; Mouly, A; Cornen, A; Mesana, T

    1994-02-01

    The case of a 44-year-old black man who presented with severe dysphagia, cough and chest pain caused by a 12-cm aneurysm developing from a Kommerell's diverticulum at the origin of an aberrant retro-oesophageal left subclavian artery is reported. The aortic arch and descending thoracic aorta were right sided. Diagnosis was established before operation by computed tomography, magnetic resonance imaging and arteriography. The aneurysm extended a considerable distance down the descending aorta and therefore the risk of postoperative paraplegia was considered to be high. Accordingly selective arteriography was performed to locate the Adamkievicz's artery which arose only 2 cm below the end of the aneurysm. Resection grafting of the aneurysm including the upper third of the descending aorta via right thoractomy was performed. The patient made an uneventful recovery and was discharged 20 days later. This case appears to be the first successful operation for this pathology.

  11. General practice visits by people with traumatic spinal cord injury: a Queensland longitudinal study.

    PubMed

    Amsters, Delena; Schuurs, Sarita; Kendall, Melissa; Pershouse, Kiley; Barker, Ruth; Kuipers, Pim

    2014-01-01

    People with traumatic spinal cord injury (SCI), although proportionally fewer in number, are known to be high users of primary health care services; however, details of their visits to GPs are unclear. This study presents information about GP utilisation patterns of 193 people with SCI over a 5-year period. Results demonstrate substantially greater GP service utilisation, particularly for young men with SCI, compared with their counterparts in the general population. Interestingly, people with paraplegia were proportionally higher users of GP services than those with tetraplegia. Results indicate the need for specialist support for GPs to meet the SCI-specific needs of this patient group. Specialist SCI outreach teams may be a useful resource to primary health care practitioners. PMID:23480823

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

    SciTech Connect

    Han, Young-Min Kwak, Ho-Sung; Jin, Gong-Young; Chung, Gyung-Ho; Song, Kyung-Jin

    2006-06-15

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

  13. The First Report of Fetal Alcohol Effect in a 12 Year-Old Child in Korea

    PubMed Central

    Ahn, Dong Hyun; Lee, Young Jin; An, Ho Young; Ahn, Joon Ho

    2009-01-01

    We present the first report of fetal alcohol effect in a 12 year-old child in Korea. The mother had consumed 162 g of alcohol per week continuously during pregnancy. His first febrile seizure occurred before he was 1 year old, and became more frequent 2 years later. He started showing signs of right paraplegia when he was 3.5 years old and brain MRI revealed periventricular leucomalacia near the left ventricle. He was microcephalic and his growth was retarded. He was irritable, impatient, impulsive, and inattentive, and showed disinterest in school activities and aggressive and dangerous behavior. After the diagnosis of attention deficit/hyperactivity disorder was made, psychopharmacological treatment and family support was initiated. After 10 months, he still had intermittent ideas of reference, although the aggressive behavior, inattentiveness, and impulsivity had improved. Using this case study, we stress the importance of maternal alcohol history in patients with these characteristics. PMID:20046374

  14. Low-Energy Laser Irradiation And The Nervous System: Method And Results

    NASA Astrophysics Data System (ADS)

    Rochkind, S.; Lubart, R.; Nissan, M.; Barr-Nea, L.

    1988-06-01

    The present study introduces a novel method for assessing the efficacy of so-called soft tissue lasers on the peripheral and central nervous systems. In any readily available method relying on low energy laser irradiation, one of the most critical factors is obviously the wavelength of the laser, for this will determine how much of the energy applied to the skin or muscle actually reaches the target nerve. The present findings reaffirm our conclusion that low energy laser irradiation is bene-ficial in the treatment of injured peripheral or central nervous system, the beneficial effect diminishing with decreasing wavelength from 632nm down to 465nm. Our results pave the way for a new approach to the treatment of traumatic paraplegia and argue in favor of a combination of laser irradiation and PNS or CNS transplantation for the treatment of spinal cord injury.

  15. Nontraumatic Myelopathy Associated With Surfing

    PubMed Central

    Avilés-Hernández, Israel; García-Zozaya, Inigo; DeVillasante, Jorge M

    2007-01-01

    Background/Objective: Ischemic nontraumatic spinal cord injury associated with surfing is a novel diagnosis believed to be related to prolonged spine hyperextension while lying prone on the surfboard. Only 9 cases have been documented. This report features possible risk factors, etiology, diagnostic imaging, and outcomes of surfer's myelopathy. Design: Case report. Results: A 37-year-old man developed T11 American Spinal Injury Association (ASIA) A paraplegia shortly after surfing. The clinical history and magnetic resonance imaging findings were compatible with an ischemic insult to the distal thoracic spinal cord. Our patient did not have any of the proposed risk factors associated with this condition, and, contrary to most reports, he sustained a complete spinal cord lesion without neurological recovery by 8 weeks post injury. Conclusions: Surfer's myelopathy, because of its proposed mechanism of injury, is amenable to medical intervention. Increased awareness of this condition may lead to early recognition and treatment, which should contribute to improved neurological outcomes. PMID:17684897

  16. Acute onset of postoperative syringohydromyelia

    PubMed Central

    Rao, K. Santosh Mohan; Balasubramaniam, Chidambaram; Subramaniam, K.

    2015-01-01

    Syringohydromyelia is a frequent finding in cases of tethered cord syndrome. The classical teaching is that the development and progression of a syrinx is a chronic process. We present a case report of an acute onset syringomyelia in an infant, who underwent an excision of a lumbosacral transitional lipoma and detethering of the cord. Immediately after recovery, the infant was found to have flaccid paraplegia. An emergency magnetic resonance imaging revealed a large acute onset syringomyelia for which he underwent an emergency midline myelotomy and release of fluid from the syrinx. Though the eventual recovery was good, this made us re-visit our understanding of the concept of syringohydromyelia. The case details and a plausible hypothesis for the rapid development of the syrinx are presented. PMID:26557165

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

    PubMed

    Renvoisé, Benoît; Blackstone, Craig

    2010-10-01

    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 presynaptic 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

  18. Brain-computer interface driven functional electrical stimulation system for overground walking in spinal cord injury participant.

    PubMed

    King, Christine E; Wang, Po T; McCrimmon, Colin M; Chou, Cathy C Y; Do, An H; Nenadic, Zoran

    2014-01-01

    The current treatment for ambulation after spinal cord injury (SCI) is to substitute the lost behavior with a wheelchair; however, this can result in many co-morbidities. Thus, novel solutions for the restoration of walking, such as brain-computer interfaces (BCI) and functional electrical stimulation (FES) devices, have been sought. This study reports on the first electroencephalogram (EEG) based BCI-FES system for overground walking, and its performance assessment in an individual with paraplegia due to SCI. The results revealed that the participant was able to purposefully operate the system continuously in real time. If tested in a larger population of SCI individuals, this system may pave the way for the restoration of overground walking after SCI.

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

    SciTech Connect

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

    2012-02-15

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

  20. Stabilizing transpelvic prosthetic socket for a patient with spinal cord injury sustaining right partial hemipelvectomy and left hip disarticulation.

    PubMed

    Nakanishi, Yoshie; Watanabe, Tetsuro; Ikeda, Atsushi; Wada, Futoshi; Hachisuka, Kenji

    2012-06-01

    A bucket-type transpelvic socket was fabricated for a man with paraplegia from spinal cord injury, who underwent right partial pelvic amputation and left hip disarticulation. His main problem was inability to sit due to asymmetrical pelvic shape. We prescribed a transpelvic prosthetic socket to enable him to sit again. The socket consisted of a dual structure: a hard frame and soft liner. The main features of the socket were redistribution of pressure to prevent recurrence of pressure ulcer, and a slightly backward tilt to maintain a comfortable sitting position. In addition, the socket had small air holes for ventilation; a big window in the abdominal area for management of stoma and cystostomy; and two straps for donning it independently. In addition, we confirmed the internal pressure distribution in the socket by a pressure mapping system to prevent reoccurrence of skin trouble. Finally, the patient regained independence in activities of daily living, including driving a car, after two months of rehabilitative training.

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

    PubMed

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

    2016-06-01

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

  2. [Recent progress in orthopaedic managements of osteoporosis-related fractures].

    PubMed

    Yamamoto, Seizo

    2011-07-01

    Recent progress in orthopaedic treatment of osteoporosis-related fractures was reviewed. In the treatment of femoral neck fractures, impacted or nondisplaced type is treated by three cannulated cancellous pins. Displaced type of femoral neck fracture is treated by bipolar prosthesis. Results of femoral neck fractures are influenced by the complications of each patients. Osteoporotic spine fractures are commonly healed within 2 or 3 months. Spinal compression with paraparesis or paraplegia is unusual complication in burst type of spine fractures. Surgical decompression, bone grafting and stabilization with instrumentation can result in some correction of deformity and neurogenic recovery. Distal radius fractures are common fractures in the eldery. Recently advances includes external fixation and plate fixation for the comminuted fractures in the distal radius. Treatments of osteoporosis-related fractures are still difficult problems to be resolved. PMID:21774371

  3. Managing chronic oedema in a patient with arterial disease and leg ulceration.

    PubMed

    Cooper, Robin

    2016-04-01

    Treating lymphoedema in patients with critical arterial disease can be contraindicated. This case study describes current methods of managing lymphoedema in a patient with arterial disease and leg ulcers. The patient, a 65-year-old male, had paraplegia and lower-limb lymphoedema with leg ulceration for 18 years, as well as arterial disease. The patient was referred to the lymphoedema/vascular service in 2013. Duplex ultrasound indicated superficial femoral occlusion. The arterial disease was treated with an angiogram and angioplasty, and when the blood supply was improved, the lymphoedema was treated. Emphasis was placed on self-care and reducing the need for community nurse involvement. Selfcare included compression bandaging, use of FarrowWrap, low-level light therapy, and ulcer dressings. Outcomes were measured using a telemedicine software programme. The patient's lymphoedema was reduced, leg ulcers healed, and quality of life transformed.

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

    PubMed

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

    2015-06-01

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

  5. Epidemiology of spinal cord injury.

    PubMed

    Kurtzke, J F

    1977-01-01

    Accidents are the cause of some 50 deaths per 100 000 population each year in the US; some 3% of these are from traumatic spinal cord injury alone. Traumatic spinal cord injury in socioeconomically advanced countries, has a probably annual incidence rate of 3 per 100 000 population. Males are affected five times as often as females, and in the US, Negroes have twice the rates of whites. Half the cases are due to motor vehicle accidents, 1/4 to falls, and 1/10 to sports injuries. Maximal ages at risk are 15 to 34; only for cord damage due to falls do this risk differ, and here elderly are the more prone. Associated injuries are common in traumatic cord injury, and head injury and pulmonary dysfunction are frequent causes of the acute deaths in traumatic SCI which is why complete quadriplegia has a high early case-fatality ratio. Late deaths in SCI are principally the direct or indirect result of the neurogenic bladder. With treatment in comprehensive spinal cord injury centers, more than 4 of 5 traumatic SCI patients will survive ten years with an average of almost 18 years. Median survival may be almost 14 years for complete quadriplegia, 17 for complete paraplegia, 19 for incomplete quadriplegia, 20 for incomplete paraplegia and 28 for cauda equina lesions. Prevalence is likely to be some 50 per 100 000 population with about 20 per 100 000 completely paralyzed (3 quadriplegic and 19 paraplegic). Some 4 out of 5 survivors of traumatic SCI should be able to live at home and perform gainful work after such treatment. PMID:616527

  6. LMNB1‐related autosomal‐dominant leukodystrophy: Clinical and radiological course

    PubMed Central

    Sundblom, Jimmy; Dahl, Niklas; Melberg, Atle; Raininko, Raili

    2015-01-01

    Objective Duplication of the LMNB1 gene encoding lamin B1 causes adult‐onset autosomal‐dominant leukodystrophy (ADLD) starting with autonomic symptoms, which are followed by pyramidal signs and ataxia. Magnetic resonance imaging (MRI) of the brain reveals characteristic findings. This is the first longitudinal study on this disease. Our objective is to describe the natural clinical and radiological course of LMNB1‐related ADLD. Methods Twenty‐three subjects in two families with LMNB1 duplications were studied over two decades with clinical assessment and MRI of the brain and spinal cord. They were 29 to 70 years old at their first MRI. Repeated MRIs were performed in 14 subjects over a time period of up to 17 years. Results Pathological MRI findings were found in the brain and spinal cord in all examinations (i.e., even preceding clinical symptoms). MRI changes and clinical symptoms progressed in a definite order. Autonomic dysfunction appeared in the fifth to sixth decade, preceding or together with gait and coordination difficulties. Motor signs developed ascending from spastic paraplegia to tetraplegia and pseudobulbar palsy in the seventh decade. There were clinical, radiological, and neurophysiological signs of myelopathy. Survival lasted more than two decades after clinical onset. Interpretation LMNB1‐related ADLD is a slowly progressive neurological disease. MRI abnormalities of the brain and spinal cord can precede clinical symptoms by more than a decade and are extensive in all symptomatic patients. Spinal cord involvement is a likely contributing factor to early autonomic symptoms and spastic paraplegia. Ann Neurol 2015;78:412–425 PMID:26053668

  7. Test bed with force-measuring crank for static and dynamic investigations on cycling by means of functional electrical stimulation.

    PubMed

    Gföhler, M; Angeli, T; Eberharter, T; Lugner, P; Mayr, W; Hofer, C

    2001-06-01

    Cycling by means of functional electrical stimulation (FES) is an attractive training method for individuals with paraplegia. The physiological benefits of FES are combined with the psychological incentive of independent locomotion. In addition, cycling has the advantage in that the generated muscle forces are converted into drive power with relatively high efficiency compared to other means of locomotion, e.g., walking. For the design of an appropriate cycling device and the development of optimal stimulation patterns, it has to be investigated how the geometry for FES cycling, influenced by individual parameters of the FES-generated drive torques and the magnitude of variations among subjects with paraplegia, can be optimized. This study shows the design of a freely adjustable test bed with additional motor drive which allows static and dynamic measurements of force components and drive torque at the crank. Furthermore, the influence of geometry and various individual parameters on FES pedaling can be tested for each subject individually. A pedal path realized by a three-bar linkage that was optimized according to preliminary simulations further increases leg cycling efficiency. Safety precautions avoid injuries in case of excessive forces, e.g., spasms. Test results illustrate the application of the test bed and measurement routines. A test series with four paraplegic test persons showed that the presented static and dynamic measurement routines allow to provide optimal stimulation patterns for individual paraplegic subjects. While pedaling with these optimal stimulation patterns only negligible negative active drive torques, due to active muscle forces, were applied to the crank and sufficient drive power was generated to power a cycle independently.

  8. Significance and function of different spinal collateral compartments following thoracic aortic surgery: immediate versus long-term flow compensation.

    PubMed

    Meffert, Philipp; Bischoff, Moritz S; Brenner, Robert; Siepe, Matthias; Beyersdorf, Friedhelm; Kari, Fabian A

    2014-05-01

    Iatrogenic paraplegia has been accompanying cardiovascular surgery since its beginning. As a result, surgeons have been developing many theories about the exact mechanisms of this devastating complication. Thus, the impact of single arteries that contribute to the spinal perfusion is one of the most discussed subjects in modern surgery. The subsequent decision of reattachment or the permanent disconnection of these intercostal arteries divides the surgical community. On the one hand, the anatomical or vascular approach pleads for the immediate reimplantation to reconstruct the anatomical situation. On the other hand, the decision of the permanent disconnection aims at avoiding stealing phenomenon away from the spinal vascular network. This spinal collateral network can be described as consisting of three components-the intraspinal and two paraspinal compartments-that feed the nutrient arteries of the spinal cord. The exact functional impact of the different compartments of the collateral network remains poorly understood. In this review, the function of the intraspinal compartment in the context of collateral network principle as an immediate emergency backup system is described. The exact structure and architectural principles of the intraspinal compartment are described. The critical parameters with regard to the risk of postoperative spinal cord ischaemia are the number of anterior radiculomedullary arteries (ARMAs) and the distance between them in relation to the longitudinal extent of aortic disease. The paraspinal network as a sleeping reserve is proposed as the long-term backup system. This sleeping reserve has to be activated by arteriogenic stimuli. These are presented briefly, and prior findings regarding arteriogenesis are discussed in the light of the collateral network concept. Finally, the role of preoperative visualization of the ARMAs in order to evaluate the risk of postoperative paraplegia is emphasized. PMID:24078102

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Frankel, H L

    2012-11-01

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

  11. Energy requirements of gamefield exercises designed for wheelchair-bound persons.

    PubMed

    Cardús, D; McTaggart, W G; Ribas-Cardús, F; Donovan, W H

    1989-02-01

    This report presents energy requirements of three athletic exercises (power ramp, climber, and chin-ups) in a free-wheeling gamefield developed by the City of Houston for wheelchair-bound persons. Heart rate was monitored by telemetry. Expired gas samples were collected in Douglas bags. Oxygen and CO2 concentrations were determined by mass spectrometry and expired gas volumes by a wet gas meter. Pulmonary ventilation, O2 consumption, and CO2 production were calculated from expired gas samples. Laboratory studies were conducted on eight men with paraplegia and ten untrained, healthy, able-bodied men. The same persons were tested on the gamefield while propelling a wheelchair over the power ramp, the climber, and doing chin-ups. Age and weight were 32 +/- 4yrs vs 31 +/- 6yrs and 79.6kg vs 79.0kg, respectively, for paraplegic and healthy men. Paraplegic men had average heart rates of 133 +/- 11bpm, 133 +/- 19bpm, and 135 +/- 21bpm, respectively, for the power ramp, climber, and chin-ups. Heart rate values for able-bodied men were 136 +/- 26bpm, 139 +/- 24bpm, and 136 +/- 26bpm, respectively, for the same three exercises. The paraplegic men's VO2 measurements were 13.2 +/- 2.2, 11.5 +/- 2.8, and 6.4 +/- 2.9ml/min/kg, respectively, for the power ramp, climber, and chin-ups. The able-bodied men's VO2 measurements were 15.8 +/- 2.8, 15.4 +/- 3.6, and 9.2 +/- 2.8 ml/min/kg for the same exercises. Patients with paraplegia seemed to outperform able-bodied men in all events. Gamefield exercises appeared to tax the cardiorespiratory system at a level comparable to that usually prescribed for training purposes. PMID:2916929

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

    PubMed Central

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

    2015-01-01

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

  13. Measuring Activity Limitation Outcomes in Youth with Spinal Cord Injury

    PubMed Central

    Slavin, Mary D.; Mulcahey, MJ; Calhoun, Christina; Ni, Pengsheng; Vogel, Lawrence C.; Haley, Stephen M.; Jette, Alan M.

    2016-01-01

    Study Design Cross-sectional Objectives The Pediatric Spinal Cord Injury Activity Measure (PEDI-SCI AM), which includes calibrated item banks (child and parent versions) for General Mobility, Daily Routines, Wheeled Mobility and Ambulation, can be administered using computerized adaptive tests (CATs) or short forms (SFs). The study objectives are: 1.) examine the psychometric properties of the PEDISCI AM item banks and 10-item CATs); 2.) develop and evaluate the psychometric properties of PEDI-SCI AM SFs. Setting U.S. Shriners Hospitals for Children (California, Illinois and Pennsylvania). Methods Calibration data from a convenience sample of 381 children and adolescents with SCI and 322 parents or caregivers were used to examine PEDI-SCI AM item banks, 10-item CATs and SF scores. We calculated group reliability, internal consistency (Cronbach's alpha), and interclass coefficients (ICCs) to assess agreement between 10-item CATs, SFs and item banks. The percent of the sample with highest (ceiling) and lowest (floor) scores was also determined. An expert panel selected items for 14 SFs. Results PEDI-SCI item banks, 10-item CATs and SFs demonstrate acceptable group reliability (0.73-0.96) and internal consistency (0.77-0.98). ICC values show strong agreement with item banks for 10-item CATs (0.72-0.99) and SFs. Floor effects are minimal (<15%). Ceiling effects are minimal for children with tetraplegia, but high in children with paraplegia for General Mobility (13.41-26.05%) and Daily Activities (12.99-32.71%). Conclusions The PEDI-SCI AM exhibited strong psychometric properties for children with tetraplegia. Replenishment of the General Mobility and Daily Routines item banks is needed to reduce ceiling effects noted for youth with paraplegia. PMID:26572606

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

    PubMed

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

    2015-09-01

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

  15. 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

  16. 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

  17. Test bed with force-measuring crank for static and dynamic investigations on cycling by means of functional electrical stimulation.

    PubMed

    Gföhler, M; Angeli, T; Eberharter, T; Lugner, P; Mayr, W; Hofer, C

    2001-06-01

    Cycling by means of functional electrical stimulation (FES) is an attractive training method for individuals with paraplegia. The physiological benefits of FES are combined with the psychological incentive of independent locomotion. In addition, cycling has the advantage in that the generated muscle forces are converted into drive power with relatively high efficiency compared to other means of locomotion, e.g., walking. For the design of an appropriate cycling device and the development of optimal stimulation patterns, it has to be investigated how the geometry for FES cycling, influenced by individual parameters of the FES-generated drive torques and the magnitude of variations among subjects with paraplegia, can be optimized. This study shows the design of a freely adjustable test bed with additional motor drive which allows static and dynamic measurements of force components and drive torque at the crank. Furthermore, the influence of geometry and various individual parameters on FES pedaling can be tested for each subject individually. A pedal path realized by a three-bar linkage that was optimized according to preliminary simulations further increases leg cycling efficiency. Safety precautions avoid injuries in case of excessive forces, e.g., spasms. Test results illustrate the application of the test bed and measurement routines. A test series with four paraplegic test persons showed that the presented static and dynamic measurement routines allow to provide optimal stimulation patterns for individual paraplegic subjects. While pedaling with these optimal stimulation patterns only negligible negative active drive torques, due to active muscle forces, were applied to the crank and sufficient drive power was generated to power a cycle independently. PMID:11474970

  18. Elephant trunk technique for hybrid aortic arch repair.

    PubMed

    Miyamoto, Yuji

    2014-03-01

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

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

    PubMed

    Simonelli, Angela Paula; Camarotto, João Alberto

    2008-01-01

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

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

    PubMed

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

    2015-09-01

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

  1. 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.

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

    PubMed Central

    Michaelson, I. Arthur; Sauerhoff, Mitchell W.

    1974-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  4. Exploring the associations between arterial stiffness and spinal cord impairment: A cross-sectional study

    PubMed Central

    Miyatani, Masae; Szeto, Maggie; Moore, Cameron; Oh, Paul I.; McGillivray, Colleen F.; Catharine Craven, B.

    2014-01-01

    Background/Objective Elevated aortic arterial stiffness (aortic pulse wave velocity: aPWV) is an independent coronary artery disease predictor among the general population. The purpose of this study was to: (1) report aPWV values in a representative cohort of patients with spinal cord injury (SCI); (2) to compare aPWV values in people with SCI based on neurological level of injury; and (3) to contrast the reported aPWV values with available normal values for the general population. Methods Adults with chronic SCI (n = 87) were divided into two groups (TETRA group, n = 37 and PARA group, n = 50). aPWV and potential confounders of aPWV were assessed. Analysis of covariance was used for comparisons between groups and adjusted for the confounders. Subjects’ aPWV values were contrasted with reference values for general population determined by “The Reference value for arterial stiffness’ collaboration” and prevalence of abnormal aPWV defined as greater than or equal to the age-specific 90th percentile was reported. Results Prevalence of abnormal aPWV in the cohort was 25.3%. After adjusting for covariates, the mean aPWV values were significantly different between two groups (TETRA: 8.0 (95% confidence interval (CI): 7.5–8.6) m/second, PARA: 9.0 (95% CI: 8.5–9.4) m/second, P = 0.010). The prevalence of abnormal aPWV was significantly higher in the PARA group (36%) compared to the TETRA group (11%) (P = 0.012). Conclusions One-quarter of the total cohort had an abnormal aPWV. Subjects with paraplegia had higher aPWV values and a higher frequency of abnormal aPWV than subjects with tetraplegia. Elevated aPWV in people with SCI, particularly those with paraplegia, may impart significant adverse cardiovascular consequences. PMID:25229737

  5. Clinical experience with the Sarns centrifugal pump.

    PubMed

    Curtis, J J; Walls, J T; Demmy, T L; Boley, T M; Schmaltz, R A; Goss, C F; Wagner-Mann, C C

    1993-07-01

    Since October 1986, we have had experience with 96 Sarns centrifugal pumps in 72 patients (pts). Heparinless left atrial to femoral artery or aorta bypass was used in 14 pts undergoing surgery on the thoracic aorta with 13 survivors (93%). No paraplegia or device-related complications were observed. In 57 patients, the Sarns centrifugal pump was used as a univentricular (27 pts) or biventricular (30 pts) cardiac assist device for postcardiotomy cardiogenic shock. In these patients, cardiac assist duration ranged from 2 to 434 h with a hospital survival rate of 29% in those requiring left ventricular assist and 13% in those requiring biventricular assist. Although complications were ubiquitous in this mortally ill patient population, in 5,235 pump-hours, no pump thrombosis was observed. Hospital survivors followed for 4 months to 6 years have enjoyed an improved functional class. We conclude that the Sarns centrifugal pump is an effective cardiac assist device when used to salvage patients otherwise unweanable from cardiopulmonary bypass. Partial left ventricular bypass using a centrifugal pump has become our procedure of choice for unloading the left ventricle and for maintenance of distal aortic perfusion pressure when performing surgery on the thoracic aorta. This clinical experience with the Sarns centrifugal pump appears to be similar to that reported with other centrifugal assist devices.

  6. Topographic maps of human motor cortex in normal and pathological conditions: mirror movements, amputations and spinal cord injuries.

    PubMed

    Cohen, L G; Bandinelli, S; Topka, H R; Fuhr, P; Roth, B J; Hallett, M

    1991-01-01

    We studied motor evoked potentials to transcranial magnetic stimulation in patients with unilateral upper limb amputations, complete T10-T12 spinal cord transection, and congenital mirror movements and in controls. Different muscles in the trunk and upper and lower extremities were evaluated at rest. In controls, muscles could be activated with stimulation of regions several centimeters wide. These areas overlapped extensively when muscles studied were from the same limb and shifted positions abruptly when muscles were from different limbs. Distal muscles were easier to activate than proximal muscles and normally evidenced exclusively a contralateral representation. Congenital defects in motor control in patients with mirror movements resulted in marked derangement of the map of outputs of distal hand muscles with enlarged and ipsilateral representations. Peripheral lesions, either acquired (amputations) or congenital (congenital absence of a limb), resulted in plastic reorganization of motor outputs targeting muscles immediately proximal to the stump. Central nervous system lesions (i.e., spinal cord injury producing paraplegia) also resulted in enlargement of the map of outputs targeting muscles proximal to the lesion. These results indicate that magnetic stimulation is a useful non-invasive tool for exploring plastic changes in human motor pathways following different types of injury.

  7. TFG-Related Neurologic Disorders: New Insights Into Relationships Between Endoplasmic Reticulum and Neurodegeneration.

    PubMed

    Yagi, Takuya; Ito, Daisuke; Suzuki, Norihiro

    2016-04-01

    The tropomyosin-receptor kinase fused gene(TFG), which is located on chromosome 3q12.2, was originally identified as a fusion partner that results in the formation of oncogenic products associated with multiple cancers. TFG protein interacts directly with Sec16, the scaffolding protein for coat protein II-coated vesicles that regulate endoplasmic reticulum (ER)-to-Golgi transport at ER exit sites. In 2012, a heterozygous mutation of TFG was identified as the causative gene for autosomal-dominant hereditary motor and sensory neuropathy with proximal dominant involvement. In 2013, a homozygous mutation of TFG was reported in a family with early onset spastic paraplegia, optic atrophy, and neuropathy. Another novel mutation in TFG was discovered in 2014 as a cause of dominant axonal Charcot-Marie-Tooth disease type 2. These findings suggest that mutations of TFG cause ER dysfunction and neurodegeneration in this disease spectrum, which is tightly associated with ER function. Here, we review the clinical phenotypes of these diseases and present recent insights that suggest causal roles of ER dysfunction in TFG-related neurologic disorders. Although the precise pathogenetic mechanisms underlying these TFG mutations remain to be elucidated, experimental manipulations suggest that the dysregulations of ER homeostasis that occur due to mutations in TFG lead to neurodegeneration. PMID:26945032

  8. [Subarachnoid hematoma and spinal anesthesia].

    PubMed

    Dupeyrat, A; Dequiré, P M; Mérouani, A; Moullier, P; Eid, G

    1990-01-01

    Two cases of spinal subarachnoid haematoma occurring after spinal anaesthesia are reported. In the first case, lumbar puncture was attempted three times in a 81-year-old man; spinal anaesthesia trial was than abandoned, and the patient given a general anaesthetic. He was given prophylactic calcium heparinate soon after surgery. On the fourth day, the patient became paraparetic. Radioculography revealed a blockage between T10 and L3. Laminectomy was performed to remove the haematoma, but the patient recovered motor activity only very partially. The second case was a 67-year-old man, in whom spinal anaesthesia was easily carried out. He was also given prophylactic calcium heparinate soon after surgery. On the fourth postoperative day, pulmonary embolism was suspected. Heparin treatment was then started. Twelve hours later, lumbar and bilateral buttock pain occurred, which later spread to the neck. On the eighth day, the patient had neck stiffness and two seizures. Emergency laminectomy was carried out, which revealed a subarachnoid haematoma spreading to a level higher than T6 and below L1, with no flow of cerebrospinal fluid, and a non pulsatile spinal cord. Surgery was stopped. The patient died on the following day. Both these cases are similar to those previously reported and point out the role played by anticoagulants. Because early diagnosis of spinal cord compression is difficult, the prognosis is poor, especially in case of paraplegia. PMID:2278424

  9. Solitary Spinal Epidural Metastasis from Gastric Cancer

    PubMed Central

    Sako, Taisei; Iida, Yasuaki; Yokoyama, Yuichirou; Tsuge, Shintaro; Hasegawa, Keiji; Wada, Akihito; Mikami, Tetsuo

    2016-01-01

    Solitary epidural space metastasis of a malignant tumor is rare. We encountered a 79-year-old male patient with solitary metastatic epidural tumor who developed paraplegia and dysuria. The patient had undergone total gastrectomy for gastric cancer followed by chemotherapy 8 months priorly. The whole body was examined for suspected metastatic spinal tumor, but no metastases of the spine or important organs were observed, and a solitary mass was present in the thoracic spinal epidural space. The mass was excised for diagnosis and treatment and was histopathologically diagnosed as metastasis from gastric cancer. No solitary metastatic epidural tumor from gastric cancer has been reported in English. Among the Japanese, 3 cases have been reported, in which the outcome was poor in all cases and no definite diagnosis could be made before surgery in any case. Our patient developed concomitant pneumonia after surgery and died shortly after the surgery. When a patient has a past medical history of malignant tumor, the possibility of a solitary metastatic tumor in the epidural space should be considered. PMID:27703825

  10. [Hereditary movement disorders].

    PubMed

    Schulz, J B

    2007-12-01

    Hereditary movement disorders comprise a group of genetically defined diseases characterized by an impaired control of movements, ataxia and/or spasticity. Affected individuals are disabled, their quality of life significantly reduced and their life expectancy shortened. One or more genetic causes have been identified for many of these diseases, including Huntington's disease, Wilson's disease, spinocerebellar ataxias, recessive ataxias, hereditary spastic paraplegia and hereditary dystonias. Due to their characteristic molecular and biochemical pathogenesis, these rare diseases can often serve as models for more common disorders such as Alzheimer's disease or Parkinson's disease. The primary tasks of the German Network of Hereditary Movement Disorders (GeNeMove), funded by the German Ministry for Education and Research (BMBF), are to co-ordinate basic scientific research and clinical research into rare hereditary movement disorders and to improve the cooperation between the German centers specializing in hereditary movement disorders. For each of the diseases in its scope, GeNeMove works at creating standardized documentation of symptoms and the disease's progressive course over time; developing rating scales for clinical examinations and guidelines for therapy; improving genetic testing; fostering genetic research; and collecting samples of DNA, tissue, CSF and blood from sufferers of the disease for biobanks.

  11. Long-Term Training with a Brain-Machine Interface-Based Gait Protocol Induces Partial Neurological Recovery in Paraplegic Patients.

    PubMed

    Donati, Ana R C; Shokur, Solaiman; Morya, Edgard; Campos, Debora S F; Moioli, Renan C; Gitti, Claudia M; Augusto, Patricia B; Tripodi, Sandra; Pires, Cristhiane G; Pereira, Gislaine A; Brasil, Fabricio L; Gallo, Simone; Lin, Anthony A; Takigami, Angelo K; Aratanha, Maria A; Joshi, Sanjay; Bleuler, Hannes; Cheng, Gordon; Rudolph, Alan; Nicolelis, Miguel A L

    2016-01-01

    Brain-machine interfaces (BMIs) provide a new assistive strategy aimed at restoring mobility in severely paralyzed patients. Yet, no study in animals or in human subjects has indicated that long-term BMI training could induce any type of clinical recovery. Eight chronic (3-13 years) spinal cord injury (SCI) paraplegics were subjected to long-term training (12 months) with a multi-stage BMI-based gait neurorehabilitation paradigm aimed at restoring locomotion. This paradigm combined intense immersive virtual reality training, enriched visual-tactile feedback, and walking with two EEG-controlled robotic actuators, including a custom-designed lower limb exoskeleton capable of delivering tactile feedback to subjects. Following 12 months of training with this paradigm, all eight patients experienced neurological improvements in somatic sensation (pain localization, fine/crude touch, and proprioceptive sensing) in multiple dermatomes. Patients also regained voluntary motor control in key muscles below the SCI level, as measured by EMGs, resulting in marked improvement in their walking index. As a result, 50% of these patients were upgraded to an incomplete paraplegia classification. Neurological recovery was paralleled by the reemergence of lower limb motor imagery at cortical level. We hypothesize that this unprecedented neurological recovery results from both cortical and spinal cord plasticity triggered by long-term BMI usage. PMID:27513629

  12. Results of Isotope Cisternography in 175 Patients with a Suspected Hydrocephalus

    PubMed Central

    Lee, Sang-Mi; Shim, Jae-Joon; Yoon, Seok-Mann; Bae, Hack-Gun; Doh, Jae-Won

    2015-01-01

    Objective Normal pressure hydrocephalus (NPH) is a syndrome characterized by gait disturbance, memory impairment and urinary incontinence. The isotope cisternography (ICG) became less useful because of low accuracy and complications. We tried to evaluate the safety and value of the ICG. Methods We retrospectively collected data on ICG of 175 consecutive patients with a suspected hydrocephalus. We classified the ICG into four types by the ventricular reflux and circulation time. The ventricular size was measured by Evans index and the width of the third ventricle. Results There were three complications including one case of paraplegia. Type 4 was the most common type, observed in 53%. Type 3 (33%), type 2 (7%), and type 1 (7%) were observed less often. Type 4 was more common in patients with large ventricles. Types of the ICG were not related to the causes of hydrocephalus, gender, or age of the patients. Shunting was more frequently performed in type 4 (71%), compared to type 1 (17%), type 2 (33%), and type 3 (46%). Surgery was more common when the cause was vascular. After the shunt surgery, 33.0% were graded as the improved. Although there were some improvements even in the not-improved patients, they still needed many helps. The improvement was related to the preoperative state. Conclusion ICG may bring a serious complication, however the incidence is very low. Although the predictability of response rate on the shunting is doubtful, ICG is a cheap and useful tool to select surgical candidates in NPH. PMID:27169059

  13. Neuropathology of experimental 3-nitro-4-hydroxyphenylarsonic acid toxicosis in pigs.

    PubMed

    Kennedy, S; Rice, D A; Cush, P F

    1986-07-01

    Twenty pigs were fed a diet containing 187.5 mg kg-1 of 3-nitro-4-hydroxyphenylarsonic acid (3-nitro). Ten pigs were euthanized at intervals up to 29 days, 3-nitro was withdrawn from the diet of the remaining pigs on day 30, and these animals were subsequently euthanized at intervals up to 49 days after commencement of the experiment. A nervous syndrome characterized by clonic convulsive episodes inducible by exercise, developed at day 11. Paraparesis was apparent at day 22 progressing to paraplegia by day 33 (3 days after cessation of 3-nitro feeding). Histopathologic examination revealed myelin and axonal degeneration in the white matter of the spinal cord coincident with the onset of nervous signs. Marchi-positive degeneration was present in the dorsal funiculus at cervical level at day 22. Lesions intensified with increasing duration of toxicosis and while degenerate fibers were seen in all funiculi, there was preferential involvement of the fasciculi gracilis and cuneatus, the peripheral regions of the ventral and lateral funiculi, and a discrete area of the dorsal region of the lateral funiculus. Peripheral and optic neuropathies were evident from day 32 but were always mild and focal. The experiment establishes 3-nitro as a central-peripheral neurotoxicant of pigs.

  14. [Intramedullary bronchogenic cyst. Apropos of 1 case. Discussion of the endo-ectodermal adhesion syndrome].

    PubMed

    Duthel, R; Brunon, J; Michel, D; Boucheron, S

    1983-01-01

    The authors report the case of a 40-year-old man who has presented for many years an intermittent progressive spastic paraplegia. Plain films of the spine show very important dysraphic abnormalities of the inferior dorsal column and the myelography shows a complete block suggesting an intramedullary space-occupying lesion at four levels above the vertebral abnormalities. The operation permits a total removal of an intramedullary "bronchogenic cyst". In the post-operative course, the neurologic deficit improves, six months later a spastic paraparesia remains. The review of the literature shows that this is an exceptional observation. Intramedullary bronchogenic cysts must be regarded as similar to intramedullary enterogenic cysts. They are not teratomas but dysembryoplasiae due to failure of the ento-ectoblastic separation between the second and the third weeks of life. These cysts form a part of the "ento-ectodermal adhesion syndrome" of Prob et al. The preoperative diagnosis is possible on the association of intermittent progressive syndrome of medullary compression and dysraphic spondylotic changes. The total surgical removal of the cyst, by micro-surgical techniques, is able to preserve the neurologic evolution with an excellent result if the operation is performed before definitive neurologic deficits occur.

  15. 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

  16. 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

  17. The mitochondrial permeability transition pore in AD 2016: An update.

    PubMed

    Biasutto, Lucia; Azzolini, Michele; Szabò, Ildikò; Zoratti, Mario

    2016-10-01

    Over the past 30years the mitochondrial permeability transition - the permeabilization of the inner mitochondrial membrane due to the opening of a wide pore - has progressed from being considered a curious artifact induced in isolated mitochondria by Ca(2+) and phosphate to a key cell-death-inducing process in several major pathologies. Its relevance is by now universally acknowledged and a pharmacology targeting the phenomenon is being developed. The molecular nature of the pore remains to this day uncertain, but progress has recently been made with the identification of the FOF1 ATP synthase as the probable proteic substrate. Researchers sharing this conviction are however divided into two camps: these believing that only the ATP synthase dimers or oligomers can form the pore, presumably in the contact region between monomers, and those who consider that the ring-forming c subunits in the FO sector actually constitute the walls of the pore. The latest development is the emergence of a new candidate: Spastic Paraplegia 7 (SPG7), a mitochondrial AAA-type membrane protease which forms a 6-stave barrel. This review summarizes recent developments of research on the pathophysiological relevance and on the molecular nature of the mitochondrial permeability transition pore. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou. PMID:26902508

  18. The N-terminal domain plays a crucial role in the structure of a full-length human mitochondrial Lon protease.

    PubMed

    Kereïche, Sami; Kováčik, Lubomír; Bednár, Jan; Pevala, Vladimír; Kunová, Nina; Ondrovičová, Gabriela; Bauer, Jacob; Ambro, Ľuboš; Bellová, Jana; Kutejová, Eva; Raška, Ivan

    2016-01-01

    Lon is an essential, multitasking AAA(+) protease regulating many cellular processes in species across all kingdoms of life. Altered expression levels of the human mitochondrial Lon protease (hLon) are linked to serious diseases including myopathies, paraplegia, and cancer. Here, we present the first 3D structure of full-length hLon using cryo-electron microscopy. hLon has a unique three-dimensional structure, in which the proteolytic and ATP-binding domains (AP-domain) form a hexameric chamber, while the N-terminal domain is arranged as a trimer of dimers. These two domains are linked by a narrow trimeric channel composed likely of coiled-coil helices. In the presence of AMP-PNP, the AP-domain has a closed-ring conformation and its N-terminal entry gate appears closed, but in ADP binding, it switches to a lock-washer conformation and its N-terminal gate opens, which is accompanied by a rearrangement of the N-terminal domain. We have also found that both the enzymatic activities and the 3D structure of a hLon mutant lacking the first 156 amino acids are severely disturbed, showing that hLon's N-terminal domains are crucial for the overall structure of the hLon, maintaining a conformation allowing its proper functioning. PMID:27632940

  19. Effect of high-frequency repetitive transcranial magnetic stimulation on motor cortical excitability and sensory nerve conduction velocity in subacute-stage incomplete spinal cord injury patients.

    PubMed

    Cha, Hyun Gyu; Ji, Sang-Goo; Kim, Myoung-Kwon

    2016-07-01

    [Purpose] The aim of the present study was to determine whether repetitive transcranial magnetic stimulation can improve sensory recovery of the lower extremities in subacute-stage spinal cord injury patients. [Subjects and Methods] This study was conducted on 20 subjects with diagnosed paraplegia due to spinal cord injury. These 20 subjects were allocated to an experimental group of 10 subjects that underwent active repetitive transcranial magnetic stimulation or to a control group of 10 subjects that underwent sham repetitive transcranial magnetic stimulation. The SCI patients in the experimental group underwent active repetitive transcranial magnetic stimulation and conventional rehabilitation therapy, whereas the spinal cord injury patients in the control group underwent sham repetitive transcranial magnetic stimulation and conventional rehabilitation therapy. Participants in both groups received therapy five days per week for six-weeks. Latency, amplitude, and sensory nerve conduction velocity were assessed before and after the six week therapy period. [Results] A significant intergroup difference was observed for posttreatment velocity gains, but no significant intergroup difference was observed for amplitude or latency. [Conclusion] repetitive transcranial magnetic stimulation may be improve sensory recovery of the lower extremities in subacute-stage spinal cord injury patients. PMID:27512251

  20. Function Over Form: Modeling Groups of Inherited Neurological Conditions in Zebrafish.

    PubMed

    Kozol, Robert A; Abrams, Alexander J; James, David M; Buglo, Elena; Yan, Qing; Dallman, Julia E

    2016-01-01

    Zebrafish are a unique cell to behavior model for studying the basic biology of human inherited neurological conditions. Conserved vertebrate genetics and optical transparency provide in vivo access to the developing nervous system as well as high-throughput approaches for drug screens. Here we review zebrafish modeling for two broad groups of inherited conditions that each share genetic and molecular pathways and overlap phenotypically: neurodevelopmental disorders such as Autism Spectrum Disorders (ASD), Intellectual Disability (ID) and Schizophrenia (SCZ), and neurodegenerative diseases, such as Cerebellar Ataxia (CATX), Hereditary Spastic Paraplegia (HSP) and Charcot-Marie Tooth Disease (CMT). We also conduct a small meta-analysis of zebrafish orthologs of high confidence neurodevelopmental disorder and neurodegenerative disease genes by looking at duplication rates and relative protein sizes. In the past zebrafish genetic models of these neurodevelopmental disorders and neurodegenerative diseases have provided insight into cellular, circuit and behavioral level mechanisms contributing to these conditions. Moving forward, advances in genetic manipulation, live imaging of neuronal activity and automated high-throughput molecular screening promise to help delineate the mechanistic relationships between different types of neurological conditions and accelerate discovery of therapeutic strategies. PMID:27458342

  1. Targeted High-Throughput Sequencing Identifies Mutations in atlastin-1 as a Cause of Hereditary Sensory Neuropathy Type I

    PubMed Central

    Guelly, Christian; Zhu, Peng-Peng; Leonardis, Lea; Papić, Lea; Zidar, Janez; Schabhüttl, Maria; Strohmaier, Heimo; Weis, Joachim; Strom, Tim M.; Baets, Jonathan; Willems, Jan; De Jonghe, Peter; Reilly, Mary M.; Fröhlich, Eleonore; Hatz, Martina; Trajanoski, Slave; Pieber, Thomas R.; Janecke, Andreas R.; Blackstone, Craig; Auer-Grumbach, Michaela

    2011-01-01

    Hereditary sensory neuropathy type I (HSN I) is an axonal form of autosomal-dominant hereditary motor and sensory neuropathy distinguished by prominent sensory loss that leads to painless injuries. Unrecognized, these can result in delayed wound healing and osteomyelitis, necessitating distal amputations. To elucidate the genetic basis of an HSN I subtype in a family in which mutations in the few known HSN I genes had been excluded, we employed massive parallel exon sequencing of the 14.3 Mb disease interval on chromosome 14q. We detected a missense mutation (c.1065C>A, p.Asn355Lys) in atlastin-1 (ATL1), a gene that is known to be mutated in early-onset hereditary spastic paraplegia SPG3A and that encodes the large dynamin-related GTPase atlastin-1. The mutant protein exhibited reduced GTPase activity and prominently disrupted ER network morphology when expressed in COS7 cells, strongly supporting pathogenicity. An expanded screen in 115 additional HSN I patients identified two further dominant ATL1 mutations (c.196G>C [p.Glu66Gln] and c.976 delG [p.Val326TrpfsX8]). This study highlights an unexpected major role for atlastin-1 in the function of sensory neurons and identifies HSN I and SPG3A as allelic disorders. PMID:21194679

  2. ["Goiters and the associated idiocy in several countries. Attempts of Vincenzo Malacarne from Saluzzo". Current interpretation of endemic cretinism].

    PubMed

    Costa, A

    1989-01-01

    Two hundred years ago V. Malacarne pathologist and surgeon, born in Saluzzo, a town on the foot of the Cottian Alps, published a booklet about goiter and endemic cretinism being diseases prevalent at that time in the countryside. In 1940-45 goiter epidemics spread through these still endemic regions. On the basis of his own observations on autoptic specimens he suggested that the main cause of cretinism was brain damage due to impeded blood circulation by the neck swelling, and invited the pathologists of the Po and Aosta Valleys to send him "il capo ed il collo (the head and the neck)" of these goitrous idiots for a control. Also today we believe the thyroid and the brain to contain crucial factors of cretinism, both sporadic and endemic, and we assume that iodine deficiency is the causal link between the two diseases. Yet we do not know either the factors which damage and prevent, in the myxedematous cretin, postnatal thyroid growth, or the aetiopathogenesis of the deaf-mutism, spastic paraplegia and severe mental deficiency of the neurological non hypothyroid cretin. While these questions remain unanswered, ample evidence has matured during the last two centuries regarding the practical importance of iodine prophylaxis to prevent these scourges, today referred to as "iodine deficiency disorders". Some recent findings on diencephalon inflammation in human and canine goitre are quoted. PMID:2499748

  3. Affective forecasting about hedonic loss and adaptation: Implications for damage awards.

    PubMed

    Greene, Edie; Sturm, Kristin A; Evelo, Andrew J

    2016-06-01

    In tort lawsuits, plaintiffs may seek damages for loss of enjoyment of life, so-called hedonic loss, which occurred as a result of an accident or injury. In 2 studies, we examined how people judge others' adaptation and hedonic loss after an injury. Laypeople's forecasts of hedonic loss are relevant to concerns about whether jurors appropriately compensate plaintiffs. Longitudinal data of subjective well-being (e.g., Binder & Coad, 2013) show that hedonic loss is domain-specific: Many physical impairments (e.g., strokes) inflict less hedonic loss than many persistent yet invisible ailments (e.g., mental illness and conditions that cause chronic pain). We used vignette methodology to determine whether laypeople (n = 68 community members and 65 students in Study 1; 87 community members and 93 students in Study 2) and rehabilitation professionals (n = 47 in Study 2) were aware of this fact. In Study 1, participants' ratings of hedonic loss subsequent to a physical injury and a comparably severe psychological impairment did not differ. In Study 2, ratings of short- and long-term hedonic loss stemming from paraplegia and chronic back pain showed that neither laypeople nor professionals understood that hedonic loss is domain-specific. These findings imply that observers may forecast a future for people who suffered serious physical injuries as grimmer than it is likely to be, and a future for people who experience chronic pain and psychological disorders as rosier than is likely. (PsycINFO Database Record

  4. 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

  5. Small bowel entrapment and ureteropelvic junction disruption associated with L3 Chance fracture-dislocation.

    PubMed

    Pesenti, Sebastien; Blondel, Benjamin; Faure, Alice; Peltier, Emilie; Launay, Franck; Jouve, Jean-Luc

    2016-09-16

    Paediatric Chance fracture are rare lesions but often associated with abdominal injuries. We herein present the case of a seven years old patient who sustained an entrapment of small bowel and an ureteropelvic disruption associated with a Chance fracture and spine dislocation following a traffic accident. Initial X-rays and computed tomographic (CT) scan showed a Chance fracture with dislocation of L3 vertebra, with an incarceration of a small bowel loop in the spinal canal and a complete section of the left lumbar ureter. Paraplegia was noticed on the initial neurological examination. A posterior L2-L4 osteosynthesis was performed firstly. In a second time she underwent a sus umbilical laparotomy to release the incarcerated jejunum loop in the spinal canal. An end-to-end anastomosis was performed on a JJ probe to suture the left injured ureter. One month after the traumatism, she started to complain of severe headaches related to a leakage of cerebrospinalis fluid. Three months after the traumatism there was a clear regression of the leakage. One year after the trauma, an anterior intervertebral fusion was done. At final follow-up, no neurologic recovery was noticed. In case of Chance fracture, all physicians should think about abdominal injuries even if the patient is asymptomatic. Initial abdominal CT scan and magnetic resonance imaging provide in such case crucial info for management of the spine and the associated lesions. PMID:27672641

  6. Prediction of functional outcome by motor capability after spinal cord injury.

    PubMed

    Lazar, R B; Yarkony, G M; Ortolano, D; Heinemann, A W; Perlow, E; Lovell, L; Meyer, P R

    1989-11-01

    The relationship between early motor status and functional outcome after spinal cord injury (SCI) was evaluated prospectively in 52 quadriplegic and 26 paraplegic patients. Motor status was measured within 72 hours of injury and quantified with the Motor Index Score (MIS). Functional status was evaluated with the Modified Barthel Index (MBI). A senior physical therapist completed the MIS and the MBI when each patient was admitted to the spinal cord intensive care unit and every 30 days during rehabilitation. Early motor function was correlated with average daily improvement in functional status including self-care and mobility (p = .001). The initial MIS strongly correlated with functional status of quadriplegics at admission (p = .001), at 60 days, and at rehabilitation discharge (p = .001). In paraplegics, the overall MBI at admission, after 60 days of rehabilitation, and at discharge was not correlated with early motor function. However, the MIS correlated significantly with the MBI self-care subscore at 60 days and at discharge (p = .01), but not with the mobility subscore. The initial MIS was also significantly correlated to functional status at discharge in patients with complete lesions (p = .001), but was not related to functional status at discharge in patients with incomplete lesions. The MIS appears to be a useful tool in predicting function during rehabilitation, although individual differences in ambulation, particularly for patients with paraplegia, limit the predictive utility of this index. PMID:2818153

  7. Spinal cord lesions shrink peripersonal space around the feet, passive mobilization of paraplegic limbs restores it.

    PubMed

    Scandola, Michele; Aglioti, Salvatore Maria; Bonente, Claudio; Avesani, Renato; Moro, Valentina

    2016-04-06

    Peripersonal space (PPS) is the space surrounding us within which we interact with objects. PPS may be modulated by actions (e.g. when using tools) or sense of ownership (e.g. over a rubber hand). Indeed, intense and/or prolonged use of a tool may induce a sense of ownership over it. Conversely, inducing ownership over a rubber hand may activate brain regions involved in motor control. However, the extent to which PPS is modulated by action-dependent or ownership-dependent mechanisms remains unclear. Here, we explored the PPS around the feet and the sense of ownership over lower limbs in people with Paraplegia following Complete spinal cord Lesions (PCL) and in healthy subjects. PCL people can move their upper body but have lost all sensory-motor functions in their lower body (e.g. lower limbs). We tested whether PPS alterations reflect the topographical representations of various body parts. We found that the PPS around the feet was impaired in PCL who however had a normal representation of the PPS around the hands. Significantly, passive mobilization of paraplegic limbs restored the PPS around the feet suggesting that activating action representations in PCL brings about short-term changes of PPS that may thus be more plastic than previously believed.

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

    PubMed Central

    Fregly, Benjamin J.

    2011-01-01

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

  9. [25 cases of traumatic rupture of the thoracic aorta: current diagnostic elements].

    PubMed

    Verdant, A; Mercier, C; Cossette, R; Dontigny, L; Pagé, A; Bernard, C

    1980-09-01

    Traumatic rupture of the descending thoracic aorta is lethal within 3 weeks in 95% of patients who do not undergo operation. In this series of 25 patients who were operated on, 84% have survived for 6 years and there have been no cases of paraplegia. The mechanism of injury is most important in the investigation of patients with traumatic injuries and must be sought either from the patient or from witnesses. A history of rapid deceleration (more than 60 km/h) following a highway collision was present in all our cases. Failure to wear seat-belts resulted in 70% of patients being ejected from a vehicle. A side-on collision resulting in lateral deceleration caused trauma to the intrathoracic aorta in 45% of cases. Vertical deceleration resulted from falls from great heights (bridge, overpass) in 25% of cases. Clinical signs of diagnostic importance were: arterial hypertension (60%), systolic murmur (35%) and the pseudocoarctation syndrome (25%). Pertinent signs on chest roentgenograms were present in 95% of cases and included widening of the mediastinum and blunting of the aortic knob. The authors conclude thoracic aortography should be carried out in trauma patients when two or more of the following are present: (a) history of rapid deceleration, ejection from a vehicle or lateral collision, (b) hypertension and (c) blunting or modification of the aortic knob. The presence of a pseudocoarctation syndrome is an absolute indication for aortography. PMID:7437955

  10. Small bowel entrapment and ureteropelvic junction disruption associated with L3 Chance fracture-dislocation

    PubMed Central

    Pesenti, Sebastien; Blondel, Benjamin; Faure, Alice; Peltier, Emilie; Launay, Franck; Jouve, Jean-Luc

    2016-01-01

    Paediatric Chance fracture are rare lesions but often associated with abdominal injuries. We herein present the case of a seven years old patient who sustained an entrapment of small bowel and an ureteropelvic disruption associated with a Chance fracture and spine dislocation following a traffic accident. Initial X-rays and computed tomographic (CT) scan showed a Chance fracture with dislocation of L3 vertebra, with an incarceration of a small bowel loop in the spinal canal and a complete section of the left lumbar ureter. Paraplegia was noticed on the initial neurological examination. A posterior L2-L4 osteosynthesis was performed firstly. In a second time she underwent a sus umbilical laparotomy to release the incarcerated jejunum loop in the spinal canal. An end-to-end anastomosis was performed on a JJ probe to suture the left injured ureter. One month after the traumatism, she started to complain of severe headaches related to a leakage of cerebrospinalis fluid. Three months after the traumatism there was a clear regression of the leakage. One year after the trauma, an anterior intervertebral fusion was done. At final follow-up, no neurologic recovery was noticed. In case of Chance fracture, all physicians should think about abdominal injuries even if the patient is asymptomatic. Initial abdominal CT scan and magnetic resonance imaging provide in such case crucial info for management of the spine and the associated lesions. PMID:27672641

  11. Phase 1 Trial of Autologous Bone Marrow Stem Cell Transplantation in Patients with Spinal Cord Injury

    PubMed Central

    Kakabadze, Zurab; Mardaleishvili, Konstantine; Chutkerashvili, Gocha; Chelishvili, Irakli; Harders, Albrecht; Loladze, George; Shatirishvili, Gocha; Kipshidze, Nodar; Chakhunashvili, David; Chutkerashvili, Konstantine

    2016-01-01

    Introduction. A total of 18 patients, with complete motor deficits and paraplegia caused by thoracic and lumbar spine trauma without muscle atrophy or psychiatric problems, were included into this study. Materials and Methods. The bone marrow was aspirated from the anterior iliac crest under local anesthesia and the mononuclear fraction was isolated by density gradient method. At least 750 million mononuclear-enriched cells, suspended in 2 mL of saline, were infused intrathecally. Results and Discussion. The study reports demonstrated improvement of motor and sensory functions of various degrees observed in 9 of the 18 (50%) cases after bone marrow stem cell transplantation. Measured by the American Spinal Injury Association (ASIA) scale, 7 (78%) out of the 9 patients observed an improvement by one grade, while two cases (22%) saw an improvement by two grades. However, there were no cases in which the condition was improved by three grades. Conclusions. Analysis of subsequent treatment results indicated that the transplantation of mononuclear-enriched autologous BMSCs is a feasible and safe technique. However, successful application of the BMSCs in the clinical practice is associated with the necessity of executing more detailed examinations to evaluate the effect of BMSCs on the patients with spinal cord injury. PMID:27433165

  12. Sialylation regulates brain structure and function

    PubMed Central

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

    2015-01-01

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

  13. Treatment of Chronic Acromioclavicular Joint Dislocation in a Paraplegic Patient with the Weaver-Dunn Procedure and a Hook-Plate

    PubMed Central

    Godry, Holger; Citak, Mustafa; Königshausen, Matthias; Schildhauer, Thomas A.; Seybold, Dominik

    2016-01-01

    In case of patients with spinal cord injury and concomitant acromioclavicular (AC) joint-dislocation the treatment is challenging, as in this special patient group the function of the shoulder joint is critical because patients depend on the upper limb for mobilization and wheelchair-locomotion. Therefore the goal of this study was to examine, if the treatment of chronic AC-joint dislocation using the Weaver-Dunn procedure augmented with a hook-plate in patients with a spinal cord injury makes early postoperative wheelchair mobilization and the wheelchair transfer with full weight-bearing possible. In this case the Weaver-Dunn procedure with an additive hook-plate was performed in a 34-year-old male patient with a complete paraplegia and a posttraumatic chronic AC-joint dislocation. The patient was allowed to perform his wheelchair transfers with full weight bearing on the first post-operative day. The removal of the hook-plate was performed four months after implantation. At the time of follow-up the patient could use his operated shoulder with full range of motion without restrictions in his activities of daily living or his wheel-chair transfers. PMID:27433301

  14. [Surgical techniques for thoracic and thoracoabdominal aneurysm repair].

    PubMed

    Imoto, K; Uchida, K

    2010-07-01

    We introduce our technique for the treatment of aneurysms arising in the descending thoracic aorta and the thoracoabdominal aorta. Thoracotomy is performed at a single site. The costal arch is transected to ensure an adequate field of vision. A lifting hook is used to open the proximal side of the aorta. The diaphragm is not totally transected to preserve respiratory function after surgery. In principle, partial extracorporeal circulation is performed using a percutaneous cardiopulmonary support system. The dose of heparin for systemic treatment is limited to 50 U/kg. The abdominal branches are perfused with the use of balloon catheters. Cardiac arrest is induced for about 10 seconds by intravenous administration of adenosine triphosphate to avoid aortic injury when the proximal aorta is clamped during partial extracorporeal circulation and to prevent massive bleeding when the elephant trunk is clamped. To prevent paraplegia, the Adamkiewics artery and 2 pairs of adjacent intercostal arteries identified by preoperative computed tomography are reconstructed, and cerebrospinal drainage and motor evoked potential monitoring are performed.

  15. 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

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

    PubMed

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

    2015-12-15

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

  17. Excess iron harms the brain: the syndromes of neurodegeneration with brain iron accumulation (NBIA).

    PubMed

    Schneider, Susanne A; Bhatia, Kailash P

    2013-04-01

    Regulation of iron metabolism is crucial: both iron deficiency and iron overload can cause disease. In recent years, our understanding of the syndromes of Neurodegeneration with Brain Iron Accumulation (NBIA) continues to grow considerably. These are characterized by excessive iron deposition in the brain, mainly the basal ganglia. Pantothenate kinase-associated neurodegeneration (PKAN, NBIA1) and PLA2G6-associated neurodegeneration (PLAN, NBIA2) are the core syndromes, but several other genetic causes have been identified (including FA2H, C19orf12, ATP13A2, CP and FTL). These conditions show a wide clinical and pathological spectrum, with clinical overlap between the different NBIA disorders and other diseases including spastic paraplegias, leukodystrophies, and neuronal ceroid lipofuscinosis. Lewy body pathology was confirmed in some clinical subtypes (C19orf12-associated neurodegeneration and PLAN). Research aims at disentangling the various NBIA genes and their related pathways to move towards pathogenesis-targeted therapies. Until then treatment remains symptomatic. Here we will introduce the group of NBIA syndromes and review the main clinical features and investigational findings.

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

    PubMed

    Vavra-Hadziahmetović, Narcisa

    2004-01-01

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

  19. A case of a traumatic chyle leak following an acute thoracic spine injury: successful resolution with strict dietary manipulation

    PubMed Central

    2011-01-01

    Background Chylothorax is a rare form of pleural effusion that can be associated with both traumatic and non-traumatic causes. Thoracic duct ligation is often the treatment of choice in postsurgical patients; however the optimal treatment of this disease process after traumatic injury remains unclear [1]. We present a rare case of a thoracic duct injury secondary to a blunt thoracic spine fracture and subluxation which was successfully treated non-operatively. Case Presentation A 51 year old male presented as a tier one trauma code due to an automobile versus bicycle collision. His examination and radiographic work-up revealed fractures and a subluxation at the third and fourth thoracic spine levels resulting in paraplegia. He also sustained bilateral hemothoraces secondary to multiple rib fractures. Drainage of the left hemothorax led to the diagnosis of a traumatic chylothorax. The thoracic spine fractures were addressed with surgical stabilization and the chylothorax was successfully treated with drainage and dietary manipulation. Conclusions This unusual and complex blunt thoracic duct injury required a multidisciplinary approach. Although the spine injury required surgical fixation, successful resolution of the chyle leak was achieved without surgical intervention. PMID:21443785

  20. Spg20−/− mice reveal multimodal functions for Troyer syndrome protein spartin in lipid droplet maintenance, cytokinesis and BMP signaling

    PubMed Central

    Renvoisé, Benoît; Stadler, Julia; Singh, Rajat; Bakowska, Joanna C.; Blackstone, Craig

    2012-01-01

    Hereditary spastic paraplegias (HSPs; SPG1-48) are inherited neurological disorders characterized by lower extremity spasticity and weakness. Loss-of-function mutations in the SPG20 gene encoding spartin cause autosomal recessive Troyer syndrome (SPG20), which has additional features of short stature, cognitive deficits and distal amyotrophy. To identify cellular impairments underlying Troyer syndrome, we generated Spg20−/− mice, which exhibit progressive gait defects. Although gross central nervous system pathology appeared largely normal, cerebral cortical neurons cultured from neonatal Spg20−/− mice exhibited increased axon branching, a phenotype suppressed by reintroducing spartin and which required its interaction with the endosomal sorting complex required for transport (ESCRT)-III protein IST1. Analysis of the bone morphogenetic protein (BMP) signaling pathway in Spg20−/− embryonic fibroblasts indicated that Smad1/5 phosphorylation is modestly elevated, possibly due to alterations in BMP receptor trafficking. Cytokinesis was impaired in embryonic fibroblasts cultured from Spg20−/− mice, and binucleated chondrocytes were prominent in epiphyseal growth plates of bones in Spg20−/− mice, perhaps explaining the short stature of patients. Finally, adipose tissue from Spg20−/− female mice exhibited increased lipid droplet (LD) numbers and alterations in perilipin levels, supporting a role for spartin in LD maintenance. Taken together, our results support multimodal functions for spartin that provide important insights into HSP pathogenesis. PMID:22619377

  1. Ornithine and Homocitrulline Impair Mitochondrial Function, Decrease Antioxidant Defenses and Induce Cell Death in Menadione-Stressed Rat Cortical Astrocytes: Potential Mechanisms of Neurological Dysfunction in HHH Syndrome.

    PubMed

    Zanatta, Ângela; Rodrigues, Marília Danyelle Nunes; Amaral, Alexandre Umpierrez; Souza, Débora Guerini; Quincozes-Santos, André; Wajner, Moacir

    2016-09-01

    Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is caused by deficiency of ornithine translocase leading to predominant tissue accumulation and high urinary excretion of ornithine (Orn), homocitrulline (Hcit) and ammonia. Although affected patients commonly present neurological dysfunction manifested by cognitive deficit, spastic paraplegia, pyramidal and extrapyramidal signs, stroke-like episodes, hypotonia and ataxia, its pathogenesis is still poorly known. Although astrocytes are necessary for neuronal protection. Therefore, in the present study we investigated the effects of Orn and Hcit on cell viability (propidium iodide incorporation), mitochondrial function (thiazolyl blue tetrazolium bromide-MTT-reduction and mitochondrial membrane potential-ΔΨm), antioxidant defenses (GSH) and pro-inflammatory response (NFkB, IL-1β, IL-6 and TNF-α) in unstimulated and menadione-stressed cortical astrocytes that were previously shown to be susceptible to damage by neurotoxins. We first observed that Orn decreased MTT reduction, whereas both amino acids decreased GSH levels, without altering cell viability and the pro-inflammatory factors in unstimulated astrocytes. Furthermore, Orn and Hcit decreased cell viability and ΔΨm in menadione-treated astrocytes. The present data indicate that the major compounds accumulating in HHH syndrome impair mitochondrial function and reduce cell viability and the antioxidant defenses in cultured astrocytes especially when stressed by menadione. It is presumed that these mechanisms may be involved in the neuropathology of this disease. PMID:27161368

  2. Adiposity and spinal cord injury

    PubMed Central

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

    2015-01-01

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

  3. 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

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

    PubMed Central

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

    2012-01-01

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

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

    SciTech Connect

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

    1995-11-01

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

  6. Percivall Pott: tuberculous spondylitis.

    PubMed

    Sternbach, G

    1996-01-01

    Tuberculous spondylitis, also known as Pott's disease, is an entity that produces a characteristic kyphotic deformity, and was described by Sir Percivall Pott in 1779 and 1782. The majority of his patients were infants and young children. Although the incidence of tuberculosis in the industrialized world has since declined dramatically, the number of cases of extrapulmonary disease, though small, has remained relatively unchanged. In developing countries, spondylitis is still generally a disease of children, but in Europe and North America, it more commonly involves older adults. Pott's spondylitis represents a reactivation of latent disease, frequently years after the initial infection. Clinical findings include complaints of back pain and symptoms of fever, chills, weight loss, malaise, and fatigue. Characteristically a late finding, paraplegia is occasionally the initial indicator of spinal involvement. There is an average delay of a year between the onset of symptoms and patient presentation. Plain spinal radiographs usually are the initial diagnostic modality utilized. Computed tomography scanning and magnetic resonance imaging can be used to further define the process. The differential diagnosis includes neoplasm, pyogenic or disseminated fungal infection, and sarcoid arthritis. PMID:8655942

  7. Arachnoiditis ossificans and syringomyelia: A unique presentation

    PubMed Central

    Opalak, Charles F.; Opalak, Michael E.

    2015-01-01

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

  8. Mutations in mitochondrial enzyme GPT2 cause metabolic dysfunction and neurological disease with developmental and progressive features

    PubMed Central

    Ouyang, Qing; Nakayama, Tojo; Baytas, Ozan; Davidson, Shawn M.; Yang, Chendong; Schmidt, Michael; Lizarraga, Sofia B.; Mishra, Sasmita; EI-Quessny, Malak; Niaz, Saima; Gul Butt, Mirrat; Imran Murtaza, Syed; Javed, Afzal; Chaudhry, Haroon Rashid; Vaughan, Dylan J.; Hill, R. Sean; Partlow, Jennifer N.; Yoo, Seung-Yun; Lam, Anh-Thu N.; Nasir, Ramzi; Al-Saffar, Muna; Barkovich, A. James; Schwede, Matthew; Nagpal, Shailender; Rajab, Anna; DeBerardinis, Ralph J.; Housman, David E.; Mochida, Ganeshwaran H.; Morrow, Eric M.

    2016-01-01

    Mutations that cause neurological phenotypes are highly informative with regard to mechanisms governing human brain function and disease. We report autosomal recessive mutations in the enzyme glutamate pyruvate transaminase 2 (GPT2) in large kindreds initially ascertained for intellectual and developmental disability (IDD). GPT2 [also known as alanine transaminase 2 (ALT2)] is one of two related transaminases that catalyze the reversible addition of an amino group from glutamate to pyruvate, yielding alanine and α-ketoglutarate. In addition to IDD, all affected individuals show postnatal microcephaly and ∼80% of those followed over time show progressive motor symptoms, a spastic paraplegia. Homozygous nonsense p.Arg404* and missense p.Pro272Leu mutations are shown biochemically to be loss of function. The GPT2 gene demonstrates increasing expression in brain in the early postnatal period, and GPT2 protein localizes to mitochondria. Akin to the human phenotype, Gpt2-null mice exhibit reduced brain growth. Through metabolomics and direct isotope tracing experiments, we find a number of metabolic abnormalities associated with loss of Gpt2. These include defects in amino acid metabolism such as low alanine levels and elevated essential amino acids. Also, we find defects in anaplerosis, the metabolic process involved in replenishing TCA cycle intermediates. Finally, mutant brains demonstrate misregulated metabolites in pathways implicated in neuroprotective mechanisms previously associated with neurodegenerative disorders. Overall, our data reveal an important role for the GPT2 enzyme in mitochondrial metabolism with relevance to developmental as well as potentially to neurodegenerative mechanisms. PMID:27601654

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

    PubMed

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

    2015-12-15

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

  10. Mutations in mitochondrial enzyme GPT2 cause metabolic dysfunction and neurological disease with developmental and progressive features.

    PubMed

    Ouyang, Qing; Nakayama, Tojo; Baytas, Ozan; Davidson, Shawn M; Yang, Chendong; Schmidt, Michael; Lizarraga, Sofia B; Mishra, Sasmita; Ei-Quessny, Malak; Niaz, Saima; Gul Butt, Mirrat; Imran Murtaza, Syed; Javed, Afzal; Chaudhry, Haroon Rashid; Vaughan, Dylan J; Hill, R Sean; Partlow, Jennifer N; Yoo, Seung-Yun; Lam, Anh-Thu N; Nasir, Ramzi; Al-Saffar, Muna; Barkovich, A James; Schwede, Matthew; Nagpal, Shailender; Rajab, Anna; DeBerardinis, Ralph J; Housman, David E; Mochida, Ganeshwaran H; Morrow, Eric M

    2016-09-20

    Mutations that cause neurological phenotypes are highly informative with regard to mechanisms governing human brain function and disease. We report autosomal recessive mutations in the enzyme glutamate pyruvate transaminase 2 (GPT2) in large kindreds initially ascertained for intellectual and developmental disability (IDD). GPT2 [also known as alanine transaminase 2 (ALT2)] is one of two related transaminases that catalyze the reversible addition of an amino group from glutamate to pyruvate, yielding alanine and α-ketoglutarate. In addition to IDD, all affected individuals show postnatal microcephaly and ∼80% of those followed over time show progressive motor symptoms, a spastic paraplegia. Homozygous nonsense p.Arg404* and missense p.Pro272Leu mutations are shown biochemically to be loss of function. The GPT2 gene demonstrates increasing expression in brain in the early postnatal period, and GPT2 protein localizes to mitochondria. Akin to the human phenotype, Gpt2-null mice exhibit reduced brain growth. Through metabolomics and direct isotope tracing experiments, we find a number of metabolic abnormalities associated with loss of Gpt2. These include defects in amino acid metabolism such as low alanine levels and elevated essential amino acids. Also, we find defects in anaplerosis, the metabolic process involved in replenishing TCA cycle intermediates. Finally, mutant brains demonstrate misregulated metabolites in pathways implicated in neuroprotective mechanisms previously associated with neurodegenerative disorders. Overall, our data reveal an important role for the GPT2 enzyme in mitochondrial metabolism with relevance to developmental as well as potentially to neurodegenerative mechanisms. PMID:27601654

  11. Further genotype-phenotype correlation emerging from two families with PLP1 exon 4 skipping.

    PubMed

    Biancheri, Roberta; Grossi, Serena; Regis, Stefano; Rossi, Andrea; Corsolini, Fabio; Rossi, Daniela Paola; Cavalli, Pietro; Severino, Mariasavina; Filocamo, Mirella

    2014-03-01

    Proteolipid protein 1 (PLP1) gene-related disorders due to mutations in the PLP1 include a wide spectrum of X-linked disorders ranging from severe connatal Pelizaeus-Merzbacher disease (PMD) to spastic paraplegia 2 (SPG2). Duplications, deletions or point mutations in coding and noncoding regions of the PLP1 gene may occur. We report the clinical, neuroradiologic and molecular findings in six patients from two unrelated families. The affected males showed severe mental retardation, spastic tetraparesis, inability of walking and pes cavus at onset in early infancy. Brain magnetic resonance imaging (MRI) showed hypomyelination and brain atrophy. Nystagmus was never observed. The affected females showed adult-onset progressive spastic paraparesis leading to wheel-chair dependency and subtle white matter changes on brain MRI. Molecular studies in the two families identified two different intronic mutations, the novel c.622+2T>C and the known c.622+1G>A, leading to the skipping of PLP1-exon 4. The clinical presentation of the affected males did not consistently fit in any of the PLP1-related disorder subtypes (i.e., connatal or classic PMD, SPG2 and 'PLP1 null syndrome'), and in addition, the carrier females were symptomatic despite the severe clinical picture of their respective probands. This study provides new insight into the genotype-phenotype correlations of patients with PLP1 splice-site mutations. PMID:23711321

  12. Inverted Pendulum Standing Apparatus for Investigating Closed-Loop Control of Ankle Joint Muscle Contractions during Functional Electrical Stimulation

    PubMed Central

    Tan, John F.; Masani, Kei; Vette, Albert H.; Zariffa, José; Robinson, Mark; Lynch, Cheryl; Popovic, Milos R.

    2014-01-01

    The restoration of arm-free standing in individuals with paraplegia can be facilitated via functional electrical stimulation (FES). In developing adequate control strategies for FES systems, it remains challenging to test the performance of a particular control scheme on human subjects. In this study, we propose a testing platform for developing effective control strategies for a closed-loop FES system for standing. The Inverted Pendulum Standing Apparatus (IPSA) is a mechanical inverted pendulum, whose angular position is determined by the subject's ankle joint angle as controlled by the FES system while having the subject's body fixed in a standing frame. This approach provides a setup that is safe, prevents falling, and enables a research and design team to rigorously test various closed-loop controlled FES systems applied to the ankle joints. To demonstrate the feasibility of using the IPSA, we conducted a case series that employed the device for studying FES closed-loop controllers for regulating ankle joint kinematics during standing. The utilized FES system stimulated, in able-bodied volunteers, the plantarflexors as they prevent toppling during standing. Four different conditions were compared, and we were able to show unique performance of each condition using the IPSA. We concluded that the IPSA is a useful tool for developing and testing closed-loop controlled FES systems for regulating ankle joint position during standing. PMID:27350992

  13. Inverted Pendulum Standing Apparatus for Investigating Closed-Loop Control of Ankle Joint Muscle Contractions during Functional Electrical Stimulation.

    PubMed

    Tan, John F; Masani, Kei; Vette, Albert H; Zariffa, José; Robinson, Mark; Lynch, Cheryl; Popovic, Milos R

    2014-01-01

    The restoration of arm-free standing in individuals with paraplegia can be facilitated via functional electrical stimulation (FES). In developing adequate control strategies for FES systems, it remains challenging to test the performance of a particular control scheme on human subjects. In this study, we propose a testing platform for developing effective control strategies for a closed-loop FES system for standing. The Inverted Pendulum Standing Apparatus (IPSA) is a mechanical inverted pendulum, whose angular position is determined by the subject's ankle joint angle as controlled by the FES system while having the subject's body fixed in a standing frame. This approach provides a setup that is safe, prevents falling, and enables a research and design team to rigorously test various closed-loop controlled FES systems applied to the ankle joints. To demonstrate the feasibility of using the IPSA, we conducted a case series that employed the device for studying FES closed-loop controllers for regulating ankle joint kinematics during standing. The utilized FES system stimulated, in able-bodied volunteers, the plantarflexors as they prevent toppling during standing. Four different conditions were compared, and we were able to show unique performance of each condition using the IPSA. We concluded that the IPSA is a useful tool for developing and testing closed-loop controlled FES systems for regulating ankle joint position during standing.

  14. 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

  15. 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

  16. Novel endovascular procedures and new developments in aortic surgery.

    PubMed

    Cheng, S W K

    2016-09-01

    Endovascular repair has evolved to become a viable mainstream treatment for aortic pathology in both acute and elective settings. As technology advanced, traditional anatomical barriers were progressively tackled using new devices and novel procedures, and there are now multiple options available to the vascular surgeon. In the abdominal aorta, advances in endovascular aneurysm repair have been in the treatment of hostile aortic necks using new sealing concepts and ancillary procedures, and in branch preservation using fenestrations and snorkels. Access challenges have been met with a percutaneous approach and low-profile devices, and standard protocols have improved mortality for ruptured aneurysms. In the thoracic aorta, more invasive hybrid procedures have given way gradually to branched endografts. Particular challenges to the anaesthetist include blood pressure control and the prevention of stroke and paraplegia. Current focus in the thoracic aorta is in treating aortic arch pathology and in optimal management of acute and chronic dissections. This review describes the latest trends in the endovascular treatment of aortic diseases and examines the current evidence for different modalities of management. PMID:27566806

  17. The mitochondrial permeability transition pore in AD 2016: An update.

    PubMed

    Biasutto, Lucia; Azzolini, Michele; Szabò, Ildikò; Zoratti, Mario

    2016-10-01

    Over the past 30years the mitochondrial permeability transition - the permeabilization of the inner mitochondrial membrane due to the opening of a wide pore - has progressed from being considered a curious artifact induced in isolated mitochondria by Ca(2+) and phosphate to a key cell-death-inducing process in several major pathologies. Its relevance is by now universally acknowledged and a pharmacology targeting the phenomenon is being developed. The molecular nature of the pore remains to this day uncertain, but progress has recently been made with the identification of the FOF1 ATP synthase as the probable proteic substrate. Researchers sharing this conviction are however divided into two camps: these believing that only the ATP synthase dimers or oligomers can form the pore, presumably in the contact region between monomers, and those who consider that the ring-forming c subunits in the FO sector actually constitute the walls of the pore. The latest development is the emergence of a new candidate: Spastic Paraplegia 7 (SPG7), a mitochondrial AAA-type membrane protease which forms a 6-stave barrel. This review summarizes recent developments of research on the pathophysiological relevance and on the molecular nature of the mitochondrial permeability transition pore. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou.

  18. Management of seat-belt syndrome in children. Gravity of 2-point seat-belt.

    PubMed

    Griffet, J; Bastiani-Griffet, F; El-Hayek, T; Dageville, C; Pebeyre, B

    2002-02-01

    We present our experience with a management of seat-belt syndrome in three children and draw particular attention to the severity of two-point fixation seat-belt injuries after a motor vehicle accident with 5 passengers whose vehicle was struck head-on by an oncoming vehicle. The parents were sitting in front, Adeline had a 2-point lap seat-belt, the 2 other children had 3-point seat-belts. The parents both had humerus fractures. The 4-year-old brother suffered a cervical and abdominal trauma with renal and splenic contusions and intestinal perforations. Adeline suffered multiple injuries, notably to the head, spine and abdominal viscera with erosions at the site of lap-seat-belt contact. The spinal injury was an L2 angular Chance fracture associated with paraplegia on the 7th day. Operative findings included a transverse tear of the left rectus abdominus muscle, an incomplete transection of the stomach and perforation of the ileum. The injuries were ultimately fatal. Given associated abdominal pain, skin erosions at the site of seatbelt contact, spinal fracture, and rectal muscle disruption apparent on emergency laparotomy, early diagnosis is important for better prognosis.

  19. Long-term user perceptions of an implanted neuroprosthesis for exercise, standing, and transfers after spinal cord injury.

    PubMed

    Agarwal, Sanjeev; Triolo, Ronald J; Kobetic, Rudi; Miller, Michael; Bieri, Carol; Kukke, Sahana; Rohde, Lori; Davis, John A

    2003-01-01

    This study was completed to understand the usage patterns, system performance, degree of satisfaction, complications, and health benefits as perceived by recipients of a surgically implanted neuroprosthesis for exercise, standing, and transfers in individuals with low-cervical or thoracic spinal cord injury (SCI). A standardized telephone survey was administered to 11 recipients of the Case Western Reserve University/Veterans Affairs (CWRU/VA) implanted standing neuroprosthesis with more than 12 months of experience with the functional electrical stimulation (FES) system. Nine implant recipients were using the neuroprosthesis regularly for standing and/or exercising at the time of the survey. All 11 implant recipients noted improved health and a reduced incidence of pressure sores, leg spasms, and urinary tract infections (UTIs). No incidents of deep-vein thrombosis, infection, cellulitis, or electrical burns because of the neuroprosthesis were noted. System recipients uniformly felt that the neuroprosthesis resulted in better overall health and general well-being. Subjects were moderately to very satisfied with the performance of the neuroprosthesis and unanimously expressed a willingness to repeat the surgery and rehabilitation to obtain the same clinical outcome. All implant recipients reported the system to be safe, reliable, and easy to use. The implanted standing neuroprosthesis appears to be a clinically acceptable and effective means of providing the ability to exercise, stand, and transfer to selected individuals with paraplegia or low tetraplegia.

  20. 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

  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.

  2. The N-terminal domain plays a crucial role in the structure of a full-length human mitochondrial Lon protease

    PubMed Central

    Kereïche, Sami; Kováčik, Lubomír; Bednár, Jan; Pevala, Vladimír; Kunová, Nina; Ondrovičová, Gabriela; Bauer, Jacob; Ambro, Ľuboš; Bellová, Jana; Kutejová, Eva; Raška, Ivan

    2016-01-01

    Lon is an essential, multitasking AAA+ protease regulating many cellular processes in species across all kingdoms of life. Altered expression levels of the human mitochondrial Lon protease (hLon) are linked to serious diseases including myopathies, paraplegia, and cancer. Here, we present the first 3D structure of full-length hLon using cryo-electron microscopy. hLon has a unique three-dimensional structure, in which the proteolytic and ATP-binding domains (AP-domain) form a hexameric chamber, while the N-terminal domain is arranged as a trimer of dimers. These two domains are linked by a narrow trimeric channel composed likely of coiled-coil helices. In the presence of AMP-PNP, the AP-domain has a closed-ring conformation and its N-terminal entry gate appears closed, but in ADP binding, it switches to a lock-washer conformation and its N-terminal gate opens, which is accompanied by a rearrangement of the N-terminal domain. We have also found that both the enzymatic activities and the 3D structure of a hLon mutant lacking the first 156 amino acids are severely disturbed, showing that hLon’s N-terminal domains are crucial for the overall structure of the hLon, maintaining a conformation allowing its proper functioning. PMID:27632940

  3. In Silico Investigation of Traditional Chinese Medicine for Potential Lead Compounds as SPG7 Inhibitors against Coronary Artery Disease.

    PubMed

    Chen, Kuen-Bao; Chen, Kuan-Chung; Chang, Ya-Lin; Chang, Kun-Lung; Chang, Pei-Chun; Chang, Tung-Ti; Chen, Yu-Chian

    2016-01-01

    Coronary artery disease (CAD) is the most common cause of heart attack and the leading cause of mortality in the world. It is associated with mitochondrial dysfunction and increased level of reactive oxygen species production. According to the Ottawa Heart Genomics Study genome-wide association study, a recent research identified that Q688 spastic paraplegia 7 (SPG7) variant is associated with CAD as it bypasses the regulation of tyrosine phosphorylation of AFG3L2 and enhances the processing and maturation of SPG7 protein. This study aims to identify potential compounds isolated from Traditional Chinese Medicines (TCMs) as potential lead compounds for paraplegin (SPG7) inhibitors. For the crystallographic structure of paraplegin, the disordered disposition of key amino acids in the binding site was predicted using the PONDR-Fit protocol before virtual screening. The TCM compounds saussureamine C and 3-(2-carboxyphenyl)-4(3H)-quinazolinone, have potential binding affinities with stable H-bonds and hydrophobic contacts with key residues of paraplegin. A molecular dynamics simulation was performed to validate the stability of the interactions between each candidate and paraplegin under dynamic conditions. Hence, we propose these compounds as potential candidates as lead drug from the compounds isolated from TCM for further study in drug development process with paraplegin protein for coronary artery disease. PMID:27164068

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

    PubMed

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

    2015-11-01

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

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

    PubMed

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

    2015-01-01

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

  6. Case Report: Myelodysplastic syndrome- associated myeloid sarcoma: an unusual clinical presentation of a rare disease.

    PubMed

    Horvath, Emoke; Demian, Smaranda; Nagy, Elod

    2016-01-01

    Myeloid sarcoma results from the extramedullary homing and proliferation of immature myeloid precursors. We present the timeline, events and diagnostic pitfalls related to a 66 year-old male patient's case, admitted to the Hematology Clinic for pancytopenia, fever, weight loss and fatigue. The severe cytopenia and the few blasts observed in his blood smear indicated a bone marrow biopsy. The bone marrow showed hypercellularity and multilineage dysplasia with the presence of 15% myeloblasts. After the biopsy, he promptly developed paraplegia and nuclear magnetic resonance revealed an epidural tumour which was then resected.In the epidural tumour mass blast-like, round cells were observed with a complex immunophenotype, characterized by myeloperoxidase, CD117, CD15, CD99, leucocyte common antigen positivity and a high Ki-67 proliferation index. Considering the main differential diagnostic issues, the final diagnosis was stated as myelodysplastic syndrome-associated myeloid sarcoma. The prognosis was unfavourable, the bone marrow was quickly invaded by proliferating blast cells, and despite chemotherapy attempts, the patient died.

  7. Case Report: Myelodysplastic syndrome- associated myeloid sarcoma: an unusual clinical presentation of a rare disease

    PubMed Central

    Horvath, Emoke; Demian, Smaranda; Nagy, Elod

    2016-01-01

    Myeloid sarcoma results from the extramedullary homing and proliferation of immature myeloid precursors. We present the timeline, events and diagnostic pitfalls related to a 66 year-old male patient’s case, admitted to the Hematology Clinic for pancytopenia, fever, weight loss and fatigue. The severe cytopenia and the few blasts observed in his blood smear indicated a bone marrow biopsy. The bone marrow showed hypercellularity and multilineage dysplasia with the presence of 15% myeloblasts. After the biopsy, he promptly developed paraplegia and nuclear magnetic resonance revealed an epidural tumour which was then resected.In the epidural tumour mass blast-like, round cells were observed with a complex immunophenotype, characterized by myeloperoxidase, CD117, CD15, CD99, leucocyte common antigen positivity and a high Ki-67 proliferation index. Considering the main differential diagnostic issues, the final diagnosis was stated as myelodysplastic syndrome-associated myeloid sarcoma. The prognosis was unfavourable, the bone marrow was quickly invaded by proliferating blast cells, and despite chemotherapy attempts, the patient died. PMID:27019694

  8. Evaluation of Neurologic Deficit Without Apparent Cause: The Importance of a Multidisciplinary Approach

    PubMed Central

    Smith, Harvey E; Rynning, Ralph E; Okafor, Chukwuka; Zaslavsky, James; Tracy, Joseph I; Ratliff, John; Harrop, James; Albert, Todd; Hilibrand, Alan; Anderson, Gregory; Sharan, Ashwini; Brown, Zoe; Vaccaro, Alexander R

    2007-01-01

    Background/Objective: A patient presenting with an acute neurologic deficit with no apparent etiology presents a diagnostic dilemma. A broad differential diagnosis must be entertained, considering both organic and psychiatric causes. Methods: A case report and thorough literature review of acute paraplegia after a low-energy trauma without a discernible organic etiology. Results: Diagnostic imaging excluded any bony malalignment or fracture and any abnormality on magnetic resonance imaging. When no organic etiology was identified, a multidisciplinary approach using neurology, psychiatry, and physical medicine and rehabilitation services was applied. Neurophysiologic testing confirmed the absence of an organic disorder, and at this juncture, diagnostic efforts focused on identifying any psychiatric disorder to facilitate appropriate treatment for this individual. The final diagnosis was malingering. Conclusions: The full psychiatric differential diagnosis should be considered in the evaluation of any patient with an atypical presentation of paralysis. A thorough clinical examination in combination with the appropriate diagnostic studies can confidently exclude an organic disorder. When considering a psychiatric disorder, the differential diagnosis should include conversion disorder and malingering, although each must remain a diagnosis of exclusion. Maintaining a broad differential diagnosis and involving multiple disciplines (neurology, psychiatry, social work, medical specialists) early in the evaluation of atypical paralysis may facilitate earlier diagnosis and initiation of treatment for the underlying etiology. PMID:18092568

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

    PubMed Central

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

    2015-01-01

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

  10. Detailed shoulder MRI findings in manual wheelchair users with shoulder pain.

    PubMed

    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

  11. Can MRI Findings Help to Predict Neurological Recovery in Paraplegics With Thoracolumbar Fracture?

    PubMed Central

    Lee, Joonchul; Koh, Seong-Eun; Jung, Heeyoune; Lee, Hye Yeon

    2015-01-01

    Objective To evaluate the usefulness of various magnetic resonance imaging (MRI) findings in the prognosis of neurological recovery in paraplegics with thoracolumbar fracture using association analysis with clinical outcomes and electrodiagnostic features. Methods This retrospective study involved 30 patients treated for paraplegia following thoracolumbar fracture. On axial and sagittal T2-weighted MRI scans, nerve root sedimentation sign, root aggregation sign, and signal intensity changes in the conus medullaris were independently assessed by two raters. A positive sedimentation sign was defined as the absence of nerve root sedimentation. The root aggregation sign was defined as the presence of root aggregation in at least one axial MRI scan. Clinical outcomes including the American Spinal Injury Association impairment scale, ambulatory capacity, and electrodiagnostic features were used for association analysis. Results Inter-rater reliability of the nerve root sedimentation sign and the root aggregation sign were κ=0.67 (p=0.001) and κ=0.78 (p<0.001), respectively. A positive sedimentation sign was significantly associated with recovery of ambulatory capacity after a rehabilitation program (χ2=4.854, p=0.028). The presence of the root aggregation sign was associated with reduced compound muscle action potential amplitude of common peroneal and tibial nerves in nerve conduction studies (χ2=5.026, p=0.025). Conclusion A positive sedimentation sign was significantly associated with recovery of ambulatory capacity and not indicative of persistent paralysis. The root aggregation sign suggested the existence of significant cauda equina injuries. PMID:26798606

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    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.

  14. Low back injury risk during repositioning of patients in bed: the influence of handling technique, patient weight and disability.

    PubMed

    Skotte, J; Fallentin, N

    2008-07-01

    The objective of the study was to investigate the low back load during repositioning of patients in bed and to assess the influence of patient's weight and disability. Nine female health care workers (HCWs) carried out six patient-handling tasks with different patient weight (59 +/- 1, 83 +/- 2 and 110 +/- 4 kg) and handicap (hemiplegia, paraplegia and near-paralysis). The tasks were performed with optional use of simple, low-tech assistant devices (draw and sliding sheets). Peak low back compression exceeded the National Institute for Occupational Safety and Health action level of 3400 N in 25% of all trials (418). The influence of the HCW, i.e. the technique and assistive devices used, was higher than the effect of weight and disability in all tasks studied. ANOVA showed that on average for the six tasks 37%, 10% and 6% of the variance in low back loading was caused by variation in the factors HCW, patient's weight and disability, respectively. The result of this study is relevant for HCWs. It is shown that the repositioning technique and use of friction-reducing devices have higher influence on the low back load of the HCW than the patient's weight and disability.

  15. Clinical usefulness of the transobturator sub-urethral tape in the treatment of stress urinary incontinence in female patients with spinal cord lesion

    PubMed Central

    Pannek, Juergen; Bartel, Peter; Gocking, Konrad

    2012-01-01

    Objectives To evaluate the clinical usefulness of transobturator sub-urethral tapes for the treatment of stress urinary incontinence in women with spinal cord injury. Method and subjects Chart review for all female patients with spinal cord injury who underwent implantation of a transobturator sub-urethral tape for treatment of stress urinary incontinence at our institution. Results Nine women, median age 45.1 years, received a sub-urethral transobturator tape in the period November 2007 to September 2010. Four patients had paraplegia and five had tetraplegia. Seven women performed intermittent catheterization. At follow up, three of the nine patients were either cured or vastly improved. One major late complication (urethral erosion) occurred. Five of the six patients without treatment success underwent second-line treatment (artificial sphincter or urinary diversion). Conclusion In our case series, implantation of transobturator sub-urethral tapes in women with stress urinary continence due to intrinsic sphincter deficiency and a low leak point pressure led to unfavorable results. PMID:22525323

  16. Multiple Myeloma. Diagnostic challenges and standard therapy.

    PubMed

    Kyle, R A

    2001-04-01

    In the diagnosis of multiple myeloma (MM), the clinician must exclude other disorders in which a plasma cell reaction may occur such as rheumatoid arthritis and connective tissue disorders, or metastatic carcinoma where the patient may have osteolytic lesions associated with bone metastases. Patients with smoldering multiple myeloma (SMM) or monoclonal gammopathy of undetermined significance (MGUS) have none of the complicating features of MM and do not require treatment with potentially toxic agents. The plasma cell labeling index can help make a differential diagnosis of MM from SMM. Patients with a high labeling index have a high risk of complications and should be monitored carefully. However, the labeling index can be low in active MM. In addition, SMM or MGUS patients have few or no circulating plasma cells. High-dose chemotherapy and stem cell support prolong overall survival in contrast to conventional therapy. If stem cell transplantation is considered, it is important to harvest the cells before using alkylating agents to obtain a sufficient number of cells. Supportive treatment consists of the occasional use of erythropoietin to maintain adequate hemoglobin levels and adequate hydration to protect renal function. Vaccination against pneumococcal infections and the prophylactic use of antibiotic therapy during the first 2 months of treatment can be beneficial. Recognizing the symptoms of spinal cord compression and initiating dexamethasone therapy promptly to prevent paraplegia are critical. PMID:11309703

  17. Spinal cord lesions shrink peripersonal space around the feet, passive mobilization of paraplegic limbs restores it

    PubMed Central

    Scandola, Michele; Aglioti, Salvatore Maria; Bonente, Claudio; Avesani, Renato; Moro, Valentina

    2016-01-01

    Peripersonal space (PPS) is the space surrounding us within which we interact with objects. PPS may be modulated by actions (e.g. when using tools) or sense of ownership (e.g. over a rubber hand). Indeed, intense and/or prolonged use of a tool may induce a sense of ownership over it. Conversely, inducing ownership over a rubber hand may activate brain regions involved in motor control. However, the extent to which PPS is modulated by action-dependent or ownership-dependent mechanisms remains unclear. Here, we explored the PPS around the feet and the sense of ownership over lower limbs in people with Paraplegia following Complete spinal cord Lesions (PCL) and in healthy subjects. PCL people can move their upper body but have lost all sensory-motor functions in their lower body (e.g. lower limbs). We tested whether PPS alterations reflect the topographical representations of various body parts. We found that the PPS around the feet was impaired in PCL who however had a normal representation of the PPS around the hands. Significantly, passive mobilization of paraplegic limbs restored the PPS around the feet suggesting that activating action representations in PCL brings about short-term changes of PPS that may thus be more plastic than previously believed. PMID:27049439

  18. Absence of alsin function leads to corticospinal motor neuron vulnerability via novel disease mechanisms.

    PubMed

    Gautam, Mukesh; Jara, Javier H; Sekerkova, Gabriella; Yasvoina, Marina V; Martina, Marco; Özdinler, P Hande

    2016-03-15

    Mutations in the ALS2 gene result in early-onset amyotrophic lateral sclerosis, infantile-onset ascending hereditary spastic paraplegia and juvenile primary lateral sclerosis, suggesting prominent upper motor neuron involvement. However, the importance of alsin function for corticospinal motor neuron (CSMN) health and stability remains unknown. To date, four separate alsin knockout (Alsin(KO)) mouse models have been generated, and despite hopes of mimicking human pathology, none displayed profound motor function defects. This, however, does not rule out the possibility of neuronal defects within CSMN, which is not easy to detect in these mice. Detailed cellular analysis of CSMN has been hampered due to their limited numbers and the complex and heterogeneous structure of the cerebral cortex. In an effort to visualize CSMN in vivo and to investigate precise aspects of neuronal abnormalities in the absence of alsin function, we generated Alsin(KO)-UeGFP mice, by crossing Alsin(KO) and UCHL1-eGFP mice, a CSMN reporter line. We find that CSMN display vacuolated apical dendrites with increased autophagy, shrinkage of soma size and axonal pathology even in the pons region. Immunocytochemistry coupled with electron microscopy reveal that alsin is important for maintaining cellular cytoarchitecture and integrity of cellular organelles. In its absence, CSMN displays selective defects both in mitochondria and Golgi apparatus. UCHL1-eGFP mice help understand the underlying cellular factors that lead to CSMN vulnerability in diseases, and our findings reveal unique importance of alsin function for CSMN health and stability. PMID:26755825

  19. WES in a family trio suggests involvement of TECPR2 in a complex form of progressive motor neuron disease.

    PubMed

    Covone, A E; Fiorillo, C; Acquaviva, M; Trucco, F; Morana, G; Ravazzolo, R; Minetti, C

    2016-08-01

    We have performed whole-exome sequencing in a family trio with a 16-year-old girl suffering of progressive motor neuron disease. There was no family history of the disease and no parental consanguinity. Our exome analysis indicated the proband as a compound heterozygote for two missense variants in the TECPR2 gene according to a recessive mode of inheritance. The TECPR2 gene has been reported as a positive regulator of autophagy which is an essential mechanism for maintaining neuron homeostasis and survival and plays a key role in major adult and pediatric neurodegenerative diseases. Variants in this gene have been found responsible for a recently described form of hereditary spastic paraplegia called SPG49 in two previous reports. We propose that both variants causing amino acid substitution, p.Leu684Val and p.Thr903Met, inherited in trans-phase compound heterozygote form, can be responsible for the phenotype observed in our patient. We also consider the possible contribution of a heterozygous variant in the SPG7 gene. Sanger sequencing confirmed the segregation of variants within the family tree including the patient's unaffected brother. PMID:27406698

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

    PubMed Central

    Martinez-Carrera, Lilian A.; Wirth, Brunhilde

    2015-01-01

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

  1. Endovascular Management of Thoracic Aortic Aneurysms

    SciTech Connect

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

    2011-12-15

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

  2. 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

  3. Obstructive hydrocephalus as a result of giant cell tumor of the thoracic spine: A case report

    PubMed Central

    WEI, CHENG-YU; CHEN, SHUO-TSUNG; TAI, HSU-CHIH; WANG, WEN-BING; CHANG, CHI-CHU; WANG, YAO-CHIN; WEI, LI; KUNG, WOON-MAN

    2016-01-01

    Giant cell tumors (GCTs) are rare bone tumors that account for ~5% of all primary bone tumors. When GCTs occur in the spine, patients usually present with localized pain and neurological symptoms, such as radiating pain or hyperesthesia. In the current report, an unusual case of a GCT of the thoracic spine associated with hydrocephalus is described. A 48-year-old male presented with urinary retention, loss of sensation in the lower limbs and inability to walk. The patient eventually developed hydrocephalus combined with altered consciousness, indicated by an inability to follow simple commands. Magnetic resonance (MR) imaging demonstrated the presence of a soft tissue mass at the T2 level, and biopsy examination of the tissue confirmed that it was a GCT. The patient experienced a sudden loss of consciousness due to an acute episode of obstructive hydrocephalus. A ventriculoperitoneal shunting procedure was performed to treat the hydrocephalus, and the patient regained normal consciousness, although the paraplegia persisted. An MR examination performed 30 months following surgery demonstrated that the tumor size was stable, consistent with the slow growth that is characteristic of GCTs. Diagnosis of GCTs may be challenging, and relies on radiographic and histopathologic findings. Although rare, acute hydrocephalus as a result of GCTs should not be excluded from a differential diagnosis. PMID:26870164

  4. The N-terminal domain plays a crucial role in the structure of a full-length human mitochondrial Lon protease.

    PubMed

    Kereïche, Sami; Kováčik, Lubomír; Bednár, Jan; Pevala, Vladimír; Kunová, Nina; Ondrovičová, Gabriela; Bauer, Jacob; Ambro, Ľuboš; Bellová, Jana; Kutejová, Eva; Raška, Ivan

    2016-01-01

    Lon is an essential, multitasking AAA(+) protease regulating many cellular processes in species across all kingdoms of life. Altered expression levels of the human mitochondrial Lon protease (hLon) are linked to serious diseases including myopathies, paraplegia, and cancer. Here, we present the first 3D structure of full-length hLon using cryo-electron microscopy. hLon has a unique three-dimensional structure, in which the proteolytic and ATP-binding domains (AP-domain) form a hexameric chamber, while the N-terminal domain is arranged as a trimer of dimers. These two domains are linked by a narrow trimeric channel composed likely of coiled-coil helices. In the presence of AMP-PNP, the AP-domain has a closed-ring conformation and its N-terminal entry gate appears closed, but in ADP binding, it switches to a lock-washer conformation and its N-terminal gate opens, which is accompanied by a rearrangement of the N-terminal domain. We have also found that both the enzymatic activities and the 3D structure of a hLon mutant lacking the first 156 amino acids are severely disturbed, showing that hLon's N-terminal domains are crucial for the overall structure of the hLon, maintaining a conformation allowing its proper functioning.

  5. 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

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

    NASA Astrophysics Data System (ADS)

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

    2012-07-01

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

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

    PubMed Central

    Sujkowski, Alyson; Rainier, Shirley; Fink, John K.; Wessells, Robert J.

    2015-01-01

    Human PNPLA6 gene encodes Neuropathy Target Esterase protein (NTE). PNPLA6 gene mutations cause hereditary spastic paraplegia (SPG39 HSP), Gordon-Holmes syndrome, Boucher-Neuhäuser syndromes, Laurence-Moon syndrome, and Oliver-McFarlane syndrome. Mutations in the Drosophila NTE homolog swiss cheese (sws) cause early-onset, progressive behavioral defects and neurodegeneration characterized by vacuole formation. We investigated sws5 flies and show for the first time that this allele causes progressive vacuolar formation in the brain and progressive deterioration of negative geotaxis speed and endurance. We demonstrate that inducible, neuron-specific expression of full-length human wildtype NTE reduces vacuole formation and substantially rescues mobility. Indeed, neuron-specific expression of wildtype human NTE is capable of rescuing mobility defects after 10 days of adult life at 29°C, when significant degeneration has already occurred, and significantly extends longevity of mutants at 25°C. These results raise the exciting possibility that late induction of NTE function may reduce or ameliorate neurodegeneration in humans even after symptoms begin. In addition, these results highlight the utility of negative geotaxis endurance as a new assay for longitudinal tracking of degenerative phenotypes in Drosophila. PMID:26671664

  8. Ornithine and Homocitrulline Impair Mitochondrial Function, Decrease Antioxidant Defenses and Induce Cell Death in Menadione-Stressed Rat Cortical Astrocytes: Potential Mechanisms of Neurological Dysfunction in HHH Syndrome.

    PubMed

    Zanatta, Ângela; Rodrigues, Marília Danyelle Nunes; Amaral, Alexandre Umpierrez; Souza, Débora Guerini; Quincozes-Santos, André; Wajner, Moacir

    2016-09-01

    Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is caused by deficiency of ornithine translocase leading to predominant tissue accumulation and high urinary excretion of ornithine (Orn), homocitrulline (Hcit) and ammonia. Although affected patients commonly present neurological dysfunction manifested by cognitive deficit, spastic paraplegia, pyramidal and extrapyramidal signs, stroke-like episodes, hypotonia and ataxia, its pathogenesis is still poorly known. Although astrocytes are necessary for neuronal protection. Therefore, in the present study we investigated the effects of Orn and Hcit on cell viability (propidium iodide incorporation), mitochondrial function (thiazolyl blue tetrazolium bromide-MTT-reduction and mitochondrial membrane potential-ΔΨm), antioxidant defenses (GSH) and pro-inflammatory response (NFkB, IL-1β, IL-6 and TNF-α) in unstimulated and menadione-stressed cortical astrocytes that were previously shown to be susceptible to damage by neurotoxins. We first observed that Orn decreased MTT reduction, whereas both amino acids decreased GSH levels, without altering cell viability and the pro-inflammatory factors in unstimulated astrocytes. Furthermore, Orn and Hcit decreased cell viability and ΔΨm in menadione-treated astrocytes. The present data indicate that the major compounds accumulating in HHH syndrome impair mitochondrial function and reduce cell viability and the antioxidant defenses in cultured astrocytes especially when stressed by menadione. It is presumed that these mechanisms may be involved in the neuropathology of this disease.

  9. 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

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

    PubMed Central

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

    2015-01-01

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

  11. 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

  12. Case Report: Myelodysplastic syndrome- associated myeloid sarcoma: an unusual clinical presentation of a rare disease.

    PubMed

    Horvath, Emoke; Demian, Smaranda; Nagy, Elod

    2016-01-01

    Myeloid sarcoma results from the extramedullary homing and proliferation of immature myeloid precursors. We present the timeline, events and diagnostic pitfalls related to a 66 year-old male patient's case, admitted to the Hematology Clinic for pancytopenia, fever, weight loss and fatigue. The severe cytopenia and the few blasts observed in his blood smear indicated a bone marrow biopsy. The bone marrow showed hypercellularity and multilineage dysplasia with the presence of 15% myeloblasts. After the biopsy, he promptly developed paraplegia and nuclear magnetic resonance revealed an epidural tumour which was then resected.In the epidural tumour mass blast-like, round cells were observed with a complex immunophenotype, characterized by myeloperoxidase, CD117, CD15, CD99, leucocyte common antigen positivity and a high Ki-67 proliferation index. Considering the main differential diagnostic issues, the final diagnosis was stated as myelodysplastic syndrome-associated myeloid sarcoma. The prognosis was unfavourable, the bone marrow was quickly invaded by proliferating blast cells, and despite chemotherapy attempts, the patient died. PMID:27019694

  13. Function Over Form: Modeling Groups of Inherited Neurological Conditions in Zebrafish

    PubMed Central

    Kozol, Robert A.; Abrams, Alexander J.; James, David M.; Buglo, Elena; Yan, Qing; Dallman, Julia E.

    2016-01-01

    Zebrafish are a unique cell to behavior model for studying the basic biology of human inherited neurological conditions. Conserved vertebrate genetics and optical transparency provide in vivo access to the developing nervous system as well as high-throughput approaches for drug screens. Here we review zebrafish modeling for two broad groups of inherited conditions that each share genetic and molecular pathways and overlap phenotypically: neurodevelopmental disorders such as Autism Spectrum Disorders (ASD), Intellectual Disability (ID) and Schizophrenia (SCZ), and neurodegenerative diseases, such as Cerebellar Ataxia (CATX), Hereditary Spastic Paraplegia (HSP) and Charcot-Marie Tooth Disease (CMT). We also conduct a small meta-analysis of zebrafish orthologs of high confidence neurodevelopmental disorder and neurodegenerative disease genes by looking at duplication rates and relative protein sizes. In the past zebrafish genetic models of these neurodevelopmental disorders and neurodegenerative diseases have provided insight into cellular, circuit and behavioral level mechanisms contributing to these conditions. Moving forward, advances in genetic manipulation, live imaging of neuronal activity and automated high-throughput molecular screening promise to help delineate the mechanistic relationships between different types of neurological conditions and accelerate discovery of therapeutic strategies. PMID:27458342

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

    SciTech Connect

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

    2007-04-15

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

  15. Neurology and diving.

    PubMed

    Massey, E Wayne; Moon, Richard E

    2014-01-01

    Diving exposes a person to the combined effects of increased ambient pressure and immersion. The reduction in pressure when surfacing can precipitate decompression sickness (DCS), caused by bubble formation within tissues due to inert gas supersaturation. Arterial gas embolism (AGE) can also occur due to pulmonary barotrauma as a result of breath holding during ascent or gas trapping due to disease, causing lung hyperexpansion, rupture and direct entry of alveolar gas into the blood. Bubble disease due to either DCS or AGE is collectively known as decompression illness. Tissue and intravascular bubbles can induce a cascade of events resulting in CNS injury. Manifestations of decompression illness can vary in severity, from mild (paresthesias, joint pains, fatigue) to severe (vertigo, hearing loss, paraplegia, quadriplegia). Particularly as these conditions are uncommon, early recognition is essential to provide appropriate management, consisting of first aid oxygen, targeted fluid resuscitation and hyperbaric oxygen, which is the definitive treatment. Less common neurologic conditions that do not require hyperbaric oxygen include rupture of a labyrinthine window due to inadequate equalization of middle ear pressure during descent, which can precipitate vertigo and hearing loss. Sinus and middle ear overpressurization during ascent can compress the trigeminal and facial nerves respectively, causing temporary facial hypesthesia and lower motor neuron facial weakness. Some conditions preclude safe diving, such as seizure disorders, since a convulsion underwater is likely to be fatal. Preventive measures to reduce neurologic complications of diving include exclusion of individuals with specific medical conditions and safe diving procedures, particularly related to descent and ascent.

  16. Effect of noradrenalin and EGb 761 pretreatment on the ischemia-reperfusion injured spinal cord neurons in rabbits.

    PubMed

    Mechírová, Eva; Domoráková, Iveta; Danková, Marianna; Danielisová, Viera; Burda, Jozef

    2009-09-01

    Short term sublethal ischemia or ischemic preconditioning gives protection to the neurons against subsequent lethal ischemic attack. This so-called ischemic tolerance can also be provided by certain drugs. We examined the effect of noradrenalin and EGb 761 on the spinal cord neurons injured by 30 min occlusion of abdominal aorta in rabbits. The animals survived 48 and 72 h. Degenerated neurons were visualized by Fluoro Jade B method, viable neurons were demonstrated immunohistochemically with NeuN and ubiquitin antibodies. The rabbits with noradrenalin administration 48 h before 30 min of ischemia and 48/72 h of reperfusion, showed significant increase of degenerated Fluoro Jade B labeled neurons. Animals of both groups were paraplegic. Rabbits pretreated 7 days with EGb 761 prior to 30 min of ischemia and with 48/72 h of reperfusion revealed significant decrease of Fluoro Jade B-positive neurons when compared with the groups with 30 min of ischemia followed by 48/72 h of reperfusion. In the NeuN sections, the number of viable neurons was moderately decreased. These animals showed no paraplegia. Ubiquitin aggregates occurred in the cytoplasm of degenerated neurons in the sections of rabbits preconditioned with noradrenalin 48 h prior to 30 min of ischemia and followed by 48 h of reperfusion while after 72 h of reperfusion, shrunk light shadows without ubiquitin reaction were visible. Our results indicate that EGb 761 could be involved in protection of spinal cord neurons against ischemic injury while effect of noradrenalin is not unambiguous.

  17. Simulating Ideal Assistive Devices to Reduce the Metabolic Cost of Running

    PubMed Central

    Uchida, Thomas K.; Seth, Ajay; Pouya, Soha; Dembia, Christopher L.; Hicks, Jennifer L.; Delp, Scott L.

    2016-01-01

    Tools have been used for millions of years to augment the capabilities of the human body, allowing us to accomplish tasks that would otherwise be difficult or impossible. Powered exoskeletons and other assistive devices are sophisticated modern tools that have restored bipedal locomotion in individuals with paraplegia and have endowed unimpaired individuals with superhuman strength. Despite these successes, designing assistive devices that reduce energy consumption during running remains a substantial challenge, in part because these devices disrupt the dynamics of a complex, finely tuned biological system. Furthermore, designers have hitherto relied primarily on experiments, which cannot report muscle-level energy consumption and are fraught with practical challenges. In this study, we use OpenSim to generate muscle-driven simulations of 10 human subjects running at 2 and 5 m/s. We then add ideal, massless assistive devices to our simulations and examine the predicted changes in muscle recruitment patterns and metabolic power consumption. Our simulations suggest that an assistive device should not necessarily apply the net joint moment generated by muscles during unassisted running, and an assistive device can reduce the activity of muscles that do not cross the assisted joint. Our results corroborate and suggest biomechanical explanations for similar effects observed by experimentalists, and can be used to form hypotheses for future experimental studies. The models, simulations, and software used in this study are freely available at simtk.org and can provide insight into assistive device design that complements experimental approaches. PMID:27656901

  18. Chooramani technique: A novel method of omental transposition in traumatic spinal cord injury

    PubMed Central

    Chooramani, Gopal S.; Singh, Girish Kumar; Srivastava, Rajeshwar Nath; Jaiswal, Pramod Kumar; Srivastava, Chhitij

    2013-01-01

    Background: Spinal cord injury often results in significant catastrophic disability. Placement of the intact omentum upon a recently traumatized spinal cord was found to be effective. It represents a very suitable organ for revascularization of the ischemic nervous tissue, due to its abundance in blood and lymph vessels and its capability to adhere to the surface of the lesion, with capillary overgrowing in 4-6 h. The traditional method of omentum transposition is a hectic and time-consuming two-stage procedure in which position is changed twice. The major disadvantage of this two-staged procedure is that it takes longer operative time, and there is high risk of infection due to change of position with an open wound. So there is a need for modifications so that the procedure can be made easier and complications can be avoided. Objective: To avoid the complications and to make the procedure easier, a single-staged procedure called ‘chooramani technique’ for omental transposition in spinal cord injury is proposed. Materials and Methods: The study was conducted on 16 patients of post-traumatic thoraco-lumbar spinal cord injury with paraplegia. Results: Complications like wound infection, incisional hernia, and CSF leak were avoided. Operative time reduced to approximately half. Conclusion: This modification of technique is relatively easy and can be adopted for patients undergoing omental transposition for spinal cord injury. PMID:24551001

  19. Drosophila Spastin Regulates Synaptic Microtubule Networks and Is Required for Normal Motor Function

    PubMed Central

    2004-01-01

    The most common form of human autosomal dominant hereditary spastic paraplegia (AD-HSP) is caused by mutations in the SPG4 (spastin) gene, which encodes an AAA ATPase closely related in sequence to the microtubule-severing protein Katanin. Patients with AD-HSP exhibit degeneration of the distal regions of the longest axons in the spinal cord. Loss-of-function mutations in the Drosophila spastin gene produce larval neuromuscular junction (NMJ) phenotypes. NMJ synaptic boutons in spastin mutants are more numerous and more clustered than in wild-type, and transmitter release is impaired. spastin-null adult flies have severe movement defects. They do not fly or jump, they climb poorly, and they have short lifespans. spastin hypomorphs have weaker behavioral phenotypes. Overexpression of Spastin erases the muscle microtubule network. This gain-of-function phenotype is consistent with the hypothesis that Spastin has microtubule-severing activity, and implies that spastin loss-of-function mutants should have an increased number of microtubules. Surprisingly, however, we observed the opposite phenotype: in spastin-null mutants, there are fewer microtubule bundles within the NMJ, especially in its distal boutons. The Drosophila NMJ is a glutamatergic synapse that resembles excitatory synapses in the mammalian spinal cord, so the reduction of organized presynaptic microtubules that we observe in spastin mutants may be relevant to an understanding of human Spastin's role in maintenance of axon terminals in the spinal cord. PMID:15562320

  20. 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

  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. L1CAM whole gene deletion in a child with L1 syndrome.

    PubMed

    Chidsey, Brandalyn A; Baldwin, Erin E; Toydemir, Reha; Ahles, Lauren; Hanson, Heather; Stevenson, David A

    2014-06-01

    L1 syndrome is a group of overlapping, X-linked disorders caused by mutations in L1CAM. Clinical phenotypes within L1 syndrome include X-linked hydrocephalus with stenosis of the aqueduct of sylvius (HSAS); mental retardation, adducted thumbs, shuffling gait, and aphasia (MASA) syndrome; spastic paraplegia type 1; and agenesis of the corpus callosum. Over 200 mutations in L1CAM have been reported; however, only a few large gene deletions have been observed. We report on a 4-month-old male with a de novo whole gene deletion of L1CAM presenting with congenital hydrocephalus, aqueductal stenosis, and adducted thumbs. Initial failure of L1CAM gene sequencing suggested the possibility of a whole gene deletion of L1CAM. Further investigation through chromosome microarray analysis showed a 62Kb deletion encompassing the first exon of the PDZD4 gene and the entire L1CAM gene. Investigations into genotype-phenotype correlations have suggested that mutations leading to truncated or absent L1 protein cause more severe forms of L1 syndrome. Based on the presentation of the proband and other reported patients with whole gene deletions, we provide further evidence that L1CAM whole gene deletions result in L1 syndrome with a severe phenotype, deletions of PDZD4 do not cause additional manifestations, and that X-linked nephrogenic diabetes insipidus reported in a subset of patients with large L1CAM deletions results from the loss of AVPR2. PMID:24668863

  3. Whole-exome sequencing in neurologic practice: Reducing the diagnostic odyssey.

    PubMed

    Johnson, Nicholas E

    2015-12-01

    The current issue of Neurology® Genetics emphasizes the unparalleled role of next-generation sequencing (NGS) in defining an expanding spectrum of genetic neurologic disorders. Clinically, NGS encompasses the use of large gene panels, whole-exome sequencing (WES), or whole-genome sequencing (WGS). The impact of NGS technology is twofold. First, researchers have discovered novel genes as the cause of neurologic disorders. This research includes the efforts of Martikainen et al.(1) to define further the phenotype of a previously reported SNCA mutation that is associated with autosomal dominant Parkinson disease. Second and more common is the connection of novel phenotypes with previously described genes. Several articles in the current issue highlight the role of NGS in this effort. For example, Schottman et al.(2) identified REEP1 mutations as the cause of a severe axonal neuropathy with a spinal muscular atrophy with respiratory distress (SMARD) phenotype. This gene was previously associated with a hereditary spastic paraplegia phenotype. Similarly, Shieh et al.(3) expand the phenotype associated with mutations in L1CAM to a neuronal migration phenotype. PMID:27066574

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  7. Screening of ARHSP-TCC patients expands the spectrum of SPG11 mutations and includes a large scale gene deletion.

    PubMed

    Denora, Paola S; Schlesinger, David; Casali, Carlo; Kok, Fernando; Tessa, Alessandra; Boukhris, Amir; Azzedine, Hamid; Dotti, Maria Teresa; Bruno, Claudio; Truchetto, Jeremy; Biancheri, Roberta; Fedirko, Estelle; Di Rocco, Maja; Bueno, Clarissa; Malandrini, Alessandro; Battini, Roberta; Sickl, Elisabeth; de Leva, Maria Fulvia; Boespflug-Tanguy, Odile; Silvestri, Gabriella; Simonati, Alessandro; Said, Edith; Ferbert, Andreas; Criscuolo, Chiara; Heinimann, Karl; Modoni, Anna; Weber, Peter; Palmeri, Silvia; Plasilova, Martina; Pauri, Flavia; Cassandrini, Denise; Battisti, Carla; Pini, Antonella; Tosetti, Michela; Hauser, Erwin; Masciullo, Marcella; Di Fabio, Roberto; Piccolo, Francesca; Denis, Elodie; Cioni, Giovanni; Massa, Roberto; Della Giustina, Elvio; Calabrese, Olga; Melone, Marina A B; De Michele, Giuseppe; Federico, Antonio; Bertini, Enrico; Durr, Alexandra; Brockmann, Knut; van der Knaap, Marjo S; Zatz, Mayana; Filla, Alessandro; Brice, Alexis; Stevanin, Giovanni; Santorelli, Filippo M

    2009-03-01

    Autosomal recessive spastic paraplegia with thinning of corpus callosum (ARHSP-TCC) is a complex form of HSP initially described in Japan but subsequently reported to have a worldwide distribution with a particular high frequency in multiple families from the Mediterranean basin. We recently showed that ARHSP-TCC is commonly associated with mutations in SPG11/KIAA1840 on chromosome 15q. We have now screened a collection of new patients mainly originating from Italy and Brazil, in order to further ascertain the spectrum of mutations in SPG11, enlarge the ethnic origin of SPG11 patients, determine the relative frequency at the level of single Countries (i.e., Italy), and establish whether there is one or more common mutation. In 25 index cases we identified 32 mutations; 22 are novel, including 9 nonsense, 3 small deletions, 4 insertions, 1 in/del, 1 small duplication, 1 missense, 2 splice-site, and for the first time a large genomic rearrangement. This brings the total number of SPG11 mutated patients in the SPATAX collection to 111 cases in 44 families and in 17 isolated cases, from 16 Countries, all assessed using homogeneous clinical criteria. While expanding the spectrum of mutations in SPG11, this larger series also corroborated the notion that even within apparently homogeneous population a molecular diagnosis cannot be achieved without full gene sequencing.

  8. In Silico Investigation of Traditional Chinese Medicine for Potential Lead Compounds as SPG7 Inhibitors against Coronary Artery Disease.

    PubMed

    Chen, Kuen-Bao; Chen, Kuan-Chung; Chang, Ya-Lin; Chang, Kun-Lung; Chang, Pei-Chun; Chang, Tung-Ti; Chen, Yu-Chian

    2016-05-05

    Coronary artery disease (CAD) is the most common cause of heart attack and the leading cause of mortality in the world. It is associated with mitochondrial dysfunction and increased level of reactive oxygen species production. According to the Ottawa Heart Genomics Study genome-wide association study, a recent research identified that Q688 spastic paraplegia 7 (SPG7) variant is associated with CAD as it bypasses the regulation of tyrosine phosphorylation of AFG3L2 and enhances the processing and maturation of SPG7 protein. This study aims to identify potential compounds isolated from Traditional Chinese Medicines (TCMs) as potential lead compounds for paraplegin (SPG7) inhibitors. For the crystallographic structure of paraplegin, the disordered disposition of key amino acids in the binding site was predicted using the PONDR-Fit protocol before virtual screening. The TCM compounds saussureamine C and 3-(2-carboxyphenyl)-4(3H)-quinazolinone, have potential binding affinities with stable H-bonds and hydrophobic contacts with key residues of paraplegin. A molecular dynamics simulation was performed to validate the stability of the interactions between each candidate and paraplegin under dynamic conditions. Hence, we propose these compounds as potential candidates as lead drug from the compounds isolated from TCM for further study in drug development process with paraplegin protein for coronary artery disease.

  9. Technique of spinal cord compression induced by inflation of epidural balloon catheter in rabbits (Oryctologus cuniculus): efficient and easy to use model.

    PubMed

    Fonseca, Antonio F B DA; Scheffer, Jussara P; Coelho, Barbara P; Aiello, Graciane; Guimarães, Arthur G; Gama, Carlos R B; Vescovini, Victor; Cabral, Paula G A; Oliveira, André L A

    2016-09-01

    The most common cause of spinal cord injury are high impact trauma, which often result in some motor impairment, sensory or autonomic a greater or lesser extent in the distal areas the level of trauma. In terms of survival and complications due to sequelae, veterinary patients have a poor prognosis unfavorable. Therefore justified the study of experimental models of spinal cord injury production that could provide more support to research potential treatments for spinal cord injuries in medicine and veterinary medicine. Preclinical studies of acute spinal cord injury require an experimental animal model easily reproducible. The most common experimental animal model is the rat, and several techniques for producing a spinal cord injury. The objective of this study was to describe and evaluate the effectiveness of acute spinal cord injury production technique through inflation of Fogarty(r) catheter using rabbits as an experimental model because it is a species that has fewer conclusive publications and contemplating. The main requirements of a model as low cost, handling convenience, reproducibility and uniformity. The technique was adequate for performing preclinical studies in neuro-traumatology area, effectively leading to degeneration and necrosis of the nervous tissue fostering the emergence of acute paraplegia.

  10. Chapter 3: neurology in ancient Egypt.

    PubMed

    York, George K; Steinberg, David A

    2010-01-01

    Neurology, in the modern sense, did not exist in ancient Egypt, where medicine was a compound of natural, magical and religious elements, with different practitioners for each form of healing. Nevertheless, Egyptian doctors made careful observations of illness and injury, some of which involved the nervous system. Modern scholars have three sources of information about Egyptian medicine: papyri, inscriptions, and mummified remains. These tell us that the Egyptians had words for the skull, brain, vertebrae, spinal fluid and meninges, though they do not say if they assigned any function to them. They described unconsciousness, quadriparesis, hemiparesis and dementia. We can recognize neurological injuries, such as traumatic hemiparesis and cervical dislocation with paraplegia, in the well known Edwin Smith surgical papyrus. Similarly recognizable in the Ebers papyrus is a description of migraine. An inscription from the tomb of the vizier Weshptah, dated c. 2455 BCE, seems to describe stroke, and Herodotus describes epilepsy in Hellenistic Egypt. We have very little understanding of how Egyptian physicians organized these observations, but we may learn something of Egyptian culture by examining them. At the same time, modern physicians feel some connection to Egyptian physicians and can plausibly claim to be filling a similar societal role. PMID:19892106

  11. 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.

  12. [A case of neuro-Behçet's disease with repeating isolated thoracic spinal cord lesion].

    PubMed

    Shiote, Mito; Kido, Yukiko; Hayashi, Takeshi; Manabe, Yasuhiro; Kashihara, Ken-ichi; Nagano, Isao; Shoji, Mikio; Abe, Koji

    2003-06-01

    We reported a 45-year-old man who had repeated isolated thoracic spinal cord lesion on MRI in the clinical course of seven years. He had transient bilateral plantar numbness and urinary retention on December, 1994. Then, spastic paraplegia, total anesthesia of feet, and severe sphincter disturbance struck him on May, 1995. He was diagnosed as incomplete Behçet's disease and neuro-Behçet's disease on June, 1995 because of recurrent oral aphta, genital ulceration, and foliculitis. T2-weighted magnetic resonance imaging showed high intensity enhanced with Gd-DTPA in thoracic spinal cord from Th 5 to 8 level. Any other abnormal lesion on brain or spinal MRI was not observed. He was treated with corticosteroids and recovered incompletely. Another two big attacks occurred to him. No new lesion but thoracic spinal cord lesion was observed. We conclude that this case is the first reported example of neuro-Behçet's disease with repeating isolated thoracic spinal cord lesion.

  13. A novel R275X mutation of the SLC25A15 gene in a Japanese patient with the HHH syndrome.

    PubMed

    Torisu, Hiroyuki; Kira, Ryutaro; Kanazawa, Naomi; Takemoto, Megumi; Sanefuji, Masafumi; Sakai, Yasunari; Tsujino, Seiichi; Hara, Toshiro

    2006-06-01

    The hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome (MIM 238970) is an autosomal recessive metabolic disorder caused by a deficiency of the mitochondrial ornithine transporter, one of the urea cycle components. Mutations in the SLC25A15 gene have been coupled to the HHH syndrome. We describe a Japanese female patient with the HHH syndrome due to a novel homozygous R275X SLC25A15 mutation and male sibling who presumably carried the same mutation. He exhibited slowly progressive deterioration with seizures, a gait disturbance due to polyneuropathy, episodic confusion, and died of acute encephalopathy at 34 years of age while the proband exhibited moderate mental retardation, seizures, mild spastic paraplegia, and deafness without neurological deterioration for more than 20 years. The clinical features of previously documented patients with the homozygous SLC25A15 mutation demonstrated that genotype did not simply correlate with clinical severity. The phenotypic variability might depend on other factors, such as dietary and other genetic ones. PMID:16376511

  14. The articles of Babinski on his sign and the paper of 1898.

    PubMed

    Bruno, Estañol; Horacio, Sentíes-Madrid; Yolanda, Elías; Guillermo, García Ramos

    2007-01-01

    In 1896 Joseph François Felix Babinski described for the first time the phenomenon of the toes; nevertheless in this first paper he simply described extension of all toes with pricking of the sole of the foot. It was not until the second paper of 1898 that he specifically described the extension of the hallux with strong tactile stimulation (stroking) of the lateral border of the sole. Babinski probably discovered his sign by a combination of chance observation and careful re-observation and replication. He also had in mind practical applications of the sign, particularly in the differential diagnosis with hysteria and in medico-legal areas. Several of the observations and physiopathological mechanisms proposed by Babinski are still valid today, e.g, he realized since 1896 that the reflex was part of the flexor reflex synergy and observed that several patients during the first hours of an acute cerebral or spinal insult had absent extensor responses. He also found that most patients with the abnormal reflex had weakness of dorsiflexion of the toes and ankles and observed a lack of correlation between hyperactive myotatic reflexes and the presence of an upgoing hallux. He discovered that not all patients with hemiplegia or paraplegia had the sign but thought erroneously that some normal subjects could have an upgoing toe. Between 1896 and 1903 Babinski continued to think on the sign that bears his name and enrich its semiological and physiopathological value.

  15. Spinal injuries due to front-end bale loaders.

    PubMed Central

    Friesen, R W; Ekong, C E

    1988-01-01

    Of 22 patients admitted to Plains Health Centre, Regina, from January 1979 to April 1986 with spinal injuries due to farming accidents, 7 had injuries related to tractor-mounted front-end bale loaders. In contrast, none of the 12 patients admitted with farm-related spinal injuries from 1974 through 1978 had injuries related to bale loaders. All seven injuries occurred when a front-end loader was used to move a large, round hay bale. In each case when the loader arms were raised past the horizontal plane the bale rolled back onto the unprotected tractor operator. There were five thoracic injuries, one cervical injury and one lumbar injury. All seven bony injuries healed. Four of the patients had permanent neurologic sequelae; two of the four had paraplegia. All seven patients suffered disability that impaired work performance; all five farmers suffered some loss of income. None of these injuries would have occurred if available safety equipment had been in place. Images Fig. 1 Fig. 2 PMID:3334917

  16. Case study to evaluate a standing table for managing constipation.

    PubMed

    Hoenig, H; Murphy, T; Galbraith, J; Zolkewitz, M

    2001-01-01

    Standing devices have been advocated as a potentially beneficial treatment for constipation in persons with spinal cord injury (SCI); however, definitive data are lacking. A case of a patient who requested a standing table to treat chronic constipation is presented as an illustration of a method to address this problem on an individual patient level. The patient was a 62-year-old male with T12-L1 ASIA B paraplegia who was injured in 1965. The patient was on chronic narcotics for severe, nonoperable shoulder pain. His bowel program had been inadequate to prevent impactions. A systematic approach was used to measure the effects of a standing table on frequency of bowel movements (BMs) and on length of bowel care episodes. There was a significant (p < 0.05) increase in frequency of BMs and a decrease in bowel care time with the use of the standing table 5 times/week versus baseline. For this patient, the use of the standing table was a clinically useful addition to his bowel care program. PMID:12035465

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

    PubMed Central

    Sunilkumar, MM; Boston, Patricia; Rajagopal, MR

    2015-01-01

    Background: Sexual dysfunction is a major concern for Indian men living with a spinal cord injury Objectives: To examine the literature related to sexuality traumatic cord injury and its impact on sexual functioning. Materials and Methods: Databases using Cumulative Index to Nursing and Allied Health Literature (CINAHL) 2000–2012, Medline 1989–2012, Applied Social Sciences Index and Abstracts (ASSIA) 1989–2012 and Google Scholar were the search engines used used for literature review. Results: The search yielded a total of 457 articles and only 75 of them were found relevant. The minimum number of articles required to meet the inclusion criteria for this review was 25–30 articles. Out of the 75 articles, 33 were considered relevant or related to the topic of sexual functioning, spinal cord injury, and paraplegia. Six areas were identified: Sexual stigmatization, physiological barriers to sexual satisfaction, clinical aspects of sexual functioning, biomedical approaches to sexual dysfunction, partner satisfaction, and lack of accessibility to sexual education. Conclusion: Spinal cord injury and sexual functioning affects a large segment of the male Indian population, yet most current research focuses on quantitative measurement with the emphasis on ejaculatory dysfunction, orgasm impairment, incontinence, and other physiological dysfunction. Further research is needed to address the subjective accounts of patients themselves with respect to the emotional and social impact of sexual disability. This would help to identify the best possible outcomes for both treatment and rehabilitation. PMID:26600694

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

    PubMed

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

    2015-02-16

    Assistive and rehabilitative powered exoskeletons for spinal cord injury (SCI) and stroke subjects have recently reached the clinic. Proper tension and joint alignment are critical to ensuring safety. Challenges still exist in adjustment and fitting, with most current systems depending on personnel experience for appropriate individual fastening. Paraplegia and tetraplegia patients using these devices have impaired sensation and cannot signal if straps are uncomfortable or painful. Excessive pressure and blood-flow restriction can lead to skin ulcers, necrotic tissue and infections. Tension must be just enough to prevent slipping and maintain posture. Research in pressure dynamics is extensive for wheelchairs and mattresses, but little research has been done on exoskeleton straps. We present a system to monitor pressure exerted by physical human-machine interfaces and provide data about levels of skin/body pressure in fastening straps. The system consists of sensing arrays, signal processing hardware with wireless transmission, and an interactive GUI. For validation, a lower-body powered exoskeleton carrying the full weight of users was used. Experimental trials were conducted with one SCI and one able-bodied subject. The system can help prevent skin injuries related to excessive pressure in mobility-impaired patients using powered exoskeletons, supporting functionality, independence and better overall quality of life.

  19. Cardiorespiratory fitness and muscular strength of wheelchair users.

    PubMed Central

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

    1981-01-01

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

  20. Epidural angiomatous meningioma of the thoracic spine: A case report

    PubMed Central

    YANG, TAO; WU, LIANG; YANG, CHENLONG; XU, YULUN

    2016-01-01

    Spinal epidural angiomatous meningiomas (AMs) are extremely rare lesions. Here, we report on a case of an epidural AM of the thoracic spine with chronic but severe cord compression. The patient underwent a T6-T8 laminectomy through the posterior approach. En bloc resection was achieved, and histopathological examination demonstrated an AM. Delayed paraplegia occurred 4 h postoperatively. The patient was treated with methylprednisolone, hyperbaric oxygen and rehabilitation. Gradually, over the next six months, the bilateral leg strength was improved compared with the preoperative status, and no tumor recurrence was noted. Although epidural AM is extremely rare, it should be included in the differential diagnosis of spinal epidural lesions. A definitive diagnosis is difficult based on magnetic resonance imaging alone due to the nonspecific characteristics of the tumor. Since AM is a histologically benign and highly vascularized tumor, timely gross total resection (GTR) is the most effective treatment. A good clinical outcome may be expected following GTR (Simpson grade I and II resection). PMID:26870233

  1. Intrafamilial variation of the phenotype in Bardet-Biedl syndrome

    PubMed Central

    Riise, R.; Andreasson, S.; Borgstrom, M.; Wright, A.; Tommerup, N.; Rosenberg, T.; Tornqvist, K.

    1997-01-01

    AIMS—To describe the variation of the phenotype within families with several individuals with Bardet-Biedl syndrome.
METHODS—The phenotypes of affected siblings in 11 Scandinavian families were compared with two or more members who had at least three of the features: retinal dystrophy, polydactyly, obesity, hypogenitalism, and mental retardation. Individuals without retinal dystrophy were excluded.
RESULTS—Intrafamilial variation of expressivity of the features obesity, polydactyly, abnormal radiograms of the extremities, hypogenitalism, short stature, paraplegia, and dental abnormalities was found. The retinal dystrophy varied with respect to both the onset of symptoms and the course of the disease. The morphology of the fundus, however, was consistent within the families. The disorder showed statistically significant genetic linkage to the BBS4 locus on chromosome 15 in the affected siblings in two of the families, but the clinical features in these patients did not differ from the other cases of Bardet-Biedl syndrome.
CONCLUSION—Comparison of siblings with the Bardet-Biedl syndrome showed variation of the typical features. In addition, the course of retinal dystrophy varied. No distinctive clinical features were found to separate the BBS4 phenotype from the remaining patients.

 PMID:9227203

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

    PubMed Central

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

    2012-01-01

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

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

    SciTech Connect

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

    2006-10-15

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

  4. Metabolic efficiency of volitional and electrically stimulated cycling in able-bodied subjects.

    PubMed

    Hunt, K J; Hosmann, D; Grob, M; Saengsuwan, J

    2013-07-01

    This study compared the metabolic efficiency of volitional cycling and functional-electrical-stimulation (FES) cycling within a subject group of able-bodied individuals, with a view to further elucidating the mechanisms underlying the low efficiency of FES cycling. Previous studies estimated the metabolic efficiency of volitional cycling and anaesthetised FES cycling in able-bodied subjects, and of FES cycling in subjects paralysed by spinal cord injury. The rationale for the experimental model chosen here, i.e. non-anaesthetised able-bodied subjects, was that this lies between normal cycling and paralysed cycling: while using FES, this group has artificial muscle activation and timing like the paralysed group; but it does not have disrupted sensory feedback and vasomotor control; this measurement therefore allows delineation of the magnitude of reduction in metabolic efficiency resulting from: (i) the FES itself and (ii) paralysis (where there is disrupted sensory feedback and vasomotor control). Furthermore, we used the same methods employed previously for estimation of metabolic efficiency in subjects with motor- and sensory-complete paraplegia. The mean metabolic efficiency of volitional cycling was found to be 29.8% and that of FES cycling was 16.4% (n=11). The low efficiency of FES cycling can be explained in large part by the crude timing of muscle activation and by non-physiological muscle fibre recruitment. In FES cycling with paralysed subjects, disrupted sensory feedback and vasomotor control may play a further, albeit smaller, role in the reduced efficiency. PMID:23253953

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

    PubMed Central

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

    2015-01-01

    A hybrid neuroprosthesis that uses an electric motor-based wearable exoskeleton and functional electrical stimulation (FES) has a promising potential to restore walking in persons with paraplegia. A hybrid actuation structure introduces effector redundancy, making its automatic control a challenging task because multiple muscles and additional electric motor need to be coordinated. Inspired by the muscle synergy principle, we designed a low dimensional controller to control multiple effectors: FES of multiple muscles and electric motors. The resulting control system may be less complex and easier to control. To obtain the muscle synergy-inspired low dimensional control, a subject-specific gait model was optimized to compute optimal control signals for the multiple effectors. The optimal control signals were then dimensionally reduced by using principal component analysis to extract synergies. Then, an adaptive feedforward controller with an update law for the synergy activation was designed. In addition, feedback control was used to provide stability and robustness to the control design. The adaptive-feedforward and feedback control structure makes the low dimensional controller more robust to disturbances and variations in the model parameters and may help to compensate for other time-varying phenomena (e.g., muscle fatigue). This is proven by using a Lyapunov stability analysis, which yielded semi-global uniformly ultimately bounded tracking. Computer simulations were performed to test the new controller on a 4-degree of freedom gait model. PMID:26734606

  6. Musculoskeletal Deterioration and Hemicorporectomy After Spinal Cord Injury

    PubMed Central

    Dudley-Javoroski, Shauna

    2014-01-01

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

  7. [Thoracoabdominal aortic aneurysm].

    PubMed

    Kalder, J; Kotelis, D; Jacobs, M J

    2016-09-01

    Thoracoabdominal aortic aneurysms (TAAA) are rare events with an incidence of 5.9 cases per 100,000 persons per year. In Germany approximately 940 TAAA procedures are performed annually. The cause of TAAA is mostly degenerative but they can also occur on the basis of an aortic dissection or connective tissue disease (e. g. Marfan's syndrome). Patients often have severe comorbidities and suffer from hypertension, coronary heart disease or chronic obstructive pulmonary disease, mostly as a result of smoking. Operative treatment is indicated when the maximum aortic diameter has reached 6 cm (> 5 cm in patients with connective tissue disease) or the aortic diameter rapidly increases (> 5 mm/year). Treatment options are open surgical aortic repair with extracorporeal circulation, endovascular repair with branched/fenestrated endografts and parallel grafts (chimneys) or a combination of open and endovascular procedures (hybrid procedures). Mortality rates after both open and endovascular procedures are approximately 8 % depending on the extent of the repair. Furthermore, there are relevant risks of complications, such as paraplegia (up to 20 %) and the necessity for dialysis. In recent years several approaches to minimize these risks have been proposed. Besides cardiopulmonary risk evaluation, clinical assessment of patients by the physician with respect to the patient-specific anatomy influences the allocation of patients to one treatment option or another. Surgery of TAAA should ideally be performed in high-volume centers in order to achieve better results. PMID:27558261

  8. Inbreeding levels in Northeast Brazil: Strategies for the prospecting of new genetic disorders

    PubMed Central

    2010-01-01

    A new autosomal recessive genetic condition, the SPOAN syndrome (an acronym for spastic paraplegia, optic atrophy and neuropathy syndrome), was recently discovered in an isolated region of the State of Rio Grande do Norte in Northeast Brazil, in a population that was identified by the IBGE (Brazilian Institute of Geography and Statistics) as belonging to the Brazilian communities with the highest rates of “deficiencies” (Neri, 2003), a term used to describe diseases, malformations, and handicaps in general. This prompted us to conduct a study of consanguinity levels in five of its municipal districts by directly interviewing their inhabitants. Information on 7,639 couples (corresponding to about 40% of the whole population of the studied districts) was obtained. The research disclosed the existence of very high frequencies of consanguineous marriages, which varied from about 9% to 32%, suggesting the presence of a direct association between genetic diseases such as the SPOAN syndrome, genetic drift and inbreeding levels. This fact calls for the introduction of educational programs for the local populations, as well as for further studies aiming to identify and characterize other genetic conditions. Epidemiological strategies developed to collect inbreeding data, with the collaboration of health systems available in the region, might be very successful in the prospecting of genetic disorders. PMID:21637472

  9. Inbreeding levels in Northeast Brazil: Strategies for the prospecting of new genetic disorders.

    PubMed

    Santos, Silvana; Kok, Fernando; Weller, Mathias; de Paiva, Francisco Rennan Lopes; Otto, Paulo A

    2010-04-01

    A new autosomal recessive genetic condition, the SPOAN syndrome (an acronym for spastic paraplegia, optic atrophy and neuropathy syndrome), was recently discovered in an isolated region of the State of Rio Grande do Norte in Northeast Brazil, in a population that was identified by the IBGE (Brazilian Institute of Geography and Statistics) as belonging to the Brazilian communities with the highest rates of "deficiencies" (Neri, 2003), a term used to describe diseases, malformations, and handicaps in general. This prompted us to conduct a study of consanguinity levels in five of its municipal districts by directly interviewing their inhabitants. Information on 7,639 couples (corresponding to about 40% of the whole population of the studied districts) was obtained. The research disclosed the existence of very high frequencies of consanguineous marriages, which varied from about 9% to 32%, suggesting the presence of a direct association between genetic diseases such as the SPOAN syndrome, genetic drift and inbreeding levels. This fact calls for the introduction of educational programs for the local populations, as well as for further studies aiming to identify and characterize other genetic conditions. Epidemiological strategies developed to collect inbreeding data, with the collaboration of health systems available in the region, might be very successful in the prospecting of genetic disorders.

  10. Coping and adaptation in adults living with spinal cord injury.

    PubMed

    Barone, Stacey Hoffman; Waters, Katherine

    2012-10-01

    Biopsychosocial adaptation remains a multifaceted challenge for individuals with spinal cord injury, their families, and healthcare providers alike. The development of frequent medical complications necessitating healthcare interventions is an ongoing, debilitating, and costly problem for those living with spinal cord injuries. Although several demographic variables have been correlated with positive adaptation in individuals with spinal cord injury, the research outcome data present limitations in understanding and facilitating which coping techniques work best to augment biopsychosocial adaptation in this population. Coping facilitates adaptation and adjustment to stress and can help to increase quality of life in people living with spinal cord injury and reduce common complications. The purpose of this study was to determine the extent to which sociodemographic characteristics and hardiness explain coping in 243 adults living with a spinal cord injury. In addition, this study examined which predictors of coping explain biopsychosocial adaptation. A descriptive explanatory design was utilized. Standardized instruments were administered nationally to assess hardiness, coping, and physiological and psychosocial adaptation. Canonical correlation and multiple regression analyses indicated that less educated, less hardy, and recently injured participants were more likely to use escape-avoidance coping and less likely to use social support, problem solving, and positive reappraisal coping behaviors (p < .05). Individuals with paraplegia had a higher level of functional ability, spent less time in rehabilitation, had a greater sense of control, and experienced less frequent complications. The control dimension of hardiness was the only dimension that significantly related to biopsychosocial adaptation within this sample.

  11. 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.

  12. Hereditary and metabolic myelopathies.

    PubMed

    Hedera, Peter

    2016-01-01

    Hereditary and metabolic myelopathies are a heterogeneous group of neurologic disorders characterized by clinical signs suggesting spinal cord dysfunction. Spastic weakness, limb ataxia without additional cerebellar signs, impaired vibration, and positional sensation are hallmark phenotypic features of these disorders. Hereditary, and to some extent, metabolic myelopathies are now recognized as more widespread systemic processes with axonal loss and demyelination. However, the concept of predominantly spinal cord disorders remains clinically helpful to differentiate these disorders from other neurodegenerative conditions. Furthermore, metabolic myelopathies are potentially treatable and an earlier diagnosis increases the likelihood of a good clinical recovery. This chapter reviews major types of degenerative myelopathies, hereditary spastic paraplegia, motor neuron disorders, spastic ataxias, and metabolic disorders, including leukodystrophies and nutritionally induced myelopathies, such as vitamin B12, E, and copper deficiencies. Neuroimaging studies usually detect a nonspecific spinal cord atrophy or demyelination of the corticospinal tracts and dorsal columns. Brain imaging can be also helpful in myelopathies caused by generalized neurodegeneration. Given the nonspecific nature of neuroimaging findings, we also review metabolic or genetic assays needed for the specific diagnosis of hereditary and metabolic myelopathies. PMID:27430441

  13. Effect of high-frequency repetitive transcranial magnetic stimulation on motor cortical excitability and sensory nerve conduction velocity in subacute-stage incomplete spinal cord injury patients

    PubMed Central

    Cha, Hyun Gyu; Ji, Sang-Goo; Kim, Myoung-Kwon

    2016-01-01

    [Purpose] The aim of the present study was to determine whether repetitive transcranial magnetic stimulation can improve sensory recovery of the lower extremities in subacute-stage spinal cord injury patients. [Subjects and Methods] This study was conducted on 20 subjects with diagnosed paraplegia due to spinal cord injury. These 20 subjects were allocated to an experimental group of 10 subjects that underwent active repetitive transcranial magnetic stimulation or to a control group of 10 subjects that underwent sham repetitive transcranial magnetic stimulation. The SCI patients in the experimental group underwent active repetitive transcranial magnetic stimulation and conventional rehabilitation therapy, whereas the spinal cord injury patients in the control group underwent sham repetitive transcranial magnetic stimulation and conventional rehabilitation therapy. Participants in both groups received therapy five days per week for six-weeks. Latency, amplitude, and sensory nerve conduction velocity were assessed before and after the six week therapy period. [Results] A significant intergroup difference was observed for posttreatment velocity gains, but no significant intergroup difference was observed for amplitude or latency. [Conclusion] repetitive transcranial magnetic stimulation may be improve sensory recovery of the lower extremities in subacute-stage spinal cord injury patients. PMID:27512251

  14. Early Experiences with the Endovascular Repair of Ruptured Descending Thoracic Aortic Aneurysm

    PubMed Central

    Choi, Jae-Sung; Oh, Se Jin; Sung, Yong Won; Moon, Hyun Jong; Lee, Jung Sang

    2016-01-01

    Background The aim of this study was to report our early experiences with the endovascular repair of ruptured descending thoracic aortic aneurysms (rDTAAs), which are a rare and life-threatening condition. Methods Among 42 patients who underwent thoracic endovascular aortic repair (TEVAR) between October 2010 and September 2015, five patients (11.9%) suffered an rDTAA. Results The mean age was 72.4±5.1 years, and all patients were male. Hemoptysis and hemothorax were present in three (60%) and two (40%) patients, respectively. Hypovolemic shock was noted in three patients who underwent emergency operations. A hybrid operation was performed in three patients. The mean operative time was 269.8±72.3 minutes. The mean total length of aortic coverage was 186.0±49.2 mm. No 30-day mortality occurred. Stroke, delirium, and atrial fibrillation were observed in one patient each. Paraplegia did not occur. Endoleak was found in two patients (40%), one of whom underwent an early and successful reintervention. During the mean follow-up period of 16.8±14.8 months, two patients died; one cause of death was a persistent type 1 endoleak and the other cause was unknown. Conclusion TEVAR for rDTAA was associated with favorable early mortality and morbidity outcomes. However, early reintervention should be considered if persistent endoleak occurs. PMID:27064672

  15. Treatment of Chronic Acromioclavicular Joint Dislocation in a Paraplegic Patient with the Weaver-Dunn Procedure and a Hook-Plate.

    PubMed

    Godry, Holger; Citak, Mustafa; Königshausen, Matthias; Schildhauer, Thomas A; Seybold, Dominik

    2016-06-27

    In case of patients with spinal cord injury and concomitant acromioclavicular (AC) joint-dislocation the treatment is challenging, as in this special patient group the function of the shoulder joint is critical because patients depend on the upper limb for mobilization and wheelchair-locomotion. Therefore the goal of this study was to examine, if the treatment of chronic AC-joint dislocation using the Weaver-Dunn procedure augmented with a hook-plate in patients with a spinal cord injury makes early postoperative wheelchair mobilization and the wheelchair transfer with full weight-bearing possible. In this case the Weaver-Dunn procedure with an additive hook-plate was performed in a 34-year-old male patient with a complete paraplegia and a posttraumatic chronic AC-joint dislocation. The patient was allowed to perform his wheelchair transfers with full weight bearing on the first post-operative day. The removal of the hook-plate was performed four months after implantation. At the time of follow-up the patient could use his operated shoulder with full range of motion without restrictions in his activities of daily living or his wheel-chair transfers. PMID:27433301

  16. Clinical variability and female penetrance in X-linked familial FTD/ALS caused by a P506S mutation in UBQLN2.

    PubMed

    Vengoechea, Jaime; David, Marjorie P; Yaghi, Shadi R; Carpenter, Lori; Rudnicki, Stacy A

    2013-12-01

    Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disease leading to progressive paralysis that is generally fatal. Only 10% of cases are familial, a subset of which overlaps with frontotemporal dementia (FTD). Up to half of ALS patients have cognitive impairment, with 15% meeting the criteria for FTD. Clinical sequencing of UBQLN2 in a family with X-linked FTD/ALS with suspected incomplete penetrance, manifesting in both genders, revealed a P506S mutation in. Affected individuals were diagnosed with various conditions including hereditary spastic paraplegia (HSP), bulbar palsy and multiple sclerosis. The mutation in UBQLN2 was first identified in a 35-year-old female who presented with one year of progressive dysarthria, dyspnea, dysphagia, and cognitive decline. EMG suggested early motor neuron disease with prominent bulbar involvement. Her cognition declined rapidly and she developed extremity weakness. Her brother, initially diagnosed with HSP, and her second cousin, with primary lateral sclerosis, also have a P506S mutation in UBQLN2. In conclusion, the P506S mutation in UBQLN2 can affect both males and females and displays great phenotypic variability within the same family. Females can potentially have a more severe and rapidly progressive presentation than their male relatives. Additionally, the P506S mutation can also cause an FTD phenotype.

  17. The challenges of axon survival: introduction to the special issue on axonal degeneration.

    PubMed

    Coleman, Michael P

    2013-08-01

    Early axon loss is a common feature of many neurodegenerative disorders. It renders neurons functionally inactive, or less active if axon branches are lost, in a manner that is often irreversible. In the CNS, there is no long-range axon regeneration and even peripheral nerve axons are unlikely to reinnervate their targets while the cause of the problem persists. In most disorders, axon degeneration precedes cell death so it is not simply a consequence of it, and it is now clear that axons have at least one degeneration mechanism that differs from that of the soma. It is important to understand these degeneration mechanisms and their contribution to axon loss in neurodegenerative disorders. In this way, it should become possible to prevent axon loss as well as cell death. This special edition considers the roles and mechanisms of axon degeneration in amyotrophic lateral sclerosis, Charcot-Marie-Tooth disease, hereditary spastic paraplegia, ischemic injury, traumatic brain injury, Alzheimer's disease, glaucoma, Huntington's disease and Parkinson's disease. Using examples from these and other disorders, this introduction considers some of the reasons for axon vulnerability. It also illustrates how molecular genetics and studies of Wallerian degeneration have contributed to our understanding of axon degeneration mechanisms. PMID:23769907

  18. The role of mitochondria in inherited neurodegenerative diseases.

    PubMed

    Kwong, Jennifer Q; Beal, M Flint; Manfredi, Giovanni

    2006-06-01

    In the past decade, the genetic causes underlying familial forms of many neurodegenerative disorders, such as Huntington's disease, Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, Friedreich ataxia, hereditary spastic paraplegia, dominant optic atrophy, Charcot-Marie-Tooth type 2A, neuropathy ataxia and retinitis pigmentosa, and Leber's hereditary optic atrophy have been elucidated. However, the common pathogenic mechanisms of neuronal death are still largely unknown. Recently, mitochondrial dysfunction has emerged as a potential 'lowest common denominator' linking these disorders. In this review, we discuss the body of evidence supporting the role of mitochondria in the pathogenesis of hereditary neurodegenerative diseases. We summarize the principal features of genetic diseases caused by abnormalities of mitochondrial proteins encoded by the mitochondrial or the nuclear genomes. We then address genetic diseases where mutant proteins are localized in multiple cell compartments, including mitochondria and where mitochondrial defects are likely to be directly caused by the mutant proteins. Finally, we describe examples of neurodegenerative disorders where mitochondrial dysfunction may be 'secondary' and probably concomitant with degenerative events in other cell organelles, but may still play an important role in the neuronal decay. Understanding the contribution of mitochondrial dysfunction to neurodegeneration and its pathophysiological basis will significantly impact our ability to develop more effective therapies for neurodegenerative diseases. PMID:16805775

  19. Further assembly required: construction and dynamics of the endoplasmic reticulum network.

    PubMed

    Park, Seong H; Blackstone, Craig

    2010-07-01

    The endoplasmic reticulum (ER) is a continuous membrane system comprising the nuclear envelope, ribosome-studded peripheral sheets and an interconnected network of smooth tubules extending throughout the cell. Although protein biosynthesis, transport and quality control in the ER have been studied extensively, mechanisms underlying the notably diverse architecture of the ER have only emerged recently; this review highlights these new findings and how they relate to ER functional specializations. Several protein families, including reticulons and DP1/REEPs/Yop1, harbour hydrophobic hairpin domains that shape high-curvature ER tubules and mediate intramembrane protein interactions. Members of the atlastin/RHD3/Sey1 family of dynamin-related GTPases mediate the formation of three-way junctions that characterize the tubular ER network, and additional classes of hydrophobic hairpin-containing ER proteins interact with and remodel the microtubule cytoskeleton. Flat ER sheets have a different complement of proteins implicated in shaping, cisternal stacking and microtubule interactions. Finally, several shaping proteins are mutated in hereditary spastic paraplegias, emphasizing the particular importance of proper ER morphology and distribution for highly polarized cells. PMID:20559323

  20. Long-Term Training with a Brain-Machine Interface-Based Gait Protocol Induces Partial Neurological Recovery in Paraplegic Patients

    PubMed Central

    Donati, Ana R. C.; Shokur, Solaiman; Morya, Edgard; Campos, Debora S. F.; Moioli, Renan C.; Gitti, Claudia M.; Augusto, Patricia B.; Tripodi, Sandra; Pires, Cristhiane G.; Pereira, Gislaine A.; Brasil, Fabricio L.; Gallo, Simone; Lin, Anthony A.; Takigami, Angelo K.; Aratanha, Maria A.; Joshi, Sanjay; Bleuler, Hannes; Cheng, Gordon; Rudolph, Alan; Nicolelis, Miguel A. L.

    2016-01-01

    Brain-machine interfaces (BMIs) provide a new assistive strategy aimed at restoring mobility in severely paralyzed patients. Yet, no study in animals or in human subjects has indicated that long-term BMI training could induce any type of clinical recovery. Eight chronic (3–13 years) spinal cord injury (SCI) paraplegics were subjected to long-term training (12 months) with a multi-stage BMI-based gait neurorehabilitation paradigm aimed at restoring locomotion. This paradigm combined intense immersive virtual reality training, enriched visual-tactile feedback, and walking with two EEG-controlled robotic actuators, including a custom-designed lower limb exoskeleton capable of delivering tactile feedback to subjects. Following 12 months of training with this paradigm, all eight patients experienced neurological improvements in somatic sensation (pain localization, fine/crude touch, and proprioceptive sensing) in multiple dermatomes. Patients also regained voluntary motor control in key muscles below the SCI level, as measured by EMGs, resulting in marked improvement in their walking index. As a result, 50% of these patients were upgraded to an incomplete paraplegia classification. Neurological recovery was paralleled by the reemergence of lower limb motor imagery at cortical level. We hypothesize that this unprecedented neurological recovery results from both cortical and spinal cord plasticity triggered by long-term BMI usage. PMID:27513629

  1. Genetic and clinical analysis of spinocerebellar ataxia type 36 in Mainland China.

    PubMed

    Zeng, S; Zeng, J; He, M; Zeng, X; Zhou, Y; Liu, Z; Xia, K; Pan, Q; Jiang, H; Shen, L; Yan, X; Tang, B; Wang, J

    2016-08-01

    Spinocerebellar ataxia type 36 (SCA36) is a new SCA subtype recently reported in Japanese and Spanish pedigrees. To assess the frequency and clinical characteristics of SCA36 in patients from Mainland China, we combined the repeat-primed polymerase chain reaction method and Southern blot analysis to detect the GGCCTG hexanucleotide repeats of NOP56 in 364 probands with SCA, 126 probands with hereditary spastic paraplegia and 99 probands with amyotrophic lateral sclerosis (ALS). Systematic and targeted clinical evaluations and investigations were conducted in the SCA36 patients. As a result, eight autosomal dominant spinocerebellar ataxia (ADCA) pedigrees (a total of 13 patients) and one sporadic SCA (S-SCA) patient were identified as SCA36 in the SCA cohort, accounting for approximately 1.60% of the cases in the ADCA group and 0.32% of those in the S-SCA group in Mainland China. The characteristics include late onset and slow progression accompanied by acoustic impairments and 'possible' ALS phenotype in patients from Mainland China.

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

    PubMed Central

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

    2015-01-01

    Dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1) encodes a necessary subunit of the cytoplasmic dynein complex, which traffics cargo along microtubules. Dominant DYNC1H1 mutations are implicated in neural diseases, including spinal muscular atrophy with lower extremity dominance (SMA-LED), intellectual disability with neuronal migration defects, malformations of cortical development (MCD), and Charcot-Marie-Tooth disease, type 2O (CMT2O). We hypothesized that additional variants could be found in these and novel motoneuron and related diseases. Therefore we analysed our database of 1,024 whole exome sequencing samples of motoneuron and related diseases for novel single nucleotide variations. We filtered these results for significant variants, which were further screened using segregation analysis in available family members. Analysis revealed six novel, rare, and highly conserved variants. Three of these are likely pathogenic and encompass a broad phenotypic spectrum with distinct disease clusters. Our findings suggest that DYNC1H1 variants can cause not only lower, but also upper motor neuron disease. It thus adds DYNC1H1 to the growing list of spastic paraplegia related genes in microtubule-dependent motor protein pathways. PMID:26100331

  3. 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

  4. Outcomes in the emergency endovascular repair of blunt thoracic aortic injuries.

    PubMed

    Martinelli, Ombretta; Malaj, Alban; Gossetti, Bruno; Bertoletti, Giovanni; Bresadola, Luciano; Irace, Luigi

    2013-09-01

    Thoracic aorta blunt injury (BAI) is a highly lethal lesion. A large number of victims die before obtaining emergency care. Thoracic endovascular aneurysm repair (TEVAR) is a less invasive method compared with open surgery and may change protocols for BAI treatment. This retrospective study was developed to evaluate the potential issues about thoracic endografting in the management of these patients. Twenty-seven patients with a BAI underwent aortic stent grafting. Intervention was preceded by the treatment of more urgent associated lesions in nine cases. In-hospital mortality was 7.4%. No paraplegia or ischemic complications developed because of the coverage of the left subclavian artery. In one case (3.2%), a type I endoleak was detected, proximal endograft infolding in two cases (7.4%) and endograft distal migration in further two cases were detected during follow-up (6-110 months). Thoracic endovascular aneurysm repair of BAI showed encouraging results in terms of perioperative mortality and morbidity. Concerns still remain about the potential mid- and long-term complications in younger patients.

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

    PubMed

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

    2012-07-01

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

  6. Shoulder joint kinetics during the push phase of wheelchair propulsion.

    PubMed

    Kulig, K; Rao, S S; Mulroy, S J; Newsam, C J; Gronley, J K; Bontrager, E L; Perry, J

    1998-09-01

    The purpose of this investigation was to quantify the forces and moments at the shoulder joint during free, level wheelchair propulsion and to document changes imposed by increased speed, inclined terrain, and 15 minutes of continuous propulsion. Data were collected using a six-camera VICON motion analysis system, a strain gauge instrumented wheel, and a wheelchair ergometer. Seventeen men with low level paraplegia participated in this study. Shoulder joint forces and moments were calculated using a three-dimensional model applying the inverse dynamics approach. During free propulsion, peak shoulder joint forces were in the posterior (46 N) and superior directions (14 N), producing a peak resultant force of 51 N at an angle of 185 degrees (180 degrees = posterior). Peak shoulder joint moments were greatest in extension (14 Newton-meters [Nm]), followed by abduction (10 Nm), and internal rotation (6 Nm). With fast and inclined propulsion, peak vertical force increased by greater than 360%, and the increase in posterior force and shoulder moments ranged from 107% to 167%. At the end of 15 minutes of continuous free propulsion, there were no significant changes compared with short duration free propulsion. The increased joint loads documented during fast and inclined propulsion could lead to compression of subacromial structures against the overlying acromion.

  7. A technological platform to optimize combinatorial treatment design and discovery for chronic spinal cord injury.

    PubMed

    Guertin, Pierre A

    2008-11-01

    Chronic spinal cord injury (SCI) is associated with the development of serious medical concerns. In fact, it is increasingly well documented that most SCI patients who survive the first 24 hr will rapidly develop, within a few months to a few years, cardiovascular problems, type II diabetes, muscle wasting, osteoporosis, immune deficiencies, and other life-threatening problems. The cellular mechanisms underlying these so-called secondary health complications remain unclear, and no drug or standard approach has been developed to specifically treat these complications. To investigate the cellular and metabolic changes associated with chronic SCI and functional recovery, work mainly from our laboratory recently has led to the characterization of a mouse model of chronic paraplegia. This review reports cellular, systemic, and metabolic changes (associated mainly with secondary health complications) occurring within a few days to a few weeks after SCI in low-thoracic spinal cord-transected mice. We also describe our research platform developed to ease technological transfer and to accelerate drug-screening studies in animals. A global understanding of the many chronic changes occurring after SCI together with efficient tools and approaches for testing new or existing drug candidates is likely to yield the design of innovative treatments against secondary complications that combine cellular plasticity-modulating agents, locomotor network-activating drugs, hormonal therapy, and exercise training.

  8. The RGO Generation II: muscle stimulation powered orthosis as a practical walking system for thoracic paraplegics.

    PubMed

    Solomonow, M; Baratta, R; Hirokawa, S; Rightor, N; Walker, W; Beaudette, P; Shoji, H; D'Ambrosia, R

    1989-10-01

    The RGO Generation II reciprocating gait orthosis was jointly developed by Louisiana State University Medical Center and Durr-Fillauer Medical, Inc, to overcome four problems encountered with the existing model: 1) The high energy cost of locomotion; 2) the great arm strength required for patients to stand up from the seated position without assistance; 3) difficulty (especially for patients with hamstring contracture) in remaining standing owing to failure of the knee latch to lock except in full extension; and 4) problems in balancing when ambulating on an incline. The RGO Generation II employs concurrent electrostimulation of the rectus femoris and hamstrings to assist in rising and balancing and a ratchet-type latching device to improve safety and stability in standing. Alternating stimulation of the rectus femoris and contralateral hamstrings are used for locomotion. Testing in six patients with thoracic paraplegia demonstrated an average 30+% reduction in energy expenditure at a walking speed of .05 m/s and a 15+% reduction at .37 m/s; improved mobility and better balance on inclines; and unassisted rising in all patients. Walking range was increased from an average of 100 m to an average of 800 m. More research is needed to provide stair-climbing ability and to further reduce energy expenditure.

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

    PubMed Central

    2011-01-01

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

  10. Real-Time Strap Pressure Sensor System for Powered Exoskeletons

    PubMed Central

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

    2015-01-01

    Assistive and rehabilitative powered exoskeletons for spinal cord injury (SCI) and stroke subjects have recently reached the clinic. Proper tension and joint alignment are critical to ensuring safety. Challenges still exist in adjustment and fitting, with most current systems depending on personnel experience for appropriate individual fastening. Paraplegia and tetraplegia patients using these devices have impaired sensation and cannot signal if straps are uncomfortable or painful. Excessive pressure and blood-flow restriction can lead to skin ulcers, necrotic tissue and infections. Tension must be just enough to prevent slipping and maintain posture. Research in pressure dynamics is extensive for wheelchairs and mattresses, but little research has been done on exoskeleton straps. We present a system to monitor pressure exerted by physical human-machine interfaces and provide data about levels of skin/body pressure in fastening straps. The system consists of sensing arrays, signal processing hardware with wireless transmission, and an interactive GUI. For validation, a lower-body powered exoskeleton carrying the full weight of users was used. Experimental trials were conducted with one SCI and one able-bodied subject. The system can help prevent skin injuries related to excessive pressure in mobility-impaired patients using powered exoskeletons, supporting functionality, independence and better overall quality of life. PMID:25690551

  11. A semi-active hybrid neuroprosthesis for restoring lower limb function in paraplegics.

    PubMed

    Kirsch, Nicholas; Alibeji, Naji; Fisher, Lee; Gregory, Chris; Sharma, Nitin

    2014-01-01

    Through the application of functional electrical stimulation (FES) individuals with paraplegia can regain lost walking function. However, due to the rapid onset of muscle fatigue, the walking duration obtained with an FES-based neuroprosthesis is often relatively short. The rapid muscle fatigue can be compensated for by using a hybrid system that uses both FES and an active orthosis. In this paper, we demonstrate the initial testing of a semi-active hybrid walking neuroprosthesis. The semi-active hybrid orthosis (SEAHO) supports a user during the stance phase and standing while the electric motors attached to the hip section of the orthosis are used to generate hip flexion/extension. FES in SEAHO is mainly used to actuate knee flexion/extension and plantar flexion of the foot. SEAHO is controlled by a finite state machine that uses a recently developed nonlinear controller for position tracking control of the hip motors and cues from the hip angle to actuate FES and other components.

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

    PubMed

    Ternovoĭ, 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.

  13. Expanding roles for lipid droplets

    PubMed Central

    Welte, Michael A.

    2015-01-01

    Summary Lipid droplets are the intracellular sites for neutral lipid storage. They are critical for lipid metabolism and energy homeostasis, and their dysfunction has been linked to many diseases. Accumulating evidence suggests that the roles lipid droplets play in biology are significantly broader than previously anticipated. Lipid droplets are the source of molecules important in the nucleus: they can sequester transcription factors and chromatin components and generate the lipid ligands for certain nuclear receptors. Lipid droplets have also emerged as important nodes for fatty acid trafficking, both inside the cell and between cells. In immunity, new roles for droplets, not directly linked to lipid metabolism, have been uncovered, as assembly platforms for specific viruses and as reservoirs for proteins that fight intracellular pathogens. Until recently, knowledge about droplets in the nervous system has been minimal, but now there are multiple links between lipid droplets and neurodegeneration: Many candidate genes for Hereditary Spastic Paraplegia also have central roles in lipid-droplet formation and maintenance, and mitochondrial dysfunction in neurons can lead to transient accumulating of lipid droplets in neighboring glial cells, an event that may, in turn, contribute to neuronal damage. As the cell biology and biochemistry of lipid droplets are increasingly well understood, the next few years should yield many new mechanistic insights into these novel functions of lipid droplets. PMID:26035793

  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. The thoracic anterior spinal cord adhesion syndrome

    PubMed Central

    Taylor, T R; Dineen, R; White, B; Jaspan, T

    2012-01-01

    Objectives This study included a series of middle-aged male and female patients who presented with chronic anterior hemicord dysfunction progressing to paraplegia. Imaging of anterior thoracic cord displacement by either a dural adhesion or a dural defect with associated cord herniation is presented. Methods This is a retrospective review of cases referred to a tertiary neuroscience centre over a 19-year period. Imaging series were classified by two experienced neuroradiologists against several criteria and correlated with clinical examination and/or findings at surgery. Results 16 cases were available for full review. Nine were considered to represent adhesions (four confirmed surgically) and four to represent true herniation (three confirmed surgically). In the three remaining cases the diagnosis was radiologically uncertain. Conclusion The authors propose “thoracic anterior spinal cord adhesion syndrome” as a novel term to describe this patient cohort and suggest appropriate clinicoradiological features for diagnosis. Several possible aetiologies are also suggested, with disc rupture and inflammation followed by disc resorption and dural pocket formation being a possible mechanism predisposing to herniation at the extreme end of a clinicopathological spectrum. PMID:22665931

  16. ALS5/SPG11/KIAA1840 mutations cause autosomal recessive axonal Charcot-Marie-Tooth disease.

    PubMed

    Montecchiani, Celeste; Pedace, Lucia; Lo Giudice, Temistocle; Casella, Antonella; Mearini, Marzia; Gaudiello, Fabrizio; Pedroso, José L; Terracciano, Chiara; Caltagirone, Carlo; Massa, Roberto; St George-Hyslop, Peter H; Barsottini, Orlando G P; Kawarai, Toshitaka; Orlacchio, Antonio

    2016-01-01

    Charcot-Marie-Tooth disease is a group of hereditary peripheral neuropathies that share clinical characteristics of progressive distal muscle weakness and atrophy, foot deformities, distal sensory loss, as well as diminished tendon reflexes. Hundreds of causative DNA changes have been found, but much of the genetic basis of the disease is still unexplained. Mutations in the ALS5/SPG11/KIAA1840 gene are a frequent cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum and peripheral axonal neuropathy, and account for ∼ 40% of autosomal recessive juvenile amyotrophic lateral sclerosis. The overlap of axonal Charcot-Marie-Tooth disease with both diseases, as well as the common autosomal recessive inheritance pattern of thin corpus callosum and axonal Charcot-Marie-Tooth disease in three related patients, prompted us to analyse the ALS5/SPG11/KIAA1840 gene in affected individuals with autosomal recessive axonal Charcot-Marie-Tooth disease. We investigated 28 unrelated families with autosomal recessive axonal Charcot-Marie-Tooth disease defined by clinical, electrophysiological, as well as pathological evaluation. Besides, we screened for all the known genes related to axonal autosomal recessive Charcot-Marie-Tooth disease (CMT2A2/HMSN2A2/MFN2, CMT2B1/LMNA, CMT2B2/MED25, CMT2B5/NEFL, ARCMT2F/dHMN2B/HSPB1, CMT2K/GDAP1, CMT2P/LRSAM1, CMT2R/TRIM2, CMT2S/IGHMBP2, CMT2T/HSJ1, CMTRID/COX6A1, ARAN-NM/HINT and GAN/GAN), for the genes related to autosomal recessive hereditary spastic paraplegia with thin corpus callosum and axonal peripheral neuropathy (SPG7/PGN, SPG15/ZFYVE26, SPG21/ACP33, SPG35/FA2H, SPG46/GBA2, SPG55/C12orf65 and SPG56/CYP2U1), as well as for the causative gene of peripheral neuropathy with or without agenesis of the corpus callosum (SLC12A6). Mitochondrial disorders related to Charcot-Marie-Tooth disease type 2 were also excluded by sequencing POLG and TYMP genes. An additional locus for autosomal recessive Charcot

  17. Multitasking a telemedicine training unit in earthquake disaster response: paraplegic rehabilitation assessment.

    PubMed

    Gul, Shahzad; Ghaffar, Hirra; Mirza, Shirin; Fizza Tauqir, Syeda; Murad, Faisal; Ali, Qasim; Zafar Malik, Asif; Merrell, Ronald C

    2008-04-01

    The objective of this work was to provide computer and telecommunications skill training for paraplegics using a telemedicine training center in a curriculum that would support connectivity and offer new skills for career applications in the rehabilitation phase and beyond. This was a hospital-based, cross-sectional study. The study was conducted from October 10, 2005 to May 10, 2006 in the hospitals of Rawalpindi Medical College and the Melody Rehabilitation Center, Rawalpindi, Pakistan. These centers provided care for casualties of the October 2005 earthquake in Pakistan. One hundred and ninety four (194) paraplegics were admitted to Rawalpindi Medical College allied hospitals after injuries in the rural mountains near the epicenter. Surveys assessed the education level of the patients, and a sample of 12 patients was enrolled in computer training classes. Of the 194 patients, 144 were female and 50 were male. The majority, 78% (151) were 16-39 years of age. Although only 60% were literate, the overall literacy rate of Pakistan is just 48.7%. Telephone service at home was available after discharge for 40% of patients. Only 8% of patients had basic computer skills. All patients participated in the survey and sought to take the course. All the enrolled patients demonstrated full competency in the skills taught. The social disruption of disaster plus the new challenge of a neurological deficit in paraplegia did not deter a remarkable number of patients from a rural area from engaging in computer and telemedicine training. This study demonstrated the feasibility of educating rural paraplegics in computer skills for telemedicine. The telemedicine training center was used for this task without special equipment or personnel, thereby increasing the utilization of the facility.

  18. Heteromeric p97/p97R155C complexes induce dominant negative changes in wild-type and autophagy 9-deficient Dictyostelium strains.

    PubMed

    Arhzaouy, Khalid; Strucksberg, Karl-Heinz; Tung, Sze Man; Tangavelou, Karthikeyan; Stumpf, Maria; Faix, Jan; Schröder, Rolf; Clemen, Christoph S; Eichinger, Ludwig

    2012-01-01

    Heterozygous mutations in the human VCP (p97) gene cause autosomal-dominant IBMPFD (inclusion body myopathy with early onset Paget's disease of bone and frontotemporal dementia), ALS14 (amyotrophic lateral sclerosis with or without frontotemporal dementia) and HSP (hereditary spastic paraplegia). Most prevalent is the R155C point mutation. We studied the function of p97 in the social amoeba Dictyostelium discoideum and have generated strains that ectopically express wild-type (p97) or mutant p97 (p97(R155C)) fused to RFP in AX2 wild-type and autophagy 9 knock-out (ATG9(KO)) cells. Native gel electrophoresis showed that both p97 and p97(R155C) assemble into hexamers. Co-immunoprecipitation studies revealed that endogenous p97 and p97(R155C)-RFP form heteromers. The mutant strains displayed changes in cell growth, phototaxis, development, proteasomal activity, ubiquitinylated proteins, and ATG8(LC3) indicating mis-regulation of multiple essential cellular processes. Additionally, immunofluorescence analysis revealed an increase of protein aggregates in ATG9(KO)/p97(R155C)-RFP and ATG9(KO) cells. They were positive for ubiquitin in both strains, however, solely immunoreactive for p97 in the ATG9(KO) mutant. A major finding is that the expression of p97(R155C)-RFP in the ATG9(KO) strain partially or fully rescued the pleiotropic phenotype. We also observed dose-dependent effects of p97 on several cellular processes. Based on findings in the single versus the double mutants we propose a novel mode of p97 interaction with the core autophagy protein ATG9 which is based on mutual inhibition. PMID:23056506

  19. Invasive carcinoma of urinary bladder in a patient with a spinal cord injury with non-functioning Brindley sacral anterior root stimulator: a case report

    PubMed Central

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

    2008-01-01

    Background Anterior sacral root stimulation combined with sacral posterior rhizotomy restores bladder function in spinal cord-injured patients suffering from hyperactive bladder. After successful implantation of bladder stimulator, urinary infection rate decreases, and patients are able to get rid of indwelling urinary catheters, which in turn reduce the risks for vesical malignancy. We present a spinal cord injury patient with non-functioning Brindley sacral anterior root stimulator, who developed carcinoma of urinary bladder. Case presentation A Caucasian male, who was born in 1943, sustained paraplegia at T-4 (ASIA-B) in 1981. This patient underwent implantation of sacral anterior root stimulator in September 1985. The bladder stimulator started giving trouble since 1996 and the patient went back to using indwelling urethral catheter. In August 2006, this patient passed blood in urine after a routine change of indwelling catheter. Cystoscopy showed unhealthy bladder mucosa. Bladder biopsy revealed carcinoma, which was infiltrating bundles of muscularis propria. Many of the nests showed evidence of squamous differentiation, while others could be transitional or squamous. This patient underwent cystectomy with lymphadenectomy in March 2007 in a hospital nearer his home. Histology showed three nodes involved. This patient has been doing well since the operation. Conclusion Occurrence of vesical malignancy in this patient with non-functioning bladder stimulator is a timely reminder to all health professionals, and health care managers that concerted efforts should be made to rectify a non-functioning sacral anterior root stimulator as soon as possible. Otherwise, facilities should be made available in the community for the spinal cord injury patient to use intermittent catheterisation and thereby, avoid permanent indwelling catheter, vesical calculi and urine infections, which are risk factors for bladder cancer. PMID:18761737

  20. Funktionelle Elektrostimulation Paraplegischer Patienten

    PubMed Central

    2014-01-01

    Functional Electrical Stimulation on Paraplegic Patients. We report on clinical and physiological effects of 8 months Functional Electrical Stimulation (FES) of quadriceps femoris muscle on 16 paraplegic patients. Each patient had muscle biopsies, CT-muscle diameter measurements, knee extension strength testing carried out before and after 8 months FES training. Skin perfusion was documented through infrared telethermography and xenon clearance, muscle perfusion was recorded through thallium scintigraphy. After 8 months FES training baseline skin perfusion showed 86 % increase, muscle perfusion was augmented by 87 %. Muscle fiber diameters showed an average increase of 59 % after 8 months FES training. Muscles in patients with spastic paresis as well as in patients with denervation showed an increase in aerob and anaerob muscle enzymes up to the normal range. Even without axonal neurotropic substances FES was able to demonstrate fiberhypertrophy, enzyme adaptation and intracellular structural benefits in denervated muscles. The increment in muscle area as visible on CT-scans of quadriceps femoris was 30 % in spastic paraplegia and 10 % in denervated patients respectively. FES induced changes were less in areas not directly underneath the surface electrodes. We strongly recommend the use of Kern’s current for FES in denervated muscles to induce tetanic muscle contractions as we formed a very critical opinion of conventional exponential current. In patients with conus-cauda-lesions FES must be integrated into modern rehabilitation to prevent extreme muscle degeneration and decubital ulcers. Using FES we are able to improve metabolism and induce positive trophic changes in our patients lower extremities. In spastic paraplegics the functions „rising and walking“ achieved through FES are much better training than FES ergometers. Larger muscle masses are activated and an increased heart rate is measured, therefore the impact on cardiovascular fitness and metabolism

  1. 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

  2. Social support and functioning in a patient with spinal cord injury: the role of social skills.

    PubMed

    Müller, Rachel; Rauch, Alexandra; Cieza, Alarcos; Geyh, Szilvia

    2013-09-01

    This study reports on a patient with spinal cord injury (SCI) in whom the interaction between social skills and social support seems to influence functioning. The International Classification of Functioning, Disability and Health (ICF) was used as a reference framework. Qualitative (i.e. observation, structured, and open interviews with the patient and health professionals) and quantitative data (i.e. spinal cord independence measure, medical records) were collected. Content analysis of the interviews was carried out to identify aspects of social skills and social support. An ICF-based documentation tool (i.e. ICF Assessment Sheet) was used to structure information about the level of functioning of body functions and structures, activity and participation, and environmental and personal factors of a 57-year-old man with incomplete paraplegia during first rehabilitation. The patient presented a variety of effective social skills (i.e. assertiveness, goal direction). However, the adaptation of skills, such as asking for help social problem-solving, sensitivity, and expressivity in social relations, became necessary to acquire. The patient received different types of social support (i.e. emotional, informational, and instrumental) from different sources (e.g. family and friends). The qualitative interviews provided indications for an interaction between social skills and social support. The impact of social skills and social support on functioning is discussed. Social skills can mobilize social support and enhance functioning. However, better understanding of social skills, social support, and their interaction in relation to functioning in SCI is required to develop targeted and effective interventions to strengthen psychosocial resources for the enhancement of functioning in patients with SCI. PMID:23337323

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

    PubMed

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

    2015-10-29

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

  4. Syndrome disintegration: Exome sequencing reveals that Fitzsimmons syndrome is a co-occurrence of multiple events.

    PubMed

    Armour, Christine M; Smith, Amanda; Hartley, Taila; Chardon, Jodi Warman; Sawyer, Sarah; Schwartzentruber, Jeremy; Hennekam, Raoul; Majewski, Jacek; Bulman, Dennis E; Suri, Mohnish; Boycott, Kym M

    2016-07-01

    In 1987 Fitzsimmons and Guilbert described identical male twins with progressive spastic paraplegia, brachydactyly with cone shaped epiphyses, short stature, dysarthria, and "low-normal" intelligence. In subsequent years, four other patients, including one set of female identical twins, a single female child, and a single male individual were described with the same features, and the eponym Fitzsimmons syndrome was adopted (OMIM #270710). We performed exome analysis of the patient described in 2009, and one of the original twins from 1987, the only patients available from the literature. No single genetic etiology exists that explains Fitzsimmons syndrome; however, multiple different genetic causes were identified. Specifically, the twins described by Fitzsimmons had heterozygous mutations in the SACS gene, the gene responsible for autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS), as well as a heterozygous mutation in the TRPS1, the gene responsible in Trichorhinophalangeal syndrome type 1 (TRPS1 type 1) which includes brachydactyly as a feature. A TBL1XR1 mutation was identified in the patient described in 2009 as contributing to his cognitive impairment and autistic features with no genetic cause identified for his spasticity or brachydactyly. The findings show that these individuals have multiple different etiologies giving rise to a similar phenotype, and that "Fitzsimmons syndrome" is in fact not one single syndrome. Over time, we anticipate that continued careful phenotyping with concomitant genome-wide analysis will continue to identify the causes of many rare syndromes, but it will also highlight that previously delineated clinical entities are, in fact, not syndromes at all. © 2016 Wiley Periodicals, Inc. PMID:27133561

  5. 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

  6. Muscle oxygenation during prolonged electrical stimulation-evoked cycling in paraplegics.

    PubMed

    Muraki, Satoshi; Fornusek, Ché; Raymond, Jacqui; Davis, Glen Macartney

    2007-06-01

    This study investigated cardiorespiratory responses and muscle oxygenation during prolonged electrical stimulation (ES)-evoked leg cycling in individuals with paraplegia (PARA). Four PARA and 6 able-bodied (AB) persons participated in this study. Subjects performed 10 min of passive cycling and 40 min of active cycling (PARA, ES cycling; AB, voluntary cycling) at workloads selected to elicit an equivalent oxygen uptake between groups. Cycling power output, cardiorespiratory responses, mechanical efficiency, and quadriceps muscle oxygenation (measured with near-infrared spectroscopy) were measured over the duration of the exercise. Oxygen uptake was similar in both groups during active cycling (PARA, 737+/-177 mL.min(-1); AB, 840+/-90 mL.min(-1)). The cycling power output for PARA individuals commenced at 8.8 W, but varied considerably over 40 min. PARA individuals demonstrated markedly lower gross mechanical efficiency (approximately 1.3%) during ES cycling compared with AB individuals performing voluntary exercise (approximately 12.6%). During ES cycling, muscle oxygen saturation (SO2) decreased to approximately 72+/-19%, whereas SO2 during volitional cycling was unaltered from resting levels. Muscle oxygenated haemoglobin initially decreased (-23%) during ES cycling, but returned to resting levels after 10 min. Deoxygenated haemoglobin initially rose during the first 5 min of ES cycling, and remained elevated by 28% thereafter. Upon cessation of ES cycling, lower-limb muscle oxygenation increased (+93%), suggesting reactive hyperaemia in PARA individuals after such exercise. During ES cycling, muscle oxygenation followed a different pattern to that observed in AB individuals performing voluntary cycling at an equivalent VO2. Equilibrium between oxygen demand and oxygen delivery was reached during prolonged ES cycling, despite the lack of neural adjustments of leg vasculature in the paralyzed lower limbs.

  7. Exome sequencing reveals a novel WDR45 frameshift mutation and inherited POLR3A heterozygous variants in a female with a complex phenotype and mixed brain MRI findings.

    PubMed

    Khalifa, Mohamed; Naffaa, Lena

    2015-08-01

    WDR45 and POLR3A are newly recognized genes; each is associated with a distinct neurodegenerative disease. WDR45 is an X-linked gene associated with a dominant form of Neurodegeneration with Brain Iron Accumulation (NBIA), manifested by progressive disabilities, dystonia, cognitive decline, spastic paraplegia, neuropsychiatric abnormalities and iron deposition in the basal ganglia on brain imaging. POLR3A, on the other hand, is an autosomal gene, and its mutations cause a recessive form of a hypomyelination with leukodystrophy disease, also known as 4H syndrome, characterized by congenital Hypomyelination with thinning of the corpus callosum, Hypodontia and Hypogonadotropic Hypogonadism. We report on a female child with severe intellectual disability, aphasia, short stature, ataxia, failure to thrive and structural brain abnormalities. Brain MRI obtained in late infancy showed hypomyelination involving the central periventricular white matter and thinning of the corpus callosum with no evidence of iron accumulation. Brain MRI obtained in childhood showed stable hypomyelination, with progressive iron accumulation in the basal ganglia, in particular in the globus pallidus and substantia nigra. Whole Exome Sequencing (WES) identified a novel WDR45 frameshift deleterious mutation in Exon 9 (c.587-588del) and also revealed three POLR3A missense heterozygous variants. The first is a maternally inherited novel missense variant in exon 4 (c.346A > G). Exon 13 carried two heterozygous missense variants, a maternally inherited variant (c.1724A > T) and a paternally inherited variant (1745G > A). These variants are considered likely damaging. The patient's complex clinical phenotype and mixed brain MRI findings might be attributed to the confounding effects of the expression of these two mutant genes.

  8. Systematic Review and Operative Technique of Recalcitrant Pressure Ulcers Using a Fillet Flap Technique

    PubMed Central

    Rao, Venkat K.

    2016-01-01

    Background: The purpose of this article is to describe the indications, operative technique, outcomes, and systematic review of the literature on the reconstruction of patients with end-stage pressure ulcers using a fillet flap technique. In this technique, the femur, tibia, and fibula are removed from the thigh and leg, and the soft tissue is used as a pedicled, or free, myocutaneous flap for reconstruction. Long-term outcomes, salient surgical technique of flap elevation, and design are detailed for patients who had a fillet of leg flap for reconstruction of extensive pressure ulcers. Methods: The indications, surgical technique, and postoperative outcomes of 5 patients who had pedicled fillet flaps are reviewed including patient age, sex, underlying comorbidities, duration of paraplegia, operative technique, and complications. A systematic review of the literature was performed searching PubMed, Cochrane Database, and Medline with the following MeSH terms: pressure ulcer, pressure sore, decubitus ulcer, fillet flap, and fillet flap. Inclusion criteria were use of a fillet technique, article data on the number of reconstructions before fillet flap, complications, and English language. Results: Most of our patients were male 75% (n = 3) with an average age of 47.5 years, had been paralyzed for an average of 16 years, and had few medical comorbidities. Two patients (3 flaps) required hip disarticulation, 1 patient had a bilateral fillet flaps, and 3 patients had resection of tibia/fibula. After following patients for an average of 1.4 years (4 mo to 2 yr), complications were limited to 1 patient who had partial-thickness flap loss at the distal skin flap that healed by secondary intention and 1 patient who had ulcer recurrence because of noncompliance. Four articles met inclusion criteria for systematic review and 3 were excluded. Conclusions: The fillet of leg flap remains a useful and reliable method of reconstructing end-stage pressure ulcers. PMID:27622082

  9. Harvey Cushing, the Spine Surgeon

    PubMed Central

    Bydon, Ali; Dasenbrock, Hormuzdiyar H.; Pendleton, Courtney; McGirt, Matthew J.; Gokaslan, Ziya L.; Quinones-Hinojosa, Alfredo

    2015-01-01

    Study Design Review of historical archival records. Objective Describe Harvey Cushing's patients with spinal pathology. Summary of Background Data Harvey Cushing was a pioneer of modern surgery but his work on spine remains largely unknown. Methods Review of the Chesney Medical Archives of the Johns Hopkins Hospital from 1896 to 1912. Results This is the first time that Cushing's spinal cases while he was at the Johns Hopkins Hospital, including those with Pott disease, have been described. Cushing treated three young men with psoas abscesses secondary to Pott disease during his residency: he drained the abscesses, debrided any accompanying necrotic vertebral bodies, irrigated the cavity with salt, and left the incision open to close by secondary intention. Although Cushing used Koch's “tuberculin therapy” (of intravenous administration of isolated tubercular bacilli) in one patient, he did not do so in the other two, likely because of the poor response of this first patient. Later in his tenure, Cushing performed a laminectomy on a patient with kyphosis and paraplegia secondary to Pott disease. Conclusion These cases provide a view of Cushing early in his career, pointing to the extraordinary degree of independence that he had during his residency under William Steward Halsted; these cases may have been important in the surgical upbringing both of Cushing and his coresident, William Stevenson Baer, who became the first professor of Orthopedics at Johns Hopkins Hospital. At the turn of the last century, Pott disease was primarily treated by immobilization with bed rest, braces, and plaster-of-paris jackets; some surgeons also employed gradual correction of the deformity by hyperextension. Patients who failed a trial of conservative therapy (of months to years) were treated with a laminectomy. However, the limitations of these strategies led to the development of techniques that form the basis of contemporary spine surgery—instrumentation and fusion. PMID

  10. Liver Transplantation for Acute Intermittent Porphyria is Complicated by a High Rate of Hepatic Artery Thrombosis

    PubMed Central

    Dowman, Joanna K; Gunson, Bridget K; Mirza, Darius F; Bramhall, Simon R; Badminton, Mike N; Newsome, Philip N

    2012-01-01

    Acute intermittent porphyria (AIP) is an autosomal-dominant condition resulting from a partial deficiency of the ubiquitously expressed enzyme porphobilinogen deaminase. Although its clinical expression is highly variable, a minority of patients suffer recurrent life-threatening neurovisceral attacks despite optimal medical therapy. Because the liver is the major source of excess precursor production, liver transplantation (LT) represents a potentially effective treatment for severely affected patients. Using data from the UK Transplant Registry, we analyzed all transplants performed for AIP in the United Kingdom and Ireland. Between 2002 and 2010, 10 patients underwent LT for AIP. In all cases, the indication for transplantation was recurrent, biochemically proven, medically nonresponsive acute attacks of porphyria resulting in significantly impaired quality of life. Five patients had developed significant neurological morbidities such as paraplegia before transplantation. The median follow-up time was 23.4 months, and there were 2 deaths from multiorgan failure at 98 days and 26 months. Eight recipients were alive for 3.2 to 109 months after transplantation. Complete biochemical and symptomatic resolution was observed in all patients after transplantation. However, there was a high rate of hepatic artery thrombosis (HAT; 4/10), with 1 patient requiring regrafting. The effects of previous neuronal damage such as joint contractures were not improved by transplantation. Thus, impaired quality of life in the surviving patients was usually a result of preoperative complications. Refractory AIP is an excellent indication for LT, and long-term outcomes for carefully selected patients are good. There is, however, an increased incidence of HAT in these patients, and we recommend routine antiplatelet therapy after transplantation. Liver Transpl 18:195–200, 2012. © 2011 AASLD. PMID:21618697

  11. Trunk robot rehabilitation training with active stepping reorganizes and enriches trunk motor cortex representations in spinal transected rats.

    PubMed

    Oza, Chintan S; Giszter, Simon F

    2015-05-01

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

  12. 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.

  13. An Investigation of Bilateral Symmetry During Manual Wheelchair Propulsion

    PubMed Central

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

    2015-01-01

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

  14. Overview of Psychosocial Health Among Youth with Spinal Cord Injury

    PubMed Central

    2013-01-01

    Background: Psychosocial health can be conceptualized as being mentally, emotionally, and socially well. Little is known about normative psychosocial development among children and adolescents with spinal cord injury (SCI). Objective: To provide a comprehensive overview of psychosocial health of 410 youth with SCI from ages 2 to 18 years. To understand developmental trends, data are presented separately for ages 2-5, 6-12, 13-15, and 16-18 years. Methods: Youth with SCI were recruited from 1 of 3 pediatric specialty hospitals within a single hospital system. Structured surveys assessing community participation, quality of life (QOL), and mental health (including anxiety and depression) were completed by youth with SCI (for ages 6-18) or their primary caregivers (for ages 2-5). Descriptive statistics were used to assess how patients scored on all standardized measures. Results: Of the 410 participants, 56% were male, 64% were Caucasian, 66% had paraplegia, and 55% had complete injuries. On average, the participants were 12 years old (SD 4.87) at interview and 7.26 years old (SD 5.97) at injury. Psychosocial health outcomes were described for each of the 4 age groups: 2-5 years (n = 52), 6-12 (n = 142), 13-15 (n = 82), and 16-18 (n = 134) years. Conclusions: As compared to published norms, this sample of youth with SCI seemed to be experiencing decreased levels of community participation and QOL, but also decreased levels of anxiety and depression. These data provide needed information to clinicians regarding how youth with SCI may typically experience psychosocial health and where their patients fit into that typical experience. PMID:23671383

  15. Neurology and diving.

    PubMed

    Massey, E Wayne; Moon, Richard E

    2014-01-01

    Diving exposes a person to the combined effects of increased ambient pressure and immersion. The reduction in pressure when surfacing can precipitate decompression sickness (DCS), caused by bubble formation within tissues due to inert gas supersaturation. Arterial gas embolism (AGE) can also occur due to pulmonary barotrauma as a result of breath holding during ascent or gas trapping due to disease, causing lung hyperexpansion, rupture and direct entry of alveolar gas into the blood. Bubble disease due to either DCS or AGE is collectively known as decompression illness. Tissue and intravascular bubbles can induce a cascade of events resulting in CNS injury. Manifestations of decompression illness can vary in severity, from mild (paresthesias, joint pains, fatigue) to severe (vertigo, hearing loss, paraplegia, quadriplegia). Particularly as these conditions are uncommon, early recognition is essential to provide appropriate management, consisting of first aid oxygen, targeted fluid resuscitation and hyperbaric oxygen, which is the definitive treatment. Less common neurologic conditions that do not require hyperbaric oxygen include rupture of a labyrinthine window due to inadequate equalization of middle ear pressure during descent, which can precipitate vertigo and hearing loss. Sinus and middle ear overpressurization during ascent can compress the trigeminal and facial nerves respectively, causing temporary facial hypesthesia and lower motor neuron facial weakness. Some conditions preclude safe diving, such as seizure disorders, since a convulsion underwater is likely to be fatal. Preventive measures to reduce neurologic complications of diving include exclusion of individuals with specific medical conditions and safe diving procedures, particularly related to descent and ascent. PMID:24365363

  16. Evaluation of pressure and durability of a low-cost wheelchair cushion designed for developing countries.

    PubMed

    Guimaraes, Evandro; Mann, William C

    2003-06-01

    Pressure sores are a medical problem for wheelchair users worldwide. In developing countries this problem is more critical because of lack of access to specialized technologies and medical assessment. Seat cushions to relieve pressure represent one of best ways to prevent pressure sores for people with spinal cord injury, amputation, cerebral palsy, and other disabilities that require use of wheelchairs for long periods of time. The purpose of this study was to evaluate the performance of a low cost cushion, called the Tuball, designed for low-income communities in developing countries. The Tuball is made from bicycle inner tubes and plastic balls. Its durability and pressure-relieving characteristics were compared with the ROHOTM cushion and the foam cushions now used in Brazil. A sample of 30 participants tested the three cushions: 15 persons with paraplegia and 15 matched able-bodied persons evaluated the capacity of the cushions to distribute pressure. This study also addressed the use of samples of persons without disabilities to test wheelchair cushions.The Tuball cushion provided significantly better pressure distribution than the foam cushion. A t-test was used to compare disabled persons and non-disabled persons as samples in testing cushions. No difference between pressure distribution between non-disabled and disabled participants was found in testing the ROHO cushion or the foam cushion. However, both capacities of pressure distribution and HICPR varied between non-disabled and disabled participants for the Tuball cushion. To determine the useful life of the Tuball cushion, a fatigue test was conducted to simulate sitting and transfer. Both the Tuball and ROHO cushions withstood the equivalent of at least 1 year of use, whereas the foam cushion broke down. PMID:12799609

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

    PubMed

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

    2015-04-01

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

  18. The Drosophila KIF1A Homolog unc-104 Is Important for Site-Specific Synapse Maturation.

    PubMed

    Zhang, Yao V; Hannan, Shabab B; Stapper, Zeenna A; Kern, Jeannine V; Jahn, Thomas R; Rasse, Tobias M

    2016-01-01

    Mutations in the kinesin-3 family member KIF1A have been associated with hereditary spastic paraplegia (HSP), hereditary and sensory autonomic neuropathy type 2 (HSAN2) and non-syndromic intellectual disability (ID). Both autosomal recessive and autosomal dominant forms of inheritance have been reported. Loss of KIF1A or its homolog unc-104 causes early postnatal or embryonic lethality in mice and Drosophila, respectively. In this study, we use a previously described hypomorphic allele of unc-104, unc-104(bris) , to investigate the impact of partial loss-of-function of kinesin-3 on synapse maturation at the Drosophila neuromuscular junction (NMJ). Unc-104(bris) mutants exhibit structural defects where a subset of synapses at the NMJ lack all investigated active zone (AZ) proteins, suggesting a complete failure in the formation of the cytomatrix at the active zone (CAZ) at these sites. Modulating synaptic Bruchpilot (Brp) levels by ectopic overexpression or RNAi-mediated knockdown suggests that the loss of AZ components such as Ca(2+) channels and Liprin-α is caused by impaired kinesin-3 based transport rather than due to the absence of the key AZ organizer protein, Brp. In addition to defects in CAZ assembly, unc-104(bris) mutants display further defects such as depletion of dense core and synaptic vesicle (SV) markers from the NMJ. Notably, the level of Rab3, which is important for the allocation of AZ proteins to individual release sites, was severely reduced at unc-104(bris) mutant NMJs. Overexpression of Rab3 partially ameliorates synaptic phenotypes of unc-104(bris) larvae, suggesting that lack of presynaptic Rab3 contributes to defects in synapse maturation. PMID:27656128

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2008-01-01

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

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

    PubMed

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

    2015-01-01

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

  2. Type B Aortic Dissection: A Review of Prognostic Factors and Meta-analysis of Treatment Options Based on a Presentation at the 2013 VEITH Symposium, November 19–23, 2013 (New York, NY, USA)

    PubMed Central

    Luebke, Thomas; Brunkwall, Jan

    2014-01-01

    According to international guidelines, stable patients with uncomplicated Type B aortic dissection (TBAD) should receive optimal medical treatment. Despite adequate antihypertensive therapy, the long-term prognosis of these patients is characterized by a significant aortic aneurysm formation in 25-30% within four years, and survival rates from 50 to 80% at five years and 30 to 60% at 10 years. In a prospective randomized trial, preemptive thoracic endovascular aortic repair (TEVAR) in patients with chronic uncomplicated TBAD was associated with an excess early mortality (due to periprocedural hazards), but the procedure showed its benefit in prevention of aortic-specific mortality at five years of follow-up. However, preemptive TEVAR may not be the treatment of choice in all patients with uncomplicated TBAD because of the inherent periprocedural complications like stroke, paraparesis, and death, as well as stent graft-induced complications (i.e., retrograde dissection or endoleaks). Thus, the TEVAR-related deaths and complications (especially paraplegia and stroke) raise concerns that moderate the better survival with TEVAR at five years. By timely identification of those patients prone for developing complications, early intervention, preferably in the subacute or early chronic phase, may improve the overall long-term outcome for these patients. Therefore, early detectable and reliable prognostic factors for adverse events are essential to stratify patients who can be treated medically and those who will benefit from rigorous follow-up and, in the long-term, from timely, or even prophylactic, TEVAR. Several studies have identified prognostic factors in TBAD such as aortic diameter, partial false lumen thrombosis, false lumen thickness, and location of the primary entry tear. Combining these clinical and radiological predictors may be essential to implement a patient-specific approach designed to intervene only in those patients who are at high risk of developing

  3. Extra skeletal Soft Tissue Ewing’s Sarcoma with Variant Translocation of Chromosome t (4; 22) (q35; q12)-A Case Report

    PubMed Central

    Nagaraj, Prashanth; H, Srinivas C; Rao, Raghavendra; Manohar, Sandesh

    2013-01-01

    Introduction: Ewing’s sarcomas is a rare primitive neuroectodermal tumour (PNET) which has an annual incidence of 2.9 /million population in USA 1Jeffery Toretsky et al (2008) They are very uncommon in African and Asian population. It is commonly associated with reciprocal translocation between chromosome 11 and 12 t (11:12) or less frequently the t(21;22)(q22;ql 2) translocation. It is highly aggressive tumor which is PAS- and CD99 (MIC2)-positive relatively few variant translocations have been reported in primary Ewing’s sarcomas (ES). Case Report: We are hereby presenting a case of extra skeletal soft tissue Ewing’s sarcoma with unusual translocation of chromosome t (4, 22) (q35, q12). Patient presented to us in advanced stage with pulmonary metastasis and lower limb neurological deficit. Relatively few variant translocations have been reported in primary Ewing’s sarcomas (ES). To date, 13 variants of the EWS fusion gene have been described in literature. They are extremely rare, representing altogether < 1% of the cases’ 23we are reporting a case of a variant simple translocation of chromosome t (4; 22) (q35;1 2). In our exhaustive literature search we could find only one case of complex translocation which was identified in a dysmorphic 15-year-old girl, t (4:11; 22)(q21; q24; q12) reported by Squire Jet al (1993). Conclusion: This type of translocation is extremely rare and has not been reported in the literature so far. Clinical presentation was initial indolent but later at the time patient presented to our institute he had developed pulmonary metastases and paraplegia due to involvement of spine. Our case report will provide new insight about rare translocation types in Ewing’s sarcoma and understand their clinical behavior of Ewing’s sarcoma with such type of translocation. PMID:27298923

  4. The Drosophila KIF1A Homolog unc-104 Is Important for Site-Specific Synapse Maturation

    PubMed Central

    Zhang, Yao V.; Hannan, Shabab B.; Stapper, Zeenna A.; Kern, Jeannine V.; Jahn, Thomas R.; Rasse, Tobias M.

    2016-01-01

    Mutations in the kinesin-3 family member KIF1A have been associated with hereditary spastic paraplegia (HSP), hereditary and sensory autonomic neuropathy type 2 (HSAN2) and non-syndromic intellectual disability (ID). Both autosomal recessive and autosomal dominant forms of inheritance have been reported. Loss of KIF1A or its homolog unc-104 causes early postnatal or embryonic lethality in mice and Drosophila, respectively. In this study, we use a previously described hypomorphic allele of unc-104, unc-104bris, to investigate the impact of partial loss-of-function of kinesin-3 on synapse maturation at the Drosophila neuromuscular junction (NMJ). Unc-104bris mutants exhibit structural defects where a subset of synapses at the NMJ lack all investigated active zone (AZ) proteins, suggesting a complete failure in the formation of the cytomatrix at the active zone (CAZ) at these sites. Modulating synaptic Bruchpilot (Brp) levels by ectopic overexpression or RNAi-mediated knockdown suggests that the loss of AZ components such as Ca2+ channels and Liprin-α is caused by impaired kinesin-3 based transport rather than due to the absence of the key AZ organizer protein, Brp. In addition to defects in CAZ assembly, unc-104bris mutants display further defects such as depletion of dense core and synaptic vesicle (SV) markers from the NMJ. Notably, the level of Rab3, which is important for the allocation of AZ proteins to individual release sites, was severely reduced at unc-104bris mutant NMJs. Overexpression of Rab3 partially ameliorates synaptic phenotypes of unc-104bris larvae, suggesting that lack of presynaptic Rab3 contributes to defects in synapse maturation.

  5. In Vivo Neuroprotective Effect of Histidine-Tryptophan-Ketoglutarate Solution in an Ischemia/Reperfusion Spinal Cord Injury Animal Model

    PubMed Central

    Kang, Shin Kwang; Kang, Min-Woong; Rhee, Youn Ju; Kim, Cuk-Seong; Jeon, Byeong Hwa; Han, Sung Joon; Cho, Hyun Jin; Na, Myung Hoon; Yu, Jae-Hyeon

    2016-01-01

    Background Paraplegia is a devastating complication following operations on the thoracoabdominal aorta. We investigated whether histidine-tryptophan-ketoglutarate (HTK) solution could reduce the extent of ischemia/reperfusion (IR) spinal cord injuries in a rat model using a direct delivery method. Methods Twenty-four Sprague-Dawley male rats were randomly divided into four groups. The sham group (n=6) underwent a sham operation, the IR group (n=6) underwent only an aortic occlusion, the saline infusion group (saline group, n=6) underwent an aortic occlusion and direct infusion of cold saline into the occluded aortic segment, and the HTK infusion group (HTK group, n=6) underwent an aortic occlusion and direct infusion of cold HTK solution into the occluded aortic segment. An IR spinal cord injury was induced by transabdominal clamping of the aorta distally to the left renal artery and proximally to the aortic bifurcation for 60 minutes. A neurological evaluation of locomotor function was performed using the modified Tarlov score after 48 hours of reperfusion. The spinal cord was harvested for histopathological and immunohistochemical examinations. Results The spinal cord IR model using direct drug delivery in rats was highly reproducible. The Tarlov score was 4.0 in the sham group, 1.17±0.75 in the IR group, 1.33±1.03 in the saline group, and 2.67±0.81 in the HTK group (p=0.04). The histopathological analysis of the HTK group showed reduced neuronal cell death. Conclusion Direct infusion of cold HTK solution into the occluded aortic segment may reduce the extent of spinal cord injuries in an IR model in rats. PMID:27525231

  6. Glial expression of Swiss cheese (SWS), the Drosophila orthologue of neuropathy target esterase (NTE), is required for neuronal ensheathment and function

    PubMed Central

    Dutta, Sudeshna; Rieche, Franziska; Eckl, Nina; Duch, Carsten; Kretzschmar, Doris

    2016-01-01

    ABSTRACT Mutations in Drosophila Swiss cheese (SWS) or its vertebrate orthologue neuropathy target esterase (NTE), respectively, cause progressive neuronal degeneration in Drosophila and mice and a complex syndrome in humans that includes mental retardation, spastic paraplegia and blindness. SWS and NTE are widely expressed in neurons but can also be found in glia; however, their function in glia has, until now, remained unknown. We have used a knockdown approach to specifically address SWS function in glia and to probe for resulting neuronal dysfunctions. This revealed that loss of SWS in pseudocartridge glia causes the formation of multi-layered glial whorls in the lamina cortex, the first optic neuropil. This phenotype was rescued by the expression of SWS or NTE, suggesting that the glial function is conserved in the vertebrate protein. SWS was also found to be required for the glial wrapping of neurons by ensheathing glia, and its loss in glia caused axonal damage. We also detected severe locomotion deficits in glial sws-knockdown flies, which occurred as early as 2 days after eclosion and increased further with age. Utilizing the giant fibre system to test for underlying functional neuronal defects showed that the response latency to a stimulus was unchanged in knockdown flies compared to controls, but the reliability with which the neurons responded to increasing frequencies was reduced. This shows that the loss of SWS in glia impairs neuronal function, strongly suggesting that the loss of glial SWS plays an important role in the phenotypes observed in the sws mutant. It is therefore likely that changes in glia also contribute to the pathology observed in humans that carry mutations in NTE. PMID:26634819

  7. New AP4B1 mutation in an African-American child associated with intellectual disability

    PubMed Central

    Lamichhane, Dronacharya

    2013-01-01

    Prevalence of intellectual disability (ID) varies from 1–3%. Genetic causes of ID are being increasingly recognized. Although multiple mutations have been identified as a cause of syndromic ID, the genetic etiology of non-syndromic ID is poorly understood. However, more than 100 loci have been mapped that are associated with non-syndromic ID. There have been a couple of reports of AP4B1 gene mutation causing severe intellectual disability, absent speech, shy character, stereotypic laughter, muscular hypotonia that progressed to spastic paraplegia, microcephaly, foot deformity, decreased muscle mass of the lower limbs, inability to walk, and growth retardation. They had structural brain abnormalities and seizures. The reported cases were from Arab families where consanguineous marriage is common. We encountered an African-American child who presented first at the age of 24 mo with language difficulties and was subsequently found to have moderate to severe intellectual disability by standardized tests. Shortly, he started to have seizures and problems with ambulation. Although he was hypotonic at the time of presentation, legs slowly became spastic at the age of 4 yr. After a thorough work up, he was found to have heterozygous mutation in the AP4B1 gene along with another missense mutation in the same gene. There has been no report of mutation in this gene in the North American population. Although AP4B1 typically is said to be an autosomal recessive disease-causing gene, our case is different in the sense that there are two mutations in the same gene one of which has never been reported before and co-exists with a known disease causing mutation. Yet, the phenotype of the case closely resembles those published previously. PMID:27625858

  8. Systematic Review and Operative Technique of Recalcitrant Pressure Ulcers Using a Fillet Flap Technique

    PubMed Central

    Rao, Venkat K.

    2016-01-01

    Background: The purpose of this article is to describe the indications, operative technique, outcomes, and systematic review of the literature on the reconstruction of patients with end-stage pressure ulcers using a fillet flap technique. In this technique, the femur, tibia, and fibula are removed from the thigh and leg, and the soft tissue is used as a pedicled, or free, myocutaneous flap for reconstruction. Long-term outcomes, salient surgical technique of flap elevation, and design are detailed for patients who had a fillet of leg flap for reconstruction of extensive pressure ulcers. Methods: The indications, surgical technique, and postoperative outcomes of 5 patients who had pedicled fillet flaps are reviewed including patient age, sex, underlying comorbidities, duration of paraplegia, operative technique, and complications. A systematic review of the literature was performed searching PubMed, Cochrane Database, and Medline with the following MeSH terms: pressure ulcer, pressure sore, decubitus ulcer, fillet flap, and fillet flap. Inclusion criteria were use of a fillet technique, article data on the number of reconstructions before fillet flap, complications, and English language. Results: Most of our patients were male 75% (n = 3) with an average age of 47.5 years, had been paralyzed for an average of 16 years, and had few medical comorbidities. Two patients (3 flaps) required hip disarticulation, 1 patient had a bilateral fillet flaps, and 3 patients had resection of tibia/fibula. After following patients for an average of 1.4 years (4 mo to 2 yr), complications were limited to 1 patient who had partial-thickness flap loss at the distal skin flap that healed by secondary intention and 1 patient who had ulcer recurrence because of noncompliance. Four articles met inclusion criteria for systematic review and 3 were excluded. Conclusions: The fillet of leg flap remains a useful and reliable method of reconstructing end-stage pressure ulcers.

  9. New pharmacological approaches against chronic bowel and bladder problems in paralytics

    PubMed Central

    Guertin, Pierre A

    2016-01-01

    Spinal cord injury (SCI) leads generally to an irreversible loss of sensory functions and voluntary motor control below injury level. Cures that could repair SCI and/or restore voluntary walking have not been yet developed nor commercialized. Beyond the well-known loss of walking capabilities, most SCI patients experience also a plethora of motor problems and health concerns including specific bladder and bowel dysfunctions. Indeed, chronic constipation and urinary retention, two significant life-threatening complications, are typically found in patients suffering of traumatic (e.g., falls or car accidents) or non-traumatic SCI (e.g., multiple sclerosis, spinal tumors). Secondary health concerns associated with these dysfunctions include hemorrhoids, abdominal distention, altered visceral sensitivity, hydronephrosis, kidney failure, urinary tract infections, sepsis and, in some cases, cardiac arrest. Consequently, individuals with chronic SCI are forced to regularly seek emergency and critical care treatments when some of these conditions occur or become intolerable. Increasing evidence supports the existence of a novel experimental approach that may be capable of preventing the occurrence or severity of bladder and bowel problems. Indeed, recent findings in animal models of SCI have revealed that, despite paraplegia or tetraplegia, it remains possible to elicit episodes of micturition and defecation by acting pharmacologically or electrically upon specialized lumbosacral neuronal networks, namely the spinal or sacral micturition center (SMC) and lumbosacral defecation center (LDC). Daily activation of SMC and LDC neurons could potentially become, new classes of minimally invasive treatments (i.e., if orally active) against these dysfunctions and their many life-threatening complications. PMID:26855887

  10. Acute Respiratory Tract Infection Visits of Veterans With Spinal Cord Injuries and Disorders: Rates, Trends, and Risk Factors

    PubMed Central

    Smith, Bridget M; Evans, Charlesnika T; Kurichi, Jibby E; Weaver, Frances M; Patel, Nayna; Burns, Stephen P

    2007-01-01

    Background/Objectives: Respiratory complications are a major cause of illness and death in persons with spinal cord injuries and dysfunction (SCI&Ds). The objectives of this study were to examine rates of outpatient visits over 5 years for acute respiratory tract infections (ARIs), including pneumonia and influenza (P&I), lower respiratory tract infections (LRIs), and upper respiratory tract infections (URIs), in veterans with SCI&Ds and to determine whether individual characteristics were associated with the number of annual visits for each type of ARI. Methods: This was a longitudinal (fiscal years 1998–2002) study of ARI visits at the Veterans Health Administration (VA) in 18,693 veterans with SCI&Ds. To examine the associations between time, patient characteristics, and annual number of ARI visits, we used random effect negative binomial models. Results: Veterans with SCI&Ds had a total of 11,113 ARI visits over the 5-year period. There was a slightly decreasing trend for LRI visits over time (P < 0.01) but no significant change for other ARIs over time. There were 30 to 35 pneumonia visits and 21 to 30 acute bronchitis visits per 1,000 SCI&D veterans per year. Older veterans were more likely than younger to have P&I visits and less likely to have URI visits (P < 0.01). Veterans with paraplegia had fewer P&I visits than subjects with tetraplegia (IRR = 0.58; CI = 0.51–0.67). Conclusions: Visit rates for ARIs are stable for veterans with SCI&Ds. Identifying risk factors associated with ARI visits is an important first step to improve prevention and treatment of ARIs and to improve the health of veterans with SCI&Ds. PMID:17853657

  11. Mitochondrial hsp60 chaperonopathy causes an autosomal-recessive neurodegenerative disorder linked to brain hypomyelination and leukodystrophy.

    PubMed

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

    2008-07-01

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

  12. [Epidural abscess due to a Mycobacterium tuberculosis strain with primary resistance to isoniazid and ethambutol].

    PubMed

    Sener, Alper; Akçalı, Alper; Karatağ, Ozan; Koşar, Sule; Değirmenci, Yıldız; Akman, Tarık

    2012-10-01

    Tuberculosis is primarily characterized by pulmonary involvement, however, one third of the cases exhibit extrapulmonary tuberculosis. In this report, a case of epidural abscess due to Mycobacterium tuberculosis with primary resistance to isoniazid and ethambutol was presented. A 57-year-old male patient was admitted to emergency service with ten days history of weakness in legs, disability of walking and fever. Neurological examination revealed paraplegia of lower extremities, numbness distal to T2 disc level and hyperactivity of deep tendon reflexes indicating transverse myelitis. Laboratory findings were as follows; ESR: 74 mm/hour, CRP: 22 g/L, ALT: 42 IU/L, AST: 45 IU/L and white blood cell count 23.000/mm3 (45% polymorphonuclear leukocyte, 45% lymphocyte, 10% monocyte). Spinal magnetic resonance imaging showed a fusiform abscess localized at anterior epidural space and extending along levels of C5-6 and C6-7. The longitudinal dimension of the abscess was 3 cm. The lesion was hypointense on T1 and hyperintense on T2 weighted MRI images with prominent rim shaped contrast enhancement on contrast-enhanced T1-weighted images. At fourth day of hospitalization the patient underwent neurosurgical management. M.tuberculosis was isolated from the cultures of operation material by Mycobacteria Growth Incubator Tube system (MGIT, BBL; BD, USA) on the 12th day. The isolate was found susceptible to streptomycin and rifampisin, but resistant to isoniazid and ethambutol. The treatment was initiated with rifampicin 600 mg/day, pyrazinamid 2 g/day, ethambutol 1.5 g/day and levofloxacin 500 mg/day. At the end of second month levofloxacin 500 mg/day and rifampisin 600 mg/day combination was sustained and total treatment period was planned as nine months. As far as the national literature was considered, this was the first case of extrapulmonary tuberculosis with primary resistance to isoniazid and ethambutol. PMID:23188583

  13. Identification of risk factors for spinal cord ischemia by the use of monitoring of somatosensory evoked potentials during coarctation repair.

    PubMed

    Dasmahapatra, H K; Coles, J G; Taylor, M J; Cass, D; Couper, G; Adler, S; Burrows, F; Sherret, H; Trusler, G A; Williams, W G

    1987-09-01

    The infrequency of spinal cord infarction and paraplegia after occlusion of the descending thoracic aorta has effectively precluded statistical identification of risk factors. Reversible spinal cord ischemia (SCI), however, is more common, can be detected by intraoperative neurophysiologic monitoring, and can lead to irreversible spinal cord damage. Spinal somatosensory evoked potentials (SEPs) were monitored intraoperatively in 38 patients (18 days to 18 years) undergoing coarctation repair (1982-1986). Although no patients sustained perioperative neurologic dysfunction, 10 of 38 (26%) patients developed reversible SCI, as reflected by greater than 75% loss of SEP N1-P1 interpeak amplitude during aortic occlusion (mean clamp time, 29.1 +/- 1.1 min). During occlusion, seven of 38 (18%) sustained complete loss of the SEP; uniform and prompt (1 to 6 min after clamp release) recovery of the signal occurred in these patients with reperfusion following completion of the repair (n = 6), or temporary institution of partial occlusion (n = 1). By multiple regression analysis the degree of SCI was negatively related to the distal aortic pressure (mean 32.4 +/- 2.4 mm Hg, p = .03), and the occlusion PCO2 (mean 33.1 +/- 1.1 mm Hg; p = .013), and positively related to the change in proximal systolic pressure with aortic occlusion (mean 19.8 +/- 3 mm Hg, p = .003). We conclude that: (1) distal hypotension and SCI commonly occur during aortic occlusion for coarctation repair, and (2) intraoperative interventions that can potentially influence distal aortic perfusion and/or PCO2 should be used judiciously.

  14. Depletion of Molecular Chaperones from the Endoplasmic Reticulum and Fragmentation of the Golgi Apparatus Associated with Pathogenesis in Pelizaeus-Merzbacher Disease*

    PubMed Central

    Numata, Yurika; Morimura, Toshifumi; Nakamura, Shoko; Hirano, Eriko; Kure, Shigeo; Goto, Yu-ich; Inoue, Ken

    2013-01-01

    Missense mutations in the proteolipid protein 1 (PLP1) gene cause a wide spectrum of hypomyelinating disorders, from mild spastic paraplegia type 2 to severe Pelizaeus-Merzbacher disease (PMD). Mutant PLP1 accumulates in the endoplasmic reticulum (ER) and induces ER stress. However, the link between the clinical severity of PMD and the cellular response induced by mutant PLP1 remains largely unknown. Accumulation of misfolded proteins in the ER generally leads to up-regulation of ER chaperones to alleviate ER stress. Here, we found that expression of the PLP1-A243V mutant, which causes severe disease, depletes some ER chaperones with a KDEL (Lys-Asp-Glu-Leu) motif, in HeLa cells, MO3.13 oligodendrocytic cells, and primary oligodendrocytes. The same PLP1 mutant also induces fragmentation of the Golgi apparatus (GA). These organelle changes are less prominent in cells with milder disease-associated PLP1 mutants. Similar changes are also observed in cells expressing another disease-causing gene that triggers ER stress, as well as in cells treated with brefeldin A, which induces ER stress and GA fragmentation by inhibiting GA to ER trafficking. We also found that mutant PLP1 disturbs localization of the KDEL receptor, which transports the chaperones with the KDEL motif from the GA to the ER. These data show that PLP1 mutants inhibit GA to ER trafficking, which reduces the supply of ER chaperones and induces GA fragmentation. We propose that depletion of ER chaperones and GA fragmentation induced by mutant misfolded proteins contribute to the pathogenesis of inherited ER stress-related diseases and affect the disease severity. PMID:23344956

  15. Proteolipid protein modulates preservation of peripheral axons and premature death when myelin protein zero is lacking.

    PubMed

    Patzig, Julia; Kusch, Kathrin; Fledrich, Robert; Eichel, Maria A; Lüders, Katja A; Möbius, Wiebke; Sereda, Michael W; Nave, Klaus-Armin; Martini, Rudolf; Werner, Hauke B

    2016-01-01

    Protein zero (P0) is the major structural component of peripheral myelin. Lack of this adhesion protein from Schwann cells causes a severe dysmyelinating neuropathy with secondary axonal degeneration in humans with the neuropathy Dejerine-Sottas syndrome (DSS) and in the corresponding mouse model (P0(null)-mice). In the mammalian CNS, the tetraspan-membrane protein PLP is the major structural myelin constituent and required for the long-term preservation of myelinated axons, which fails in hereditary spastic paraplegia (SPG type-2) and the relevant mouse model (Plp(null)-mice). The Plp-gene is also expressed in Schwann cells but PLP is of very low abundance in normal peripheral myelin; its function has thus remained enigmatic. Here we show that the abundance of PLP but not of other tetraspan myelin proteins is strongly increased in compact peripheral myelin of P0(null)-mice. To determine the functional relevance of PLP expression in the absence of P0, we generated P0(null)*Plp(null)-double-mutant mice. Compared with either single-mutant, P0(null)*Plp(null)-mice display impaired nerve conduction, reduced motor functions, and premature death. At the morphological level, axonal segments were frequently non-myelinated but in a one-to-one relationship with a hypertrophic Schwann cell. Importantly, axonal numbers were reduced in the vital phrenic nerve of P0(null)*Plp(null)-mice. In the absence of P0, thus, PLP also contributes to myelination by Schwann cells and to the preservation of peripheral axons. These data provide a link between the Schwann cell-dependent support of peripheral axons and the oligodendrocyte-dependent support of central axons. PMID:26393339

  16. 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

  17. The Drosophila KIF1A Homolog unc-104 Is Important for Site-Specific Synapse Maturation

    PubMed Central

    Zhang, Yao V.; Hannan, Shabab B.; Stapper, Zeenna A.; Kern, Jeannine V.; Jahn, Thomas R.; Rasse, Tobias M.

    2016-01-01

    Mutations in the kinesin-3 family member KIF1A have been associated with hereditary spastic paraplegia (HSP), hereditary and sensory autonomic neuropathy type 2 (HSAN2) and non-syndromic intellectual disability (ID). Both autosomal recessive and autosomal dominant forms of inheritance have been reported. Loss of KIF1A or its homolog unc-104 causes early postnatal or embryonic lethality in mice and Drosophila, respectively. In this study, we use a previously described hypomorphic allele of unc-104, unc-104bris, to investigate the impact of partial loss-of-function of kinesin-3 on synapse maturation at the Drosophila neuromuscular junction (NMJ). Unc-104bris mutants exhibit structural defects where a subset of synapses at the NMJ lack all investigated active zone (AZ) proteins, suggesting a complete failure in the formation of the cytomatrix at the active zone (CAZ) at these sites. Modulating synaptic Bruchpilot (Brp) levels by ectopic overexpression or RNAi-mediated knockdown suggests that the loss of AZ components such as Ca2+ channels and Liprin-α is caused by impaired kinesin-3 based transport rather than due to the absence of the key AZ organizer protein, Brp. In addition to defects in CAZ assembly, unc-104bris mutants display further defects such as depletion of dense core and synaptic vesicle (SV) markers from the NMJ. Notably, the level of Rab3, which is important for the allocation of AZ proteins to individual release sites, was severely reduced at unc-104bris mutant NMJs. Overexpression of Rab3 partially ameliorates synaptic phenotypes of unc-104bris larvae, suggesting that lack of presynaptic Rab3 contributes to defects in synapse maturation. PMID:27656128

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

    PubMed Central

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

    2015-01-01

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

  19. Bronchial hyperresponsiveness testing in athletes of the Swiss Paralympic team

    PubMed Central

    2013-01-01

    Background The aim of this study was to assess airway hyperresponsiveness to eucapnic voluntary hyperventilation and dry powder mannitol challenge in athletes aiming to participate at the Paralympic Games 2008 in Beijing, especially in athletes with spinal cord injury. Methods Forty-four athletes with a disability (27 with paraplegia (group 1), 3 with tetraplegia (group 2) and 14 with other disabilities such as blindness or single limb amputations (group 3) performed spirometry, skin prick testing, measurement of exhaled nitric oxide, eucapnic voluntary hyperventilation challenge test (EVH) and mannitol challenge test (MCT). A fall in FEV1 of ≥10% in either challenge test was deemed positive for exercise-induced bronchoconstriction. Results Fourteen (32%) athletes were atopic and 7 (16%) had a history of physician-diagnosed asthma. Absolute lung function values were significantly lower in patients of group 1 and 2 compared to group 3. Nine (20%) athletes were positive to EVH (8 paraplegics, 1 tetraplegic), and 8 (18%) athletes were positive to MCT (7 paraplegics, 1 tetraplegic). Fourteen (22.7%) subjects were positive to at least one challenge; only three athletes were positive to both tests. None of the athletes in group 3 had a positive test. Both challenge tests showed a significant association with physician-diagnosed asthma status (p = 0.0001). The positive and negative predictive value to diagnose physician-diagnosed asthma was 89% and 91% for EHV, and 75% and 86% for MCT, respectively. Conclusion EVH and MCT can be used to identify, but especially exclude asthma in Paralympic athletes. PMID:23845126

  20. 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.