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Sample records for paraplegia

  1. Genetics Home Reference: Spastic paraplegia type 8

    MedlinePLUS

    ... Hereditary spastic paraplegias are divided into two types: pure and complex. The pure types involve only the nerves and muscles controlling ... the body. Spastic paraplegia type 8 is a pure hereditary spastic paraplegia. Like all hereditary spastic paraplegias, ...

  2. Genetics Home Reference: Spastic paraplegia type 2

    MedlinePLUS

    ... OMIM Genetic disorder catalog Conditions > Spastic paraplegia type 2 On this page: Description Genetic changes Inheritance Diagnosis ... Reviewed March 2008 What is spastic paraplegia type 2? Spastic paraplegia type 2 is part of a ...

  3. Genetics Home Reference: Spastic paraplegia type 2

    MedlinePLUS

    ... spastic paraplegia type 2? ataxia ; atrophy ; carrier ; cell ; central nervous system ; chromosome ; dementia ; disability ; gene ; hereditary ; inheritance ; inherited ; involuntary ; leukodystrophy ; mutation ; nervous system ; nystagmus ; paraplegia ; peripheral ; peripheral nervous system ; prevalence ; protein ; recessive ; sensory cells ; ...

  4. Genetics Home Reference: Spastic paraplegia type 11

    MedlinePLUS

    ... the left and right halves of the brain (corpus callosum) is abnormally thin. People with this form of ... 11? autosomal recessive spastic paraplegia complicated with thin corpus callosum autosomal recessive spastic paraplegia with mental impairment and ...

  5. 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

  6. Genetics Home Reference: Spastic paraplegia type 4

    MedlinePLUS

    ... Information Center - Information about genetic conditions and rare diseases Additional NIH Resources - National Institutes of Health National Institute of Neurological Disorders and Stroke: Hereditary Spastic Paraplegia Educational resources - Information pages (3 links) ...

  7. Genetics Home Reference: Spastic paraplegia type 31

    MedlinePLUS

    ... Information Center - Information about genetic conditions and rare diseases Additional NIH Resources - National Institutes of Health National Institute of Neurological Disorders and Stroke: Hereditary Spastic Paraplegia Information Page Educational resources - Information pages ( ...

  8. Genetics Home Reference: Spastic paraplegia type 11

    MedlinePLUS

    ... spine (scoliosis), and involuntary movements of the eyes (nystagmus). The onset of symptoms varies greatly; however, abnormalities ... inherited ; involuntary ; motor ; muscle tone ; nervous system ; neuropathy ; nystagmus ; paraplegia ; peripheral ; peripheral nervous system ; pes cavus ; prevalence ; ...

  9. Genetics Home Reference: Spastic paraplegia type 8

    MedlinePLUS

    ... Patients and Families Resources for Health Professionals What glossary definitions help with understanding spastic paraplegia type 8? ... many other terms in the Genetics Home Reference Glossary . See also Understanding Medical Terminology . References (4 links) ...

  10. Genetics Home Reference: Spastic paraplegia type 4

    MedlinePLUS

    ... also involved in transporting cell components and facilitating cell division. Spastin likely helps restrict microtubule length and disassemble ... spastic paraplegia type 4? autosomal ; autosomal dominant ; cell ; cell division ; cytoskeleton ; gene ; hereditary ; inherited ; microtubule ; mutation ; nervous system ; ...

  11. Spinal Tuberculosis with Paraplegia in Pregnancy.

    PubMed

    Kaushal, S; Dora, S K; Thakur, S

    2015-01-01

    Spinal tuberculosis leading to paraplegia is uncommon in pregnancy and is a diagnostic and therapeutic challenge. We report a case of tubercular paraplegia presenting at 35 weeks of gestation. She was managed with Anti-tubercular drugs and did not require surgical intervention. Her neurological status improved and she was allowed to go in labour. She delivered a healthy term infant by cesarean. At three months follow-up, both mother and child are doing well. PMID:26994033

  12. Genetics Home Reference: Spastic paraplegia type 3A

    MedlinePLUS

    ... paraplegia type 3A? autosomal ; autosomal dominant ; axons ; cell ; central nervous system ; gene ; hereditary ; inherited ; mutation ; nervous system ; neuropathy ; paraplegia ; peripheral ; peripheral neuropathy ; pes cavus ; prevalence ; protein ; scoliosis ; spasticity ; ...

  13. Familial spastic paraplegia with Kallmann's syndrome.

    PubMed Central

    Tuck, R R; O'Neill, B P; Gharib, H; Mulder, D W

    1983-01-01

    A sibship is reported in which two males have spastic paraparesis and Kallmann's syndrome (hypogonadotrophic hypogonadism and anosmia). One of the brothers also is color blind. The association of familial spastic paraplegia and Kallmann's syndrome has not been described previously. PMID:6604133

  14. Complete paraplegia resulting from surfer's myelopathy.

    PubMed

    Takakura, Tomokazu; Yokoyama, Osamu; Sakuma, Fujiko; Itoh, Ryousuke; Romero, Ray R

    2013-09-01

    Three patients with diagnoses of surfer's myelopathy (24-31 yrs old; two men, one woman) were admitted to our rehabilitation hospital. All three patients were novice surfers and had a typical clinical course of onset: rapid progression of paraplegia after back pain while taking surfing lessons. Despite months of rehabilitation at our hospital, in all three patients, complete paraplegia (T9-T12) and bladder-bowel dysfunction remained. Our case profiles suggest that the neurologic outcome of surfer's myelopathy is potentially catastrophic, as has been suggested in previous reports. Surfer's myelopathy has been estimated to be an ischemic thoracic myelopathy. From our case profiles and review of the literature, not only the prolonged prone hyperextended posture of paddling but also the repetitive mechanical stress caused by flexion-extension of the spinal column may be related to its pathogenesis. To prevent surfer's myelopathy and to avoid progressive deterioration of neurologic function, increased education and awareness are essential. PMID:22257974

  15. 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

  16. Rare presentations of hyperthyroidism--Basedow's paraplegia and pancytopenia.

    PubMed

    Chen, Yi-Hsien; Lin, Hung-Jung; Chen, Kuo-Tai

    2009-02-01

    Typical presentations of hyperthyroidism are palpitation, nervousness, tremor, malaise, and weight loss. Hyperthyroidism affects nearly every system in the body, and some patients may manifest neurologic or hematologic symptoms. Atypical presentations of hyperthyroidism often pose a great challenge in diagnosis and treatment. We report a case of Basedow's paraplegia and pancytopenia that was precipitated by hyperthyroidism. The unusual manifestations led to unnecessary examinations and delayed the treatment of hyperthyroidism. The classical symptoms of Basedow's paraplegia are subacute symmetric weakness of the lower extremities with areflexia and sparing sensation or sphincter involvement. Control of the hyperthyroidism mitigated the neurologic and hematologic complications and prevented unnecessary studies. PMID:19371562

  17. Migrated Disc at Cervicothoracic Junction Presenting as Acute Paraplegia.

    PubMed

    Mahore, Amit; Agarwal, Monit; Ramdasi, Raghvendra; Tikeykar, Vishakha

    2015-06-01

    Herein, we report on an inferior migration of an intervertebral disc C6-7 to the cervicothoracic junction manifesting as acute paraplegia. The patient showed a remarkable recovery after the surgery. The diagnostic dilemma and management difficulties of such an entity are briefly discussed. PMID:26097662

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

    PubMed

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

    2010-02-01

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

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

    PubMed

    Batt, Michel; Rogopoulos, Andr; Benchimol, Daniel; Chapot, Ren; Jean-Baptiste, Elixne; Baque, Patrick

    2008-10-01

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

  20. Clinical features and management of hereditary spastic paraplegia.

    PubMed

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

    2014-03-01

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

  1. Paraplegia Due to Spinal Cord Infarction After Coronary Artery Bypass Graft Surgery.

    PubMed

    Sevuk, Utkan; Kaya, Sedat; Ayaz, Firat; Aktas, Ulas

    2016-01-01

    Paraplegia is an extremely rare complication after coronary artery bypass grafting (CABG) and the underlying mechanisms remain poorly understood. We report a patient who developed paraplegia after CABG and review the literature on spinal cord ischemia following CABG surgery. doi: 10.1111/jocs.12666 (J Card Surg 2016;31:51-56). PMID:26553407

  2. Rapidly progressive paraplegia and pleural empyema: how does that correlate?

    PubMed

    Lescan, Mario; Lepski, Guilherme; Steger, Volker; Schlensak, Christian; Walker, Tobias

    2013-11-01

    A 74-year-old man presented with progressive dyspnea after a 10-days latency following a thoracic trauma. CT imaging showed multiple rib fracture and an empyema that was primarily treated by a chest tube. In the course of the hospital stay, a rapidly progressive paraplegia developed and the MR imaging revealed a peridural abscess caused by a pleural empyema. Due to trauma-related barrier damage and the initial delay of the operative therapy a usually less invasive pathogen (streptococcus intermedius) could affect the peridural space. The successful therapy consisted of urgent laminectomy and a subsequent video-assisted thoracoscopy supported by systemic antibiotic therapy. PMID:23275088

  3. Implications of elbow arthrodesis for individuals with paraplegia.

    PubMed

    Young, J H

    1993-03-01

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

  4. 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

  5. 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. PMID:26644641

  6. Spontaneous Recovery of Paraplegia Caused by Spinal Epidural Hematoma after Removal of Epidural Catheter

    PubMed Central

    Nitahara, Keiichi

    2014-01-01

    We report a patient who developed paraplegia caused by a spinal epidural hematoma after removal of an epidural catheter, which resolved spontaneously. A 60-year-old woman underwent thoracoscopic partial resection of the left lung under general anesthesia combined with epidural anesthesia. She neither was coagulopathic nor had received anticoagulants. Paraplegia occurred 40 minutes after removal of the epidural catheter on the first postoperative day. Magnetic resonance images revealed a spinal epidural hematoma. Surgery was not required as the paraplegia gradually improved until, within 1 hour, it had completely resolved. Hypoesthesia had completely resolved by the third postoperative day. PMID:24876976

  7. Spontaneous spinal epidural hematoma presenting as paraplegia after cardiac surgery.

    PubMed

    Kin, Hajime; Mukaida, Masayuki; Koizumi, Junichi; Kamada, Takeshi; Mitsunaga, Yoshino; Iwase, Tomoyuki; Ikai, Akio; Okabayashi, Hitoshi

    2016-03-01

    An 86-year-old woman was scheduled to undergo aortic valve replacement and coronary artery bypass graft. On postoperative day 3, she developed sudden-onset neck pain followed by weakness in the right arm. Her symptoms worsened with time, and she developed paraplegia. At 60 h after the first complaint, spontaneous spinal epidural hematoma (SSEH) from C2 to C6 with spinal cord compression was diagnosed from a magnetic resonance image of the cervical region. We decided on conservative therapy because operative recovery was impossible. Delayed diagnosis led to grievous results in the present case. When neurological abnormalities follow neck or back pain after open heart surgery, SSEH must be considered in the differential diagnosis. Further, if it is suspected, early cervical computed tomography/magnetic resonance imaging and surgery should be considered. PMID:24722959

  8. 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. PMID:26885305

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

    PubMed Central

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

    2016-01-01

    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. PMID:26885305

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

    PubMed Central

    Hiremath, Shivayogi V.; Ding, Dan

    2011-01-01

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

  11. Strumpellin and Spartin, Hereditary Spastic Paraplegia Proteins, are Binding Partners

    PubMed Central

    Zhao, Jiali; Hedera, Peter

    2015-01-01

    Hereditary spastic paraplegia (HSP) is one of the most heterogeneous neurodegenerative diseases with more than 50 identified genes causing a relatively stereotypical phenotypic presentation. Recent studies of HSP pathogenesis have suggested the existence of shared biochemical pathways that are crucial for axonal maintenance and degeneration. We explored possible interactions of several proteins associated with this condition. Here we report interactions of endogenous and overexpressed strumpellin with another HSP-associated protein, spartin. This biochemical interaction does not appear to be a part of the WiskottAldrich syndrome protein and Scar homologue (WASH) complex because spartin is not co-immunoprecipitated with WASH1 protein. The spartinstrumpellin association does not require the presence of the microtubule interacting and trafficking domain of spartin. Over-expression of mutant forms of strumpellin with the introduced HSP-causing mutations does not alter the colocalization of these two proteins. Knockdown of strumpellin in cultured cortical rat neurons interferes with development of neuronal branching and results in reduced expression of endogenous spartin. Proteosomal inhibition stabilized the levels of spartin and WASH1 proteins, supporting increased spartin degradation in the absence of strumpellin. PMID:25987849

  12. Clinical Spectrum of Hereditary Spastic Paraplegia in Children

    PubMed Central

    Koul, Roshan; Al-Murshedi, Fathiya M.; Al-Azri, Faisal M.; Mani, Ranjit; Abdelrahim, Rana A.; Koul, Vivek; Alfutaisi, Amna M.

    2013-01-01

    Objectives: The aim of the study was to explore the spectrum of hereditary spastic paraplegia (HSP) in children in Oman. Methods: This retrospective study was carried out between January 1994 and August 2011 on children with delayed development, gait disorders and motor handicaps, with signs of symmetrical pyramidal tract involvement. A detailed perinatal and family history, including the age of onset of symptoms, was recorded. The children were labelled as having either the pure or complicated form of HSP based on the established diagnostic criteria. In families with more than one affected child, parents and all other siblings were also examined. Results: Within the study, 74 children from 31 families were diagnosed with HSP. Parental consanguinity was seen in 91% of cases, with 44 children (59.4%) experiencing onset of the disease under one year of age. Complicated HSP was the most common type, seen in 81.1%. Speech involvement, mental retardation, and epilepsy were the most common associated abnormalities. Nonspecific white matter changes and corpus callosum abnormalities were noted in 24.3% of cases on magnetic resonance imaging. Conclusion: The study described clinical features of 74 children with HSP. Autosomal recessive complicated HSP was seen in 81.1% of cases. PMID:23984021

  13. 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

  14. Hereditary "pure" spastic paraplegia: a study of nine families.

    PubMed Central

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

    1993-01-01

    The genetic and clinical features of 46 patients in nine families with "pure" hereditary spastic paraplegia are described. Inheritance was autosomal dominant in seven families and autosomal recessive in two. In dominant kinships, five families corresponded to type I with onset below 35 years, and two to type II with onset over 35 years. In early onset dominant families, in spite of apparent complete penetrance before 20, variable expression and incomplete penetrance occurred. Irrespective of genetic type, serial evaluation revealed that the main symptom consisted of slowly progressive spastic gait, extremely variable in severity, associated in some patients with decreased vibratory sense and micturition disorders generally as late features. In dominant families, the disease tended to be more severe in late onset cases. No patient had symptoms in the upper limbs and plantar responses were flexor in six symptomatic patients. Central motor conduction time studied by transcranial magnetic stimulation was always normal in the upper limbs and increased in the lower limbs in five of the eight patients on whom it was performed. Monomorphic and stereotyped clinical pattern in this series does not support the concept of multisystem involvement of the central nervous system as a hallmark of the disease. PMID:8382269

  15. Spastin gene mutations in Bulgarian patients with hereditary spastic paraplegia.

    PubMed

    Ivanova, N; Lfgren, A; Tournev, I; Rousev, R; Andreeva, A; Jordanova, A; Georgieva, V; Deconinck, T; Timmerman, V; Kremensky, I; De Jonghe, P; Mitev, V

    2006-12-01

    Hereditary spastic paraplegia (HSP) is an extremely heterogeneous group of neurodegenerative disorders affecting the longest axons in the central nervous system. The most common genetic form accounting for about 40% of the autosomal-dominant HSP (ADHSP) cases is spastin gene, SPG4. We performed mutation screening of the spastin gene on 36 unrelated HSP patients from three different ethnic groups (Bulgarian, Turks and Gypsies) and found four new mutations and one already reported. The phenotype-genotype correlations in Bulgarian SPG4 patients showed a great difference in the age at disease onset between patients with missense mutations and those harboring deletions and splice-site mutations. Our study is the first to present corroborative clinical data in favor of the general hypothesis that the clinical course of the disease is related to the type of the spastin mutation. The clinical and genealogical findings in Bulgarian SPG4 patients suggest that a positive family history for inheritance as an autosomal-dominant trait is a strong indication for spastin mutation screening. PMID:17100993

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

    PubMed

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

    2015-12-01

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

  17. Endemic Burkitt Lymphoma: Long-term Outcome in 87 Patients Who Presented With Paraplegia in Cameroon.

    PubMed

    Hesseling, P B; Mbah, G; Kouya, F; Kimbi, C; Nfor, P; Kaah, J; Kuruvilla, R; Best, A; Wharin, P

    2015-11-01

    The reported long-term outcome of endemic Burkitt lymphoma (eBL) patients who present with paraplegia is largely unknown. Records of BL patients treated with comparable short-interval cyclophosphamide chemotherapy schedules between 2004 and 2014 at three Baptist mission hospitals in Cameroon were reviewed. Survivors were followed up and examined at home or in hospital. Eighty-seven of 948 (9.2%) patients had paraplegia at diagnosis. The survival rate in eBL patients with paraplegia at diagnosis was 33% (n = 29) after follow-up of between 2 and 96 (median 40) months. Seven patients (24%) had neurological sequelae and needed rehabilitation. There was no relationship between the duration of symptoms (<2, 2-4, >4 weeks) and the survival rate or the risk to have neurological sequelae. The survival rate and risk for sequelae were similar in patients with confirmed St. Jude stage III and IV diseases. PMID:26606160

  18. 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

  19. 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.

  20. Recessively inherited spastic paraplegia associated with ataxia, congenital cataracts, thin corpus callosum and axonal neuropathy.

    PubMed

    Yamashita, I; Sasaki, H; Yabe, I; Kikuchi, S; Chin, S; Fukazawa, T; Okumura, H; Tashiro, K

    2000-07-01

    We investigated a consanguineous Japanese family with a complicated form of familial spastic paraplegia (FSP). Three siblings were affected, probably by autosomal recessive inheritance. All showed ataxia, subnormal mentality, congenital cataracts, and slight cerebellar atrophy on CT scans. Spastic paraplegia was predominant in 2 siblings, while ataxia was more marked in the other. Slight but definite atrophy of the corpus callosum and axonal neuropathy were demonstrated in 1 sibling who underwent detailed investigation. Review of similar cases reported in the literature indicates that this recessively inherited disorder probably represents a homogeneous group within the heterogeneous cluster of complicated FSP. PMID:10893066

  1. 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"

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

    PubMed Central

    2013-01-01

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

  3. 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"…

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed Central

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

    2015-01-01

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

  6. Confirmation of locus heterogeneity in the pure form of familial spastic paraplegia

    SciTech Connect

    Speer, M.C.; Gaskell, P.C.; Robinson, L.C.

    1995-08-14

    Familial spastic paraplegia (FSP), characterized by progressive spasticity of the lower extremities, is in its {open_quotes}pure{close_quotes} form generally of autosomal dominant inheritance pattern. Hazen et al. reported tight linkage of a large FSP family to the highly polymorphic microsatellite marker D14S269 with z ({sub {theta}}) = 8.49 at {sub {theta}} = 0.00. They further demonstrated evidence for locus heterogeneity when they showed that 2 FSP families were unlinked to this region. We have subsequently studied 4 FSP families (3 American, one British) and excluded the disease locus in these families for approximately 30 cM on either side of D14S269, thereby confirming evidence for locus heterogeneity within the spastic paraplegia diagnostic classification. 28 refs., 2 figs., 4 tabs.

  7. Study on a family with anderson--Fabry's disease and associated familial spastic paraplegia.

    PubMed Central

    Pierides, A M; Holti, G; Crombie, A L; Roberts, D F; Gardiner, S E; Colling, A; Anderson, J

    1976-01-01

    A family in the north-east of England with Anderson--Fabry's disease is presented. Alpha-galactosidase activity in plasma and white cells was significantly reduced in three adult male members of the family. One of them had an abnormal chromosome karyotype pattern with an extra Y chromosome (47,XYY) and he was clinically less severely affected than his brothers. Coincidentally five other members of the family suffered from a form of familial spastic paraplegia. Images PMID:828204

  8. Motor protein mutations cause a new form of hereditary spastic paraplegia

    PubMed Central

    Caballero Oteyza, Andrs; Battalo?lu, Esra; Ocek, Levent; Lindig, Tobias; Reichbauer, Jennifer; Rebelo, Adriana P.; Gonzalez, Michael A.; Zorlu, Yasar; Ozes, Burcak; Timmann, Dagmar; Bender, Benjamin; Woehlke, Gnther; Zchner, Stephan; Schls, Ludger

    2014-01-01

    Objective: To identify a novel disease gene in 2 families with autosomal recessive hereditary spastic paraplegia (HSP). Methods: We used whole-exome sequencing to identify the underlying genetic disease cause in 2 families with apparently autosomal recessive spastic paraplegia. Endogenous expression as well as subcellular localization of wild-type and mutant protein were studied to support the pathogenicity of the identified mutations. Results: In 2 families, we identified compound heterozygous or homozygous mutations in the kinesin gene KIF1C to cause hereditary spastic paraplegia type 58 (SPG58). SPG58 can be complicated by cervical dystonia and cerebellar ataxia. The same mutations in a heterozygous state result in a mild or subclinical phenotype. KIF1C mutations in SPG58 affect the domains involved in adenosine triphosphate hydrolysis and microtubule binding, key functions for this microtubule-based motor protein. Conclusions: KIF1C is the third kinesin gene involved in the pathogenesis of HSPs and is characterized by a mild dominant and a more severe recessive disease phenotype. The identification of KIF1C as an HSP disease gene further supports the key role of intracellular trafficking processes in the pathogenesis of hereditary axonopathies. PMID:24808017

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

    PubMed

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

    2014-11-01

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

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

    PubMed

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

    2002-08-01

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

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

    PubMed Central

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

    2014-01-01

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

  12. TDP-43 pathology in a case of hereditary spastic paraplegia with a NIPA1/SPG6 mutation.

    PubMed

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

    2012-08-01

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

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

    PubMed

    Prez-Brangul, 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; Schltzer-Schrehardt, Ursula; Winkler, Jrgen; Winner, Beate

    2014-09-15

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

  14. 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

  15. Endovascular Coil Embolization of Segmental Arteries Prevents Paraplegia After Subsequent TAAA Repair An Experimental Model

    PubMed Central

    Geisbsch, S; Stefanovic, A; Koruth, JS; Lin, HM; Morgello, S; Weisz, DJ; Griepp, RB; Di Luozzo, G

    2013-01-01

    Objective To test a strategy for minimizing ischemic spinal cord injury (SCI) following extensive thoracoabdominal aneurysm (TAAA) repair, we occluded a small number of segmental arteries (SAs) endovascularly one week before simulated aneurysm repair in an experimental model. Methods 30 juvenile Yorkshire pigs (25.21.7kg) were randomized into three groups. All SAsintercostal and lumbarwere sacrificed by a combination of surgical ligation of the lumbar SAs and occlusion of intercostal SAs with thoracic endovascular stent grafting (TEVAR). 710 days before this simulated TAAA replacement, SAs in the lower thoracic/upper lumbar region were occluded using embolization coils: 1.50.5 SAs in Group 1 (T13/L1), and 4.50.5 in Group 2 (T11-L3). No SAs were coiled in the controls. Hind limb function was evaluated blindly from daily videotapes using a modified Tarlov score: 0=paraplegia; 9=full recovery. After sacrifice, each segment of spinal cord was graded histologically using the 9-point Kleinman score: 0=normal, 8=complete necrosis. Results Hind limb function remained normal after coil embolization. After simulated TAAA repair, paraplegia occurred in 6/10 control pigs, but only 2/10 pigs in Group 1: no pigs in Group 2 had SCI. Tarlov scores were significantly better in Group 2 (Control vs 1 p=0.06; Control vs 2 p= 0.0002; 1 vs 2 p=0.05). A dramatic reduction in histologic damagemost prominently in the coiled regionwas seen when SAs were embolized before simulated TAAA repair. Conclusions Endovascular coiling of 24 SAs prevents paraplegia in an experimental model of extensive hybrid TAAA repair, and helps protect the spinal cord from ischemic histopathological injury. A clinical trial in a selected patient population at high risk for postoperative SCI may be appropriate. PMID:24220154

  16. 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; Hbner, 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 curvatureinducing 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

  17. 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; Hbner, Christian A

    2013-10-01

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

  18. Bladder and rectal incontinence without paraplegia or paraparesis after endovascular aneurysm repair.

    PubMed

    Nishioka, Naritomo; Kurimoto, Yoshihiko; Maruyama, Ryushi; Ujihira, Kosuke; Iba, Yutaka; Hatta, Eiichiro; Yamada, Akira; Nakanishi, Katsuhiko

    2016-12-01

    Spinal cord ischemia is a well-known potential complication of endovascular aneurysm repair (EVAR), and it is usually manifested by paraplegia or paraparesis. We describe a case in which spinal cord ischemia after EVAR presented by isolated bladder and rectal incontinence without other neurological deficits. A 63-year-old woman presented with intermittent claudication secondary to an infrarenal abdominal aortic aneurysm (AAA), and a left common iliac artery obstruction, for which she underwent EVAR using an aorto-uniiliac (AUI) device and ilio-femoral artery bypass. On postoperative day 3, she developed urinary and fecal incontinence without signs of paraplegia or paraparesis. Magnetic resonance imaging (MRI) showed a hyper-intense signal in the spinal cord. She received hyperbaric oxygen (HBO) therapy and was discharged after 18 days when her urinary and fecal incontinence were almost resolved. This report suggests that spinal cord ischemia after EVAR for aortoiliac occlusive disease might present as bladder and rectal incontinence without other neurological manifestations. PMID:26943687

  19. 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

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

    PubMed

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

    2013-07-01

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

  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. PMID:18228054

  2. Adolescent paraplegia, morbid obesity, and pickwickian syndrome: outcome of gastric bypass surgery.

    PubMed

    Miyano, Go; Kalra, Maninder; Inge, Thomas H

    2009-03-01

    Loss of mobility, such as what occurs as a consequence of spinal cord injury or malformation, is a risk factor for excess weight gain and can confound weight management efforts. Despite well-documented outcomes of bariatric surgery in ambulatory patients, little information is available regarding weight loss surgery in adult or adolescent paraplegic patients. A 15-year-old adolescent boy with a body mass index of 60 kg/m(2) and complete paraplegia caused by spina bifida developed metabolic dysfunction, severe obstructive sleep apnea, and hypoxemia syndrome. In an effort to avoid a tracheostomy for worsening pickwickian syndrome, he was referred for weight loss surgery. Laparoscopic Roux-en-Y gastric bypass surgery was safely performed and resulted in loss of 55% of body weight (83.8% excess weight loss) for 2 years. Risk factors for cardiovascular disease markedly improved, and polysomnography demonstrated complete reversal of sleep apnea with substantial subjective improvement in daytime breathlessness and quality of life. Body composition analysis demonstrated preferential reduction in body fat mass compared with lean mass, without detrimental effect on bone mineral density. This case illustrates that paraplegia does not necessarily impair either weight loss efficacy or comorbidity resolution after Roux-en-Y gastric bypass surgery. PMID:19302844

  3. 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

  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. [Dynamic decision making in emergency medicine. Example of paraplegia after a traffic accident].

    PubMed

    Mller, M; Bergmann, B; Koch, T; Heller, A

    2005-08-01

    Dynamic decision making is one of the key skills in crew resource management training in aviation. In emergency medicine it is important to practice this skill as a prerequisite for effective treatment of patients. We report a case of paraplegia after a road traffic accident and cervical spine injury. During the prehospital treatment the patient's state was re-evaluated at different times. Although the patient was initially unconscious the physician at the scene decided not to intubate the trachea as the level of consciousness improved during resuscitation. In the emergency room a C5 fracture and a prolapsed intervertebral disc were diagnosed and immediate decompression and stabilisation of the cervical spine were performed. Dynamic decision-making has been in practise for a long time in aviation, similarities to decisions in medicine and the psychological background are described on the basis of the case report. PMID:15895199

  6. 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

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

    PubMed Central

    Castro-Fernndez, Cristina; Arias, Manuel; Blanco-Arias, Patricia; Santom-Collazo, Luis; Amigo, Jorge; Carracedo, ngel; Sobrido, Maria-Jess

    2015-01-01

    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. PMID:26937357

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

    SciTech Connect

    Fink, J.K.; Wu, C.B.; Jones, S.M.; Lesicki, A.; Reinglass, T.; Sharp, G.B.; Lange, B.M.; Varvil, T.; Otterud, B.; Leppert, M.

    1995-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  10. 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

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

    PubMed Central

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

    2014-01-01

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

  12. 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

  13. Gray and white matter alterations in hereditary spastic paraplegia type SPG4 and clinical correlations.

    PubMed

    Lindig, Tobias; Bender, Benjamin; Hauser, Till-Karsten; Mang, Sarah; Schweikardt, Daniel; Klose, Uwe; Karle, Kathrin N; Schle, Rebecca; Schls, Ludger; Rattay, Tim W

    2015-08-01

    Hereditary spastic paraplegias (HSP) are a group of clinically and genetically heterogeneous disorders with the hallmark of progressive spastic gait disturbance. We used advanced neuroimaging to identify brain regions involved in SPG4, the most common HSP genotype. Additionally, we analyzed correlations between imaging and clinical findings. We performed 3T MRI scans including isotropic high-resolution 3D T1, T2-FLAIR, and DTI sequences in 15 adult patients with genetically confirmed SPG4 and 15 age- and sex-matched healthy controls. Brain volume loss of gray and white matter was evaluated through voxel-based morphometry (VBM) for supra- and infratentorial regions separately. DTI maps of axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD), fractional anisotropy (FA), and measured anisotropy (MA1) were analyzed through tract-based special statistics (TBSS). VBM and TBSS revealed a widespread affection of gray and white matter in SPG4 including the corpus callosum, medio-dorsal thalamus, parieto-occipital regions, upper brainstem, cerebellum, and corticospinal tract. Significant correlations with correlation coefficients r>0.6 between clinical data and DTI findings could be demonstrated for disease duration and disease severity as assessed by the spastic paraplegia rating scale for the pontine crossing tract (AD) and the corpus callosum (RD and FA). Imaging also provided evidence that SPG4 underlies a primarily axonal rather than demyelinating damage in accordance with post-mortem data. DTI is an attractive tool to assess subclinical affection in SPG4. The correlation of imaging findings with disease duration and severity suggests AD, RD, and FA as potential progression markers in interventional studies. PMID:26050637

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

    PubMed

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

    1991-04-01

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

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

    PubMed Central

    2012-01-01

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

  16. Identification of Novel Mutations in Spatacsin and Apolipoprotein B Genes in a Patient with Spastic Paraplegia and Hypobetalipoproteinemia

    PubMed Central

    Peddareddygari, Leema Reddy; Grewal, Raji P.

    2015-01-01

    Complicated hereditary spastic paraplegia (HSP) presents with complex neurological and nonneurological manifestations. We report a patient with autosomal recessive (AR) HSP in whom laboratory investigations revealed hypobetalipoproteinemia raising the possibility of a shared pathophysiology of these clinical features. A lipid profile of his parents disclosed a normal maternal lipid profile. However, the paternal lipid profile was similar to that of the patient suggesting autosomal dominant transmission of this trait. Whole exome sequence analysis was performed and novel mutations were detected in both the SPG11 and the APOB genes. Genetic testing of the parents showed that both APOB variants were inherited from the father while the SPG11 variants were inherited one from each parent. Our results indicate that, in this patient, the hypobetalipoproteinemia and spastic paraplegia are unrelated resulting from mutations in two independent genes. This clinical study provides support for the use of whole exome sequencing as a diagnostic tool for identification of mutations in conditions with complex presentations. PMID:26064709

  17. 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

  18. Congenital neuroblastoma presenting with paraplegia following spinal puncture in a neonate. Case report and review of the literature.

    PubMed

    Kilani, M; Hammami, S; Darmoul, M; Haddad, S; Ben Nsir, A; Mnari, W; Hattab, M-N

    2016-03-01

    Neuroblastoma is the most common intraspinal solid tumor of childhood. Neurological deterioration due to an intratumoral hemorrhage following a spinal puncture is extremely rare. We report on the case of a 23-day-old neonate who was admitted to our institution for the onset of a paraplegia following a diagnostic lumbar puncture. The MRI showed an epidural tumor with massive intratumoral hemorrhage. Operatively and with histologic confirmation, the mass was determined to be a neuroblastoma. Following surgery, neurological function improved. PMID:26724980

  19. Strumpellin is a novel valosin-containing protein binding partner linking hereditary spastic paraplegia to protein aggregation diseases.

    PubMed

    Clemen, Christoph S; Tangavelou, Karthikeyan; Strucksberg, Karl-Heinz; Just, Steffen; Gaertner, Linda; Regus-Leidig, Hanna; Stumpf, Maria; Reimann, Jens; Coras, Roland; Morgan, Reginald O; Fernandez, Maria-Pilar; Hofmann, Andreas; Müller, Stefan; Schoser, Benedikt; Hanisch, Franz-Georg; Rottbauer, Wolfgang; Blümcke, Ingmar; von Hörsten, Stephan; Eichinger, Ludwig; Schröder, Rolf

    2010-10-01

    Mutations of the human valosin-containing protein gene cause autosomal-dominant inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia. We identified strumpellin as a novel valosin-containing protein binding partner. Strumpellin mutations have been shown to cause hereditary spastic paraplegia. We demonstrate that strumpellin is a ubiquitously expressed protein present in cytosolic and endoplasmic reticulum cell fractions. Overexpression or ablation of wild-type strumpellin caused significantly reduced wound closure velocities in wound healing assays, whereas overexpression of the disease-causing strumpellin N471D mutant showed no functional effect. Strumpellin knockdown experiments in human neuroblastoma cells resulted in a dramatic reduction of axonal outgrowth. Knockdown studies in zebrafish revealed severe cardiac contractile dysfunction, tail curvature and impaired motility. The latter phenotype is due to a loss of central and peripheral motoneuron formation. These data imply a strumpellin loss-of-function pathogenesis in hereditary spastic paraplegia. In the human central nervous system strumpellin shows a presynaptic localization. We further identified strumpellin in pathological protein aggregates in inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia, various myofibrillar myopathies and in cortical neurons of a Huntington's disease mouse model. Beyond hereditary spastic paraplegia, our findings imply that mutant forms of strumpellin and valosin-containing protein may have a concerted pathogenic role in various protein aggregate diseases. PMID:20833645

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2015-01-01

    This paper presents an assessment of a lower limb exoskeleton for providing legged mobility to people with paraplegia. In particular, the paper presents a single-subject case study comparing legged locomotion using the exoskeleton to locomotion using kneeanklefoot 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 subjects ability to stand, walk, turn, and sit. The exertion associated with each assessment instrument was assessed using the Physiological Cost Index. Results indicate that the subject was able to perform the respective assessment instruments 25%, 70%, and 80% faster with the exoskeleton relative to the KAFOs for the timed up-and-go test, the 10 MWT, and the 6 MWT, respectively. Measurements of exertion indicate that the exoskeleton requires 1.6, 5.2, and 3.2 times less exertion than the KAFOs for each respective assessment instrument. The results indicate that the enhancement in speed and reduction in exertion are more significant during walking than during gait transitions. PMID:23797285

  2. A Method for the Autonomous Control of Lower Limb Exo-skeletons for Persons with Paraplegia.

    PubMed

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

    2012-12-12

    Efforts have recently been reported by several research groups on the development of computer-controlled lower limb orthoses to enable legged locomotion in persons with paraplegia. Such systems must employ a control framework that provides essential movements to the paraplegic user (i.e., sitting, standing, and walking), and ideally enable the user to autonomously command these various movements in a safe, reliable, and intuitive manner. This paper describes a control method that enables a paraplegic user to perform sitting, standing, and walking movements, which are commanded based on postural information measured by the device. The proposed user interface and control structure was implemented on a powered lower limb orthosis, and the system was tested on a paraplegic subject with a T10 complete injury. Experimental data is presented that indicates the ability of the proposed control architecture to provide appropriate user-initiated control of sitting, standing, and walking. The authors also provide a link to a video that qualitatively demonstrates the user's ability to independently control basic movements via the proposed control method. PMID:23505407

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

    PubMed Central

    Tesson, Christelle; Nawara, Magdalena; Salih, MustafaA.M.; Rossignol, Rodrigue; Zaki, MahaS.; AlBalwi, Mohammed; Schule, Rebecca; Mignot, Cyril; Obre, Emilie; Bouhouche, Ahmed; Santorelli, FilippoM.; Durand, ChristelleM.; Oteyza, AndrsCaballero; El-Hachimi, KhalidH.; AlDrees, Abdulmajeed; Bouslam, Naima; Lamari, Foudil; Elmalik, SalahA.; Kabiraj, MohammadM.; Seidahmed, MohammedZ.; Esteves, Typhaine; Gaussen, Marion; Monin, Marie-Lorraine; Gyapay, Gabor; Lechner, Doris; Gonzalez, Michael; Depienne, Christel; Mochel, Fanny; Lavie, Julie; Schols, Ludger; Lacombe, Didier; Yahyaoui, Mohamed; AlAbdulkareem, Ibrahim; Zuchner, Stephan; Yamashita, Atsushi; Benomar, Ali; Goizet, Cyril; Durr, Alexandra; Gleeson, JosephG.; Darios, Frederic; Brice, Alexis; Stevanin, Giovanni

    2012-01-01

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

  4. Acute spontaneous spinal subdural haematoma presenting as paraplegia and complete recovery with non-operative treatment

    PubMed Central

    Al, Behet; Yildirim, Cuma; Zengin, Suat; Genc, Sinan; Erkutlu, Ibrahim; Mete, Ahmet

    2009-01-01

    Spontaneous spinal subdural haematoma (SSDH) with no underlying pathology is a very rare condition. Only 20 cases have been previously reported. It can be caused by abnormalities of coagulation, blood dyscrasia, or trauma, underlying neoplasm, and arteriovenous malformation. It occurs most commonly in the thoracic spine and presents with sudden back pain radiating to the arms, legs or trunk, and varying degrees of motor, sensory, and autonomic disturbances. Although the main approach to management is surgical decompression, conservative management is used as well. We report the case of a 57-year-old man who presented with sudden severe low back pain followed by rapid onset of complete paraplegia. Magnetic resonance imaging (MRI) revealed an anterior subdural haematoma from T9 to L1 with cord compression. Corticosteroid treatment was administered. The patient showed substantial clinical improvement after 7 days of bed rest and an intense rehabilitation programme. An MRI scan and a computed tomography angiogram did not reveal any underlying pathology to account for the subdural haematoma. PMID:22065983

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

    PubMed

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

    2013-01-01

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

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

    PubMed

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

    2013-11-01

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

  7. Development of an indoor rowing machine with manual FES controller for total body exercise in paraplegia.

    PubMed

    Davoodi, Rahman; Andrews, Brian J; Wheeler, Garry D; Lederer, Robert

    2002-09-01

    Concept 2 indoor rowing machine (Concept 2 Inc., USA) was modified for functional electrical stimulation (FES) rowing exercise in paraplegia. A new seating system provides trunk stability and constrains the leg motion to the sagittal plane. A 4-channel electrical stimulator activates the quadriceps and hamstrings in Drive and Recovery phases of the rowing cycle, respectively. Two force-sensing resistors (FSR) on the handle measure the thumb press as the command signal to the electrical stimulator. Optical encoders measure the positions of the seat and handle during rowing. To synchronize the voluntarily controlled upper body movement with the FES controlled leg movement, a novel manual control system was developed. It uses the voluntary thumb presses to control the timing of the stimulation to the paralyzed leg muscles. The manual control system was intuitive and easy to learn and resulted in well-coordinated rowing. Evaluation of the modified rower by paraplegic volunteers showed that it is effective, safe, and affordable exercise alternative for paraplegics. PMID:12503785

  8. A Newly Identified Missense Mutation in FARS2 Causes Autosomal-Recessive Spastic Paraplegia.

    PubMed

    Yang, Ying; Liu, Wei; Fang, Zhipeng; Shi, Juan; Che, Fengyu; He, Chunxia; Yao, Libo; Wang, Enduo; Wu, Yuanming

    2016-02-01

    Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by spasticity of the lower limbs due to pyramidal tract dysfunction. Here, we report that a missense homozygous mutation c.424G>T (p.D142Y) in the FARS2 gene, which encodes a mitochondrial phenylalanyl tRNA synthetase (mtPheRS), causes HSP in a Chinese consanguineous family by using combination of homozygous mapping and whole-exome sequencing. Immunohistochemical experiments were performed showing that the FARS2 protein was highly expressed in the Purkinje cells of rat cerebellum. The aminoacylation activity of mtPheRS was severely disrupted by the p.D142Y substitution in vitro not only in the first aminoacylation step but also in the last transfer step. Taken together, our results indicate that a missense mutation in FARS2 contributes to HSP, which has the clinical significance of the regulation of tRNA synthetases in human neurodegenerative diseases. PMID:26553276

  9. 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

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

    PubMed

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

    2014-05-01

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

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

    SciTech Connect

    Dube, M.P.; Kibar, Z.; Rouleau, G.A.

    1997-03-01

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

  12. Pathogenesis of autosomal dominant hereditary spastic paraplegia (SPG6) revealed by a rat model.

    PubMed

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

    2013-11-01

    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-hNIPA1) 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 NIPA1 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-hNIPA1 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

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

    PubMed Central

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

    2013-01-01

    Although SPG11 is the most common complicated hereditary spastic paraplegia, our knowledge of the long-term prognosis and life expectancy is limited. We therefore studied the disease course of all patients with a proven SPG11 mutation as tested in our laboratory, the single Dutch laboratory providing SPG11 mutation analysis, between 1 January 2009 and 1 January 2011. We identified nine different SPG11 mutations, four of which are novel, in nine index patients. Eighteen SPG11 patients from these nine families were studied by means of a retrospective chart analysis and additional interview/examination. Ages at onset were between 4 months and 14 years; 39% started with learning difficulties rather than gait impairment. Brain magnetic resonance imaging showed a thin corpus callosum and typical periventricular white matter changes in the frontal horn region (known as the ears-of the lynx'-sign) in all. Most patients became wheelchair bound after a disease duration of 1 to 2 decades. End-stage disease consisted of loss of spontaneous speech, severe dysphagia, spastic tetraplegia with peripheral nerve involvement and contractures. Several patients died of complications between ages 30 and 48 years, 34 decades after onset of gait impairment. Other relevant features during the disease were urinary and fecal incontinence, obesity and psychosis. Our study of 18 Dutch SPG11-patients shows the potential serious long-term consequences of SPG11 including a possibly restricted life span. PMID:23443022

  14. The m-AAA protease defective in hereditary spastic paraplegia controls ribosome assembly in mitochondria.

    PubMed

    Nolden, Mark; Ehses, Sarah; Koppen, Mirko; Bernacchia, Andrea; Rugarli, Elena I; Langer, Thomas

    2005-10-21

    AAA proteases comprise a conserved family of membrane bound ATP-dependent proteases that ensures the quality control of mitochondrial inner-membrane proteins. Inactivation of AAA proteases causes pleiotropic phenotypes in various organisms, including respiratory deficiencies, mitochondrial morphology defects, and axonal degeneration in hereditary spastic paraplegia (HSP). The molecular basis of these defects, however, remained unclear. Here, we describe a regulatory role of an AAA protease for mitochondrial protein synthesis in yeast. The mitochondrial ribosomal protein MrpL32 is processed by the m-AAA protease, allowing its association with preassembled ribosomal particles and completion of ribosome assembly in close proximity to the inner membrane. Maturation of MrpL32 and mitochondrial protein synthesis are also impaired in a HSP mouse model lacking the m-AAA protease subunit paraplegin, demonstrating functional conservation. Our findings therefore rationalize mitochondrial defects associated with m-AAA protease mutants in yeast and shed new light on the mechanism of axonal degeneration in HSP. PMID:16239145

  15. The hereditary spastic paraplegia proteins NIPA1, spastin and spartin are inhibitors of mammalian BMP signalling.

    PubMed

    Tsang, Hilda T H; Edwards, Thomas L; Wang, Xinnan; Connell, James W; Davies, Rachel J; Durrington, Hannah J; O'Kane, Cahir J; Luzio, J Paul; Reid, Evan

    2009-10-15

    The hereditary spastic paraplegias (HSPs) are genetic conditions characterized by distal axonopathy of the longest corticospinal tract axons, and so their study provides an important opportunity to understand mechanisms involved in axonal maintenance and degeneration. A group of HSP genes encode proteins that localize to endosomes. One of these is NIPA1 (non-imprinted in Prader-Willi/Angelman syndrome 1) and we have shown recently that its Drosophila homologue spichthyin inhibits bone morphogenic protein (BMP) signalling, although the relevance of this finding to the mammalian protein was not known. We show here that mammalian NIPA1 is also an inhibitor of BMP signalling. NIPA1 physically interacts with the type II BMP receptor (BMPRII) and we demonstrate that this interaction does not require the cytoplasmic tail of BMPRII. We show that the mechanism by which NIPA1 inhibits BMP signalling involves downregulation of BMP receptors by promoting their endocytosis and lysosomal degradation. Disease-associated mutant versions of NIPA1 alter the trafficking of BMPRII and are less efficient at promoting BMPRII degradation than wild-type NIPA1. In addition, we demonstrate that two other members of the endosomal group of HSP proteins, spastin and spartin, are inhibitors of BMP signalling. Since BMP signalling is important for distal axonal function, we propose that dysregulation of BMP signalling could be a unifying pathological component in this endosomal group of HSPs, and perhaps of importance in other conditions in which distal axonal degeneration is found. PMID:19620182

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

    SciTech Connect

    Figlewicz, D.A.; Dube, M.P.; Rouleau, G.A.

    1994-09-01

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

  17. 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. PMID:26284655

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

    PubMed

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

    1992-09-01

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

  19. 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

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

    PubMed Central

    Esteves, Typhaine; Durr, Alexandra; Mundwiller, Emeline; Loureiro, JosL.; Boutry, Maxime; Gonzalez, MichaelA.; Gauthier, Julie; El-Hachimi, KhalidH.; Depienne, Christel; Muriel, Marie-Paule; AcostaLebrigio, RafaelF.; Gaussen, Marion; Noreau, Anne; Speziani, Fiorella; Dionne-Laporte, Alexandre; Deleuze, Jean-Franois; Dion, Patrick; Coutinho, Paula; Rouleau, GuyA.; Zuchner, Stephan; Brice, Alexis; Stevanin, Giovanni; Darios, Frdric

    2014-01-01

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

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

    PubMed

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

    2014-02-01

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

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

    PubMed Central

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

    2013-01-01

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

  3. 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.

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

    SciTech Connect

    Hentati, A.; Wasserman, B.; Siddique, T.

    1994-09-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

    Lpez, Eva; Casasnovas, Carlos; Gimnez, Javier; Santamara, Ral; Terrazas, Jess M; Volpini, Vctor

    2015-11-15

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

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

    PubMed

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

    2013-02-01

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

  8. [Medical factors relevant to the course of vocational rehabilitation of spinal cord injured clients with complete paraplegia (author's transl)].

    PubMed

    Wahle, H

    1981-02-01

    A group of 40 clients with complete paraplegia, selected on a number of criteria (such as extent and location of the spinal cord lesion, age, financially responsible agency) had been followed up from the onset of paralysis. At the end of the 5th year post-onset, the following was stated in the 37 survivors: 28 of the 37 paraplegics (75.7 percent) have achieved vocational resettlement (in the broadest possible meaning of that term); of these 28, 16 (43.3 percent) were employed in standard-remuneration occupations; 6 (16.2 percent) had entered training or retraining programmes; 6 (16.2 percent) were engaged in domiciliary activities for at least 5 hours a day or employed in a sheltered setting. None of the paraplegics drew unemployment benefits at the report time; 9 (24.3 percent) had not been resettled vocationally. The article reports on those factors of paraplegia that have comparatively favourable effect on a return to occupational activity (such as use of both arms, absence of psycho-organic syndromes, stability of the neurological syndrome), on permanently detrimental consequences of omitted or insufficient early treatment, as well as on the importance of secondary prevention measures following discharge from inpatient treatment. PMID:6971460

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

    PubMed Central

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

    2012-01-01

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

  10. 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

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

    PubMed Central

    Fink, John K.

    2014-01-01

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

  12. Hereditary spastic paraplegia SPG4: what is known and not known about the disease.

    PubMed

    Solowska, Joanna M; Baas, Peter W

    2015-09-01

    Mutations in more than 70 distinct loci and more than 50 mutated gene products have been identified in patients with hereditary spastic paraplegias, a diverse group of neurological disorders characterized predominantly, but not exclusively, by progressive lower limb spasticity and weakness resulting from distal degeneration of corticospinal tract axons. Mutations in the SPAST (previously known as SPG4) gene that encodes the microtubule-severing protein called spastin, are the most common cause of the disease. The aetiology of the disease is poorly understood, but partial loss of microtubule-severing activity resulting from inactivating mutations in one SPAST allele is the most postulated explanation. Microtubule severing is important for regulating various aspects of the microtubule array, including microtubule number, length, and mobility. In addition, higher numbers of dynamic plus-ends of microtubules, resulting from microtubule-severing events, may play a role in endosomal tubulation and fission. Even so, there is growing evidence that decreased severing of microtubules does not fully explain HSP-SPG4. The presence of two translation initiation codons in SPAST allows synthesis of two spastin isoforms: a full-length isoform called M1 and a slightly shorter isoform called M87. M87 is more abundant in both neuronal and non-neuronal tissues. Studies on rodents suggest that M1 is only readily detected in adult spinal cord, which is where nerve degeneration mainly occurs in humans with HSP-SPG4. M1, due to its hydrophobic N-terminal domain not shared by M87, may insert into endoplasmic reticulum membrane, and together with reticulons, atlastin and REEP1, may play a role in the morphogenesis of this organelle. Some mutated spastins may act in dominant-negative fashion to lower microtubule-severing activity, but others have detrimental effects on neurons without further lowering microtubule severing. The observed adverse effects on microtubule dynamics, axonal transport, endoplasmic reticulum, and endosomal trafficking are likely caused not only by diminished severing of microtubules, but also by neurotoxicity of mutant spastin proteins, chiefly M1. Some large deletions in SPAST might also affect the function of adjacent genes, further complicating the aetiology of the disease. PMID:26094131

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

    PubMed

    Zempel, Hans; Mandelkow, Eva-Maria

    2015-01-01

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

  14. Spastin, a new AAA protein, is altered in the most frequent form of autosomal dominant spastic paraplegia.

    PubMed

    Hazan, J; Fonknechten, N; Mavel, D; Paternotte, C; Samson, D; Artiguenave, F; Davoine, C S; Cruaud, C; Dürr, A; Wincker, P; Brottier, P; Cattolico, L; Barbe, V; Burgunder, J M; Prud'homme, J F; Brice, A; Fontaine, B; Heilig, B; Weissenbach, J

    1999-11-01

    Autosomal dominant hereditary spastic paraplegia (AD-HSP) is a genetically heterogeneous neurodegenerative disorder characterized by progressive spasticity of the lower limbs. Among the four loci causing AD-HSP identified so far, the SPG4 locus at chromosome 2p2-1p22 has been shown to account for 40-50% of all AD-HSP families. Using a positional cloning strategy based on obtaining sequence of the entire SPG4 interval, we identified a candidate gene encoding a new member of the AAA protein family, which we named spastin. Sequence analysis of this gene in seven SPG4-linked pedigrees revealed several DNA modifications, including missense, nonsense and splice-site mutations. Both SPG4 and its mouse orthologue were shown to be expressed early and ubiquitously in fetal and adult tissues. The sequence homologies and putative subcellular localization of spastin suggest that this ATPase is involved in the assembly or function of nuclear protein complexes. PMID:10610178

  15. Bluish discolouration of urine drainage tube and bag in a female patient with spina bifida, paraplegia, and suprapubic cystostomy.

    PubMed

    Vaidyanathan, Subramanian; Soni, Bakul M

    2007-01-01

    We present a female patient with spina bifida, paraplegia, suprapubic cystostomy, and chronic constipation, who became anxious when she noticed a bluish discolouration of her urine drainage system. Urine microbiology revealed growth of Providencia stuartii and Staphylococcus aureus. There were no systemic features of infection and, therefore, antibiotics were not prescribed for asymptomatic bacteriuria. This patient was advised to change the urine bag every day, and was prescribed senna to facilitate bowel evacuation. She was reassured that bluish discolouration of the urine drainage tube and bag was a transient, benign phenomenon and not indicative of any underlying pathology. Over the next 7 days, the bluish discolouration gradually faded away. Clinical characteristics of patients who are likely to develop this phenomenon and the underlying biochemical mechanism for bluish discolouration of the urine drainage system are discussed in brief. PMID:17619789

  16. 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; Schls, Ludger; Kessels, Michael; Braulke, Thomas; Qualmann, Britta; Kurth, Ingo; Beetz, Christian; Hbner, 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

  17. 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; Schls, Ludger; Kessels, Michael; Braulke, Thomas; Qualmann, Britta; Kurth, Ingo; Beetz, Christian; Hbner, 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

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

    PubMed Central

    2014-01-01

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

  19. [An autopsy case of complicated form of spastic paraplegia with amyotrophy, mental deficiency, sensory impairment, and parkinsonism].

    PubMed

    Iwabuchi, K; Yagishita, S; Amano, N; Yokoi, S; Honda, H; Tanabe, T; Kinoshita, J; Kosaka, K

    1990-11-01

    An autopsied case of complicated form of spastic paraplegia with many unusual clinical and pathological features is reported. Present case: a 31-year-old male. His parents are first cousins. Pregnancy and delivery had been unremarkable. Though he was mentally retarded, his physical development was normal. He was considered normal until age 10. He suffered from progressive disturbance in gait at the age of 11. He could not walk without assistance at the age of 22. Neurological examination revealed the following findings. He was obese and mentally deteriorated. Spastic paraplegia with increased tendon reflexes and pathological reflexes was prominent. Though slight sensory disturbance was present in the lower extremities, neither involuntary movement nor cerebellar ataxia was observed. In the age of late 20's, dementia, general muscular atrophy, and Parkinsonism developed. At the age of 30, he could not move by himself. He was apathic and indifferent, and showed forced laughing. Muscle tonus was flaccid because of general muscular atrophy and peripheral neuropathy. He died of acute gastric enlargement. Neuropathological findings were characterized by mal-development of the central nervous system (CNS) and the multisystem degeneration. There existed cerebral white matter hypoplasia with hypogenesis of the corpus callosum and ectopia of neurons of the cerebral and cerebellar cortex. Hypoplasia of melanin pigment was also observed in the remaining neurons of the substantia nigra and the locus ceruleus. Many neurons in the CNS included lipofuscin granules of variable shapes. Some of them showed clusters of several block-like inclusions which were green with luxol fast blue and cresyl violet stain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2076353

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

    PubMed Central

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

    2015-01-01

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

  1. Factors associated with recovery from paraplegia in dogs with loss of pain perception in the pelvic limbs following intervertebral disk herniation.

    PubMed

    Jeffery, Nick D; Barker, Andrew K; Hu, Hilary Z; Alcott, Cody J; Kraus, Karl H; Scanlin, Elizabeth M; Granger, Nicolas; Levine, Jonathan M

    2016-02-15

    OBJECTIVE To investigate associations between recovery of locomotion and putative prognostic factors in dogs with loss of deep pain perception in the pelvic limbs caused by intervertebral disk herniation (IVDH). DESIGN Prospective cohort study. ANIMALS 78 client-owned dogs evaluated for IVDH that underwent spinal decompression surgery. PROCEDURES Dogs with complete loss of deep pain perception in the pelvic limbs and tail underwent routine examinations, advanced imaging, and spinal decompression surgery in accordance with standards of practice and owner consent. For each dog, information was prospectively collected on duration of clinical signs prior to onset of paraplegia; delay between onset of paraplegia and initial referral evaluation; date of recovery of locomotion, death, or euthanasia (3-month follow-up period); and whether dogs had received corticosteroid drugs before surgery. Severity of spinal cord compression at the lesion epicenter was measured via CT or MRI. RESULTS 45 of 78 (58%) of dogs recovered the ability to ambulate independently within 3 months after spinal decompression surgery. No evidence of prognostic value was identified for any of the investigated factors; importantly, a greater delay between onset of paraplegia and referral evaluation was not associated with a poorer prognosis. CONCLUSIONS AND CLINICAL RELEVANCE In this group of dogs with IVDH, immediacy of surgical treatment had no apparent association with outcome. The prognosis for recovery may instead be strongly influenced by the precise nature of the initiating injury. PMID:26829270

  2. 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.

  3. Emergency closed reduction of a c4/5 fracture dislocation with complete paraplegia resulting in profound neurologic recovery.

    PubMed

    Müller, Christian W; Decker, Sebastian; Thietje, Roland; Krettek, Christian

    2013-01-01

    Introduction. Cervical spinal cord injuries due to traumatic fractures are associated with persistent neurological deficits. Although clinical evidence is weak, early decompression, defined as <24-72 h, has been frequently proposed. Animal studies show better outcomes after early decompression within one hour or less, which can hardly ever be achieved in clinical practice. Case Presentation. A 37-year-old patient was hospitalized after being hit by a shying horse. After diagnosis of C4/5 fracture dislocation and complete paraplegia, she was intubated and sedated with deep relaxation. Emergency reduction was performed at approximately 120 minutes after trauma. Subsequently, a standard anterior decompression, discectomy, and fusion were carried out. She was then transferred to a specialized rehabilitation hospital. Her neurologic function improved from AIS grade A on admission to grade B postoperatively and grade D after four months of rehabilitation. One year after the accident, she was ambulatory without walking aids and restarted horse riding. Discussion and Conclusion. Rarely in clinical practice, decompression of the spine canal can be performed as early as in this case. This case highlights the potential benefit of utmost early reduction in cervical fracture dislocations with compression of the spinal cord. PMID:24151573

  4. Emergency Closed Reduction of a C4/5 Fracture Dislocation with Complete Paraplegia Resulting in Profound Neurologic Recovery

    PubMed Central

    Mller, Christian W.; Decker, Sebastian; Thietje, Roland; Krettek, Christian

    2013-01-01

    Introduction. Cervical spinal cord injuries due to traumatic fractures are associated with persistent neurological deficits. Although clinical evidence is weak, early decompression, defined as <2472?h, has been frequently proposed. Animal studies show better outcomes after early decompression within one hour or less, which can hardly ever be achieved in clinical practice. Case Presentation. A 37-year-old patient was hospitalized after being hit by a shying horse. After diagnosis of C4/5 fracture dislocation and complete paraplegia, she was intubated and sedated with deep relaxation. Emergency reduction was performed at approximately 120 minutes after trauma. Subsequently, a standard anterior decompression, discectomy, and fusion were carried out. She was then transferred to a specialized rehabilitation hospital. Her neurologic function improved from AIS grade A on admission to grade B postoperatively and grade D after four months of rehabilitation. One year after the accident, she was ambulatory without walking aids and restarted horse riding. Discussion and Conclusion. Rarely in clinical practice, decompression of the spine canal can be performed as early as in this case. This case highlights the potential benefit of utmost early reduction in cervical fracture dislocations with compression of the spinal cord. PMID:24151573

  5. Unusual Presentation of a Primary Ewings Sarcoma of the Spine with Paraplegia: A Case Report

    PubMed Central

    Sundarapandian, Rajkumar Jayachandran; Surulivel, Vignesh Jayabalan

    2015-01-01

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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2015-09-11

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

  8. Acute ascending motoric paraplegia following intrathecal chemotherapy for treatment of acute lymphoblastic leukemia in children: case reports and review of the literature.

    PubMed

    Rolf, N; Boehm, H; Kaindl, A M; Lauterbach, I; Suttorp, M

    2006-01-01

    Severe side effects of chemotherapy in pediatric patients with acute lymphoblastic leukemia are rare, but well-known. We present two pediatric patients who developed ascending motoric paraplegia (AMP) following intrathecal chemotherapy. Both patients suffered from progressive weakness of their lower extremities, neurogenic bladder dysfunction, autonomous neural dysregulation and minor sensory deficits. Despite an initially similar clinical picture, progression and outcome were fairly different. There is convincing evidence that AMP is caused by spinal cord toxicity of intrathecally applied toxic agents such as cytarabin and/or methotrexate leading to spinal demyelinisation as demonstrated by elevated myelin basic protein in cerebrospinal fluid. PMID:17080338

  9. Mutational analysis of the CYP7B1, PNPLA6 and C19orf12 genes in autosomal recessive hereditary spastic paraplegia.

    PubMed

    Schubert, Sarah F; Hoffjan, Sabine; Dekomien, Gabriele

    2016-02-01

    The hereditary spastic paraplegias (HSPs) comprise a group of genetically heterogeneous neurodegenerative diseases. Here, we evaluated the spectrum and frequency of mutations in the CYP7B1, PNPLA6 and C19orf12 genes (causative for the subtypes SPG5A, SPG39 and SPG43, respectively) in a cohort of 63 unrelated HSP patients with suspected autosomal recessive inheritance. Two novel homozygous mutations (one frameshift and one missense mutation) were detected in CYP7B1 (SPG5A), while no disease-causing mutation was identified for SPG39 or SPG43. PMID:26714052

  10. Exceptional results in neuroendocrine-metastases-caused paraplegia treated with [90Y-DOTA]-D-Phe1-Tyr3-octreotide (90Y-DOTATOC), a radiolabelled somatostatin analogue.

    PubMed

    Waldherr, C; Haldemann, A; Maecke, H R; Crazzolara, A; Mueller-Brand, J

    2000-01-01

    The case history is presented of a patient with paraplegia caused by progressive spinal cord compression due to bone metastases of a neuroendocrine pulmonary tumour. After failed external radiotherapy, the patient received targeted internal radiotherapy administered as a fractionated treatment with intravenous injections of a total of 7400 MBq/m2 of [90YDOTA]-D-Phe1-Tyr3-octreotide (90Y-DOTATOC), a radiolabelled somatostatin analogue. This case history highlights the value of 90Y-DOTATOC in the treatment of neuroendocrine tumours and the importance and possibility of good palliation of neuroendocrine bone metastases. PMID:10853753

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

    PubMed

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

    2015-12-15

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

  12. Hereditary Spastic Paraplegia

    MedlinePLUS

    ... NINDS Funding Information Research Programs Training & Career Awards Enhancing Diversity Find People About NINDS NINDS Hereditary Spastic ... Funding | News From NINDS | Find People | Training | Research | Enhancing Diversity Careers@NINDS | FOIA | Accessibility Policy | Contact Us | ...

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

    SciTech Connect

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

    1995-01-01

    Three large pedigrees of Germany descent with autosomal dominant {open_quotes}pure{close_quotes} 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 pedigree D and S, the gene locus could be excluded from the whole FSP1 region, confirming the locus heterogeneity of autosomal dominant FSP. 11 refs., 2 figs., 2 tabs.

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

    PubMed Central

    Thal, Dietmar R.; Zchner, Stephan; Gierer, Stephan; Schulte, Claudia; Schls, Ludger; Schle, Rebecca; Synofzik, Matthis

    2015-01-01

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

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

    PubMed

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

    2014-12-15

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

  16. Inactivation of the hereditary spastic paraplegia-associated Hspd1 gene encoding the Hsp60 chaperone results in early embryonic lethality in mice

    PubMed Central

    Nielsen, Marit N.; Hansen, Jakob; Füchtbauer, Annette; Füchtbauer, Ernst-Martin; West, Mark; Corydon, Thomas J.; Gregersen, Niels; Bross, Peter

    2010-01-01

    The mitochondrial Hsp60 chaperonin plays an important role in sustaining cellular viability. Its dysfunction is related to inherited forms of the human diseases spastic paraplegia and hypomyelinating leukodystrophy. However, it is unknown whether the requirement for Hsp60 is neuron specific or whether a complete loss of the protein will impair mammalian development and postnatal survival. In this study, we describe the generation and characterization of a mutant mouse line bearing an inactivating gene-trap insertion in the Hspd1 gene encoding Hsp60. We found that heterozygous mice were born at the expected ratio compared to wild-type mice and displayed no obvious phenotype deficits. Using quantitative reverse transcription PCR, we found significantly decreased levels of the Hspd1 transcript in all of the tissues examined, demonstrating that the inactivation of the Hspd1 gene is efficient. By Western blot analysis, we found that the amount of Hsp60 protein, compared to either cytosolic tubulin or mitochondrial voltage-dependent anion-selective channel protein 1/porin, was decreased as well. The expression of the nearby Hspe1 gene, which encodes the Hsp10 co-chaperonin, was concomitantly down regulated in the liver, and the protein levels in all tissues except the brain were reduced. Homozygous Hspd1 mutant embryos, however, died shortly after implantation (day 6.5 to 7.5 of gestation, Theiler stages 9–10). Our results demonstrate that Hspd1 is an essential gene for early embryonic development in mice, while reducing the amount of Hsp60 by inactivation of one allele of the gene is compatible with survival to term as well as postnatal life. PMID:20393889

  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. PMID:25552650

  18. Measurement of peripheral muscle resistance in rats with chronic ischemia-induced paraplegia or morphine-induced rigidity using a semi-automated computer-controlled muscle resistance meter.

    PubMed

    Marsala, Martin; Hefferan, Michael P; Kakinohana, Osamu; Nakamura, Seiya; Marsala, Jozef; Tomori, Zoltan

    2005-11-01

    In experimental and clinical studies, an objective assessment of peripheral muscle resistance represents one of the key elements in determining the efficacy of therapeutic manipulations (e.g. pharmacological, surgical) aimed to ameliorate clinical signs of spasticity and/or rigidity. In the present study, we characterize a newly developed limb flexion resistance meter which permits a semi-automated, computer-controlled measurement of peripheral muscle resistance (PMR) in the lower extremities during a forced flexion of the ankle in the awake rat. Ischemic paraplegia was induced in Sprague-Dawley rats by transient aortic occlusion (10 min) in combination with systemic hypotension (40 mm Hg). After ischemia the presence of spasticity component was determined by the presence of an exaggerated EMG activity recorded from gastrocnemius muscle after nociceptive or proprioceptive afferent activation and by velocity-dependent increase in muscle resistance. Rigidity was induced by high dose (30 mg/kg, i.p.) of morphine. Animals with defined ischemic spasticity or morphine-induced rigidity were then placed into a plastic restrainer and a hind paw attached by a tape to a metal plate driven by a computer-controlled stepping motor equipped with a resistance transducer. The resistance of the ankle to rotation was measured under several testing paradigms: (i) variable degree of ankle flexion (40 degrees, 50 degrees, and 60 degrees), (ii) variable speed/rate of ankle flexion (2, 3, and 4 sec), (iii) the effect of inhalation anesthesia, (iv) the effect of intrathecal baclofen, (v) the effect of dorsal L2-L5 rhizotomy, or (vi) systemic naloxone treatment. In animals with ischemic paraplegia an increased EMG response after peripheral nociceptive or proprioceptive activation was measured. In control animals average muscle resistance was 78 mN and was significantly increased in animals with ischemic spasticity (981-7900 mN). In ischemic-spastic animals a significant increase in measured muscle resistance was seen after increased velocity (4 > 3 > 2 sec) and the angle (40 degrees > 50 degrees > 60 degrees) of the ankle rotation. In spastic animals, deep halothane anesthesia, intrathecal baclofen or dorsal rhizotomy decreased muscle resistance to 39-80% of pretreatment values. Systemic treatment with morphine induced muscle rigidity and corresponding increase in muscle resistance. Morphine-induced increase in muscle resistance was independent on the velocity of the ankle rotation and was reversed by naloxone. These data show that by using this system it is possible to objectively measure the degree of peripheral muscle resistance. The use of this system may represent a simple and effective experimental tool in screening new pharmacological compounds and/or surgical manipulations targeted to modulate spasticity and/or rigidity after a variety of neurological disorders such as spinal cord traumatic or ischemic injury, multiple sclerosis, cerebral palsy, or Parkinson's disease. PMID:16305323

  19. Successful pregnancy in a woman with paraplegia

    PubMed Central

    Castro, Jorge Santos; Lourenço, Cátia; Carrilho, Marcelina

    2014-01-01

    Pregnancy is a rare occurrence in patients suffering from spinal cord injury (SCI). Pregnancy in these patients presents unique challenges to obstetric care providers, who need to become familiar with the general principles of care in this setting. SCI alters the function of multiple organ systems and chronic medical conditions are common in this patient population. Certain medical complications such as urinary tract infections and autonomic hyper-reflexia, or autonomic dysreflexia, are expectable and can be managed successfully. A multidisciplinary team should care for delivery in these patients. The authors present a case of a pregnancy in a paraplegic woman whose lesion was at the level of T4. She received epidural analgesia and had a caesarian section. From this case, the authors aim to point out the specific concerns of the management of pregnancy and delivery in this setting emphasising the importance of a multidisciplinary team, specially obstetricians and anaesthetists. PMID:24671318

  20. Genetics Home Reference: Spastic paraplegia type 15

    MedlinePLUS

    ... the left and right halves of the brain (corpus callosum) is abnormally thin and becomes thinner over time. ... bradykinesia ; breakdown ; cell ; cell division ; cerebellum ; cerebral cortex ; corpus callosum ; cytokinesis ; disability ; gene ; hereditary ; hypotonia ; inherited ; macula ; motor ; ...

  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. 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 ...

  3. Genetics Home Reference: Spastic paraplegia type 7

    MedlinePLUS

    ... The m-AAA protease is responsible for assembling ribosomes (cellular structures that process the cell's genetic instructions ... system ; pes cavus ; phosphorylation ; prevalence ; protease ; protein ; recessive ; ribosomes ; scoliosis ; sensory cells ; sensory neuropathy ; spasticity ; wasting You ...

  4. Genetics Home Reference: Spastic paraplegia type 15

    MedlinePLUS

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

  5. 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 ...

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

    PubMed Central

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

    2014-01-01

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

  7. 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.

  8. 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

  9. A new case of cervical intramedullary sinus histiocytosis causing paraplegia and review of the literature

    PubMed Central

    Rocha-Maguey, Jesús; Felix-Torrontegui, José-Angel; Cabrera-López, Myriam; Gutiérrez-Castro, Macrina; Montante-Montes de Oca, Daniel

    2016-01-01

    Background: Rosai–Dorfman disease (RDD) is an uncommon, benign histiocytic proliferative disorder of unknown origin. It predominantly affects the lymph nodes, but can also be found extranodal in different organs. Nervous system involvement is rare, and the most cases are intracranial. Surgical treatment is indicated when the central nervous system (CNS) in compromised. Case Description: We herein describe the management of a 27-year-old woman who presented progressive spinal cord symptoms, secondary to an isolated intramedullary lesion, which had a histological confirmation of RDD. To our knowledge, this is the 6th case reported in English written manuscripts. We review these cases and analyze some of the literature concerning the disease. Conclusions: RDD shows some variability in the involvement of the entire neuraxis, and because its ability to mimic meningeal and primary brain tumors, it is essential to be aware of this entity and consider RDD in the differential diagnosis of various lesions of the CNS. The conclusive diagnosis must be obtained by histological methods, so surgical approaches have to be discussed. Although it is not considered as a malignancy, options for postoperative medical treatment are variable and include radiation, chemotherapy or maybe monoclonal antibodies for refractory or recurrent cases. PMID:26862448

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

    PubMed Central

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

    2013-01-01

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

  11. 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

  12. I Cant Walk! Acute Thrombosis of Descending Aorta Causing Paraplegia

    PubMed Central

    Mitchell, Matthew L.; Yucebey, Elif; Weaver, Mitchell R.; Jaehne, A. Kathrin; Rivers, Emanuel P.

    2013-01-01

    A 50-year-old man presented to the emergency department (ED) with acute, bilateral lower extremity weakness and loss of sensation, as well as absent pulses bilaterally. Computed tomography angiography showed complete occlusion of the aorta below the inferior mesenteric artery, extending to the iliac bifurcations. Echocardiographic findings showed severe systolic dysfunction (ejection fraction of 15%) and cryptic cardiogenic shock in spite of stable vital signs. Prior to early operative intervention, an early goal-oriented hemodynamic strategy of shock management resulted in the resolution of motor and sensory deficits.After definitive surgical intervention, the patient was discharged neurologically intact. Acute aortic occlusion is frequently accompanied by myocardial dysfunction, which can be from mild to severe. The most severe form can even occur with normal vital signs or occult cardiogenic shock. Early detection and goal-directed preoperative hemodynamic optimization, along with surgical intervention in the ED, is required to optimize outcomes. PMID:24106532

  13. Interference of Different Types of Seats on Postural Control System during a Forward-Reaching Task in Individuals with Paraplegia

    ERIC Educational Resources Information Center

    de Abreu, Daniela Cristina Carvalho; Takara, Kelly; Metring, Nathalia Lopes; Reis, Julia Guimaraes; Cliquet, Alberto, Jr.

    2012-01-01

    We aimed to evaluate the influence of different types of wheelchair seats on paraplegic individuals' postural control using a maximum anterior reaching test. Balance evaluations during 50, 75, and 90% of each individual's maximum reach in the forward direction using two different cushions on seat (one foam and one gel) and a no-cushion condition…

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

    PubMed Central

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

    2013-01-01

    Objective To use vertical ground reaction force (vGRF) to show the magnitude and pattern of mechanical loading in persons with spinal cord injury (SCI) during powered exoskeleton-assisted walking. Research design A cross-sectional study was performed to analyze vGRF during powered exoskeleton-assisted walking (ReWalk: Argo Medical Technologies, Inc, Marlborough, MA, USA) compared with vGRF of able-bodied gait. Setting Veterans Affairs Medical Center. Participants Six persons with thoracic motor-complete SCI (T1T11 AIS A/B) and three age-, height-, weight- and gender-matched able-bodied volunteers participated. Interventions SCI participants were trained to ambulate over ground using a ReWalk. vGRF was recorded using the F-Scan system (TekScan, Boston, MA, USA). Outcome measures Peak stance average (PSA) was computed from vGRF and normalized across all participants by percent body weight. Peak vGRF was determined for heel strike, mid-stance, and toe-off. Relative linear impulse and harmonic analysis provided quantitative support for analysis of powered exoskeletal gait. Results Participants with motor-complete SCI, ambulating independently with a ReWalk, demonstrated mechanical loading magnitudes and patterns similar to able-bodied gait. Harmonic analysis of PSA profile by Fourier transform contrasted frequency of stance phase gait components between able-bodied and powered exoskeleton-assisted walking. Conclusion Powered exoskeleton-assisted walking in persons with motor-complete SCI generated vGRF similar in magnitude and pattern to that of able-bodied walking. This suggests the potential for powered exoskeleton-assisted walking to provide a mechanism for mechanical loading to the lower extremities. vGRF profile can be used to examine both magnitude of loading and gait mechanics of powered exoskeleton-assisted walking among participants of different weight, gait speed, and level of assist. PMID:23820147

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

    PubMed

    Kobravi, Hamid-Reza; Erfanian, Abbas

    2012-01-01

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

  16. Self-directed EMG training for the control of pain and spasticity in paraplegia: a case study.

    PubMed

    Bodenhamer, E; Coleman, C; Achterberg, J

    1986-09-01

    A 25-year-old paraplegic woman was able to gain control of her debilitating leg and bladder spasms and abdominal pain using self-directed EMG biofeedback. The case is significant in that she previously had only cursory exposure to biofeedback as an undergraduate student and received only minimal support and direction from an instructor. She proceeded through daily home practice using a borrowed EMG unit and audiotapes from Lester Fehmi's Open Focus series. Records were kept of the frequency and intensity of her pain and spasms, as well as the frequency and procedures of her home practice. She also maintained a record of specific psychosocial events in her life, which, over time, showed a strong, consistent pattern of influence on the recurrence and severity of her symptoms. The woman's physician declared her medical progress remarkable and encouraged her biofeedback work. At 2-year follow-up, she remains virtually symptom- and medication-free. Her successful biofeedback training program provides support for the value of client-directed biofeedback in selected cases. PMID:3607087

  17. 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

  18. 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

  19. 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

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

    ERIC Educational Resources Information Center

    Davis, Kay

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

  1. The spectrum of "complicated spastic paraplegia, MASA syndrome and X-linked hydrocephalus". Contribution of DNA linkage analysis in genetic counseling of individual families.

    PubMed

    Schrander-Stumpel, C; Meyer, H; Merckx, D; Jones, M; Israel, J; Sommer, A; Stevens, C; Tinschert, S; Wilson, G; Willems, P

    1994-01-01

    X-linked hydrocephalus and the X-linked MASA syndrome (Mental retardation. Adducted thumbs, Shuffling gait and Aphasia) both have a variable clinical spectrum with great overlap. Data from DNA linkage analysis placed the locus for both conditions at Xq28. On clinical and molecular grounds it has been hypothesized that both MASA syndrome and X-linked hydrocephalus are caused by a mutation in the same gene at Xq28. There is no significant clinical marker in the obligate female carriers and prenatal diagnosis by ultrasound is not reliable; DNA analysis can offer an improved genetic counseling for the families and more reliable prenatal diagnosis. In the gene encoding for Ll, a neural cell adhesion molecule and located at Xq28, several different mutations have been reported in X-linked hydrocephalus families and in a MASA family. We report data on DNA linkage analysis in 6 families with X-linked hydrocephalus/MASA syndrome. These data illustrate the importance of DNA linkage analysis in the individual family; they also show, however, the problem of studying small families. Genetic heterogeneity cannot be excluded. PMID:8031529

  2. 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

  3. Genetics Home Reference: Fatty acid hydroxylase-associated neurodegeneration

    MedlinePLUS

    ... may have a loss of sharp vision (reduced visual acuity), decreased field of vision, impaired color perception, ... paraplegia ; perception ; pneumonia ; pyramidal tract ; recessive ; spasticity ; strabismus ; visual acuity ; white matter You may find definitions for ...

  4. Genetics Home Reference: Paralysis

    MedlinePLUS

    ... paraplegia type 8 Troyer syndrome You may also search Genetics Home Reference for ... a page outside Genetics Home Reference. Links to web sites outside the Federal Government do not constitute ...

  5. Guide to Surgical Specialists

    MedlinePLUS

    ... Cancer Liaison Program Commission on Cancer National Cancer Data Base Oncology Medical Home Accreditation Pilot Program Stereotactic Breast ... central or peripheral nervous system lesions such as cerebral palsy, paraplegia, or stroke, as well as conditions that ...

  6. Genetics Home Reference: Troyer syndrome

    MedlinePLUS

    ... Hereditary spastic paraplegias are divided into two types: pure and complex. The pure types involve the lower limbs. The complex types ... testing , particularly the difference between clinical tests and research tests . To locate a healthcare provider, see How ...

  7. Genetics Home Reference: Mitochondrial membrane protein-associated neurodegeneration

    MedlinePLUS

    ... visual information from the eyes to the brain (optic atrophy), which can impair vision; problems with speech (dysarthria); ... trembling ; iron ; lipid ; mitochondria ; mutation ; nervous system ; neurological ; optic atrophy ; paraplegia ; parkinsonism ; protein ; recessive ; spasticity You may find ...

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

    PubMed Central

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

    2015-01-01

    Objective Examine psychosocial outcomes of youth with spinal cord injury (SCI) as a function of neurological level (paraplegia/tetraplegia) and severity (American Spinal Injury Association (ASIA) Impairment Scale (AIS)). Design Survey research. Setting Three pediatric SCI specialty centers in the USA. Participants Youth with SCI ages 518 with neurological impairment classifications of: tetraplegia AIS ABC (tetraplegia ABC), paraplegia AIS ABC (paraplegia ABC), or AIS D. Outcome Measures Children's Assessment of Participation and Enjoyment, Pediatric Quality of Life Inventory, Revised Children's Manifest Anxiety Scale, and Children's Depression Inventory. Results Three hundred and forty youth participated; 57% were male; 60% were Caucasian, 21% Hispanic, 7% African-American, 2% Native American, and 3% reported other. Their mean age was 8.15 years (standard deviation (SD)=5.84) at injury and 13.18 years (SD=3.87) at interview. Ninety-six youth (28%) had tetraplegia ABC injuries, 191 (56%) paraplegia ABC injuries, and 53 (16%) AIS D injuries. Neurological impairment was significantly related to participation and quality of life (QOL). Specifically, youth with paraplegia ABC and AIS D injuries participated in more activities than youth with tetraplegia ABC (P=0.002; P=0.018, respectively) and youth with paraplegia ABC participated more often than youth with tetraplegia ABC (P=0.006). Youth with paraplegia ABC reported higher social QOL than youth with tetraplegia ABC (P=0.001) and AIS D injuries (P=0.002). Groups did not differ regarding mental health. Conclusion Interventions should target youth with tetraplegia ABC, as they may need support in terms of participation, and both youth with tetraplegia ABC and AIS D injuries in terms of social integration. PMID:24621027

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

    PubMed

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

    2015-01-01

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

  10. 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.

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

    PubMed

    Silver, John R; Weiner, M-F

    2013-05-01

    Two centuries ago, electricity was being used for the treatment of paraplegia and trials were taking place in France. This study aims to identify cases of traumatic paraplegia treated with electricity in the 19th century in order to assess the therapeutic benefit. Only four such cases were identified, none with a complete transection of the spinal cord since these patients would have died from pressure sores and urinary tract infections. The personalities involved, William Gull, William Erb, Guillaume Duchenne and Cyril Henry Golding Bird are portrayed and contemporaneous views on electrotherapy analysed. While the four patients apparently benefited from the treatment, the lack of follow-up and the incomplete data prevented a definitive conclusion on the therapeutic value of electrical treatment in traumatic paraplegia. PMID:24585746

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

    PubMed

    Houtman, S; Oeseburg, B; Hughson, R L; Hopman, M T

    2000-08-01

    The relationship between sympathetic nervous system activity and cardiovascular responses to head-up tilt in patients with spinal cord injuries and in able-bodied subjects was studied. Twenty-seven adults, nine in each of the three groups (tetraplegia, paraplegia, and able-bodied subjects) were tilted 70 degrees, head up, for 12 minutes after 20 minutes supine rest. Differences between steady-state measurements of mean arterial pressure, stroke volume, and sympathetic nervous system activity were estimated in both positions. Sympathetic nervous system activity was reflected by the low-frequency peak of the blood pressure variability spectrum. From supine rest to head-up tilt, low-frequency power increased in able-bodied subjects (median, 0.42 mm Hg2, p = 0.003), which was different (p = 0.015) from patients with tetraplegia and paraplegia (-0.15 and -0.10 mm Hg2, respectively). Stroke volume and mean arterial pressure decreased in patients with tetraplegia (-40% and -9 mm Hg, respectively; p = 0.008, both variables) more than in able-bodied subjects (-33%, 11 mm Hg, respectively) or patients with paraplegia (-24%, 8 mm Hg, respectively). Results indicated increased sympathetic nervous system activity during head-up tilt in able-bodied subjects, but not in patients with paraplegia or tetraplegia, whereas patients with tetraplegia, but not paraplegia, showed poorer cardiovascular homeostasis than able-bodied subjects. This suggests that patients with paraplegia maintained cardiovascular homeostasis during head-up tilt without increased sympathetic nervous system activity. PMID:11029019

  13. Subacute post-traumatic ascending myelopathy (SPAM): two cases of SPAM following surgical treatment of thoracolumbar fractures.

    PubMed

    Farooque, Kamran; Kandwal, Pankaj; Gupta, Ankit

    2014-01-01

    To report two cases of traumatic paraplegia who developed Sub-acute Post-Traumatic Ascending Myelopathy (SPAM) following surgical decompression.We hereby report two cases (both 35yr old male) with traumatic paraplegia that developed ascending weakness at 3rd and 5th Post-Op day respectively following surgical decompression. Both the patients experienced remarkable improvement in Neurology after treatment with steroids. The authors conclude by emphasizing on minimum cord handling during surgical decompression of the spinal cord to avoid this potentially life threatening complication. PMID:24823733

  14. [Renal-rachidian venous trunk. Replacement of the left renal vein. A danger for the spinal cord (author's transl)].

    PubMed

    Frantz, P; Aboulker, P; Küss, R; Jardin, A

    1977-01-01

    In two cases of paraplegia due to an inondation of the intrarachidian plexus by venous blood from the left venal vein, we studied the frequency with which the renal-rachidian trunk connected the left renal vein and the intrarachidian plexus. We show in these rare cases how it is possible, with a simple procedure, the ligature of the renal-rachidian trunk, to bring about a marked regression in the paraplegia. This procedure has been carried out five times, and it should be seen within the wider framework of a serie of procedures on the cava system, which are now practised for more than forty years. PMID:599610

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

    ERIC Educational Resources Information Center

    Bross, Michael H.; Spellicy, Martin J.

    1994-01-01

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

  16. Acute pneumococcal myelitis in an adult patient.

    PubMed

    Vikovi?, Klaudija; Mustapi?, Matej; Kutlea, Marko; Lepur, Dragan

    2014-04-01

    Pneumococcal meningitis represents the most severe community-acquired bacterial meningitis. The disease is frequently associated with various complications. We present a case of pneumococcal meningitis in an immunocompetent adult patient treated with hypothermia. The disease course was complicated with severe myelitis and consequent paraplegia which is an extremely rare complication of pneumococcal disease. PMID:24926167

  17. 16 CFR 1116.2 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... including coma and spinal cord injuries; (v) Paraplegia, quadriplegia, or permanent paralysis or paresis, to... January 1, 1993 and ends on December 31, 1994, and so forth. (b) Grievous bodily injury includes, but is not limited to, any of the following categories of injury: (1) Mutilation or...

  18. 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).…

  19. 34 CFR 373.4 - What definitions apply?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...), paraplegia, quadriplegia and other spinal cord conditions, sickle-cell anemia, specific learning disabilities... HIV. (b) Individuals in the acute stages of injury or illness, including, but not limited to, diabetes, traumatic brain injury, stroke, burns, or amputation. (Authority: 29 U.S.C. 711(c)) Employment outcome...

  20. 34 CFR 377.5 - What definitions apply?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... stroke and epilepsy), spinal cord conditions (including paraplegia and quadriplegia), sickle cell anemia..., autism, blindness, burn injury, cancer, cerebral palsy, cystic fibrosis, deafness, head injury, heart... this part are defined in 34 CFR 77.1: Applicant Application Award Budget period Department...

  1. 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).

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

    PubMed

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

    1975-01-01

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

  3. 78 FR 12264 - Criteria for a Catastrophically Disabled Determination for Purposes of Enrollment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-22

    ..., 344.03, 344.04, 3.44.09), paraplegia (ICD-9-CM Code 344.1), blindness (ICD-9-CM Code 369.4...) through (e)(1)(xviii). In addition, we would replace the word ``blindness'' with ``legal blindness defined....'' The term ``blindness'' in and of itself is ambiguous. The regulation associates ``blindness'' with...

  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. Complete absence of evening melatonin increase in tetraplegics.

    PubMed

    Verheggen, Rebecca J H M; Jones, Helen; Nyakayiru, Jean; Thompson, Andrew; Groothuis, Jan T; Atkinson, Greg; Hopman, Maria T E; Thijssen, Dick H J

    2012-07-01

    Individuals with a spinal cord injury (SCI), especially with tetraplegia, experience poor sleep quality, and this may be related to impaired control of circadian rhythmicity. Here, we examined the evening onset of melatonin secretion, an important hormone for the initiation of sleep, in people with a complete cervical (tetraplegia) and thoracic (paraplegia) SCI, and age- and sex-matched able-bodied control participants. Multiple samples of salivary melatonin were obtained during the evening hours and analyzed by ELISA methods in 10 control partcipants, 9 individuals with paraplegia, and 6 individuals with tetraplegia. Sleep quality was assessed using questionnaires. Interactive effects of group and time were found for melatonin levels (P=0.022). In the control and paraplegia groups, the mean melatonin level increased significantly from 2.59 ± 1.04 and 4.28 ± 3.28 pg/ml at 7 PM to 10.62 ± 4.59 and 13.10 ± 7.39 pg/ml at 11 PM, respectively (P<0.001). In the tetraplegia group, melatonin level was 5.25 ± 3.72 at 7 PM but only 2.41 ± 1.25 pg/ml at 11 PM (P>0.05). Decreased sleep quality was more prevalent in individuals with tetraplegia (83%) and paraplegia (75%) compared with controls (20%; P=0.02). Unlike in the control and paraplegia groups, the evening increase in melatonin concentration was completely absent in the tetraplegia group. This provides biological insight into sleep regulation in humans and provides better understanding of the poor sleep quality in people with tetraplegia. PMID:22474242

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

    PubMed Central

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

    2014-01-01

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

  7. Central serotonin receptor sensitivity in rats with experimental allergic encephalomyelitis.

    PubMed

    White, S R; Bieger, D

    1980-11-01

    Serotonin mediated bulbospinal motor activities were examined in rats with experimental allergic encephalomyelitis (EAE)-induced-paraplegia. Treatment with monoamine oxidase inhibitors and L-tryptophan failed to elicit the components of the serotonin syndrome which involved levels of the neuraxis manifesting flaccid paralysis. Straub tail, hindlimb abduction and hindlimb rigidity did not occur. The motor responses represented at spinal segments just above the level of paraplegia, lateral head weaving and forepaw treading, were present but altered in the diseased rats. No impairment was evident in the production of head tremor or hyper-reactivity to accoustic and tactile stimuli. Similarly, in urethane-anesthetized EAE rats, serotonergically-evoked automatic swallowing activity was unchanged as judged by the effects of serotonin receptor agonists, and a serotonin precursor, a reuptake blocker and an antagonist. Our data support the conclusion that EAE-induced impairment of serotonergic neurotransmission is correlated with motor deficits manfested during the acute paralytic stage of the disease. PMID:6969416

  8. 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

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

    PubMed Central

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

    1985-01-01

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

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

    PubMed

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

    1995-01-01

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

  11. 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

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

    PubMed Central

    CruzArmbulo, 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

  13. 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

  14. Pedicolaminar Fracture-Dislocation.

    PubMed

    Silverstein, Michael P; Vallurupalli, Santaram; Brigeman, Scott; Moore, Timothy A; Bancroft, Laura W

    2016-03-01

    A 28-year-old man presented to a level 1 trauma center with significant cervical spine pain after sliding into third base during a softball game. He struck his head on the thigh of the defensive player and had immediate pain in his neck and arm. He reported no loss of consciousness, no transient tetraplegia/paraplegia, and no loss of bowel and bladder control. After initial imaging, enhanced computed tomography scans were obtained. PMID:26881464

  15. Recurrent null mutation in SPG20 leads to Troyer syndrome.

    PubMed

    Tawamie, Hasan; Wohlleber, Eva; Uebe, Steffen; Schml, Christine; Nthen, Markus M; Abou Jamra, Rami

    2015-10-01

    Troyer syndrome is an autosomal recessive form of complex hereditary spastic paraplegia. To date, the disorder has only been described in the Amish and in kindred from Oman. In Amish, all affected individuals have a homozygous one nucleotide deletion; c.1110delA. In the Omani kindred, all affected have a homozygous two nucleotides deletion; c.364_365delTA (p.Met122ValfsTer2). Here we report the results of homozygosity mapping and whole exome sequencing in two siblings of a consanguineous Turkish family with mild intellectual disability, spastic paraplegia, and muscular dystrophy. We identified the same deletion that has been identified in the Omani kindred, but haplotype analysis suggests a recurrent event, and not a founder mutation. We summarize current knowledge of Troyer syndrome, and propose wider use of whole exome sequencing in routine diagnostics. This applies in particular to nonspecific phenotypes with high heterogeneity, such as spastic paraplegia, intellectual disability, and muscular dystrophy, since in such cases the assignment of a definite diagnosis is frequently delayed. PMID:26003402

  16. 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; Nrnberg, Gudrun; Altmller, Janine; Saxena, Renu; Chapman, Edwin R.; Dent, Erik W.; Nrnberg, 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

  17. GENE AND PROTEIN EXPRESSION ASSOCIATED WITH PROTEIN SYNTHESIS AND BREAKDOWN IN PARAPLEGIC SKELETAL MUSCLE

    PubMed Central

    DRUMMOND, MICAH J.; GLYNN, ERIN L.; LUJAN, HEIDI L.; DICARLO, STEPHEN E.; RASMUSSEN, BLAKE B.

    2009-01-01

    Spinal cord injury reduces the rate of skeletal muscle protein synthesis and increases protein breakdown, resulting in rapid muscle loss. The purpose of this study was to determine whether long-term paraplegia would eventually result in a downregulation of muscle mRNA and protein expression associated with both protein synthesis and breakdown. After 10 weeks of spinal cord transection, soleus muscle from 12 rats (6 sham-control, 6 paraplegic) was studied for mRNAs and proteins associated with protein synthesis and breakdown using real-time polymerase chain reaction and immunoblotting techniques. Protein kinase B (PKB/Akt), ribosomal S6 kinase 1 (S6K1), and myogenin mRNA were downregulated, whereas muscle ring finger 1 (MuRF1) and phospho-forkhead transcription factor 4 (FoxO4) protein were increased in paraplegic rats. We conclude that gene and protein expression of pathways associated with protein synthesis are reduced, whereas some markers of protein breakdown remain elevated following chronic paraplegia. Clinical interventions designed to increase muscle protein synthesis may be helpful in preventing excessive muscle loss during long-term paraplegia. PMID:18236467

  18. [Spinal cord infarction and recurrent venous thrombosis in association with estrogens and the 20210A allele of the prothrombin gene].

    PubMed

    González-Ordóñez, A J; Uria, D F; Ferreiro, D; Barragán, M J; Fernández-Carreira, J M; Fernández-Alvarez, C R; Peliz, M G; Alvarez, M V

    2001-11-01

    The acute spinal cord infarction is a rare cause of acute-onset paraplegia. Furthermore, it is specially uncommon that the infarction occurs in patients with apparent low predisposition to vascular disease. The 20210A allele of the prothrombin gene (causing a threefold-increased risk in venous thromboembolism) was recently associated with unexplained spinal cord infarction in young women under treatment with estrogens (contraceptive pill). We report a case of anterior spinal artery syndrome resulting from an ischaemic infarction at the anterior aspect of the spinal cord in a healthy 50-year-old woman, carrying this mutation, being the first published case under treatment with transdermal estradiol. She referred the typical sudden-onset back pain associated to clinical anterior spinal artery syndrome with sphincter dysfunction and nontraumatic paraplegia. A possible multiple sclerosis was ruled out and the steroids or immunoglobulin therapy induced no clinical improvement. Cerebrospinal fluid and other investigations were all negative. Sequential MRI scans revealed development of spinal cord infarction from T10 to T11, with increased signal in T2-weighted image (T2). Because she referred a previous thrombophlebitis and suffered a deep-vein thrombosis one month after paraplegia, a complete coagulation study was performed. Antithrombin, proteins C and S, homocysteine, factor V Leiden, lupus anticoagulant and anticardiolipin antibodies were all normal or negatives. In opposite, the 20210A variation was positive (heterozygous) and the factor VIIIc level was very high (280 U/dl eight months later). We argue the relative importance of both findings. The patient had no a substantial recovery over a period of 20 months.Certainly, the prothrombin 20210A seems to be associated with unexplained ischemic myelopathy among the young women with estrogens. PMID:11742625

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

    NASA Astrophysics Data System (ADS)

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

    2006-10-01

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

  20. 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

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

    PubMed

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

    2015-01-01

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

  2. [Surgical management of thoracic aortic lesions. Aneurysm, dissection and traumatic rupture].

    PubMed

    Schumacher, H; Bckler, D; Allenberg, J-R

    2004-09-01

    Surgical management of distinct thoracic aneurysmal lesions stands at the crossroads. Until recently, the only treatment options for thoracic aortic lesions were surgical repair or medical management. There is increasing evidence that endovascular therapy will be useful in treating thoracic aortic disease, possibly becoming the preferred approach. Endovascular surgery will affect the incidence of open thoracic aortic surgery not only by producing a lower mortality risk but also a significantly lower incidence of paraplegia. In designing adequate treatment options of complex and difficult-to-treat thoracic aortic lesions, novel three-dimensional imaging reconstructions are mandatory. PMID:15316640

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

    PubMed Central

    PIOMBINO, P.; ORABONA, G. DELLAVERSANA; ABBATE, V.; FINI, G.; LIBERATORE, G.M.; MICI, E.; BELLI, E.

    2013-01-01

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

  4. 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.

  5. 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.

  6. Spinal cord monitoring.

    PubMed

    Nuwer, M R

    1999-12-01

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

  7. [Case report: resuscitation of a hypothermic patient - "Nothing's like it seems!"].

    PubMed

    Manke, Florian; Keil, Thorsten

    2016-01-01

    We report about a prolonged resuscitation of a hypothermic patient (26.2C) in stadium HT III of the Swiss Staging System (SSS). A mechanical chest compression with the Lund University Cardiac Assist System (LUCAS) and the rewarming with a haemodialysis device were implemented. After a resuscitation time of 200min and a body temperature of 32.1C ventricular fibrillation occurred. After the defibrillation a return of spontaneous circulation (ROSC) was established. The patient achieved a very good cognitive-mnestic result after the resuscitation but he suffered a neurological deficit in the meaning of paraplegia. PMID:26859469

  8. Spinal arteriovenous malformation presenting with prolapsed intervertebral disc: a diagnostic dilemma.

    PubMed

    Farina, M Y; Harunarashid, H; Faridzal, F; Jegan, T; Das, S

    2012-11-01

    The availability of multiple investigating modalities should be utilized to arrive at the correct diagnosis of the spinal arteriovenous malformation (AVM). We hereby report the case of a 21-year-old, obese female, who presented with paraplegia and impaired bowel control two years after an episode of the fall. The Magnetic Resonance Imaging (MRI) of her spine not only revealed disc prolapse at T11-T12, but also tortuous dilated spinal veins and cord oedema. A diagnosis of a spinal arterio-venous fistula was confirmed after a spinal angiogram. The dilemma of treating the right pathology for the clinical signs and symptoms are being discussed. PMID:23306743

  9. Treatment of a prolapsed lumbar intervertebral disc in a ferret.

    PubMed

    Lu, D; Lamb, C R; Patterson-Kane, J C; Cappello, R

    2004-10-01

    A seven-month-old, male ferret had acute paraplegia and radiographs showed signs of disc prolapse between the second and third lumbar vertebrae (L2/3). Hemilaminectomy was performed to decompress the spinal cord. Histological examination revealed that the extradural material was consistent with annulus fibrosus and the L2/3 articular facets were enlarged as a result of bone remodelling. The ferret became ambulatory one month postoperatively. Five months postoperatively, the ferret had normal posture with mild proprioceptive deficits in the pelvic limbs, and fusion of the L2 and L3 vertebral bodies. PMID:15515799

  10. Primary extradural hydatid cyst extended to paraspinal muscles

    PubMed Central

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

    2012-01-01

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

  11. 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

  12. [Isolated sixth nerve palsy--presenting sign of multiple myeloma].

    PubMed

    Zahavi, Alon; Manor, Riri S; Lahav, Meir; Bakon, Mati; Kalish, Hadas

    2013-02-01

    Multiple myeloma is a disease caused by neoplastic plasma cells. Initial symptoms in most cases described in the literature include chest and lumbar pain, paresthesia, paraplegia, general weakness and renal failure. We report a case of isolated sixth nerve palsy causing diplopia as the presenting sign of multiple myeloma. Awareness of such a rare clinical presentation - especially when the existence of multiple myeloma is ignored after visualization of a cranial mass with magnetic resonance imaging (MRI) and computerized tomography (CT)--can prevent unnecessary surgical intervention and delay the appropriate treatment. PMID:23513504

  13. Modeling Axonal Phenotypes with Human Pluripotent Stem Cells.

    PubMed

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

    2016-01-01

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

  14. Voiding Dysfunction Induced by Tetanus: A Case Report

    PubMed Central

    Kira, Satoru; Sawada, Norifumi; Aoki, Tadashi; Kobayashi, Hideki; Takeda, Masayuki

    2016-01-01

    A 34-year-old man presented with sudden voiding dysfunction and lower limb paraplegia. As a central nervous system disorder was suspected, he was referred to the neurology department. Under the diagnosis of neurosarcoidosis, steroid pulse therapy was initiated. To ensure the effect of this therapy, the patient was referred back for urodynamic testing. Urodynamic testing indicated that the urethral sphincter was not relaxed and could not void. Due to the sudden appearance of repeated and refractory opisthotonus, tetanus was strongly suspected. After administration of antibiotics and tetanus immune globulin, those symptoms disappeared. PMID:26793588

  15. [Thoracic spinal cord avulsion without radiologic abnormalities: case report].

    PubMed

    Falavigna, Asdrubal; Mattana, Marcelo; Teles, Alisson Roberto; Persh, Karina Nunes

    2006-09-01

    Spinal cord injury without radiologic abnormalities is a rare condition that occurs more frequently in children and contributes to a high rate of morbidity among these patients. We report the case of a five-month-old infant, victim of automobile accident, who was brought to our service with a sensitive level in T2 and bilateral crural paraplegia. Radiographic exams and computed tomography of spine did not evidence of bone or ligaments injuries. Magnetic resonance image showed complete spinal cord transection and spine avulsion in the segment between T3 and T7. We discuss this pathology according to its epidemiology, pathophysiology, diagnosis, treatment and prognostic aspects. PMID:17057905

  16. An atypical case of acute disseminated encephalomyelitis associated with cytomegalovirus infection.

    PubMed

    De Fino, Chiara; Nociti, Viviana; Modoni, Anna; Bizzarro, Alessandra; Mirabella, Massimiliano

    2016-01-01

    We present the case of a young man admitted to our hospital for persistent headache associated with fever, retrorbitary pain and vomiting, who rapidly developed encephalopathy with drowsiness, paraplegia, hypoesthesia with a D6 sensory level and urinary retention. Brain and spinal cord MRI revealed findings compatible with acute disseminated encephalomyelitis (ADEM) and microbiological tests documented a cytomegalovirus (CMV) infection. CMV infection is extraordinarily associated with ADEM, but must be included in microbiological tests, because early diagnosis and treatment ameliorate the neurological outcome. PMID:26856946

  17. 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

  18. Voiding Dysfunction Induced by Tetanus: A Case Report.

    PubMed

    Kira, Satoru; Sawada, Norifumi; Aoki, Tadashi; Kobayashi, Hideki; Takeda, Masayuki

    2016-03-01

    A 34-year-old man presented with sudden voiding dysfunction and lower limb paraplegia. As a central nervous system disorder was suspected, he was referred to the neurology department. Under the diagnosis of neurosarcoidosis, steroid pulse therapy was initiated. To ensure the effect of this therapy, the patient was referred back for urodynamic testing. Urodynamic testing indicated that the urethral sphincter was not relaxed and could not void. Due to the sudden appearance of repeated and refractory opisthotonus, tetanus was strongly suspected. After administration of antibiotics and tetanus immune globulin, those symptoms disappeared. PMID:26793588

  19. Tuberculosis of spine: neurological deficit.

    PubMed

    Jain, Anil K; Kumar, Jaswant

    2013-06-01

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

  20. Consumer perspectives on mobility: implications for neuroprosthesis design.

    PubMed

    Brown-Triolo, Denise L; Roach, Mary Joan; Nelson, Kristine; Triolo, Ronald J

    2002-01-01

    The purpose of this study was to systematically assess mobility issues from the point of view of persons with spinal cord injuries (SCIs), so as to guide clinicians, researchers, and developers of assistive technologies. A telephone survey was developed through focus groups and discussions with individuals with SCI and rehabilitation experts. Telephone interviews were conducted with 94 individuals with paraplegia (51.4% response rate) from a Midwestern regional rehabilitation hospital's SCI database. Respondents were asked to prioritize desired mobility functions, to identify the acceptable quality of the activities, and to assess their willingness to experience related risks. Respondents ranked walking and then standing as top priorities (64% and 25%, respectively), regardless of injury level. For most, the acceptable quality of new mobility maneuvers did not have to approach premorbid function. Invasive procedures such as surgery were often as acceptable as less-invasive therapy and exercise. Qualities and costs of standing and walking were related to what respondents had to gain or lose relative to their current level of function. Contrary to opinions based on anecdotal evidence, persons with paraplegia were willing to accept high costs for limited function in certain mobility activities. These findings should encourage clinicians to consider the needs of persons with disabilities during the development of treatment interventions. PMID:17943668

  1. 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; Kortm, Fanny; Beckstette, Michael; Seemanova, Eva; Komrek, Vladimr; 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

  2. Adult Hip Flexion Contracture due to Neurological Disease: A New Treatment ProtocolSurgical Treatment of Neurological Hip Flexion Contracture

    PubMed Central

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

    2014-01-01

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

  3. Tropical myelopathies.

    PubMed

    Romn, 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

  4. Spinal cord ischemia after cardiac arrest.

    PubMed

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

    1994-01-01

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

  5. 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.

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

    PubMed

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

    2011-01-01

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

  7. Monitored anesthesia care in a case of pheochromocytoma and atrial myxoma

    PubMed Central

    Manvikar, Laxmi P.; Adhye, Bharati A.

    2012-01-01

    Anesthesia for a patient with pheochromocytoma is challenging; irrespective of whether it is a diagnosed case for planned surgery or an occult case, it can be a nightmare. The patient may be given anesthesia for removal of the primary tumor or for surgery other than for the removal of the primary tumor. Hemodynamic derangements like hypertension and arrhythmia can be catastrophic. Monitored anesthesia care, though used for many cases, is unusual for a patient with diagnosed pheochromocytoma, with vertebral metastasis leading to paraplegia and atrial myxoma. In the case described below, the patient was operated for closed reduction, internal fixation with interlock nail femur, for pathological fracture. Surgery was done under monitored anesthesia care as there was no need for regional, spinal, or general anesthesia because of coexisting paraplegia. Surgery was uneventful and the postoperative period was smooth. This case is presented for its uniqueness of multiple diseases and uneventful recovery without any complications of anesthesia. The nightmare of pheochromocytoma eased without any morbidity for the patient, but this may not always be the case. PMID:25885632

  8. Mutations in a new cytochrome P450 gene in lamellar ichthyosis type 3.

    PubMed

    Lefvre, Caroline; Bouadjar, Bakar; Ferrand, Vronique; Tadini, Gianluca; Mgarban, Andr; Lathrop, Mark; Prud'homme, Jean-Franois; Fischer, Judith

    2006-03-01

    We report the identification of mutations in a non-syndromic autosomal recessive congenital ichthyosis (ARCI) in a new gene mapping within a previously identified locus on chromosome 19p12-q12, which has been defined as LI3 in the OMIM database (MIM 604777). The phenotype usually presents as lamellar ichthyosis and hyperlinearity of palms and soles. Seven homozygous mutations including five missense mutations and two deletions were identified in a new gene, FLJ39501, on chromosome 19p12 in 21 patients from 12 consanguineous families from Algeria, France, Italy and Lebanon. FLJ39501 encodes a protein which was found to be a cytochrome P450, family 4, subfamily F, polypeptide 2 homolog of the leukotriene B4-omega-hydroxylase (CYP4F2) and could catalyze the 20-hydroxylation of trioxilin A3 from the 12(R)-lipoxygenase pathway. Further oxidation of this substrate by the fatty alcohol:nicotinamide-adenine dinucleotide oxidoreductase (FAO) enzyme complex, in which one component, ALDH3A2, is known to be mutated in Sjgren-Larsson syndrome (characterized by ichthyosis and spastic paraplegia), would lead to 20-carboxy-(R)-trioxilin A3. This compound could be involved in skin hydration and would be the essential missing product in most forms of ARCI. Its chiral homolog, 20-carboxy-(S)-trioxilin A3, could be implicated in spastic paraplegia and in the maintenance of neuronal integrity. PMID:16436457

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2015-02-01

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

  13. 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

  14. Motor Evoked Potentials in 43 High Risk Spine Deformities

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2003-08-01

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

  16. Recent surprising similarities between plant cells and neurons

    PubMed Central

    2010-01-01

    Plant cells and neurons share several similarities, including non-centrosomal microtubules, motile post-Golgi organelles, separated both spatially/structurally and functionally from the Golgi apparatus and involved in vesicular endocytic recycling, as well as cell-cell adhesion domains based on the actin/myosin cytoskeleton which serve for cell-cell communication. Tip-growing plant cells such as root hairs and pollen tubes also resemble neurons extending their axons. Recently, surprising discoveries have been made with respect to the molecular basis of neurodegenerative disorders known as Hereditary Spastic Paraplegias and tip-growth of root hairs. All these advances are briefly discussed in the context of other similarities between plant cells and neurons. PMID:20150757

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

    PubMed Central

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

    2015-01-01

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

  18. Aneurysmal dilation of the ascending thoracic aorta and the aortic arch following surgical repair of type A dissection

    PubMed Central

    Cormack, Suzanne M; Owens, W Andrew

    2012-01-01

    This report describes the case of a 71-year-old lady who was diagnosed with a Stanford type A dissecting aortic aneurysm which resulted in paraplegia secondary to spinal artery injury at T12 level. She had surgical repair with a tube graft. At a routine review CT scan 2?years postdissection, she presents with asymptomatic but significant dilation, of maximum diameter 78?mm, of the superior part of the ascending thoracic aorta, extending into the arch, suggestive of false aneurysm formation at the surgical anastomoses. There was also thrombosis of the false lumen in the distal arch and descending thoracic aorta. She is a candidate for urgent resection of the aortic arch and reimplantation of the brachiocephalic vessels. PMID:23076699

  19. 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

  20. Acute transverse myelitis caused by Coxsackie virus B4 infection: a case report.

    PubMed

    Ku, B; Lee, K

    1998-08-01

    Acute transverse myelitis is a rare clinical manifestation of Coxsackie virus infection which cause acute and progressive debilitating illness associated with loss of spinal cord function in the affected patients. A 62 year-old female developed symptoms of rapidly progressive paraplegia with sensory loss. On spinal MRI, T2 sagittal image showed increased signal intensity with cord swelling at T11-L2 level and 8 folds or greater rise of Coxsackie virus B4 neutralizing antibody titers was observed in the CSF. There is only one previous report of acute transverse myelitis caused by Coxsackie virus B4 infection to our knowledge. The presence of specific viral antibody titers change in the CSF and a corresponding spinal cord lesion are sufficient to suggest a causal relationship between the virus and the illness. This article is a case report of an unusual acute transverse myelitis caused by Coxsackie virus B4 infection. PMID:9741555

  1. Unique Imaging Features of Spinal Neurenteric Cyst

    PubMed Central

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

    2015-01-01

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

  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. 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.

  4. [Subacute myelitis revealed by human immunodeficiency virus infection].

    PubMed

    Feki, I; Belahsen, F; Ben Jemaa, M; Mhiri, C

    2003-05-01

    A 35 year-old heterosexual man had a six months history of cervical myelitis with progressive paraplegia, leg weakness and paresthesia of the four extremities. Spinal cord MRI showed a high T2 signal intramedullary lesion wide from the bulbo-medullary junction to D4. Post gadolinium T1 sequence revealed an enhancement in front of C3-C4 vertebrae. VIH serology was positive. Corticosteroid treatment achieved a marked improvement. In addition to vacuolar myelopathy, well-known at the advanced stages of the HIV infection (AIDS), myelitis and clinical pictures simulating multiple sclerosis were described during early stages of the infection. These inflammatory lesions of the central nervous system and sometimes of the peripheral nervous system seems to be related to the immune response dysfunction induced by the VIH. PMID:12773905

  5. [Rehabilitation for cancer patients].

    PubMed

    Tanuma, Akira

    2013-09-01

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

  6. Severe penile erosion after use of a vacuum suction device for management of erectile dysfunction in a spinal cord injured patient. Case report.

    PubMed

    LeRoy, S C; Pryor, J L

    1994-02-01

    We report a case of severe erosion and cellulitis at the base of the penis as a result of vacuum suction device constriction bands left on for 4 hours in a spinal cord injured patient with paraplegia and hypesthesia of the genital area. All patients using vacuum suction devices need to be properly educated regarding usage and risks with adequate follow up; patients with hypesthesias and spinal cord injuries need information specifically related to their decreased or absent level of sensation. Only two out of seven vacuum suction device brochures reviewed warn of the risk to patients with decreased sensation in the penis, but none specifically address usage or risks to men with spinal cord injuries. PMID:8015845

  7. Car seat heaters: a potential hazard for burns.

    TOXLINE Toxicology Bibliographic Information

    Maguia P; Palmieri TL; Greenhalgh DG

    2003-09-01

    Car seat heaters have gained popularity in America and worldwide. They offer comfort by heating the sitting surface to a soothing temperature. Several cases of heating-element malfunction resulted in burn injuries and have triggered recalls of thousands of cars by the manufacturers. We present a case of a 48-year-old patient with long-standing paraplegia who sustained third-degree burns on his buttock during the initial drive of a new car with seat heaters. Car seat heaters can cause severe burns. Patients with decreased sensation or immobility are at increased risk and should not use car seat heaters. This case illustrates the need for design modifications and consumer education regarding the risks associated with car seat heaters.

  8. 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

  9. Prevention of urinary tract infections in persons with spinal cord injury in home health care.

    PubMed

    Eves, Faith J; Rivera, Natacha

    2010-04-01

    More than 250,000 persons in the United States live with spinal cord injury (SCI), and 10,000 to 12,000 new injuries occur each year. Of these spinal cord injured persons, 53% have tetraplegia, 46% have paraplegia, and less than 1% experience complete neurologic recovery. About 48% have complete injuries (i.e., full quadriplegia) and 52% have incomplete injuries (; ). Almost all persons with neurologic impairment related to SCI have voiding dysfunction. Urinary tract infections (UTIs) have long been problematic for those living with SCI. Once the leading cause of death, urinary complications remain the leading cause of morbidity and the most common infection in persons with SCI (). This article provides a brief overview of spinal cord injuries and the effect of SCI on the urinary system. Factors that increase the risk for UTI will also be described. PMID:20520263

  10. 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.

  11. Mutations in GALC cause late-onset Krabbe disease with predominant cerebellar ataxia.

    PubMed

    Shao, Yi-Hong; Choquet, Karine; La Piana, Roberta; Tétreault, Martine; Dicaire, Marie-Josée; Boycott, Kym M; Majewski, Jacek; Brais, Bernard

    2016-04-01

    Mutations in GALC cause Krabbe disease. This autosomal recessive leukodystrophy generally presents in early infancy as a severe disorder, but sometimes manifests as a milder adult-onset disease with spastic paraplegia as the main symptom. We recruited a family with five affected individuals presenting with adult-onset predominant cerebellar ataxia with mild spasticity. Whole exome sequencing (WES) revealed one novel and one previously reported compound heterozygous variants in GALC. Magnetic resonance imaging (MRI) confirmed the presence of typical Krabbe features. Our findings expand the phenotypic spectrum of adult-onset Krabbe disease and demonstrate the usefulness of combining WES and pattern-specific MRI for the diagnosis of neurodegenerative diseases. PMID:26915362

  12. 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.

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

    PubMed

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

    2015-04-01

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

  14. Recurrent lead poisoning in a child with immobilization osteoporosis.

    PubMed

    Shannon, M; Lindy, H; Anast, C; Graef, J

    1988-12-01

    Lead poisoning associated with progressive osteoporosis in patients who have been previously lead poisoned has been described but poorly documented. We managed a 4-year-old child with a prior history of plumbism who developed recurrent blood lead elevations (as high as 70 mcg/dl), requiring multiple courses of EDTA, after acute paraplegia from transverse myelitis. The patient was hospitalized throughout these periods of chelation. No exogenous sources of lead were found. Calcium, phosphate, magnesium, alkaline phosphatase and parathyroid hormone levels remained normal while vitamin D levels were depressed. Metabolic studies revealed negative calcium balance with an elevated urinary calcium:creatinine ratio. Long-bone radiographs were remarkable for progressive osteoporosis with no evidence of metallic foreign bodies. This case illustrates that bone, the major repository of lead, can become a source of significant lead level elevations in conditions associated with accelerated resorption. PMID:3149814

  15. The neurological manifestations of dissecting aneurysm of the aorta

    PubMed Central

    Condon, John R.; Rose, F. Clifford

    1969-01-01

    Six cases of dissecting aneurysm of the aorta, four with cerebral manifestations, one with peripheral neuropathy and one with ischaemic necrosis of the spinal cord are reported. Cerebral manifestations include confusion and stupor, syncope, grand mal epilepsy, ischaemia of the spinal medulla, carotid artery occlusion and cerebral hemisphere infarction. Ischaemic neuropathy is characterized by severe limb pain not of peripheral nerve distribution, but associated with areflexia and a peripheral pattern of sensory loss. Ischaemic necrosis of the cord is characterized by flaccid paraplegia and sphincter disturbances with segmental sensory loss exhibiting an upper level on the trunk. The differential diagnosis of the neurological complications of aortic dissection is discussed and a brief review of advances in management made. ImagesFig. 1 PMID:5789681

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

    PubMed

    Boros, kos; Fenyvesi, Hajnalka; Pankovics, Pter; Bir, Hunor; Phan, Tung Gia; Delwart, Eric; Reuter, Gbor

    2015-05-01

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

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

    PubMed Central

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

    2015-01-01

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

  18. Spinal cord injury in an inner city hospital.

    PubMed

    Macauley, C A; Weiss, L

    1978-02-01

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

  19. Acute onset of postoperative syringohydromyelia.

    PubMed

    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

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

    PubMed Central

    Jeong, Deok-Ki

    2015-01-01

    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

  1. 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

  2. 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.

  3. Aggressive hemangioma of the spine in a pregnant female: a case report and literature review.

    PubMed

    Demirkale, İsmail; De Iure, Federico; Terzi, Silvia; Gasbarrini, Alessandro

    2016-04-01

    Type and timing of treatment for symptomatic hemangiomas in pregnant females are challenging due to fetus survival and conflicts in neurological recovery. In this article, we report a 40-year-old female patient at pregnancy week 23 with a complicated hemangioma at T1 level. Physical examination revealed an incomplete spastic paraplegia. Patient did not accept any surgery due to child's death risk. Patient was started corticoid treatment and no more weight bearing was allowed. At the 28th week of pregnancy, the patient underwent cesarean section immediately followed by selective arterial embolization, decompression, fixation, and radiotherapy. At two-year follow-up, the patient was pain free, without any signs of local recurrence and with complete neurological recovery. A multidisciplinary approach is mandatory to save the life of the fetus without damaging the spinal cord functions of the mother. PMID:26874635

  4. Spinal cord ischemia is multifactorial: what is the best protocol?

    PubMed

    Melissano, Germano; Bertoglio, Luca; Mascia, Daniele; Rinaldi, Enrico; Del Carro, Ubaldo; Nardelli, Pasquale; Chiesa, Roberto

    2016-04-01

    Despite the improved understanding of spinal cord anatomy and spinal cord ischemia pathophysiology, the rate of debilitating postoperative paraparesis or paraplegia is still not negligible after procedures for thoracic or thoracoabdominal aortic disease. Single studies have demonstrated the role of different treatment modalities to prevent or treat spinal cord ischemia. A multimodal approach, however, is advocated by most authors. Even after the employment of endovascular techniques become routine, the rate of spinal cord ischemia after treatment of thoracoabdominal aortic pathology remained unchanged over time. Spinal cord ischemia is often treatable by different means that concur to improve indirect spinal perfusion through collateral circulation; it should, therefore, be managed promptly and aggressively due to its potential reversibility. Ongoing technical improvements of non-invasive diagnostic tools may allow a better preoperative assessment of the spinal vascular network and a better planning of both open and endovascular thoracic or thoracoabdominal repair. PMID:26731537

  5. Unique Imaging Features of Spinal Neurenteric Cyst.

    PubMed

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

    2015-12-01

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

  6. 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

  7. The Crossroads of Synaptic Growth Signaling, Membrane Traffic and Neurological Disease: Insights from Drosophila.

    PubMed

    Deshpande, Mugdha; Rodal, Avital A

    2016-02-01

    Neurons require target-derived autocrine and paracrine growth factors to maintain proper identity, innervation, homeostasis and survival. Neuronal growth factor signaling is highly dependent on membrane traffic, both for the packaging and release of the growth factors themselves, and for regulation of intracellular signaling by their transmembrane receptors. Here, we review recent findings from the Drosophila larval neuromuscular junction (NMJ) that illustrate how specific steps of intracellular traffic and inter-organelle interactions impinge on signaling, particularly in the bone morphogenic protein, Wingless and c-Jun-activated kinase pathways, regulating elaboration and stability of NMJ arbors, construction of synapses and synaptic transmission and homeostasis. These membrane trafficking and signaling pathways have been implicated in human motor neuron diseases including amyotrophic lateral sclerosis and hereditary spastic paraplegia, highlighting their importance for neuronal health and survival. PMID:26538429

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

    PubMed Central

    2011-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  10. Motion of the body centre of gravity as a summary indicator of the mechanics of human pathological gait.

    PubMed

    Detrembleur, C; van den Hecke, A; Dierick, F

    2000-12-01

    Abnormal movements of the body segments due to lowest level gait disorders such as musculoskeletal disorders, peripheral neuropathies and radiculopathies or middle-level disorders such as hemiplegia, paraplegia and dystonia influence the motion of the centre of gravity (CG) during walking. The translation of the CG can be studied by the work done by muscles (WExt) with respect to the ground. The efficacy of gait's mechanism can be quantified by the energy transferred between gravitational potential and kinetic energies (recovery). WExt and recovery were investigated in lowest and middle-level gait disorders during level walking. No statistical significant difference was observed between patients with lowest-level gait disorders and normal subjects. However, WExt was increased for the patients with middle-level gait disorders and recovery decreased up to 20%. The measurement of changes in mechanical energy of the CG might be a summary indicator for the mechanics of pathological gait. PMID:11154935

  11. 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

  12. [Operative treatment for lumbar disc protrusion with fragment of nucleus pulposus in the dural sac].

    PubMed

    Wang, Q P

    1992-12-01

    Four cases of lumbar disc protrusion with fragments of nucleus pulposus in the dural sac are reported, representing 0.3% of 1555 cases surgically treated over the past 35 years. All four cases were severely affected with distinct clinical manifestations of prolapsed disc, acute onset or sudden deterioration, pain, numbness, weakness, partial or complete paraplegia, and disturbances of urination and defecation accompanied by symptoms of severe and extensive spinal stenosis. They were treated with total laminectomy, section of dural sac, separation of adhesion and removal of fragments of nucleus pulposus. The results were excellent in one, Good in two and fair in one patient as revealed by the follow-up study which ranged from 4 months to 6 years. The clinical features, pathology, cause of prolapse, diagnosis, some points for attention concerning its management as well as that of adhesive arachnoiditis are discussed. PMID:1339746

  13. Anterior spinal hernia: an increasingly recognised cause of thoracic cord dysfunction.

    PubMed

    White, B D; Firth, J L

    1994-11-01

    Two cases of anterior spinal hernia are presented. The medical literature is reviewed, the syndrome characterised, and its cause and treatment discussed. The patient is typically middle aged with a history of stepwise slowly progressive mid-thoracic anterior hemicord syndrome manifesting as hemianalgesia below the affected segment, followed by contralateral lower limb spasticity that develops into an asymmetric paraparesis with sparing of dorsal column sensation. Radiological investigation demonstrates an enlarged dorsal arachnoid space in association with an apparently focally narrowed thoracic cord, kinked towards the anterior dura. At operation the cord is found to be prolapsed into an anterolateral dural diverticulum. The most likely cause of this syndrome is anterior spinal artery segmental branch ischaemia, in a cord chronically incarcerated in a congenital anterior meningocele. This readily treatable condition should be considered in all cases of thoracic cord dysfunction and surgical repair effected early to prevent stepwise progression to paraplegia. PMID:7964829

  14. [2 cases of vertebral hydatidosis treated by the association of surgery and mebendazole].

    PubMed

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

    1983-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

    Kmoch, S; Majewski, J; Ramamurthy, V; Cao, S; Fahiminiya, S; Ren, H; MacDonald, I M; Lopez, I; Sun, V; Keser, V; Khan, A; Stránecký, V; Hartmannová, H; 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; Banin, E; Sharon, D; Dutta, S; Grebler, R; Helfrich-Foerster, C; Pedroso, J L; Kretzschmar, D; Cayouette, M; Koenekoop, R K

    2015-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

    Renvois, Benot; Blackstone, Craig

    2010-01-01

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

  19. 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

  20. A case of dural arteriovenous fistula at the craniocervical junction, which spinal MRI findings reveals increased intensity signal in Th3-medullary cone.

    PubMed

    Ueda, Masamichi; Ueda, Miki; Takeuchi, Yuko; Ochiai, Jun; Mabuchi, Chiyuki; Hattori, Shinnosuke

    2016-01-29

    A 60-year-old woman had transient weakness of the legs and urinary retention for six weeks. She presented with a gait disorder and was admitted to the hospital. She showed symptoms of paraplegia, tingling in the lower extremities, dysuria. She underwent an MRI, and T2-weighted images showed an enlargement of the thoracolumbar spinal cord and high intensity signal from Th3 to the medullary cone, and a contrast-enhanced T1-weighted image showed abnormal vessels anterior to the spine cord. Cervical and spinal angiography documented a dural arteriovenous fistula at the craniocervical junction that was fed by the right vertebral artery and the right ascending pharyngeal arteries and drained into the perimedullary veins. Surgical therapy improved her symptoms and MRI images. Craniocervical junction DAVF with thoracic-medullary cones lesion is rare. PMID:26616488

  1. Spina Bifida Cystica

    PubMed Central

    Lorber, John

    1972-01-01

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

  2. 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

  3. A Case of Cervical Spine Tuberculosis in an Infant

    PubMed Central

    Bhatt, Trilok C; Kumar, Savit; Chauhan, Vikas; Pandey, Anjali

    2016-01-01

    Tuberculosis of cervical spine is an extremely rare entity in infants with only few case reports available in the literature. The diagnosis is often delayed due to less dramatic effects of paraplegia or quadriplegia in an infant as compared to older paediatric population. Along with clinical and laboratory investigations, imaging plays a crucial role in defining the extent of involvement, evaluation of complications, providing suitable differential diagnosis and monitoring response to treatment. Tuberculosis typically involves the discovertebral complex while involvement of isolated vertebral body or multiple vertebrae without involving the intervertebral discs is much less common. We present such an unusual case of cervical spine tuberculosis in an infant involving a single vertebral body without adjacent intervertebral disc involvement complicated with tuberculous meningitis (TBM) and communicating hydrocephalus. The early medical intervention in this case resulted in early diagnosis, active treatment and resultant near normal recovery. PMID:26894144

  4. Adaptor protein complexes and intracellular transport

    PubMed Central

    Park, SangYoon; Guo, Xiaoli

    2014-01-01

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

  5. Human genetic disorders of sphingolipid biosynthesis.

    PubMed

    Astudillo, Leonardo; Sabourdy, Frdrique; Therville, Nicole; Bode, Heiko; Sgui, Bruno; Andrieu-Abadie, Nathalie; Hornemann, Thorsten; Levade, Thierry

    2015-01-01

    Monogenic defects of sphingolipid biosynthesis have been recently identified in human patients. These enzyme deficiencies affect the synthesis of sphingolipid precursors, ceramides or complex glycosphingolipids. They are transmitted as autosomal recessive or dominant traits, and their resulting phenotypes often replicate the abnormalities seen in murine models deficient for the corresponding enzymes. In quite good agreement with the known critical roles of sphingolipids in cells from the nervous system and the epidermis, these genetic defects clinically manifest as neurological disorders, including paraplegia, epilepsy or peripheral neuropathies, or present with ichthyosis. The present review summarizes the genetic alterations, biochemical changes and clinical symptoms of this new group of inherited metabolic disorders. Hypotheses regarding the molecular pathophysiology and potential treatments of these diseases are also discussed. PMID:25141825

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

    PubMed

    Gray, Kendra M; Derosa, Angela

    2013-12-01

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

  7. A Case of Cervical Spine Tuberculosis in an Infant.

    PubMed

    Singh, S N; Bhatt, Trilok C; Kumar, Savit; Chauhan, Vikas; Pandey, Anjali

    2016-01-01

    Tuberculosis of cervical spine is an extremely rare entity in infants with only few case reports available in the literature. The diagnosis is often delayed due to less dramatic effects of paraplegia or quadriplegia in an infant as compared to older paediatric population. Along with clinical and laboratory investigations, imaging plays a crucial role in defining the extent of involvement, evaluation of complications, providing suitable differential diagnosis and monitoring response to treatment. Tuberculosis typically involves the discovertebral complex while involvement of isolated vertebral body or multiple vertebrae without involving the intervertebral discs is much less common. We present such an unusual case of cervical spine tuberculosis in an infant involving a single vertebral body without adjacent intervertebral disc involvement complicated with tuberculous meningitis (TBM) and communicating hydrocephalus. The early medical intervention in this case resulted in early diagnosis, active treatment and resultant near normal recovery. PMID:26894144

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

    PubMed Central

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

    2015-01-01

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

  9. Hemophilia A in a Senior Patient: A Case Report of Spinal Epidural Hematoma as First Presentation

    PubMed Central

    Jung, Woo Shik; Lee, Jae Il

    2015-01-01

    Hemophilia A is a hereditary coagulation disorder. Most cases are diagnosed at birth or at least during childhood. A spontaneous spinal epidural hematoma was developed in a 74-year-old male patient who hadn't had a family or past medical history of bleeding disorders. On magnetic resonance imaging, epidural hematoma at L1-2 was accompanied by spinal stenosis at L4-5 and spondylolytic spondylolisthesis at L5. Hematoma evacuation and surgery for distal lumbar lesions were performed at once. After transient improvement, complete paraplegia was developed due to redevelopment of large epidural hematomas at L1-2 and L4-S1 which blocked epidural canal completely. Emergency evacuation was performed and we got to know that he had a hemophilia A. Factor VIII was 28% of normal value. Mild type hemophilia A could have not been diagnosed until adulthood. Factor VIII should have been replaced before the surgical decompression. PMID:26097663

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

    PubMed Central

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

    2007-01-01

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

  11. 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

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

    PubMed

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

    2008-09-01

    A 13-yr-old Amur tiger (Panthera tigris altaica) was presented for an acute onset of paraplegia. Spinal imaging that included plain radiographs, myelography, and computed tomography performed under general anesthesia revealed lateralized spinal cord compression at the intervertebral disc space L4-5 caused by intervertebral disc extrusion. This extrusion was accompanied by an extensive epidural hemorrhage from L3 to L6. Therefore, a continuous hemilaminectomy from L3 to L6 was performed, resulting in complete decompression of the spinal cord. The tiger was ambulatory again 10 days after the surgery. This case suggests that the potential benefit of complete spinal cord decompression may outweigh the risk of causing clinically significant spinal instability after extensive decompression. PMID:18817014

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

    PubMed Central

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

    2013-01-01

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

  14. The history of multiple sclerosis: the changing frame of the disease over the centuries.

    PubMed

    Murray, T Jock

    2009-02-01

    For centuries, it was recognised that there was a condition characterised by episodic and progressive neurological deterioration, classified as 'paraplegia'. Some early cases of 'paraplegia' have been described in sufficient detail to recognise a condition resembling what we now call multiple sclerosis and these cast an interesting light on the approach to therapy before the disease had a name. Multiple sclerosis was differentiated and 'framed' as a separate identifiable entity by von Frerichs, Vulpian, Charcot and others in the mid-nineteenth century. Once framed by its pathology, clinical picture, course and prognosis, cases were diagnosed by others around the world. As knowledge of the disease increased, theories of cause and approaches to treatment increased so that a review in 1935 covered 158 treatments used in MS. There were subsequent waves of therapies including anticoagulants, antibiotics, histamine desensitisation, various diets, vaccines and anti-cancer agents, as well as numerous claims of 'cures'. After the 1960s the methodology for carrying out randomised clinical trials became better defined, aided by improved disease classification and disability scales. As data accumulated, theories were tested to account for observations of genetic influences, environmental factors, geographical variations, infections and immunological changes. The development of multiple sclerosis societies advanced research and public education and changed attitudes towards the disease. At the same time, attitudes of physicians towards management of people with multiple sclerosis changed. In the last fifty years, the major advances have been in basic research to elucidate the mechanisms and processes underlying the disease, the development of imaging techniques (MRI) and the development of immunomodulatory drugs which, for the first time, are altering the outcome of the disease. We have now entered the therapeutic era of multiple sclerosis, with continual major advances bringing hope and benefit to people with multiple sclerosis. PMID:19200863

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

    PubMed Central

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

    2015-01-01

    Adaptor proteins (AP 15) are heterotetrameric complexes that facilitate specialized cargo sorting in vesicular-mediated trafficking. Mutations in AP5Z1, encoding a subunit of the AP-5 complex, have been reported to cause hereditary spastic paraplegia (HSP), although their impact at the cellular level has not been assessed. Here we characterize three independent fibroblast lines derived from skin biopsies of patients harbouring nonsense mutations in AP5Z1 and presenting with spastic paraplegia accompanied by neuropathy, parkinsonism and/or cognitive impairment. In all three patient-derived lines, we show that there is complete loss of AP-5 ? protein and a reduction in the associated AP-5 5 protein. Using ultrastructural analysis, we show that these patient-derived lines consistently exhibit abundant multilamellar structures that are positive for markers of endolysosomes and are filled with aberrant storage material organized as exaggerated multilamellar whorls, striated belts and fingerprint bodies. This phenotype can be replicated in a HeLa cell culture model by siRNA knockdown of AP-5 ?. The cellular phenotype bears striking resemblance to features described in a number of lysosomal storage diseases (LSDs). Collectively, these findings reveal an emerging picture of the role of AP-5 in endosomal and lysosomal homeostasis, illuminates a potential pathomechanism that is relevant to the role of AP-5 in neurons and expands the understanding of recessive HSPs. Moreover, the resulting accumulation of storage material in endolysosomes leads us to propose that AP-5 deficiency represents a new type of LSDs. PMID:26085577

  16. 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

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

    PubMed

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

    2015-04-01

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

  18. Adult Polyglucosan Body Disease: Natural History and Key Magnetic Resonance Imaging Findings

    PubMed Central

    Mochel, Fanny; Schiffmann, Raphael; Steenweg, Marjan E.; Akman, Hasan O.; Wallace, Mary; Sedel, Frdric; Lafort, Pascal; Levy, Richard; Powers, J. Michael; Demeret, Sophie; Maisonobe, Thierry; Froissart, Roseline; Da Nobrega, Bruno Barcelos; Fogel, Brent L.; Natowicz, Marvin R.; Lubetzki, Catherine; Durr, Alexandra; Brice, Alexis; Rosenmann, Hanna; Barash, Varda; Kakhlon, Or; Gomori, J. Moshe; van der Knaap, Marjo S.; Lossos, Alexander

    2015-01-01

    Objective Adult polyglucosan body disease (APBD) is an autosomal recessive leukodystrophy characterized by neurogenic bladder, progressive spastic gait, and peripheral neuropathy. Polyglucosan bodies accumulate in the central and peripheral nervous systems and are often associated with glycogen branching enzyme (GBE) deficiency. To improve clinical diagnosis and enable future evaluation of therapeutic strategies, we conducted a multinational study of the natural history and imaging features of APBD. Methods We gathered clinical, biochemical, and molecular findings in 50 APBD patients with GBE deficiency from Israel, the United States, France, and the Netherlands. Brain and spine magnetic resonance images were reviewed in 44 patients. Results The most common clinical findings were neurogenic bladder (100%), spastic paraplegia with vibration loss (90%), and axonal neuropathy (90%). The median age was 51 years for the onset of neurogenic bladder symptoms, 63 years for wheelchair dependence, and 70 years for death. As the disease progressed, mild cognitive decline may have affected up to half of the patients. Neuroimaging showed hyperintense white matter abnormalities on T2 and fluid attenuated inversion recovery sequences predominantly in the periventricular regions, the posterior limb of the internal capsule, the external capsule, and the pyramidal tracts and medial lemniscus of the pons and medulla. Atrophy of the medulla and spine was universal. p.Y329S was the most common GBE1 mutation, present as a single heterozygous (28%) or homozygous (48%) mutation. Interpretation APBD with GBE deficiency, with occasional exceptions, is a clinically homogenous disorder that should be suspected in patients with adult onset leukodystrophy or spastic paraplegia with early onset of urinary symptoms and spinal atrophy. PMID:23034915

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

    PubMed

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

    2015-06-01

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

  20. Anterolateral Radical Debridement and Interbody Bone Grafting Combined With Transpedicle Fixation in the Treatment of Thoracolumbar Spinal Tuberculosis

    PubMed Central

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

    2015-01-01

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

  1. Aculaser therapy for the treatment of cerebral palsy

    NASA Astrophysics Data System (ADS)

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

    2012-03-01

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

  2. Treating cerebral palsy with aculaser therapy

    NASA Astrophysics Data System (ADS)

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

    2008-03-01

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

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

    PubMed

    Gfhler, 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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Trbovich, Michelle

    2014-01-01

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

  6. The Risk Factors and Outcomes of Acute Kidney Injury after Thoracic Endovascular Aortic Repair

    PubMed Central

    Jeon, Yun-Ho; Bae, Chi-Hoon

    2016-01-01

    Background We aimed to evaluate the incidence, predictive factors, and impact of acute kidney injury (AKI) after thoracic endovascular aortic repair (TEVAR). Methods A total of 53 patients who underwent 57 TEVAR operations between 2008 and 2015 were reviewed for the incidence of AKI as defined by the RIFLE (risk, injury, failure, loss, and end-stage kidney disease risk) consensus criteria. The estimated glomerular filtration rate was determined in the perioperative period. Comorbidities and postoperative outcomes were retrospectively reviewed. Results Underlying aortic pathologies included 21 degenerative aortic aneurysms, 20 blunt traumatic aortic injuries, six type B aortic dissections, five type B intramural hematomas, three endoleaks and two miscellaneous diseases. The mean age of the patients was 61.2±17.5 years (range, 15 to 85 years). AKI was identified in 13 (22.8%) of 57 patients. There was an association of preoperative stroke and postoperative paraparesis and paraplegia with AKI. The average intensive care unit (ICU) stay in patients with AKI was significantly longer than in patients without AKI (5.3 vs. 12.7 days, p=0.017). The 30-day mortality rate in patients with AKI was significantly higher than patients without AKI (23.1% vs. 4.5%, p=0.038); however, AKI did not impact long-term survival. Conclusion Preoperative stroke and postoperative paraparesis and paraplegia were identified as predictors for AKI. Patients with AKI experienced longer average ICU stays and greater 30-day mortality than those without AKI. Perioperative identification of high-risk patients, as well as nephroprotective strategies to reduce the incidence of AKI, should be considered as important aspects of a successful TEVAR procedure. PMID:26889441

  7. Efficacy and vasodilatory benefit of magnesium prophylaxis for protection against spinal cord ischemia.

    PubMed

    Kohno, Hiroki; Ishida, Atsushi; Imamaki, Mizuho; Shimura, Hitoshi; Miyazaki, Masaru

    2007-05-01

    Prevention of paraplegia remains an imperative issue in thoracoabdominal aortic surgery. The aim of this study was to assess the efficacy of a prophylactic magnesium infusion in a rat spinal cord ischemia model and to demonstrate spinal blood flow increase caused by the infusion. The study was conducted in two parts. Firstly, the neuroprotective effect of magnesium was assessed using a rat model with two different ischemic times: 10 min and 14 min. Spinal cord ischemia was induced by occlusion of the descending aorta. Rats in the treatment group were given a 100 mg/kg magnesium sulfate infusion before ischemia. Secondly, relative changes in spinal cord blood flow before and during ischemia were recorded using the laser Doppler flowmetry technique. Changes in blood flow were compared between the magnesium and control groups. Rats pretreated with magnesium showed good overall recovery after both 10 min (incidence of paraplegia 62.5% control vs. 37.5% Mg, n = 8 each) and 14 min (85.7% control vs. 57.1% Mg, n = 7 each) of ischemia, although the differences compared with controls were statistically insignificant. However, the magnesium group showed significantly better neurological performance during the early postischemic period. Comparison of changes in spinal circulation revealed less reduction in blood flow during ischemia in the magnesium-treated group. In conclusion, magnesium may have potential prophylactic benefits during ischemia by exerting a neuroprotective effect through vasodilation of the spinal cord vasculature. To our knowledge, this vasodilatory effect on the spinal cord has not previously been investigated. Optimization of the treatment regimen, however, is required. PMID:17484971

  8. Preventive Effect of Intrathecal Paracetamol on Spinal Cord Injury in Rats

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    Boone, PhilipM.; Yuan, Bo; Campbell, IanM.; Scull, JenniferC.; Withers, MarjorieA.; Baggett, BrettC.; Beck, ChristineR.; Shaw, ChristineJ.; Stankiewicz, Pawel; Moretti, Paolo; Goodwin, WendyE.; Hein, Nichole; Fink, JohnK.; Seong, Moon-Woo; Seo, SooHyun; Park, SungSup; Karbassi, IzabelaD.; Batish, SatDev; Ordez-Ugalde, Andrs; Quintns, Beatriz; Sobrido, Mara-Jess; Stemmler, Susanne; Lupski, JamesR.

    2014-01-01

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

  10. Gait Analysis in Cervical Spondylotic Myelopathy

    PubMed Central

    Endo, Kenji; Suzuki, Hidekazu; Tanaka, Hidetoshi; Shishido, Takaaki; Yamamoto, Kengo

    2015-01-01

    Study Design Gait analysis of patients with cervical spondylotic myelopathy (CSM) by using a sheet-type gait analysis system. Purpose The aim of this study was to compare the gait patterns of patients with CSM, evaluated by the Nurick grades, and to determine the threshold values of gait parameters predicting the occurrence of a fall by using a gait recorder. Overview of Literature Gait disorder due to CSM may progress to severe paraplegia, following even a minor trauma such as a fall. The indications for the surgery of CSM without severe paralysis remain controversial. The quantitative gait analysis and the decision for decompressive surgery in patients with CSM are important in order to prevent severe paraplegia from a fall. Methods One hundred thirty-two subjects (normal, 34; CSM, 98) underwent gait analysis by using a sensor sheet. Measurements of gait cycle parameters included the step and stride length, step width, foot angle, swing phase, and stance phase. CSM was assessed by Nurick grade. Results Although the clinical symptoms were lacking, Nurick grade 1 had significant abnormalities in the parameters of velocity, step length, and step angle (p<0.05). Regarding the Nurick grade and walking phase, the length of the stance phase was increased to more than 70% of the entire walking cycle in Nurick grade 4. Conclusions Gait analysis was an objective tool for evaluating the gait stability. Our results suggested that when the percentage of the stance phase in the gait cycle increases to above 70%, the CSM patients have an increased fall risk. PMID:26097646

  11. Normative Blood Pressure and Heart Rate in Pediatric Spinal Cord Injury

    PubMed Central

    2013-01-01

    Background: Cardiovascular measures in children with spinal cord injury (SCI) may vary depending on the childs age and physical development in addition to injury-related factors. Developmental changes should be considered when addressing cardiovascular complications in this population. Objectives: To determine baseline blood pressure (BP) and heart rate (HR) measurements in youth with SCI, and to investigate differences in BP and HR in relation to age, gender, body mass index (BMI), and injury-related factors. Methods: Retrospective chart review was conducted for youth under 19 years who had been admitted for rehabilitation at 1 of 2 pediatric SCI programs. Systolic (SBP) and diastolic (DBP) blood pressures and HR were collected in the morning and afternoon on 3 consecutive days. Mean SBP, DBP, and HR were compared among 4 age groups (0-5 years, 6-12 years, 13-15 years, and 16-18 years) and by gender. Diurnal variations were determined according to level and severity of injury. Associations with BMI and injury-related factors were examined. Charts of 315 youths were reviewed: mean age was 12.3 years, 59% were male, 75% were Caucasian, 62% had complete injury, and 66% had paraplegia. Results: With increasing age, SBP and DBP increased and HR decreased. SBP and DBP were positively correlated with BMI. SBP was higher in males, those with incomplete injury, and those with paraplegia. HR was higher in females. There was no association between cardiovascular measures and injury duration. Conclusion: BP and HR are a function of age, BMI, and completeness and level of injury in youth with SCI. Awareness of baseline measures will allow for more effective management of cardiovascular complications, especially in youth presenting with atypical symptoms. PMID:23671378

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

    PubMed Central

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

    2015-01-01

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

  13. 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): 7.58.6) m/second, PARA: 9.0 (95% CI: 8.59.4) 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

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

    PubMed Central

    Chan, Sam Chi Chung; Chan, Alice Po Shan

    2013-01-01

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

  15. 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

  16. 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

  17. 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 weight changes, blood and brain lead content, and brain serotonin (5HT), norepinephrine (NE), dopamine (DA), and ?-aminobutyric acid (GABA). We have found that a lactating mother rat eating 5% lead acetate (2.73% Pb) produced milk containing 25 ppm lead. When the mothers' diet is changed at day 16 from 5% PbAc to one containing 25 ppm Pb, and neonates allowed free access to the solid diet, the sucklings still have retarded body growth but do not develop paraplegia or grossly apparent vascular damage of the cerebellum. However, during the fourth week these animals exhibit a less severe form of encephalopathy consisting of hyperactivity, tremors, and stereotype behavior. Pair-fed controls coetaneous to experimental groups do not display such activities. There was no change in brain 5HT, GABA, or NE, but a 1520% decrease in brain DA. Change in DA relative to other monoamines suggests a relationship between CNS dysfunction due to lead and DA metabolism in the brain. The experimental design as discribed provides a model of CNS dysfunction due to lead exposure without debilitating histopathologies. It is possible that our findings on increased motor activity and changes in brain dopamine may correspond to early responses to lead exposure before recognized overt signs of toxicity. ImagesFIGURE 1.FIGURE 2. PMID:4831141

  18. Brain-computer interface controlled robotic gait orthosis

    PubMed Central

    2013-01-01

    Background Excessive reliance on wheelchairs in individuals with tetraplegia or paraplegia due to spinal cord injury (SCI) leads to many medical co-morbidities, such as cardiovascular disease, metabolic derangements, osteoporosis, and pressure ulcers. Treatment of these conditions contributes to the majority of SCI health care costs. Restoring able-body-like ambulation in this patient population can potentially reduce the incidence of these medical co-morbidities, in addition to increasing independence and quality of life. However, no biomedical solution exists that can reverse this loss of neurological function, and hence novel methods are needed. Brain-computer interface (BCI) controlled lower extremity prostheses may constitute one such novel approach. Methods One able-bodied subject and one subject with paraplegia due to SCI underwent electroencephalogram (EEG) recordings while engaged in alternating epochs of idling and walking kinesthetic motor imagery (KMI). These data were analyzed to generate an EEG prediction model for online BCI operation. A commercial robotic gait orthosis (RoGO) system (suspended over a treadmill) was interfaced with the BCI computer to allow for computerized control. The subjects were then tasked to perform five, 5-min-long online sessions where they ambulated using the BCI-RoGO system as prompted by computerized cues. The performance of this system was assessed with cross-correlation analysis, and omission and false alarm rates. Results The offline accuracy of the EEG prediction model averaged 86.30% across both subjects (chance: 50%). The cross-correlation between instructional cues and the BCI-RoGO walking epochs averaged across all subjects and all sessions was 0.8120.048 (p-value <10?4). Also, there were on average 0.8 false alarms per session and no omissions. Conclusion These results provide preliminary evidence that restoring brain-controlled ambulation after SCI is feasible. Future work will test the function of this system in a population of subjects with SCI. If successful, this may justify the future development of BCI-controlled lower extremity prostheses for free overground walking for those with complete motor SCI. Finally, this system can also be applied to incomplete motor SCI, where it could lead to improved neurological outcomes beyond those of standard physiotherapy. PMID:24321081

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

    PubMed

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

    2015-09-01

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

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

    PubMed Central

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

    1990-01-01

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

  1. 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

  2. The Vocational Training FacilityAn Interactive Learning Program to Return Persons With Physical Disabilities to Employment.

    PubMed

    Hammel, J M; Van Der Loos, H F; Lepage, P; Burgar, C; Perkash, I; Shafer, D; Topp, E; Lees, D

    1994-01-01

    This paper describes the results of the program-development phase of the Vocational Training Facility (VTF) taking place at the Palo Alto Veterans Affairs Medical Center Rehabilitation Research and Development Center. The VTF staff has developed a self-paced, multimedia curriculum comprised of adapted training packages, interactive videos, and additional training and testing materials designed to teach entry-level desktop publishing and reasonable accommodation skills to individuals with spinal cord injuries. The curriculum is taught via the Macintosh computer to allow independent, "hands-off" access to training materials. Each student is given an integrated workstation that is equipped with the Desktop Vocational Assistant Robot (De VAR); a set of low-and high-technology assistive hardware, software, and devices; and ergonomic furniture and adaptations customized to fit individual learning and access needs. Each student completes a 12-week, full-time training program followed by a 3-month internship with a local corporate sponsor. This paper summarizes the evaluation results of the VTF program by the first nine students, with spinal cord injuries ranging paraplegia to high-level quadriplegia, who have completed the program. PMID:24441006

  3. 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

  4. 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

  5. Spinal tuberculosis: A review

    PubMed Central

    Garg, Ravindra Kumar; Somvanshi, Dilip Singh

    2011-01-01

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

  6. 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

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

    PubMed Central

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

    2012-01-01

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

  8. Proteolipid Protein Is Required for Transport of Sirtuin 2 into CNS Myelin

    PubMed Central

    Werner, Hauke B.; Kuhlmann, Katja; Shen, Siming; Uecker, Marina; Schardt, Anke; Dimova, Kalina; Orfaniotou, Foteini; Dhaunchak, Ajit; Brinkmann, Bastian G.; Mbius, Wiebke; Guarente, Lenny; Casaccia-Bonnefil, Patrizia; Jahn, Olaf; Nave, Klaus-Armin

    2009-01-01

    Mice lacking the expression of proteolipid protein (PLP)/DM20 in oligodendrocytes provide a genuine model for spastic paraplegia (SPG-2). Their axons are well myelinated but exhibit impaired axonal transport and progressive degeneration, which is difficult to attribute to the absence of a single myelin protein. We hypothesized that secondary molecular changes in PLPnull myelin contribute to the loss of PLP/DM20-dependent neuroprotection and provide more insight into glia-axonal interactions in this disease model. By gel-based proteome analysis, we identified >160 proteins in purified myelin membranes, which allowed us to systematically monitor the CNS myelin proteome of adult PLPnull mice, before the onset of disease. We identified three proteins of the septin family to be reduced in abundance, but the nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase sirtuin 2 (SIRT2) was virtually absent. SIRT2 is expressed throughout the oligodendrocyte lineage, and immunoelectron microscopy revealed its association with myelin. Loss of SIRT2 in PLPnull was posttranscriptional, suggesting that PLP/DM20 is required for its transport into the myelin compartment. Because normal SIRT2 activity is controlled by the NAD+/NADH ratio, its function may be coupled to the axo-glial metabolism and the long-term support of axons by oligodendrocytes. PMID:17634366

  9. Common injuries in preadolescent and adolescent athletes. Recommendations for prevention.

    PubMed

    Stanitski, C L

    1989-01-01

    In general, children and youth sports are safe. The great majority of injuries which are sustained are minor and self-limiting. Fortunately, catastrophic acute injuries such as paraplegia, quadriplegia and major limb insults are rare. The 2 mechanisms of injuries at these age groups are acute traumatic insults and unresolved sequelae of repetitive microtrauma. The latter usually results from inappropriate training and coaching techniques. In the United States, adolescents and children are becoming involved in sport at earlier ages and with higher levels of intensity and competition. Factors which lead to injury include the athlete and his/her own psychobiology, inappropriate equipment, the sports environment (playing surfaces, temperature), training and coaching errors, and parental influences. Preparticipation assessment usually reveals extremely healthy children with rare factors which contribute to non-sports participation. Preventative efforts must be made to provide these children with the appropriate equipment and coaching to limit the number of overuse injuries. Management of acute sports problems and rehabilitation of significant injuries are as important in childhood and youth sports as in those of their older sibs in order to prevent lifelong sequelae of musculoskeletal injury. The appropriate goal of children and youth sports must remain one of enjoyment with acquisition of sport-specific skills. PMID:2652244

  10. 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

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

    PubMed

    Fakhoury, Marc

    2015-01-01

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

  12. 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

  13. Data supporting mitochondrial morphological changes by SPG13-associated HSPD1 mutants.

    PubMed

    Miyamoto, Yuki; Megumi, Funakoshi-Tago; Hasegawa, Nanami; Eguchi, Takahiro; Tanoue, Akito; Tamura, Hiroomi; Yamauchi, Junji

    2016-03-01

    The data is related to the research article entitled "Hypomyelinating leukodystrophy-associated missense mutation in HSPD1 blunts mitochondrial dynamics" [1]. In addition to hypomyelinating leukodystrophy (HLD) 4 (OMIM no. 612233), it is known that spastic paraplegia (SPG) 13 (OMIM no. 605280) is caused by HSPD1's amino acid mutation. Two amino acid mutations Val-98-to-Ile (V98I) and Gln-461-to-Glu (Q461E) are associated with SPG13 [2]. In order to investigate the effects of HSPD1's V98I or Q461E mutant on mitochondrial morphological changes, we transfected each of the respective mutant-encoding genes into Cos-7 cells. Either of V98I or Q461E mutant exhibited increased number of mitochondria and short length mitochondrial morphologies. Using MitoTracker dye-incorporating assay, decreased mitochondrial membrane potential was also observed in both cases. The data described here supports that SPG13-associated HSPD1 mutant participates in causing aberrant mitochondrial morphological changes with decreased activities. PMID:26900593

  14. 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.

  15. Imaging features and differentials in surfer's myelopathy: a case report.

    PubMed

    Teixeira, Stephanie; Moser, Franklin; Kotton, Ryan H

    2016-02-01

    Surfer's myelopathy is a rare non-traumatic cause of myelopathy found in novice surfers. We present a case of a 23-year-old female who developed acute and rapidly progressive bilateral lower extremity paraplegia, paresthesia, and anesthesia, accompanied by lower back discomfort and bowel and bladder dysfunction after surfing for the first time. She had a past history of auto-resolved lower extremity weakness that could be related to anatomy variation of spinal cord vascular supply. This individual variation could have increased the risk for ischemic myelopathy after prolonged prone position with back hyperextension on the surf board. We discuss radiological findings of acute spinal cord infarct and longitudinal extensive transverse myelitis (LETM) as possible differentials in this case. The diagnosis of surfer's myelopathy relies on a first time surfing history since the clinical and radiological presentations can be similar to other entities in some cases. Thus, we highlight the importance of a full clinical report and efficient communication between referring clinicians and radiologists for a precise and early diagnosis. PMID:26394636

  16. 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.

  17. 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.

  18. 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.

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

    PubMed Central

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

    2015-01-01

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

  20. 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 4013 years, time since injury 1210 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 3.4kJ (16%) higher (P=0.006) than during handcycling. Furthermore, compared with handcycling, the overall heart rate and ventilation during hybrid cycling was 11bpm (11%) and 5.3l/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

  1. 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-Neuhuser 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 29C, when significant degeneration has already occurred, and significantly extends longevity of mutants at 25C. 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

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

    PubMed Central

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

    2015-01-01

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

  3. Neuromuscular scoliosis.

    PubMed

    Allam, Anand M; Schwabe, Aloysia L

    2013-11-01

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

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

    PubMed

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

    2015-01-01

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

  5. Motor neuron diseases and neurotoxic substances: a possible link?

    PubMed

    Chang, Ping-An; Wu, Yi-Jun

    2009-07-15

    The motor neuron diseases (MNDs) are a group of related neurodegenerative diseases that cause the relative selective progressive death of motor neurons. Exploring the molecular mechanisms underlying MND phenotypes has been hampered by their multifactorial nature and high incidence of sporadic cases, although genetic factors are considered to play a considerable role at present. However, environmental factors, especial exposure to neurotoxic substances, could induce neurotoxicity with the same phenotypes of specific MNDs. Organophosphate-induced delayed neuropathy (OPIDN) is a neurodegenerative disorder characterized by ataxia and progression to paralysis, with a concomitant distal axonal degeneration and secondary demyelination of central and peripheral axons. The inhibition and subsequent aging of neuropathy target esterase (NTE) by organophosphate has been proposed to be the initiating event in OPIDN. NTE is characterized to be a lysophospholipase/phospholipase B mostly in the nervous system to regulate phospholipid homeostasis. Brain-specific deletion of mouse NTE contributes to the behavioral defects characterized by neuronal loss. Recently, mutations in human NTE have also been shown to cause a hereditary spastic paraplegia called NTE-related motor neuron disorder with the same characteristics of OPIDN, which supported the role of NTE abnormalities in OPIDN, and raised the possibility that NTE pathway disturbances contribute to other MNDs. Together with the identified association of paraoxonase polymorphisms with amyotrophic lateral sclerosis, there is a possibility that neurotoxic substances contribute to MND in genetically vulnerable people by gene-environment interactions. PMID:19497409

  6. 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

  7. Physical activity is related to lower levels of pain, fatigue, and depression in individuals with spinal cord injury: A correlational study

    PubMed Central

    Tawashy, A; Eng, JJ; Lin, KH; Tang, PF; Hung, C

    2011-01-01

    Study Design This was a prospective cross-sectional study for people with chronic SCI. Objectives To (1) evaluate the intensity level and nature of physical activity in community-dwelling individuals living with SCI, and (2) explore the relation between descriptive individual variables (e.g. lesion level), secondary complications, and participation in physical activity. Setting Urban community setting Methods Forty-nine subjects with SCI who used a manual wheelchair for primary mode of mobility (mean years since injury, 11.8; mean age, 43.7 years; 67% paraplegia) completed the physical activity recall assessment for people with spinal cord injury (PARA-SCI). Results Approximately 50% of reported physical activity among individuals with SCI is due to activities of daily living. The amount of physical activity was not related to lesion level, age, BMI, or waistline size. Greater heavy intensity activity was related to lower levels of pain and fatigue and higher levels of self efficacy while higher amounts of mild intensity activity and total activity were related to less depressive symptoms. Conclusions Activities of daily living are a large component for physical activity among individuals with SCI. It appears that greater physical activity is associated with less secondary complications (pain, fatigue and depression) in individuals with SCI. PMID:18936771

  8. 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

  9. Radiotherapy of Bone Metastasis in Breast Cancer Patients Current Approaches

    PubMed Central

    Feyer, Petra C.; Steingraeber, Maria

    2012-01-01

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

  10. Loss of phosphatidylinositol 4-kinase 2? activity causes late onset degeneration of spinal cord axons

    PubMed Central

    Simons, J. Paul; Al-Shawi, Raya; Minogue, Shane; Waugh, Mark G.; Wiedemann, Claudia; Evangelou, Stylianos; Loesch, Andrzej; Sihra, Talvinder S.; King, Rosalind; Warner, Thomas T.; Hsuan, J. Justin

    2009-01-01

    Phosphoinositide (PI) lipids are intracellular membrane signaling intermediates and effectors produced by localized PI kinase and phosphatase activities. Although many signaling roles of PI kinases have been identified in cultured cell lines, transgenic animal studies have produced unexpected insight into the in vivo functions of specific PI 3- and 5-kinases, but no mammalian PI 4-kinase (PI4K) knockout has previously been reported. Prior studies using cultured cells implicated the PI4K2? isozyme in diverse functions, including receptor signaling, ion channel regulation, endosomal trafficking, and regulated secretion. We now show that despite these important functions, mice lacking PI4K2? kinase activity initially appear normal. However, adult Pi4k2aGT/GT animals develop a progressive neurological disease characterized by tremor, limb weakness, urinary incontinence, and premature mortality. Histological analysis of aged Pi4k2aGT/GT animals revealed lipofuscin-like deposition and gliosis in the cerebellum, and loss of Purkinje cells. Peripheral nerves are essentially normal, but massive axonal degeneration was found in the spinal cord in both ascending and descending tracts. These results reveal a previously undescribed role for aberrant PI signaling in neurological disease that resembles autosomal recessive hereditary spastic paraplegia. PMID:19581584

  11. 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

  12. An ESCRTspastin interaction promotes fission of recycling tubules from the endosome

    PubMed Central

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

    2013-01-01

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

  13. 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

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

    PubMed Central

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

    2013-01-01

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

  15. 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

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

    PubMed

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

    2012-06-01

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

  17. 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

  18. Sexual issues of women with spinal cord injuries.

    PubMed

    Charlifue, S W; Gerhart, K A; Menter, R R; Whiteneck, G G; Manley, M S

    1992-03-01

    The need for research addressing problems unique to women with spinal cord injuries is well documented. Consequently, 231 such women, ages 18 to 45, were surveyed. Demographic characteristics and data relating to physician usage, female hygiene, pregnancy, contraception and sexuality were collected. Analysis revealed that 60% of the respondents had post injury amenorrhea; the average time until menses resumption was 5 months. The group's post injury pregnancy rate was one-third its pre injury rate, but women with incomplete paraplegia had significantly more pregnancies than those with complete quadriplegia. Of 47 women who did carry babies to delivery, one-half had vaginal deliveries; 49% used no anesthesia. Problems during pregnancy included autonomic hyperreflexia, decubitus ulcers, urinary tract infections, water retention, bladder and bowel problems, anemia, spotting, fatigue, cardiac irregularity and toxemia. Many of these problems plagued the women during labor and delivery and in the post partum period as well. Sixty-nine percent of the women were satisfied with their post injury sexual experiences, although self confidence, spasticity, and lack of spontaneity were issues. Although satisfied with care received from physicians, many women were not content with the information provided during rehabilitation, and felt a need for more literature, counselling, and peer support. PMID:1630847

  19. WASH and WAVE actin regulators of the WiskottAldrich syndrome protein (WASP) family are controlled by analogous structurally related complexes

    PubMed Central

    Jia, Da; Gomez, Timothy S.; Metlagel, Zoltan; Umetani, Junko; Otwinowski, Zbyszek; Rosen, Michael K.; Billadeau, Daniel D.

    2010-01-01

    We recently showed that the WiskottAldrich syndrome protein (WASP) family member, WASH, localizes to endosomal subdomains and regulates endocytic vesicle scission in an Arp2/3-dependent manner. Mechanisms regulating WASH activity are unknown. Here we show that WASH functions in cells within a 500kDa core complex containing Strumpellin, FAM21, KIAA1033 (SWIP), and CCDC53. Although recombinant WASH is constitutively active toward the Arp2/3 complex, the reconstituted core assembly is inhibited, suggesting that it functions in cells to regulate actin dynamics through WASH. FAM21 interacts directly with CAPZ and inhibits its actin-capping activity. Four of the five core components show distant (approximately 15% amino acid sequence identify) but significant structural homology to components of a complex that negatively regulates the WASP family member, WAVE. Moreover, biochemical and electron microscopic analyses show that the WASH and WAVE complexes are structurally similar. Thus, these two distantly related WASP family members are controlled by analogous structurally related mechanisms. Strumpellin is mutated in the human disease hereditary spastic paraplegia, and its link to WASH suggests that misregulation of actin dynamics on endosomes may play a role in this disorder. PMID:20498093

  20. Systemic interleukin 12 displays anti-tumour activity in the mouse central nervous system.

    PubMed Central

    Kishima, H.; Shimizu, K.; Miyao, Y.; Mabuchi, E.; Tamura, K.; Tamura, M.; Sasaki, M.; Hakakawa, T.

    1998-01-01

    In various systemic cancers, interleukin 12 (IL-12) induces anti-tumour immunity mediated by T lymphocytes and natural killer cells. To determine whether IL-12 has anti-tumour activity against malignant gliomas in the central nervous system (CNS), which is considered to be an immunologically privileged site, we treated mice with meningeal gliomatosis by intraperitoneal (i.p.) or intrathecal (i.t.) administration of recombinant murine IL-12. Although untreated mice revealed symptoms, such as body weight loss or paraplegia as a result of the meningeal gliomatosis within 8 days after tumour inoculation, 80% of the mice treated with IL-12 at 0.5 microg i.p. were cured. Many lymphocytes, mostly CD4+ and CD8+ cells, infiltrated to the tumours of IL-12-treated mice. The numbers of these cells increased in the cervical lymph nodes, into which the cerebrospinal fluid drains, and there they secreted a considerable amount of interferon-gamma. Mice cured by IL-12 rejected subcutaneous or i.t. rechallenge with their original glioma cells, but the same mice were not able to reject other syngeneic tumour cells. These results indicate that the immune system recognizes malignant glioma cells in the subarachnoid space of the CNS and that systemic IL-12 may produce effective anti-tumour activity and long-lasting tumour-specific immunity. Images Figure 1 Figure 4 PMID:9716025

  1. Mitochondria-associated membranes as hubs for neurodegeneration.

    PubMed

    Krols, Michiel; van Isterdael, Gert; Asselbergh, Bob; Kremer, Anna; Lippens, Saskia; Timmerman, Vincent; Janssens, Sophie

    2016-04-01

    There is a growing appreciation that membrane-bound organelles in eukaryotic cells communicate directly with one another through direct membrane contact sites. Mitochondria-associated membranes are specialized subdomains of the endoplasmic reticulum that function as membrane contact sites between the endoplasmic reticulum and mitochondria. These sites have emerged as major players in lipid metabolism and calcium signaling. More recently also autophagy and mitochondrial dynamics have been found to be regulated at ER-mitochondria contact sites. Neurons critically depend on mitochondria-associated membranes as a means to exchange metabolites and signaling molecules between these organelles. This is underscored by the fact that genes affecting mitochondrial and endoplasmic reticulum homeostasis are clearly overrepresented in several hereditary neurodegenerative disorders. Conversely, the processes affected by the contact sites between the endoplasmic reticulum and mitochondria are widely implicated in neurodegeneration. This review will focus on the most recent data addressing the structural composition and function of the mitochondria-associated membranes. In addition, the 3D morphology of the contact sites as observed using volume electron microscopy is discussed. Finally, it will highlight the role of several key proteins associated with these contact sites that are involved not only in dementias, amyotrophic lateral sclerosis and Parkinson's disease, but also in axonopathies such as hereditary spastic paraplegia and Charcot-Marie-Tooth disease. PMID:26744348

  2. 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

  3. Tuberculous radiculomyelitis (arachnoiditis): myelographic (and CT myelographic) appearances.

    PubMed

    Phadke, R V; Kohli, A; Jain, V K; Gupta, R K; Kumar, S; Gujral, R B

    1994-02-01

    Tuberculous radiculomyelitis (arachnoiditis) remains one of the important causes of paraplegia in India. The diagnosis usually rests on clinical history and examination, and on laboratory findings in the cerebro-spinal fluid (CSF). Few descriptive reports are available of the myelographic appearance, with water-soluble contrast media, in tuberculous radioculomyelitis (arachnoiditis). A retrospective review of 21 myelograms and 10 computed tomographic (CT) myelograms, in 14 patients with tuberculous radiculomyelitis, was carried out, with a view to describing, in detail, the radiographic features. An attempt was made to assess the use of the radiologic procedures in diagnosis and follow up in these patients. Conventional myelographic findings included block (8/14), irregular subarachnoid space (9/14), filling defects (8/14), sluggish contrast flow (2/14), root thickening (3/14) and atrophic cord (2/14). Computed tomographic myelography showed reduced contrast density in portions of the opacified CSF ring around the cord in affected region (6/7) and, in addition, demonstrated septa and adhesions. Intravenous contrast CT was not found to be useful (2/2). Follow-up studies showed partial resolution (3/6), deterioration (1/6) and status quo of radiological findings (2/6). Although these changes can be seen in chronic radiculomyelitis (arachnoiditis) from other causes, such as leukaemic infiltration/lymphoma, other chronic central nervous system infections and iatrogenic causes, including repeated intrathecal injections, conventional myelography appeared to be useful for diagnosis and follow up in tuberculous radiculomyelitis (arachnoiditis). PMID:8147791

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

    PubMed

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

    2015-09-01

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

  5. 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

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

    PubMed Central

    Martinez-Carrera, Lilian A.; Wirth, Brunhilde

    2015-01-01

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

  7. Disruption of axonal transport in motor neuron diseases.

    PubMed

    Ikenaka, Kensuke; Katsuno, Masahisa; Kawai, Kaori; Ishigaki, Shinsuke; Tanaka, Fumiaki; Sobue, Gen

    2012-01-01

    Motor neurons typically have very long axons, and fine-tuning axonal transport is crucial for their survival. The obstruction of axonal transport is gaining attention as a cause of neuronal dysfunction in a variety of neurodegenerative motor neuron diseases. Depletions in dynein and dynactin-1, motor molecules regulating axonal trafficking, disrupt axonal transport in flies, and mutations in their genes cause motor neuron degeneration in humans and rodents. Axonal transport defects are among the early molecular events leading to neurodegeneration in mouse models of amyotrophic lateral sclerosis (ALS). Gene expression profiles indicate that dynactin-1 mRNA is downregulated in degenerating spinal motor neurons of autopsied patients with sporadic ALS. Dynactin-1 mRNA is also reduced in the affected neurons of a mouse model of spinal and bulbar muscular atrophy, a motor neuron disease caused by triplet CAG repeat expansion in the gene encoding the androgen receptor. Pathogenic androgen receptor proteins also inhibit kinesin-1 microtubule-binding activity and disrupt anterograde axonal transport by activating c-Jun N-terminal kinase. Disruption of axonal transport also underlies the pathogenesis of spinal muscular atrophy and hereditary spastic paraplegias. These observations suggest that the impairment of axonal transport is a key event in the pathological processes of motor neuron degeneration and an important target of therapy development for motor neuron diseases. PMID:22312314

  8. Disruption of Axonal Transport in Motor Neuron Diseases

    PubMed Central

    Ikenaka, Kensuke; Katsuno, Masahisa; Kawai, Kaori; Ishigaki, Shinsuke; Tanaka, Fumiaki; Sobue, Gen

    2012-01-01

    Motor neurons typically have very long axons, and fine-tuning axonal transport is crucial for their survival. The obstruction of axonal transport is gaining attention as a cause of neuronal dysfunction in a variety of neurodegenerative motor neuron diseases. Depletions in dynein and dynactin-1, motor molecules regulating axonal trafficking, disrupt axonal transport in flies, and mutations in their genes cause motor neuron degeneration in humans and rodents. Axonal transport defects are among the early molecular events leading to neurodegeneration in mouse models of amyotrophic lateral sclerosis (ALS). Gene expression profiles indicate that dynactin-1 mRNA is downregulated in degenerating spinal motor neurons of autopsied patients with sporadic ALS. Dynactin-1 mRNA is also reduced in the affected neurons of a mouse model of spinal and bulbar muscular atrophy, a motor neuron disease caused by triplet CAG repeat expansion in the gene encoding the androgen receptor. Pathogenic androgen receptor proteins also inhibit kinesin-1 microtubule-binding activity and disrupt anterograde axonal transport by activating c-Jun N-terminal kinase. Disruption of axonal transport also underlies the pathogenesis of spinal muscular atrophy and hereditary spastic paraplegias. These observations suggest that the impairment of axonal transport is a key event in the pathological processes of motor neuron degeneration and an important target of therapy development for motor neuron diseases. PMID:22312314

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

    PubMed

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

    2015-01-01

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

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

    PubMed

    Jordan, Lorraine M; Quraishi, Jihan A

    2015-10-01

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

  11. Autologous mesenchymal stem cells applied on the pressure ulcers had produced a surprising outcome in a severe case of neuromyelitis optica.

    PubMed

    Dulamea, Adriana Octaviana; Sirbu-Boeti, Mirela-Patricia; Bleotu, Coralia; Dragu, Denisa; Moldovan, Lucia; Lupescu, Ioana; Comi, Giancarlo

    2015-11-01

    Recent studies provided evidence that mesenchymal stem cells (MSCs) have regenerative potential in cutaneous repair and profound immunomodulatory properties making them a candidate for therapy of neuroimmunologic diseases. Neuromyelitis optica (NMO) is an autoimmune, demyelinating central nervous system disorder characterized by a longitudinally extensive spinal cord lesion. A 46-year-old male diagnosed with NMO had relapses with paraplegia despite treatment and developed two stage IV pressure ulcers (PUs) on his legs. The patient consented for local application of autologous MSCs on PUs. MSCs isolated from the patient's bone marrow aspirate were multiplied in vitro during three passages and embedded in a tridimensional collagen-rich matrix which was applied on the PUs. Eight days after MSCs application the patient showed a progressive healing of PUs and improvement of disability. Two months later the patient was able to walk 20 m with bilateral assistance and one year later he started to walk without assistance. For 76 months the patient had no relapse and no adverse event was reported. The original method of local application of autologous BM-MSCs contributed to healing of PUs. For 6 years the patient was free of relapses and showed an improvement of disability. The association of cutaneous repair, sustained remission of NMO and improvement of disability might be explained by a promotion/optimization of recovery mechanisms in the central nervous system even if alternative hypothesis should be considered. Further studies are needed to assess the safety and efficacy of mesenchymal stem cells in NMO treatment. PMID:26807122

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

    PubMed Central

    Jara, Javier H.; Gen, Bar??; Klessner, Jodi L.; zdinler, P. Hande

    2014-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  14. Endovascular interventions for descending thoracic aortic aneurysms: The pivotal role of the clinical nurse in postoperative care.

    PubMed

    Dolinger, Cami; Strider, David V

    2010-12-01

    Descending thoracic aortic aneurysms (dTAA) comprise 40% of all aneurysms arising from the thoracic aorta. Because rupture of thoracic aneurysms is associated with a 94% mortality rate, timely detection, surveillance and treatment is imperative. Endovascular stent-graft repair of thoracic aneurysms was first performed in 1992 and has become an accepted treatment option for this condition in select candidates. There is an abundance of information for the care of patients after open surgical repair of dTAA. However, still relatively few written guidelines exist in the nursing literature for postoperative care and complications associated with endovascular stent-graft repair. The prevalence of aortic endografting, however, now makes it necessary for nurses to have a solid knowledge base in the operative procedure, complications and postoperative care for this patient population. Ideal candidates for aortic endografting undergo CTA or MRI preoperatively and fit a set of strict anatomic criteria to ensure proper delivery and fixation of the device. The early postoperative care focuses on minimizing pulmonary complications, paraplegia, renal failure and embolic complications such as stroke and limb ischemia through skilled nursing assessment and interventions. Late complications such as stent-graft migration, kinking, stent fracture and endoleak are often without symptoms, making it necessary for patients to be educated about these potential complications and to be encouraged to comply with lifelong follow up. This overview provides a sound cognitive framework for nurses practicing in a vascular surgery milieu. PMID:21074117

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

    PubMed Central

    Kang, Eun-Na; Shin, Hyung-Ik

    2014-01-01

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

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

    PubMed

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

    2014-04-01

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

  17. Veno-venous extracorporeal membrane oxygenation therapy of a severely injured patient after secondary survey.

    PubMed

    Stoll, M C; Rademacher, F; Klak, K; Strauch, J; Schildhauer, T A; Swol, J

    2014-10-01

    Thoracic injury following a major trauma can be life threatening. Veno-venous extracorporeal membrane oxygenation (vv-ECMO) can be used as a support to mechanical ventilation when acute respiratory distress syndrome is present. We report the case of an 18-year-old male driver who strayed from the road and fell 15 m into a backyard by landing on the roof of its car. The injury severity score was 51 for his pattern of injuries (hemopneumothorax left, sternum fracture, pneumothorax right, pneumomediastinum, intracerebral bleeding, scalping injury occipital, fracture of the ninth thoracic vertebral body, and complete paraplegia). The patient was transferred to our hospital 12 hours after the accident. As we started the secondary survey, the patient was cannulated for vv-ECMO due to deterioration in his oxygenation status. We implanted a double-lumen cannula (Avalon31F catheter, right internal jugular vein) during fluoroscopy. The patient developed posttraumatic systemic inflammatory response syndrome, which began to resolve after 72 hours, and he started breathing spontaneously. After 7 days, he was weaned from vv-ECMO and recovered in a rehabilitation facility. The use of vv-ECMO therapy in cases of major trauma has become a rescue strategy. The use of vv-ECMO was performed without anticoagulation because of his traumatic brain injury and severe spinal cord injury. PMID:24848416

  18. Introduction: Chronic Medical Conditions and Depression: the View from Primary Care

    PubMed Central

    Kravitz, Richard L.; Ford, Daniel

    2009-01-01

    Martin Hickman maneuvered his way into the office and pulled up his sleeve as the medical assistant put the brake on his wheelchair and attached the blood pressure cuff around his oversized upper arm. A bulky 56-year-old man with a heavy shock of gray hair teetering on the edge of his forehead, his problem list included type 2 diabetes, chronic obstructive pulmonary disease, hypertension, obesity, and hyperlipidemia. For the past 15 years he has used a wheelchair due to T4 paraplegia from a gunshot wound. He has also suffers from bouts of major depression that respond to sertraline but never fully remit. As the medical assistant inflated the cuff, Mr. Hickman smiled weakly and maintained a cheerful faade even after she informed him that his blood pressure was 164/88 mm Hg and his glucose was 267 mg/dl (both well above goal). Later, on more careful questioning by his primary care physician, Hickman admitted that he was feeling more down than usual and that he sometimes neglected to take his diabetes medicine and blood pressure pills. Thinking back over the years he had cared for this patient, the physician recalled that December tended to be a particularly bad month. Social isolation, tolerable for most of the year, became painful around the holidays. December also happened to mark the anniversary of Hickman's spinal cord injury. The clock was running, the waiting room was full, and the physician realized he was already falling behind. PMID:18954587

  19. Visceral Debranching for the Treatment of Thoracoabdominal Aortic Aneurysms

    PubMed Central

    Damrauer, Scott M.; Fairman, Ron M.

    2015-01-01

    Surgical repair of thoracoabdominal aortic aneurysms (TAAA) is associated with significant morbidity and mortality. Hybrid approaches that involve visceral debranching and aortic endografting allow for an alternative approach in certain high-risk patients. In most circumstances the visceral vessels can be bypassed in a retrograde manner from the iliac arteries via a midline laparotomy, and the aortic aneurysm subsequently excluded with standard aortic endografts. These procedures avoid the extensive two-cavity exposure, aortic cross-clamping, and mechanical circulatory support that comprise open TAAA repair, and offer the theoretical advantage of being less invasive. Despite this, outcomes have been mixed with reported perioperative mortality rates of 0% and 34% and permanent paraplegia rates of 0% to 13% in most major series. The reported outcomes, as well as the variation between centers, highlight the importance of patient selection in undertaking hybrid repair. In practice, the best outcomes are achieved in patients who have high-risk anatomy, rather than high-risk comorbidities. PMID:26798760

  20. Rehabilitation and long-term course of nontraumatic myelopathy associated with surfing.

    PubMed

    Aoki, Masahiro; Moriizumi, Shigehiro; Toki, Megumi; Murakami, Takanori; Ishiai, Sumio

    2013-09-01

    A nontraumatic spinal cord injury related to surfing is called surfer's myelopathy. The case of a 26-yr-old man who became paraplegic after surfing without apparent traumatic events is described. Physical examination revealed a spinal cord injury at T12 according to the American Spinal Injury Association Impairment Scale A. The initial magnetic resonance image revealed a fusiform swelling of the spinal cord from T7-8 to the conus, which was hyperintense on T2-weighted images. After 6 mos of rehabilitation, the patient was followed for more than 1 yr after onset. He became able to walk with knee-ankle-foot-orthoses without assistance. A magnetic resonance image obtained 1 yr after the onset of paraplegia showed an atrophic spinal cord from T7-8 to the conus. The course of the neurologic findings and the imaging studies suggest that the pathogenesis of surfer's myelopathy may be ischemia of the anterior spinal artery territory induced by the abnormal trunk posture while surfing. PMID:22019977

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

    PubMed

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

    2015-02-01

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

  2. A novel GBA2 gene missense mutation in spastic ataxia.

    PubMed

    Votsi, Christina; Zamba-Papanicolaou, Eleni; Middleton, Lefkos T; Pantzaris, Marios; Christodoulou, Kyproula

    2014-01-01

    Autosomal recessive cerebellar ataxias (ARCA) encompass a heterogeneous group of rare diseases that affect the cerebellum, the spinocerebellar tract and/or the sensory tracts of the spinal cord. We investigated a consanguineous Cypriot family with spastic ataxia, aiming towards identification of the causative mutation. Family members were clinically evaluated and studied at the genetic level. Linkage analysis at marker loci spanning known ARCA genes/loci revealed linkage to the APTX locus. Thorough investigation of the APTX gene excluded any possible mutation. Whole genome linkage screening using microsatellite markers and whole genome SNP homozygosity mapping using the Affymetrix Genome-Wide Human SNP Array 6.0 enabled mapping of the disease gene/mutation in this family to Chromosome 9p21.1-p13.2. Due to the large number of candidate genes within this region, whole-exome sequencing of the proband was performed and further analysis of the obtained data focused on the mapped interval. Further investigation of the candidate variants resulted in the identification of a novel missense mutation in the GBA2 gene. GBA2 mutations have recently been associated with hereditary spastic paraplegia and ARCA with spasticity. We hereby report a novel GBA2 mutation associated with spastic ataxia and suggest that GBA2 mutations may be a relatively frequent cause of ARCA. PMID:24252062

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

    PubMed

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

    2015-02-17

    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

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

    PubMed

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

    2015-04-01

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

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

    PubMed Central

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

    2015-01-01

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

  6. 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

  7. 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

  8. [High voltage accidents, characteristics and treatment].

    PubMed

    Hlsbergen-Krger, S; Pitzler, D; Partecke, B D

    1995-04-01

    High-voltage injuries cause localised entrance and exit burns, extensive arc, flame and flash burns and, even more dangerous, necrosis of the underlying muscles on the pathway of the current through the body. Therefore it should be recognized that the ensuing disease is more like a crush injury than a thermal burn. The extent of injury cannot be judged by the percentage and depth of the skin burn. Diagnostic fasciotomies, radical debridement, and in many cases early amputation are necessary to prevent life-threatening complications. Over a period of 10 years, 43 patients with high-voltage injuries have been treated at the Hamburg Burn Center, 36 of them in primary care. Common causes of injury were accidents in railway areas (28%), using portable aluminium ladders near overhead power lines (9.3%), and working on electrical equipment (30.2%). Six of the primary care patients died (16.6%), and 34.9% had an amputation of one or more extremities. Nearly all patients underwent several debridement and split-skin graft procedures. In 30% of cases additional free and pedicled flaps were needed to cover soft tissue defects. Ten patients (23.3%) sustained fractures and other injuries from falls, seven (16.3%) of them severe polytrauma. Initial cardiac arrhythmics were diagnosed in 16.6% of the primarily treated patients. Thirty per cent of our patients had neurological complications such as peripheral paresis, tetraplegia and paraplegia, 20.7% of these caused solely by the electric current. PMID:7761869

  9. Absence of alsin function leads to corticospinal motor neuron vulnerability via novel disease mechanisms

    PubMed Central

    Gautam, Mukesh; Jara, Javier H.; Sekerkova, Gabriella; Yasvoina, Marina V.; Martina, Marco; Özdinler, P. Hande

    2016-01-01

    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 (AlsinKO) 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 AlsinKO-UeGFP mice, by crossing AlsinKO 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

  10. Spinal injuries at the University Hospital of the West Indies.

    PubMed

    Bruce, C A; Donaldson, G; Palmer, W; Crandon, I W

    2000-09-01

    Acute spinal damage forms a small percentage of total trauma injury but it has tremendous significance because of the resultant disability, poor prognosis, economic and social cost and the burden on victims, family, taxpayers and health workers. Of fifty-five patients admitted to the University Hospital of the West Indies (UHWI), Mona, Jamaica, over a seven-year period, forty form the basis of this report. Young males accounted for most victims and 85% of the injuries were non-intentional. The cervical spine, most commonly C6, was the region most frequently injured, followed by the lumbar and the thoracic regions. On admission, the mean Glasgow Coma Score was 14.6 and the mean Modified Injury Severity Score 12.7. Five patients were admitted in Frankel Grade A, complete paraplegia. Of eighteen patients treated with steroids, only eleven had methylprednisolone and only six of these appropriately. Nine patients had surgery after a mean time of 10.1 days. The average length of hospital stay was 18.2 days. Of 35 patients whose outcomes were known, eleven improved; two patients died in hospital. With the modernization of the management of this condition, we recommend that attention be focused on prevention, pre-hospital immobilization and transport, prompt resuscitation, the standardization of written protocols and early operative intervention. Also essential is the continuing medical education of all levels of personnel and the formalization of a well-coordinated and rehearsed Spine team. PMID:11076213

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-06-01

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

  13. 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

  14. 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

  15. Data supporting mitochondrial morphological changes by SPG13-associated HSPD1 mutants

    PubMed Central

    Miyamoto, Yuki; Megumi, Funakoshi-Tago; Hasegawa, Nanami; Eguchi, Takahiro; Tanoue, Akito; Tamura, Hiroomi; Yamauchi, Junji

    2016-01-01

    The data is related to the research article entitled “Hypomyelinating leukodystrophy-associated missense mutation in HSPD1 blunts mitochondrial dynamics” [1]. In addition to hypomyelinating leukodystrophy (HLD) 4 (OMIM no. 612233), it is known that spastic paraplegia (SPG) 13 (OMIM no. 605280) is caused by HSPD1’s amino acid mutation. Two amino acid mutations Val-98-to-Ile (V98I) and Gln-461-to-Glu (Q461E) are associated with SPG13 [2]. In order to investigate the effects of HSPD1’s V98I or Q461E mutant on mitochondrial morphological changes, we transfected each of the respective mutant-encoding genes into Cos-7 cells. Either of V98I or Q461E mutant exhibited increased number of mitochondria and short length mitochondrial morphologies. Using MitoTracker dye-incorporating assay, decreased mitochondrial membrane potential was also observed in both cases. The data described here supports that SPG13-associated HSPD1 mutant participates in causing aberrant mitochondrial morphological changes with decreased activities. PMID:26900593

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

    PubMed

    Tamez-Duque, Jess; 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

  17. A mild case of giant axonal neuropathy without central nervous system manifestation.

    PubMed

    Koichihara, Reiko; Saito, Takashi; Ishiyama, Akihiko; Komaki, Hirofumi; Yuasa, Shota; Saito, Yoshiaki; Nakagawa, Eiji; Sugai, Kenji; Shiihara, Takashi; Shioya, Ayako; Saito, Yuko; Higuchi, Yujiro; Hashiguchi, Akihiro; Takashima, Hiroshi; Sasaki, Masayuki

    2016-03-01

    An 11-year-old boy presented with progressive walking disturbances. He exhibited severe equinovarus feet that together presented with hyperreflexia of the patellar tendon and extensor plantar, resembling spastic paraplegia or upper neuron disease. He showed mild distal muscle atrophy, as well. We did not observe signs of cognitive impairment, cerebellar signs, or brain magnetic resonance imaging abnormalities. Nerve biopsy showed giant axon swellings filled with neurofilaments. Gene analysis revealed novel compound heterozygous missense mutations in the gigaxonin gene, c.808G>A (p.G270S) and c.1727C>A (p.A576E). He was diagnosed with mild giant axonal neuropathy (GAN) without apparent central nervous system involvement. Patients with classical GAN manifest their symptoms during early childhood. Mild GAN, particularly in early stages, can be misdiagnosed because of lack of typical hair features and incomplete or indistinct peripheral and central nervous system symptoms. This case is important since it can aid to identify atypical and milder clinical courses of GAN. This report widens the mild GAN clinical spectrum, alerting physicians for correct diagnosis. PMID:26381321

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

    PubMed Central

    2013-01-01

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

  19. 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).

  20. Spontaneous cord transection due to invasive aspergillus spondylitis in an immunocompetent child.

    PubMed

    Karthik, K; Shetty, Ajoy Prasad; Rajasekaran, S

    2011-07-01

    Invasive spinal aspergillosis in an immunocompetent child is rare and often there is a considerable delay in diagnosis. A 13-year-old male child treated medically as tuberculosis of spine elsewhere for 1year, came with complete paraplegia, dorsolumbar kyphosis and intermittently discharging sinus in the back. The child was taken up for surgical decompression and stabilization. Intraoperatively black granulomatous material was noted inside the canal extending anteriorly towards the vertebral body. There was complete cord transection with severe vertebral destruction and osteoporosis. The pathology and microbiology confirmed aspergillosis and the child was started on antifungal treatment. At further follow up, the infection was found to spread to the lung and caused further vertebral destruction. A change in the antifungal medication controlled further spread but failed to eradicate the infection at 2-year follow-up. In this patient, the delay led to extensive vertebral destruction with spine deformity and spontaneous cord transection. Retrospective review of the clinical and radiological findings suggests that this complication could have been prevented if these findings were carefully interpreted. In this era of transplantation and increase in use of immunosuppressive drugs the authors suggests having fungal infection as a differential diagnosis for infections of the spine. PMID:20596734

  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. The clinical maze of mitochondrial neurology

    PubMed Central

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

    2014-01-01

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

  3. Systemic thrombolysis in anterior spinal artery syndrome: what has to be considered?

    PubMed

    Koch, Mia; Sepp, Dominik; Prothmann, Sascha; Poppert, Holger; Seifert, Christian L

    2016-04-01

    Anterior spinal artery syndrome (ASAS) often leads to complete motor paralysis with poor clinical outcome. There is a lack of controlled clinical trials on acute treatment strategies in ASAS. However, systemic thrombolysis with recombinant tissue-plasminogen activator (rt-PA) might be a useful therapeutic option in ASAS. We report the management of a patient with ASAS below thoracic level 10, who was treated with intravenous thrombolysis. An 81 year old patient presented with flaccid paraplegia. After exclusion of aortal dissection, spinal tumour or haemorrhage, the patient was treated with intravenous rt-PA 3 h 40 min after symptom onset. The follow up magnetic resonance imaging (MRI) showed spinal infarction below thoracic segment 10. In the clinical course, the patient partially recovered lower limb muscle strength and was able to walk with assistance. To the best of our knowledge, this is the first case in the literature of ASAS with MRI-proven spinal ischemia and the application of rt-PA. Systemic thrombolysis seems to be justifiable in patients with ASAS after the rule-out of aortal dissection and spinal bleeding. PMID:26386968

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

    PubMed Central

    Renvois, Benot; 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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  7. 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

  8. Multiple Myeloma. Diagnostic challenges and standard therapy.

    TOXLINE Toxicology Bibliographic Information

    Kyle RA

    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.

  9. 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

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

    PubMed

    Sujkowski, Alyson; Rainier, Shirley; Fink, John K; Wessells, Robert J

    2015-01-01

    Human PNPLA6 gene encodes Neuropathy Target Esterase protein (NTE). PNPLA6 gene mutations cause hereditary spastic paraplegia (SPG39 HSP), Gordon-Holmes syndrome, Boucher-Neuhuser 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 29C, when significant degeneration has already occurred, and significantly extends longevity of mutants at 25C. 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

  11. Pseudoclavibacter Otitis Media in a 3-Year-Old Boy With Pulmonary and Spinal Tuberculosis

    PubMed Central

    Ayuthaya, Satja Issaranggoon na; Leelaporn, Amornrut; Kiratisin, Pattarachai; Oberdorfer, Peninnah

    2015-01-01

    Abstract Pseudoclavibacter has rarely been documented as an etiologic agent of infection in humans. We presented the first case report of Pseudoclavibacter otitis media in a boy with pulmonary and spinal tuberculosis. A 3-year-old boy was referred to our hospital due to prolonged fever and progressive paraplegia for 3 months. He had yellowish discharge from both ear canals. The pleural fluid culture was positive for Mycobacterium tuberculosis. The discharge from both ears culture yielded yellow colonies of gram-positive bacilli with branching. This organism was positive for modified acid-fast bacilli stain but negative for acid-fast bacilli stain. Biochemical characteristics of this isolate were positive for catalase test but negative for oxidase, nitrate, esculin, and sugar utilization tests. The organism was further subjected to be identified by 16S ribosomal deoxyribonucleic acid gene sequencing. The result yielded Pseudoclavibacter species (99.4% identical), which could be most likely a potential pathogen in immunocompromised host like this patient. He responded well with intravenous trimetroprim-sulfamethoxazole for 6 weeks. This is the first case report of Pseudoclavibacter otitis media in children, and this case could emphasize Pseudoclavibacter species as a potential pathogen in immunocompromised host. PMID:25929901

  12. Autologous mesenchymal stem cells applied on the pressure ulcers had produced a surprising outcome in a severe case of neuromyelitis optica

    PubMed Central

    Dulamea, Adriana Octaviana; Sirbu-Boeti, Mirela-Patricia; Bleotu, Coralia; Dragu, Denisa; Moldovan, Lucia; Lupescu, Ioana; Comi, Giancarlo

    2015-01-01

    Recent studies provided evidence that mesenchymal stem cells (MSCs) have regenerative potential in cutaneous repair and profound immunomodulatory properties making them a candidate for therapy of neuroimmunologic diseases. Neuromyelitis optica (NMO) is an autoimmune, demyelinating central nervous system disorder characterized by a longitudinally extensive spinal cord lesion. A 46-year-old male diagnosed with NMO had relapses with paraplegia despite treatment and developed two stage IV pressure ulcers (PUs) on his legs. The patient consented for local application of autologous MSCs on PUs. MSCs isolated from the patient's bone marrow aspirate were multiplied in vitro during three passages and embedded in a tridimensional collagen-rich matrix which was applied on the PUs. Eight days after MSCs application the patient showed a progressive healing of PUs and improvement of disability. Two months later the patient was able to walk 20 m with bilateral assistance and one year later he started to walk without assistance. For 76 months the patient had no relapse and no adverse event was reported. The original method of local application of autologous BM-MSCs contributed to healing of PUs. For 6 years the patient was free of relapses and showed an improvement of disability. The association of cutaneous repair, sustained remission of NMO and improvement of disability might be explained by a promotion/optimization of recovery mechanisms in the central nervous system even if alternative hypothesis should be considered. Further studies are needed to assess the safety and efficacy of mesenchymal stem cells in NMO treatment. PMID:26807122

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

    PubMed Central

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

    2015-01-01

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

  14. Zebrafish models for the functional genomics of neurogenetic disorders.

    PubMed

    Kabashi, Edor; Brustein, Edna; Champagne, Nathalie; Drapeau, Pierre

    2011-03-01

    In this review, we consider recent work using zebrafish to validate and study the functional consequences of mutations of human genes implicated in a broad range of degenerative and developmental disorders of the brain and spinal cord. Also we present technical considerations for those wishing to study their own genes of interest by taking advantage of this easily manipulated and clinically relevant model organism. Zebrafish permit mutational analyses of genetic function (gain or loss of function) and the rapid validation of human variants as pathological mutations. In particular, neural degeneration can be characterized at genetic, cellular, functional, and behavioral levels. Zebrafish have been used to knock down or express mutations in zebrafish homologs of human genes and to directly express human genes bearing mutations related to neurodegenerative disorders such as spinal muscular atrophy, ataxia, hereditary spastic paraplegia, amyotrophic lateral sclerosis (ALS), epilepsy, Huntington's disease, Parkinson's disease, fronto-temporal dementia, and Alzheimer's disease. More recently, we have been using zebrafish to validate mutations of synaptic genes discovered by large-scale genomic approaches in developmental disorders such as autism, schizophrenia, and non-syndromic mental retardation. Advances in zebrafish genetics such as multigenic analyses and chemical genetics now offer a unique potential for disease research. Thus, zebrafish hold much promise for advancing the functional genomics of human diseases, the understanding of the genetics and cell biology of degenerative and developmental disorders, and the discovery of therapeutics. This article is part of a Special Issue entitled Zebrafish Models of Neurological Diseases. PMID:20887784

  15. Cochlear Implantation in Neurobrucellosis

    PubMed Central

    Bajin, Münir Demir; Savaş, Özden; Aslan, Filiz; Sennaroğlu, Levent

    2016-01-01

    Background: Neurobrucellosis is a disease consisting of a wide spectrum of complications such as peripheral neuropathy, cranial nerve involvement, ataxia, meningeal irritation, paraplegia, seizures, coma, and even death. The vestibulocochlear nerve seems to be the most commonly affected cranial nerve (10%). We present a patient with neurobrucellosis whose auditory perception and speech intelligibility skill performances improved after cochlear implantation. Case Report: A 35 year-old woman was admitted to another hospital 2 years ago with the symptoms of headache, nausea, and altered consciousness, who was finally diagnosed with neurobrucellosis. She developed bilateral profound sensorineural hearing loss during the following 6 months. There was no benefit of using hearing aids. After successful treatment of her illness, she was found to be suitable for cochlear implantation. After the operation, her auditory perception skills improved significantly with a Categories of Auditory Performance (CAP) score of 5. According to clinical observations and her family members’ statements, her Speech Intelligibility Rating (SIR) score was 3. Her speech intelligibility skills are still improving. Conclusion: Our case report represents the second case of hearing rehabilitation with cochlear implantation after neurobrucellosis. Cochlear implantation is a cost-effective and time-proven successful intervention in post-lingual adult patients with sensorineural hearing loss. Early timing of the surgery after appropriate treatment of meningitis helps the patient to achieve better postoperative results. PMID:26966626

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

    PubMed

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

    1985-12-01

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

  17. Sialylation regulates brain structure and function.

    PubMed

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

    2015-07-01

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

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

    PubMed

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

    2015-06-30

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

  19. 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

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

    PubMed

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

    2009-04-01

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

  1. Complications of pedicle screws in lumbar and lumbosacral fusions in 105 consecutive primary operations.

    PubMed

    Jutte, P C; Castelein, R M

    2002-12-01

    Pedicle screw fixation is technically demanding and associated with high complication rates. The aim of this study was to identify and quantify the pedicle screw-related complications in 105 consecutive operations. We retrospectively analysed 105 consecutive primary operations. We found complications of varying severity in 54% of the patients. Deep infections were found in 4.7%, all successfully cured by debridement and antibiotics. There were no permanent neurological complications related to the screws. One serious neurological sequela, a T10 paraplegia, was unrelated to screw placement between L3 and S1. Screw misplacement was found in 6.5% of the screws. Screw breakage occurred in 12.4% of the patients, inevitably leading to loss of correction. Reduced spondylolisthesis L5-S1 without anterior support was found to be especially prone to screw breakage. The study confirmed that pedicle screw placement is a technically demanding procedure with a high complication rate. Fortunately, most complications are not severe. Infections can be dealt with by thorough debridement and parenteral antibiotics. Neurological sequelae can be minimised by careful tactile technique. To avoid screw breakage and subsequent loss of correction, anterior support should be provided, through either posterior or anterior lumbar interbody fusion (PLIF or ALIF) techniques, in reduced spondylolisthesis L5-S1. PMID:12522719

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

    PubMed Central

    Chang, Jaerak; Blackstone, Craig

    2014-01-01

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

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

    PubMed

    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

  4. Methotrexate myelopathy with extensive transverse necrosis: report of an autopsy case.

    PubMed

    Shintaku, Masayuki; Toyooka, Nao; Koyama, Takashi; Teraoka, Shunsuke; Tsudo, Mitsuru

    2014-12-01

    The patient was a 70-year-old woman with lymphoplasmacytic lymphoma which showed a predominantly diffuse involvement of the bone marrow and kidney. Because atypical lymphocytes appeared in the cerebrospinal fluid, the intrathecal administration of methotrexate (MTX) and cytosine arabinoside (Ara-C) was repeated several times. The patient developed flaccid paraplegia 8 months after the beginning of intrathecal administration, and died 4 months later. Autopsy demonstrated extensive transverse necrosis involving the lower thoracic cord and marked vacuolar degeneration of the white matter of the cervical, upper thoracic and lumbo-sacral cord. Focal vacuolar degeneration of the white matter was also noted in the left parietal lobe. Although vacuolar degeneration of the white matter is a common feature in MTX myelopathy, extensive transverse necrosis is rare. In the present case, an overlapping of two mechanisms, that is, injury of vascular endothelial cells and the direct toxic effect of MTX and Ara-C on the white matter, probably played a crucial role in the pathogenesis of severe myelopathy. Because severe myelopathy occurs infrequently, considering the large number of patients receiving the intrathecal administration of MTX, it is possible that a constitutional predisposition or abnormal sensitivity to MTX was involved in the pathogenesis in the present patient. PMID:24985097

  5. The Fifth Adaptor Protein Complex

    PubMed Central

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

    2011-01-01

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

  6. 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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  9. Pseudoclavibacter otitis media in a 3-year-old boy with pulmonary and spinal tuberculosis.

    PubMed

    Ayuthaya, Satja Issaranggoon na; Leelaporn, Amornrut; Kiratisin, Pattarachai; Oberdorfer, Peninnah

    2015-05-01

    Pseudoclavibacter has rarely been documented as an etiologic agent of infection in humans. We presented the first case report of Pseudoclavibacter otitis media in a boy with pulmonary and spinal tuberculosis.A 3-year-old boy was referred to our hospital due to prolonged fever and progressive paraplegia for 3 months. He had yellowish discharge from both ear canals. The pleural fluid culture was positive for Mycobacterium tuberculosis. The discharge from both ears culture yielded yellow colonies of gram-positive bacilli with branching. This organism was positive for modified acid-fast bacilli stain but negative for acid-fast bacilli stain. Biochemical characteristics of this isolate were positive for catalase test but negative for oxidase, nitrate, esculin, and sugar utilization tests. The organism was further subjected to be identified by 16S ribosomal deoxyribonucleic acid gene sequencing. The result yielded Pseudoclavibacter species (99.4% identical), which could be most likely a potential pathogen in immunocompromised host like this patient. He responded well with intravenous trimetroprim-sulfamethoxazole for 6 weeks.This is the first case report of Pseudoclavibacter otitis media in children, and this case could emphasize Pseudoclavibacter species as a potential pathogen in immunocompromised host. PMID:25929901

  10. 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

  11. 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

  12. 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

  13. Schistosomiasis of the nervous system.

    PubMed

    Coyle, Christina Marie

    2013-01-01

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

  14. Mitochondrial dysfunction in hereditary spastic paraparesis with mutations in DDHD1/SPG28.

    PubMed

    Mignarri, Andrea; Rubegni, Anna; Tessa, Alessandra; Stefanucci, Stefano; Malandrini, Alessandro; Cardaioli, Elena; Meschini, Maria Chiara; Stromillo, Maria Laura; Doccini, Stefano; Federico, Antonio; Santorelli, Filippo Maria; Dotti, Maria Teresa

    2016-03-15

    Mutations in DDHD1 cause the SPG28 subtype of hereditary spastic paraplegia (HSP). Recent studies suggested that mitochondrial dysfunction occurs in SPG28. Here we describe two siblings with SPG28, and report evidence of mitochondrial impairment in skeletal muscle and skin fibroblasts. Patient 1 (Pt1) was a 35-year-old man with spastic paraparesis and urinary incontinence, while his 25-year-old brother (Pt2) had gait spasticity and motor axonal neuropathy. In these patients we identified the novel homozygous c.1429C>T/p.R477* mutation in DDHD1, using a next-generation sequencing (NGS) approach. Histochemical analyses in muscle showed mitochondrial alterations, and multiple mitochondrial DNA (mtDNA) deletions were evident. In Pt1, respiratory chain enzyme activities were altered in skeletal muscle, mitochondrial ATP levels reduced, and analysis of skin fibroblasts revealed mitochondrial fragmentation. It seems possible that the novel nonsense mutation identified abolishes DDHD1 protein function thus altering oxidative metabolism. Qualitative alterations of mtDNA could have a pathogenetic significance. We suggest to perform DDHD1 analysis in patients with multiple mtDNA deletions. PMID:26944165

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

    PubMed

    Melo, Uir S; Macedo-Souza, Lucia I; Figueiredo, Thalita; Muotri, Alysson R; Gleeson, Joseph G; Coux, Gabriela; Armas, Pablo; Calcaterra, Nora B; Kitajima, Joo P; Amorim, Simone; Olvio, 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

  16. Visceral Debranching for the Treatment of Thoracoabdominal Aortic Aneurysms: Based on a Presentation at the 2013 VEITH Symposium, November 19-23, 2013 (New York, NY, USA).

    PubMed

    Damrauer, Scott M; Fairman, Ron M

    2015-04-01

    Surgical repair of thoracoabdominal aortic aneurysms (TAAA) is associated with significant morbidity and mortality. Hybrid approaches that involve visceral debranching and aortic endografting allow for an alternative approach in certain high-risk patients. In most circumstances the visceral vessels can be bypassed in a retrograde manner from the iliac arteries via a midline laparotomy, and the aortic aneurysm subsequently excluded with standard aortic endografts. These procedures avoid the extensive two-cavity exposure, aortic cross-clamping, and mechanical circulatory support that comprise open TAAA repair, and offer the theoretical advantage of being less invasive. Despite this, outcomes have been mixed with reported perioperative mortality rates of 0% and 34% and permanent paraplegia rates of 0% to 13% in most major series. The reported outcomes, as well as the variation between centers, highlight the importance of patient selection in undertaking hybrid repair. In practice, the best outcomes are achieved in patients who have high-risk anatomy, rather than high-risk comorbidities. PMID:26798760

  17. Morbid obesity after spinal cord injury: an ailment not to be treated?

    PubMed

    Wong, S; Barnes, T; Coggrave, M; Forbes, A; Pounds-Cornish, E; Appleton, S; Belci, M

    2013-09-01

    A 28-year-old man with a T12 incomplete paraplegia after a spinal cord injury (SCI) was referred for weight management in October 2011. He reported a weight gain from about 120 to 180.3 kg since his SCI. He put on a further 11.4 kg in January 2012 despite intensive dietetic treatment, including very low-caloric diet, anti obesity medication and active physiotherapy programme. He had undergone an uncomplicated laparoscopic Roux-en-Y gastric bypass successfully in March 2012. For the first 7 months after surgery, his total weight loss was 32.4 kg. He has shown functional improvement (6 min walking distance and Berg balance score). There were important improvements in body mass index; waist circumference; mid-upper arm circumference; triceps-skinfold thickness; mid-arm muscle circumference; total cholesterol; high-density lipoprotein-cholesterol; and low-density lipoprotein-cholesterol and triglycerides. This report describes the first UK morbidly obese SCI patient who has undergone gastric bypass surgery and highlights the provision of bariatric surgery as an option to consider if all nonsurgical interventions have been tried. PMID:23859992

  18. Effects of Krankcycle Training on Performance and Body Composition in Wheelchair Users

    PubMed Central

    ?icho?, Rostislav; Maszczyk, Adam; Stastny, Petr; Uhl?, Petr; Petr, Miroslav; Doubrava, Ond?ej; Mostowik, Aleksandra; Go?a?, Artur; Cieszczyk, Pawe?; ?mijewski, Piotr

    2015-01-01

    Innovation in training equipment is important for increasing training effectiveness, performance and changes in body composition, especially in wheelchair users with paraplegia. The main objective of a workout session is to induce an adaptation stimulus, which requires overload of involved muscles by voluntary effort, yet this overload may be highly influenced by the size of the spinal cord lesion. Krancykl construction is designed to allow exercise on any wheelchair and with adjustable height or width of crank handles, where even the grip handle may be altered. The aim of this study was to determine the differences in body composition, performance and the rate of perceived exertion (RPE) in paraplegics with a different level of paralyses after a 12 week training programme of a unilateral regime on Krankcycle equipment (a crank machine). The study sample included four men and one women at a different spine lesion level. The 12 weeks programme was successfully completed by four participants, while one subject got injured during the intervention process. Three participants were paraplegics and one was quadriplegic with innervation of the biceps humeri, triceps humeri and deltoideus. The Krankcycle 30 min programme was followed by four other exercises, which were performed after themselves rather than in a circuit training manner as the latter would result in much longer rest periods between exercises, because paraplegics have to be fixed by straps during exercise on hydraulic machines. The RPE after the workout decreased following the twelve week adaptation period. PMID:26834875

  19. Magnetic resonance imaging in degenerative ataxic disorders.

    PubMed Central

    Ormerod, I E; Harding, A E; Miller, D H; Johnson, G; MacManus, D; du Boulay, E P; Kendall, B E; Moseley, I F; McDonald, W I

    1994-01-01

    MRI of the brain was performed in 53 patients with a variety of degenerative ataxias and related disorders and 96 control subjects. Atrophy of intracranial structures was not seen in patients with the pure type of hereditary spastic paraplegia, or in early cases of Friedreich's ataxia. In advanced Friedreich's ataxia there was atrophy of the vermis and medulla. The MRI features of early onset cerebellar ataxia with retained reflexes were variable, and suggest heterogeneity. In autosomal dominant cerebellar ataxias, most patients had cerebellar and brainstem atrophy, probably reflecting the pathological process of olivopontocerebellar atrophy; there was no clearly defined group with both clinical and imaging features of isolated cerebellar involvement. The MRI abnormalities in idiopathic late onset cerebellar ataxia were predominantly those of cerebellar and brainstem atrophy or pure cerebellar atrophy. The clinical and imaging features of brainstem abnormalities were discordant in several patients. Pure cerebellar atrophy was associated with slower progression of disability. Cerebral atrophy was common in the late onset ataxias. Cerebral white matter lesions, although usually few in number, were observed in significantly more patients than controls, particularly those aged over 50 years. Images PMID:8301305

  20. 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. PMID:25570512

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

    PubMed Central

    2012-01-01

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

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

    PubMed

    Tazoe, Toshiki; Perez, Monica A

    2015-04-01

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

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

    PubMed

    Davidovic, L; Ilic, N; Koncar, I

    2015-10-01

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

  4. 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

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

    PubMed

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

    2011-07-01

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

  6. 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

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

    SciTech Connect

    Alexander, T.S.

    1987-01-01

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

  8. 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.

  9. 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 (50200 ?l/kg). After embolism, the development of spasticity was measured using computer-controlled ankle rotation. Animals receiving 150 or 200 ?l of intra-aortic air injections displayed motor dysfunction with developed spastic (5060% of animals) or flaccid (2535% of animals) paraplegia at 57 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

  10. Targeted disruption of the mouse Npal3 gene leads to deficits in behavior, increased IgE levels, and impaired lung function.

    PubMed

    Grzmil, P; Konietzko, J; Boehm, D; Hlter, S M; Hoelter, S M; Aguilar-Pimentel, A; Aguilar, A; Javaheri, A; Kalaydjiev, S; Adler, T; Bolle, I; Adham, I; Dixkens, C; Wolf, S; Fuchs, H; Gailus-Durner, V; Gailus-Durne, V; Wurst, W; Ollert, M; Busch, D H; Busch, D; Schulz, H; de Angelis, M Hrabe; Burfeind, P

    2009-01-01

    The non-imprinted in Prader-Willi/Angelman syndrome (NIPA) proteins are highly conserved receptors or transporters. Translocation of NIPA genes were found in patients with Prader-Willi syndrome, and loss-of-function of the NIPA1 gene was identified in hereditary spastic paraplegia. The family of NIPA-like domain containing (NPAL) proteins is closely related to the NIPA proteins, but to date nothing is known about their function. Here, we could demonstrate that both human NPAL3 and mouse NPAL3 are ubiquitously expressed and encode highly conserved proteins. To further elucidate the function of the Npal3 gene, knockout (Npal3(-/-)) mice were generated. Intensive phenotypic analyses revealed that disruption of the Npal3 gene results in a pleiotropic phenotype. The function of the nervous system was impaired in both mutant males and females which could be demonstrated in behavioral tests. In addition, in NPAL3 mutants the number of NK cells was decreased and changes in IgM, IgG(2), and IgA were observed, indicating that the immune system is also affected. Interestingly, increased IgE levels as well as impaired lung functions were observed in mutant males but not in mutant females. It should be noted that the human Npal3 gene is located at 1p36.12-->p35.1, and atopic diseases were previously linked to this genomic region. Thus, the Npal3(-/-) mice could serve as a valuable model system for studying atopic diseases. PMID:19738379

  11. 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, Jos 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-Marie-Tooth disease type 2H on chromosome 8q13-21.1 was excluded by linkage analysis. Pedigrees originated in Italy, Brazil, Canada, England, Iran, and Japan. Interestingly, we identified 15 ALS5/SPG11/KIAA1840 mutations in 12 families (two sequence variants were never reported before, p.Gln198* and p.Pro2212fs*5). No large deletions/duplications were detected in these patients. The novel mutations seemed to be pathogenic since they co-segregated with the disease in all pedigrees and were absent in 300 unrelated controls. Furthermore, in silico analysis predicted their pathogenic effect. Our results indicate that ALS5/SPG11/KIAA1840 is the causative gene of a wide spectrum of clinical features, including autosomal recessive axonal Charcot-Marie-Tooth disease.media-1vid110.1093/brain/awv320_video_abstractawv320_video_abstract. PMID:26556829

  12. Mutations in B4GALNT1 (GM2 synthase) underlie a new disorder of ganglioside biosynthesis.

    PubMed

    Harlalka, Gaurav V; Lehman, Anna; Chioza, Barry; Baple, Emma L; Maroofian, Reza; Cross, Harold; Sreekantan-Nair, Ajith; Priestman, David A; Al-Turki, Saeed; McEntagart, Meriel E; Proukakis, Christos; Royle, Louise; Kozak, Radoslaw P; Bastaki, Laila; Patton, Michael; Wagner, Karin; Coblentz, Roselyn; Price, Joy; Mezei, Michelle; Schlade-Bartusiak, Kamilla; Platt, Frances M; Hurles, Matthew E; Crosby, Andrew H

    2013-12-01

    Glycosphingolipids are ubiquitous constituents of eukaryotic plasma membranes, and their sialylated derivatives, gangliosides, are the major class of glycoconjugates expressed by neurons. Deficiencies in their catabolic pathways give rise to a large and well-studied group of inherited disorders, the lysosomal storage diseases. Although many glycosphingolipid catabolic defects have been defined, only one proven inherited disease arising from a defect in ganglioside biosynthesis is known. This disease, because of defects in the first step of ganglioside biosynthesis (GM3 synthase), results in a severe epileptic disorder found at high frequency amongst the Old Order Amish. Here we investigated an unusual neurodegenerative phenotype, most commonly classified as a complex form of hereditary spastic paraplegia, present in families from Kuwait, Italy and the Old Order Amish. Our genetic studies identified mutations in B4GALNT1 (GM2 synthase), encoding the enzyme that catalyzes the second step in complex ganglioside biosynthesis, as the cause of this neurodegenerative phenotype. Biochemical profiling of glycosphingolipid biosynthesis confirmed a lack of GM2 in affected subjects in association with a predictable increase in levels of its precursor, GM3, a finding that will greatly facilitate diagnosis of this condition. With the description of two neurological human diseases involving defects in two sequentially acting enzymes in ganglioside biosynthesis, there is the real possibility that a previously unidentified family of ganglioside deficiency diseases exist. The study of patients and animal models of these disorders will pave the way for a greater understanding of the role gangliosides play in neuronal structure and function and provide insights into the development of effective treatment therapies. PMID:24103911

  13. Spastin Binds to Lipid Droplets and Affects Lipid Metabolism

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  15. Untangling the web: Mechanisms underlying ER network formation

    PubMed Central

    Goyal, Uma; Blackstone, Craig

    2013-01-01

    The ER is a continuous membrane system consisting of the nuclear envelope, flat sheets often studded with ribosomes, and a polygonal network of highly-curved tubules extending throughout the cell. Although protein and lipid biosynthesis, protein modification, vesicular transport, Ca2+dynamics, and protein quality control have been investigated in great detail, mechanisms that generate the distinctive architecture of the ER have been uncovered only recently. Several protein families including the reticulons and REEPs/DP1/Yop1p harbor hydrophobic hairpin domains that shape high-curvature ER tubules and mediate intramembrane protein interactions. Members of the atlastin/RHD3/Sey1p family of dynamin-related GTPases interact with the ER-shaping proteins and mediate the formation of three-way junctions responsible for the polygonal structure of the tubular ER network, with Lunapark proteins acting antagonistically. Additional classes of tubular ER proteins including some REEPs and the M1 spastin ATPase interact with the microtubule cytoskeleton. Flat ER sheets possess a different complement of proteins such as p180, CLIMP-63 and kinectin implicated in shaping, cisternal stacking and cytoskeletal interactions. The ER is also in constant motion, and numerous signaling pathways as well as interactions among cytoskeletal elements, the plasma membrane, and organelles cooperate to position and shape the ER dynamically. Finally, many proteins involved in shaping the ER network are mutated in the most common forms of hereditary spastic paraplegia, indicating a particular importance for proper ER morphology and distribution in large, highly-polarized cells such as neurons. PMID:23602970

  16. SPG20 Protein Spartin Is Recruited to Midbodies by ESCRT-III Protein Ist1 and Participates in Cytokinesis

    PubMed Central

    Renvois, Benot; Parker, Rell L.; Yang, Dong; Bakowska, Joanna C.; Hurley, James H.

    2010-01-01

    Hereditary spastic paraplegias (HSPs, SPG1-46) are inherited neurological disorders characterized by lower extremity spastic weakness. Loss-of-function SPG20 gene mutations cause an autosomal recessive HSP known as Troyer syndrome. The SPG20 protein spartin localizes to lipid droplets and endosomes, and it interacts with tail interacting protein 47 (TIP47) as well as the ubiquitin E3 ligases atrophin-1-interacting protein (AIP)4 and AIP5. Spartin harbors a domain contained within microtubule-interacting and trafficking molecules (MIT) at its N-terminus, and most proteins with MIT domains interact with specific ESCRT-III proteins. Using yeast two-hybrid and in vitro surface plasmon resonance assays, we demonstrate that the spartin MIT domain binds with micromolar affinity to the endosomal sorting complex required for transport (ESCRT)-III protein increased sodium tolerance (Ist)1 but not to ESCRT-III proteins charged multivesicular body proteins 17. Spartin colocalizes with Ist1 at the midbody, and depletion of Ist1 in cells by small interfering RNA significantly decreases the number of cells where spartin is present at midbodies. Depletion of spartin does not affect Ist1 localization to midbodies but markedly impairs cytokinesis. A structure-based amino acid substitution in the spartin MIT domain (F24D) blocks the spartinIst1 interaction. Spartin F24D does not localize to the midbody and acts in a dominant-negative manner to impair cytokinesis. These data suggest that Ist1 interaction is important for spartin recruitment to the midbody and that spartin participates in cytokinesis. PMID:20719964

  17. Congenital disorders of autophagy: an emerging novel class of inborn errors of neuro-metabolism.

    PubMed

    Ebrahimi-Fakhari, Darius; Saffari, Afshin; Wahlster, Lara; Lu, Jenny; Byrne, Susan; Hoffmann, Georg F; Jungbluth, Heinz; Sahin, Mustafa

    2016-02-01

    Single gene disorders of the autophagy pathway are an emerging, novel and diverse group of multisystem diseases in children. Clinically, these disorders prominently affect the central nervous system at various stages of development, leading to brain malformations, developmental delay, intellectual disability, epilepsy, movement disorders, and neurodegeneration, among others. Frequent early and severe involvement of the central nervous system puts the paediatric neurologist, neurogeneticist, and neurometabolic specialist at the forefront of recognizing and treating these rare conditions. On a molecular level, mutations in key autophagy genes map to different stages of this highly conserved pathway and thus lead to impairment in isolation membrane (or phagophore) and autophagosome formation, maturation, or autophagosome-lysosome fusion. Here we discuss 'congenital disorders of autophagy' as an emerging subclass of inborn errors of metabolism by using the examples of six recently identified monogenic diseases: EPG5-related Vici syndrome, beta-propeller protein-associated neurodegeneration due to mutations in WDR45, SNX14-associated autosomal-recessive cerebellar ataxia and intellectual disability syndrome, and three forms of hereditary spastic paraplegia, SPG11, SPG15 and SPG49 caused by SPG11, ZFYVE26 and TECPR2 mutations, respectively. We also highlight associations between defective autophagy and other inborn errors of metabolism such as lysosomal storage diseases and neurodevelopmental diseases associated with the mTOR pathway, which may be included in the wider spectrum of autophagy-related diseases from a pathobiological point of view. By exploring these emerging themes in disease pathogenesis and underlying pathophysiological mechanisms, we discuss how congenital disorders of autophagy inform our understanding of the importance of this fascinating cellular pathway for central nervous system biology and disease. Finally, we review the concept of modulating autophagy as a therapeutic target and argue that congenital disorders of autophagy provide a unique genetic perspective on the possibilities and challenges of pathway-specific drug development. PMID:26715604

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

    PubMed Central

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

    2015-01-01

    Background: Spinal Cord Injury (SCI) is one of the biggest health problems. Disabilities resulting from injuries such as spinal disability requires special attention because of their potential reduced to cause adverse effects in different systems of the body. Today, improving the Quality of Life (QOL) in patients with SCIs is an important goal of treatment. Objectives: The purpose of this study was to determine the QOL and related factors among people with SCIs. Patients and Methods: In this cross-sectional descriptive study, 106 patients with SCI were selected through sampling based on census. Data were collected using a demographic questionnaire and a Short-Form 36 (SF-36) health survey questionnaire for measuring the QOL among patients. Data were analyzed using SPSS 14 software and descriptive and inferential statistics. P < 0.05 was considered statistically significant. Results: The mean QOL in these patients was 37.1 1.7 years (21 - 65 years) and mean disease duration was 7.36 years. The most common injury was paraplegia. Most of the patients have moderate QOL (54.7 %). The results showed a significant relationship between QOL and marital status and employment status (P < 0.05). Also, results showed a significant relationship between QOL and education levels (P = 0.002), age (P = 0.001), and duration of illness (P = 0.001).The highest and lowest scores were 64 7.1 and 36 5.3 for understanding General Health (GH) and role physical, respectively. Conclusions: The results show that patients with SCI have a moderate health-related QOL Determining the QOL is needed to focus on the strengths and weaknesses of patients with spinal cord injuries. Planning principles is recommended in order to reform the disability. PMID:26557639

  19. 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

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

    SciTech Connect

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

    2013-02-15

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

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

    PubMed Central

    2011-01-01

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

  3. 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.

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

    PubMed

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

    2015-01-01

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

  5. Multi-system neurological disease is common in patients with OPA1 mutations

    PubMed Central

    Yu-Wai-Man, P.; Griffiths, P.G.; Gorman, G.S.; Lourenco, C.M.; Wright, A.F.; Auer-Grumbach, M.; Toscano, A.; Musumeci, O.; Valentino, M.L.; Caporali, L.; Lamperti, C.; Tallaksen, C.M.; Duffey, P.; Miller, J.; Whittaker, R.G.; Baker, M.R.; Jackson, M.J.; Clarke, M.P.; Dhillon, B.; Czermin, B.; Stewart, J.D.; Hudson, G.; Reynier, P.; Bonneau, D.; Marques, W.; Lenaers, G.; McFarland, R.; Taylor, R.W.; Turnbull, D.M.; Votruba, M.; Zeviani, M.; Carelli, V.; Bindoff, L.A.; Horvath, R.; Amati-Bonneau, P.

    2010-01-01

    Additional neurological features have recently been described in seven families transmitting pathogenic mutations in OPA1, the most common cause of autosomal dominant optic atrophy. However, the frequency of these syndromal dominant optic atrophy plus variants and the extent of neurological involvement have not been established. In this large multi-centre study of 104 patients from 45 independent families, including 60 new cases, we show that extra-ocular neurological complications are common in OPA1 disease, and affect up to 20% of all mutational carriers. Bilateral sensorineural deafness beginning in late childhood and early adulthood was a prominent manifestation, followed by a combination of ataxia, myopathy, peripheral neuropathy and progressive external ophthalmoplegia from the third decade of life onwards. We also identified novel clinical presentations with spastic paraparesis mimicking hereditary spastic paraplegia, and a multiple sclerosis-like illness. In contrast to initial reports, multi-system neurological disease was associated with all mutational subtypes, although there was an increased risk with missense mutations [odds ratio = 3.06, 95% confidence interval = 1.446.49; P = 0.0027], and mutations located within the guanosine triphosphate-ase region (odds ratio = 2.29, 95% confidence interval = 1.084.82; P = 0.0271). Histochemical and molecular characterization of skeletal muscle biopsies revealed the presence of cytochrome c oxidase-deficient fibres and multiple mitochondrial DNA deletions in the majority of patients harbouring OPA1 mutations, even in those with isolated optic nerve involvement. However, the cytochrome c oxidase-deficient load was over four times higher in the dominant optic atrophy + group compared to the pure optic neuropathy group, implicating a causal role for these secondary mitochondrial DNA defects in disease pathophysiology. Individuals with dominant optic atrophy plus phenotypes also had significantly worse visual outcomes, and careful surveillance is therefore mandatory to optimize the detection and management of neurological disability in a group of patients who already have significant visual impairment. PMID:20157015

  6. 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

  7. Swiss Cheese, a protein involved in progressive neurodegeneration acts as a non-canonical regulatory subunit for PKA-C3

    PubMed Central

    da Cruz, Alexandre Bettencourt; Wentzell, Jill; Kretzschmar, Doris

    2008-01-01

    The Drosophila Swiss Cheese (SWS) protein and its vertebrate orthologue Neuropathy Target Esterase (NTE) are required for neuronal survival and glial integrity. In humans, NTE is the target of organophosphorous compounds which cause a paralyzing axonal degeneration and recently mutations in NTE have been shown to cause a Hereditary Spastic Paraplegia called NTE-related Motor-Neuron Disorder. SWS and NTE are concentrated in the endoplasmic reticulum and both have been shown to have an esterase function against an artificial substrate. However, the functional mechanisms and the pathways in which SWS/NTE are involved in are still widely unknown. Here we show that SWS interacts specifically with the C3 catalytic subunit of cAMP activated protein kinase (PKA-C3) which together with orthologues in mouse (Pkare) and human (PrKX) forms a novel class of catalytic subunits of unknown function. This interaction requires a domain of SWS which shows homology to regulatory subunits of PKA and, like conventional regulatory subunits, the binding of SWS to the PKA-C3 inhibits is function. Consistent with this result, expression of additional PKA-C3 induces degeneration and enhances the neurodegenerative phenotype in sws mutants. We also show that the complex formation with the membrane-bound SWS tethers PKA-C3 to membranes. We therefore propose a model in which SWS acts as a non-canonical subunit for PKA-C3, whereby the complex formation regulates the localization and kinase activity of PKA-C3, and that disruption of this regulation can induce neurodegeneration. PMID:18945896

  8. Transforming growth factor-β signaling in motor neuron diseases.

    PubMed

    Katsuno, M; Adachi, H; Banno, H; Suzuki, K; Tanaka, F; Sobue, G

    2011-02-01

    Transforming growth factor β (TGF-β), a pleiotropic cytokine, regulates a diverse range of cellular responses, such as proliferation, differentiation, migration, and apoptosis. The TGF-β1, -β2, and -β3 isoforms are expressed by neurons and glial cells, and their receptors are expressed throughout the central nervous system. Several lines of evidence demonstrate that TGF-β signaling protects neurons from glutamate-mediated excitotoxicity, a putative mechanism underlying the pathogenesis of various neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS). Recent studies indicate that the TGF-β-Smad2/3 pathway restores motor function in a mouse model of ALS, and that disruption of TGF-β signaling due to the transcriptional dysregulation of its receptor is associated with polyglutamine-induced motor neuron damage in spinal and bulbar muscular atrophy. Moreover, the TGF-β-Smad2/3 pathway regulates the function of glial cells, although the implication of this regulation in neurodegeneration remains elusive. Conversely, myostatin, a member of the TGF-β superfamily, has gained attention as a potential therapeutic target for neuromuscular disorders because genetic deletion of this factor results in increased muscle volume. Signal transduction by BMP, a member of the TGF-β super family, regulates the function and growth of the neuromuscular junction, while the disruption of this signaling has been reported in animal models of hereditary spastic paraplegia. These findings support the hypothesis that the disruption of TGF-β signaling is an important molecular event in the pathogenesis of motor neuron diseases, and that the modification of this signaling pathway represents a new therapeutic strategy against these devastating disorders. PMID:21189118

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  11. 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. PMID:25948267

  12. Selective motor neuron death and heat shock protein induction after spinal cord ischemia in rabbits.

    PubMed

    Sakurai, M; Aoki, M; Abe, K; Sadahiro, M; Tabayashi, K

    1997-01-01

    Paraplegia is a serious complication that sometimes results from operation on the thoracic aorta. The mechanism of spinal cord injury has been thought to involve tissue ischemia, and spinal motor neurons are suggested to be vulnerable to ischemia. The exact mechanism, however, is not fully understood. To evaluate the mechanism of such vulnerability of motor neurons, we attempted to make a reproducible model for spinal cord ischemia and statistically analyzed cell damage. With this model, induction of heat shock protein 70 (HSP70) and heat shock cognate protein (HSC70) messenger ribonucleic acid molecules were investigated with Northern blot analysis for up to 7 days of reperfusion after 5 or 15 minutes of ischemia. Immunohistochemical studies of their proteins were also done. (heat shock proteins are a set of markers of neuronal injury after ischemia.) After 5 minutes of ischemia, there was no induction of HSP70 and HSC70 messenger ribonucleic acid molecules or their proteins, and all cells remained intact. In contrast, after 15 minutes of ischemia, HSP70 messenger ribonucleic acid was induced at 8 hours of reperfusion, and HSC70 messenger ribonucleic acid was expressed continuously at the control level. Immunoreactivity of HSP70 protein was slightly induced at 8 hours of reperfusion selectively in motor neurons, and about 70% of motor neuron cells showed selective cell death after 7 days of reperfusion. This study demonstrated induction of HSP70 messenger ribonucleic acid and its protein in motor neuron cells after transient ischemia in the spinal cord. This phenomenon was not accompanied by HSC70 induction. PMID:9011685

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2011-08-01

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

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

    PubMed

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

    2013-09-01

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

  17. 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

  18. Comparison of a Double Poling Ergometer and Field Test for Elite Cross Country Sit Skiers

    PubMed Central

    Forbes, Scott C.; Craven, Bruce; Bhambhani, Yagesh

    2010-01-01

    Background Sport specific ergometers are important for laboratory testing (i.e. peak oxygen consumption (VO2)) and out of season training. Objectives The purpose of this study was to compare cardiorespiratory variables during exercise on a double poling ergometer to a field test in elite sit skiers. Methods Three male and four female athletes from the Canadian National / Developmental team (17-54 years of age, six with complete paraplegia and one with cerebral palsy) completed a field test and a double poling ergometer protocol separated by at least 24 hours. Both protocols consisted of three maximal trials of skiing of three minutes duration separated by 1.5 minutes of rest. A wireless metabolic system and heart rate monitor were used to measure cardiorespiratory responses [peak heart rate, peak VO2, and peak respiratory exchange ratio (RER)] during each test. Arterialized blood lactate was measured before the beginning of exercise, after each trial and at 5, 10 and 15 minutes post exercise. Results No significant differences existed between the field and ergometer tests for peak oxygen consumption (VO2) (field=34.75.5 mLkg?1min?1 vs. ergometer=33.46.9 mLkg?1min?1). Significantly higher peak heart rate and RER were found during the ergometer test. Significantly higher lactates were found during the ergometer test after trial 2 and trial 3. Conclusion The double poling ergometer is similar to a field test for evaluating peak VO2 in elite cross country sit skiers; however, the ergometer test elicits a higher heart rate and anaerobic response. PMID:21589660

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

    PubMed

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

    2015-11-01

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

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

    PubMed Central

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

    2015-01-01

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

  1. The association of resting state heart rate variability and 24-hour blood pressure variability in spinal cord injury.

    PubMed

    Thayer, Julian F; Sollers, John J; Clamor, Annika; Koenig, Julian; Hagglund, Kristofer J

    2016-02-15

    Patients with high cervical complete spinal cord injuries (tetraplegia) sustain damage to the autonomic neural pathways that influence cardiovascular functioning and produce variability in the heart rate (HR) and blood pressure (BP). In non-injured individuals, an inverse relationship exists between resting autonomic control of the heart (as evidenced by HR variability (HRV)) and BP variability (BPV). This study examined the relationship between HRV, BP and BPV in individuals with tetraplegic (n=10) and paraplegic (n=10) spinal cord injuries, and a group of healthy controls (n=14). Resting HRV at baseline and 24-hour ambulatory BP measurements were collected from electrocardiogram measures of each participant. HRV was quantified using time- and frequency-domain measures. The standard deviation of the BP measurements was used as an index of BPV. Multivariate analyses of variance were performed to examine group differences for laboratory-based and 24-h dependent variables. The MANOVAs for HRV parameters (?(14,50)=.352, p=.010, ?(2)=.407) and for BP indices and HR (?(16,48)=.318, p=.013, ?(2)=.436) were significant. Furthermore, in line with existing evidence, we found that vagally mediated HRV was inversely related to BPV in healthy controls. However, this relationship did not hold for the tetraplegia group (?<|.42|), and mixed results were found for the paraplegia group (e.g., ?<|.29| for time domain HRV, ?>|.65| for low-frequency power). These results support the conclusion that the damage to the spinal sympathetic pathways to the heart found in people with tetraplegia causes a significant disruption in baroreflex control of BP. PMID:26810517

  2. Clinical Investigations on the Spinal Osteoblastic Metastasis Treated by Combination of Percutaneous Vertebroplasty and 125I Seeds Implantation Versus Radiotherapy

    PubMed Central

    Tan, Jing; Zhao, Ruilian; Wang, Jiaping; Sun, Hongpu; Wang, Xiaoxue; Xu, Lei; Jiang, Hua; Zhang, Jinlei

    2013-01-01

    Abstract To investigate the clinical efficacy of combining digital subtraction angiography-guided percutaneous vertebroplasty (PVP) and 125I seeds implantation for the treatment of spinal osteoplastic metastasis. A combination of PVP and 125I implantation was conducted for 50 patients with spinal osteoplastic metastasis, while the other 50 patients who received regular radiation therapy were used as a comparison. Visual analogue pain scale (VAS) and score of life quality (EORTCQLQ-30) were determined for all the patients. Surgery was successful in 89 spinal segments of vertebral body in 50 patients. Each segment of vertebral body was injected with 15?mL (2.8?mL for thoracic and 3.1?mL for lumbar vertebral body on average) of bone cement. Postoperative X-ray and CT examination showed that all the patients in the PVP group achieved spinal stability. During the follow-up examination from 6 months to 5 years, 49 patients (98.0%) had significantly relieved back pain, and only 1 case (2.0%) had no obvious improvement. Postoperative VAS score and Karnofsky performance score (KPS) were significantly different from the preoperative scores (p<0.05); and compared to the regular treatment group, PVP combined 125I seeds showed much better clinical efficacy (p<0.05). PVP is a minimally invasive treatment with easy operation and less complications. PVP can effectively relieve the pain, stabilize the spine, improve the life quality, and reduce the occurrence of paraplegia in patients with spinal osteoplastic metastasis. Utilization of 125I seeds with PVP can enhance the clinical efficacy. PMID:23009581

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

    PubMed

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

    2014-08-01

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

  4. 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. PMID:18570553

  5. New pharmacological approaches against chronic bowel and bladder problems in paralytics.

    PubMed

    Guertin, Pierre A

    2016-02-01

    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

  6. Type B Aortic Dissection: A Review of Prognostic Factors and Meta-analysis of Treatment Options

    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 complications to improve the long-term outcomes of patients with uncomplicated Type B aortic dissection. PMID:26798745

  7. N-methyl-D-aspartate receptor antagonist MK-801 prevents apoptosis in rats that have undergone fetal spinal cord transplantation following spinal hemisection

    PubMed Central

    ZHANG, QIANG; SHAO, YANG; ZHAO, CHANGSONG; CAI, JUAN; SUN, SHENG

    2014-01-01

    Spinal cord injury is the main cause of paraplegia, but effective therapies for it are lacking. Embryonic spinal cord transplantation is able to repair spinal cord injury, albeit with a large amount of neuronal apoptosis remaining in the spinal cord. MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, is able to reduce cell death by decreasing the concentration of excitatory amino acids and preventing extracellular calcium ion influx. In this study, the effect of MK-801 on the apoptosis of spinal cord neurons in rats that have received a fetal spinal cord (FSC) transplant following spinal hemisection was investigated. Wistar rats were divided into three groups: Spinal cord hemisection injury with a combination of FSC transplantation and MK-801 treatment (group A); spinal cord hemisection injury with FSC transplantation (group B); and spinal cord injury with insertion of a Gelfoam pledget (group C). The rats were sacrificed 1, 3, 7 and 14 days after the surgery. Apoptosis in spinal slices from the injured spinal cord was examined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling reaction, and the expression of B-cell lymphoma-2 (Bcl-2) was measured by immunohistochemistry. The positive cells were quantitatively analyzed using a computer image analysis system. The rate of apoptosis and the positive expression of Bcl-2 protein in the spinal cord neurons in the three groups decreased in the following order: C>B>A (P<0.05) and A>B>C (P<0.05), respectively. This indicates that treatment with the NMDA receptor antagonist MK-801 prevents apoptosis in the spinal cord neurons of rats that have undergone FSC transplantation following spinal hemisection. PMID:25371724

  8. 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. GLIA 2016;64:155-174. PMID:26393339

  9. 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

  10. Cholecalciferol (Vitamin D3) Improves Myelination and Recovery after Nerve Injury

    PubMed Central

    Chabas, Jean-Francois; Stephan, Delphine; Marqueste, Tanguy; Garcia, Stephane; Lavaut, Marie-Noelle; Nguyen, Catherine; Legre, Regis; Khrestchatisky, Michel

    2013-01-01

    Previously, we demonstrated i) that ergocalciferol (vitamin D2) increases axon diameter and potentiates nerve regeneration in a rat model of transected peripheral nerve and ii) that cholecalciferol (vitamin D3) improves breathing and hyper-reflexia in a rat model of paraplegia. However, before bringing this molecule to the clinic, it was of prime importance i) to assess which form – ergocalciferol versus cholecalciferol – and which dose were the most efficient and ii) to identify the molecular pathways activated by this pleiotropic molecule. The rat left peroneal nerve was cut out on a length of 10 mm and autografted in an inverted position. Animals were treated with either cholecalciferol or ergocalciferol, at the dose of 100 or 500 IU/kg/day, or excipient (Vehicle), and compared to unlesioned rats (Control). Functional recovery of hindlimb was measured weekly, during 12 weeks, using the peroneal functional index. Ventilatory, motor and sensitive responses of the regenerated axons were recorded and histological analysis was performed. In parallel, to identify the genes regulated by vitamin D in dorsal root ganglia and/or Schwann cells, we performed an in vitro transcriptome study. We observed that cholecalciferol is more efficient than ergocalciferol and, when delivered at a high dose (500 IU/kg/day), cholecalciferol induces a significant locomotor and electrophysiological recovery. We also demonstrated that cholecalciferol increases i) the number of preserved or newly formed axons in the proximal end, ii) the mean axon diameter in the distal end, and iii) neurite myelination in both distal and proximal ends. Finally, we found a modified expression of several genes involved in axogenesis and myelination, after 24 hours of vitamin supplementation. Our study is the first to demonstrate that vitamin D acts on myelination via the activation of several myelin-associated genes. It paves the way for future randomised controlled clinical trials for peripheral nerve or spinal cord repair. PMID:23741446

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

    SciTech Connect

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

    2007-11-15

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

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

    PubMed

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

    2015-11-01

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

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

    PubMed

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

    2014-07-01

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

  14. Conservative Management of Spinal Tuberculosis: Initial Series from Pakistan

    PubMed Central

    Rizvi, Syed Raza Haider; Mahesri, Mufaddal; Salahuddin, Hisham Raza Aleem

    2013-01-01

    Study Design A prospective study on spinal tuberculosis (TB) at a tertiary care hospital in an endemic region. Purpose The aim of the study is to reiterate the importance of conservative management of spinal TB. Overview of Literature Spinal tuberculosis can present with wide spectrum of symptoms, with back pain being the most common symptom. It is the leading cause of non-traumatic paraplegia in developing countries. There is an emerging trend to operate on patients early with spinal TB. Methods Forty-seven (M=14, F=33) patients were enrolled in the study during the four year study period. Initially, all the patients were subjected to computed tomography guided percutaneous needle aspiration (PCNA) followed by antituberculous therapy (ATT) for 12 months. Indications for surgery included patients with moderate to severe symptoms in which PCNA either failed, was impossible to carry out, or produced minimal improvement within 48 hours. Results Presenting complaints included pain (95.7%), weakness (85.1%) and sphincter involvement (12.8%). On the magnetic resonance imaging, a paravertebral abscess was seen in 37 (78.7%), disc and body destruction in 29 (61.7%), and an epidural abscess in 12 (25.9%) patients. Of the 47 patients, 9 (19.1%) required surgery, 4 of whom had failed PCNA attempts and 5 demonstrated indications despite successful PCNA. Conclusions The results of conservative treatment consisting of PCNA and ATT for at least 12 months in compliant patients are excellent. A combined approach using clinical staging, PCNA, and ATT can minimize surgical intervention in most patients. However, ATT remains to be the cornerstone of management of spinal TB. PMID:23741543

  15. 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. PMID:26096995

  16. 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

  17. Downregulation of matrix metalloproteinase-2 (MMP-2) utilizing adenovirus-mediated transfer of small interfering RNA (siRNA) in a novel spinal metastatic melanoma model.

    PubMed

    Tsung, Andrew J; Kargiotis, Odysseas; Chetty, Chandramu; Lakka, Sajani S; Gujrati, Meena; Spomar, Daniel G; Dinh, Dzung H; Rao, Jasti S

    2008-03-01

    Matrix metalloproteinases (MMPs) comprise a class of secreted zinc-dependent endopeptidases implicated in the metastatic potential of tumor cells due to their ability to degrade the extracellular matrix (ECM) and basement membrane. Matrix metalloproteinase-2 (MMP-2) has been detected in high levels and correlates with invasiveness in human melanoma. We have studied the effect of adenovirus-mediated transfer of small interfering RNA (siRNA) against MMP-2 in the human melanoma cell line A2058. The delivery of these double-stranded RNA molecules represents an efficient technology in silencing disease-causing genes with known sequences at the post-transcriptional level. siRNA against MMP-2 mRNA (Ad-MMP-2) was found to decrease MMP-2 protein expression and activity in melanoma cells as demonstrated by western blotting and gelatin zymography. Furthermore, infection of cells with Ad-MMP-2 inhibited cellular migration and invasion as indicated by spheroid and matrigel assays. We also observed dose-dependent suppression of vascular network formation in an angiogenesis assay. Finally, we developed a nude mouse spinal metastatic model to investigate the local effects of tumor metastasis. Intravenous tail vein injection with Ad-MMP-2 on days 5, 9 and 11 after tumor implantation resulted in complete retention of neurological function as compared to control and scrambled vector (Ad-SV)-treated groups that showed complete paraplegia by day 14+/-2 days. Hematoxylin and eosin staining revealed decreased tumor size in the Ad-MMP-2-treated animals. This novel experimental model revealed that adenoviral-mediated transfer of RNA interference against MMP-2 results in the retention of neurological function and significantly inhibited tumor growth. PMID:18292932

  18. Glial expression of Swiss cheese (SWS), the Drosophila orthologue of neuropathy target esterase (NTE), is required for neuronal ensheathment and function.

    PubMed

    Dutta, Sudeshna; Rieche, Franziska; Eckl, Nina; Duch, Carsten; Kretzschmar, Doris

    2016-03-01

    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

  19. Delayed homicides and the proximate cause.

    PubMed

    Lin, Peter; Gill, James R

    2009-12-01

    Delayed homicides result from complications of remote injuries inflicted by "the hands of another." The investigation of delayed homicides may be a challenge due to a number of factors including: failure to report the death to the proper authorities, lack of ready and adequate documentation of the original injury and circumstances, and jurisdictional differences between the places of injury and death. The certification of these deaths also requires the demonstration of a pathophysiologic link between the remote injury and death. In sorting through these issues, it is helpful to rely upon the definition of the proximate cause of death. Over a 2-year period in New York City, there were 1211 deaths certified as homicide of which 42 were due to injuries sustained greater than 1 year before death. The survival interval ranged from 1.3 to 43.2 years. The most common immediate causes of death were: infections (22), seizures (7), and intestinal obstructions/hernias (6). Common patterns of complications included infection following a gunshot wound of the spinal cord, seizure disorder due to blunt head trauma, and intestinal obstruction/hernia due to adhesions from an abdominal stab wound. Spinal cord injuries resulted in paraplegia in 14 instances and quadriplegia in 8. The mean survival interval for paraplegics was 20.3 years and 14.8 years for quadriplegics; infections were a frequent immediate cause of death in both groups, particularly infections due to chronic bladder catheterization. The definition of proximate cause originated with civil law cases and was later applied to death certification as the proximate cause of death. The gradual extinction of the "year and a day rule" for the limitation of bringing homicide charges in delayed deaths may result in more of these deaths going to trial. Medical examiners/coroners must be able to explain the reasoning behind these death certifications and maintain consistent standards for the certification of all delayed deaths due to any injury (homicides, suicides, and accidents). PMID:19901806

  20. The Hsp60 folding machinery is crucial for manganese superoxide dismutase folding and function.

    PubMed

    Magnoni, R; Palmfeldt, J; Hansen, J; Christensen, J H; Corydon, T J; Bross, P

    2014-02-01

    Even though the deleterious effects of increased reactive oxygen species (ROS) levels have been implicated in a variety of neurodegenerative disorders, the triggering events that lead to the increased ROS and successive damages are still ill-defined. Mitochondria are the key organelles controlling the ROS balance, being their main source and also counteracting them by the action of the ROS scavenging system. Mitochondria, moreover, control the presence of ROS-damaged proteins by action of the protein quality control (PQC) system. One of its components is the mitochondrial chaperone Hsp60 assisting the folding of a subset of mitochondrial matrix proteins. Mutations in Hsp60 cause a late onset form of the neurodegenerative disease hereditary spastic paraplegia (SPG13). In this study, we aimed to address the molecular consequences of Hsp60 shortage. We here demonstrate that a heterozygous knockout Hsp60 model that recapitulates features of the human disease and exhibits increased oxidative stress in neuronal tissues. Moreover, we indicate that the increase of ROS is, at least in part, due to impaired folding of the manganese superoxide dismutase (MnSOD), a key antioxidant enzyme. We observed that the Hsp60 and MnSOD proteins interact. Based on these results, we propose that MnSOD is a substrate of the Hsp60 folding machinery and that under conditions of diminished availability of Hsp60, MnSOD is impaired in reaching the native state. This suggests a possible link between Hsp60-dependent PQC and the ROS scavenging systems that may have the function to increase ROS production under conditions of folding stress. PMID:24151936