Science.gov

Sample records for paraplegia

  1. Hysterical paraplegia.

    PubMed Central

    Baker, J H; Silver, J R

    1987-01-01

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

  2. Hereditary Spastic Paraplegia

    MedlinePlus

    ... there any treatment? What is the prognosis? What research is being done? Clinical Trials Organizations What is Hereditary Spastic Paraplegia? Hereditary spastic paraplegia (HSP), also called familial spastic paraparesis (FSP), refers to a group of inherited disorders that ...

  3. Problems and perspectives in paraplegia

    NASA Technical Reports Server (NTRS)

    Nashold, B.

    1974-01-01

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

  4. Basedow paraplegia: A possible misnomer.

    PubMed

    Smith, L; Kemp, T; van der Meyden, C H; Schutte, C-M

    2015-10-01

    Thyrotoxic myopathy frequently occurs in clinical practice; however, the association of hyperthyroidism with a flaccid, areflexic paraplegia, so-called Basedow paraplegia, appears to represent a controversial and doubtful entity. An 18-year-old female with undiagnosed and untreated Graves’ disease presented with acute onset of global weakness predominantly in the lower limbs, but also affecting the upper limbs. The weakness was accompanied by hypotonia and areflexia. Clinically, the patient had a goitre and signs of thyroid ocular disease. Laboratory testing confirmed the presence of hyperthyroidism, and thyroid-stimulating hormone receptor antibodies were positive. The cerebrospinal fluid protein level was raised. The electroneuronographic and needle examinations were compatible with a clear denervation process, such as acute motor axonal neuropathy, a variant of Guillain-Barre syndrome. Intravenous immunoglobulin therapy, carbimazole and propranolol were administered. The occurrence of hyperthyroidism with a flaccid, areflexic paraplegia appears to represent more of a fortuitous than a causative association. It is important to consider and treat other causes, such as acute idiopathic polyneuritis. PMID:26636154

  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 8

    MedlinePlus

    ... exaggerated reflexes (hyperreflexia), a decreased ability to feel vibrations, muscle wasting (amyotrophy), and reduced bladder control. The ... 1 link) National Institute of Neurological Disorders and Stroke: Hereditary Spastic Paraplegia Educational Resources (7 links) Disease ...

  7. 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

  8. Paraplegia with lymphoedema - a rare case report.

    PubMed

    Patel, R; Mehta, Vk; Singh, Dp; Jain, A; Bhatnagar, M

    2012-01-01

    Arachnoid cysts are a congenital disorder, and most cases begin during infancy; however, onset may be delayed until adolescence. Here we present an unusual case of atypical Paraplegia with Lymphoedema, with onset during adolescence and rapid progression in a young female patient who showed the characteristic appearance of cyst on magnetic resonance imaging (MRI) of spinal cord. This report intends to highlight paraplegia with lymphoedema, as a rare cause of spinal cord compression in pediatric population along with congenital defect manifestations and an interesting radiology finding of the disease. PMID:25205964

  9. Genetics Home Reference: spastic paraplegia type 31

    MedlinePlus

    ... 0163-z. Epub 2008 Nov 26. Züchner S, Wang G, Tran-Viet KN, Nance MA, Gaskell PC, Vance JM, Ashley-Koch AE, Pericak-Vance MA. Mutations in the novel mitochondrial protein REEP1 cause hereditary spastic paraplegia type 31. Am ...

  10. Genetics Home Reference: spastic paraplegia type 11

    MedlinePlus

    ... change the structure of the spatacsin protein. The effect that the altered spatacsin protein has on the nervous system is not known. Researchers suggest that mutations in spatacsin may cause the signs and symptoms of spastic paraplegia type 11 by interfering with the protein's proposed role ...

  11. Genetics Home Reference: spastic paraplegia type 4

    MedlinePlus

    ... Jul 11;67(1):45-51. Erratum in: Neurology. 2009 Apr 28;72(17):1534. Reid E. Science in motion: common molecular ... hereditary spastic paraplegia protein spastin. Nature. 2008 Jan 17;451(7176):363-7. doi: ... Functions in health and disease. J Neurosci Res. 2007 Sep;85(12):2778- ...

  12. 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

  13. 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

  14. Evidence for an Exaggerated Postprandial Lipemia in Chronic Paraplegia

    PubMed Central

    Nash, Mark S; deGroot, Joris; Martinez-Arizala, Alberto; Mendez, Armando J

    2005-01-01

    Background/Objective: Excessive delay in triglyceride (TG) metabolism after ingestion of dietary fat represents a significant cardiovascular disease (CVD) risk. The objective of this study was to compare the postprandial lipemic responses of individuals with paraplegia with those of healthy nondisabled individuals. Methods: The ability of 3 recreationally active individuals with paraplegia having normal fasting TG (mean = 103 mg/dL) to metabolize TG after ingestion of a high-fat test meal was compared with a previously published cohort of 21 recreationally active individuals without paraplegia (TG mean = 86 mg/dL) who underwent identical testing. The subjects with paraplegia had venous blood taken under fasting conditions, and then ingested a milkshake containing premium ice cream blended with heavy whipping cream (~92% of calories from fat). Additional blood samples were obtained at 2, 4, and 6 hours after ingestion. The area under the curve (AUC) for TG clearance for both subject groups was measured with an area planimeter. Results: TG uptake for both groups was almost identical for the first 2 hours after ingestion. At 4 and 6 hours after ingestion, the TG levels were 50 and 35 mg/dL higher, respectively, in subjects with paraplegia than in nondisabled subjects. When corrected for small baseline differences in TG concentrations (16 mg/dL), the AUC was 46.5% greater for the group with paraplegia than in the nondisabled group. A near mirror association across time was observed between postprandial serum high-density lipoprotein cholesterol (HDL-C) and TG levels in subjects with paraplegia. Conclusion: This case series finds an exaggerated postprandial lipemia (PPL) in persons with paraplegia with normal fasting TGs. This finding is the first evidence, in a small population, of an unreported potential CVD risk in persons with paraplegia. PMID:16396382

  15. Acute paraplegia in a preterm infant with cerebral sinovenous thrombosis.

    PubMed

    Hobbs, J; Tekes, A; Klein, J; Lemmon, M; Felling, R J; Chavez-Valdez, R

    2015-06-01

    We report the case of a 1-month old, 28-week gestational age infant who presented with acute paraplegia after cardiopulmonary arrest. Later imaging confirms cerebral sinovenous thrombosis (CSVT) and a suspected infarction in the conus medullaris of the spinal cord. A prothrombotic state may explain the numerous areas of infarction visualized on neuroimaging. To our knowledge this is the first case report of acute and persistent paraplegia in an infant with CSVT and conus medullaris injury, which may be due to venous infarction of the spinal cord. PMID:26012477

  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. Strümpell's familial spastic paraplegia: genetics and neuropathology

    PubMed Central

    Behan, Wilhelmina M. H.; Maia, Maria

    1974-01-01

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

  18. Predominant cerebellar phenotype in spastic paraplegia 7 (SPG7)

    PubMed Central

    Yahikozawa, Hiroyuki; Yoshida, Kunihiro; Sato, Shunichi; Hanyu, Norinao; Doi, Hiroshi; Miyatake, Satoko; Matsumoto, Naomichi

    2015-01-01

    We report a Japanese family with spastic paraplegia 7 (SPG7) that carries a deleterious homozygous p.R398X mutation in SPG7. The patients showed a predominant cerebellar ataxia phenotype. SPG7 is quite rare in Japan, but it should be included in the differential diagnosis for hereditary spastic-ataxic syndromes, even if the cerebellar signs are much more pronounced than the pyramidal tract signs.

  19. 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

  20. Alteration of Ganglioside Biosynthesis Responsible for Complex Hereditary Spastic Paraplegia

    PubMed Central

    Boukhris, Amir; Schule, Rebecca; Loureiro, José L.; Lourenço, Charles Marques; Mundwiller, Emeline; Gonzalez, Michael A.; Charles, Perrine; Gauthier, Julie; Rekik, Imen; Acosta Lebrigio, Rafael F.; Gaussen, Marion; Speziani, Fiorella; Ferbert, Andreas; Feki, Imed; Caballero-Oteyza, Andrés; Dionne-Laporte, Alexandre; Amri, Mohamed; Noreau, Anne; Forlani, Sylvie; Cruz, Vitor T.; Mochel, Fanny; Coutinho, Paula; Dion, Patrick; Mhiri, Chokri; Schols, Ludger; Pouget, Jean; Darios, Frédéric; Rouleau, Guy A.; Marques, Wilson; Brice, Alexis; Durr, Alexandra; Zuchner, Stephan; Stevanin, Giovanni

    2013-01-01

    Hereditary spastic paraplegias (HSPs) form a heterogeneous group of neurological disorders. A whole-genome linkage mapping effort was made with three HSP-affected families from Spain, Portugal, and Tunisia and it allowed us to reduce the SPG26 locus interval from 34 to 9 Mb. Subsequently, a targeted capture was made to sequence the entire exome of affected individuals from these three families, as well as from two additional autosomal-recessive HSP-affected families of German and Brazilian origins. Five homozygous truncating (n = 3) and missense (n = 2) mutations were identified in B4GALNT1. After this finding, we analyzed the entire coding region of this gene in 65 additional cases, and three mutations were identified in two subjects. All mutated cases presented an early-onset spastic paraplegia, with frequent intellectual disability, cerebellar ataxia, and peripheral neuropathy as well as cortical atrophy and white matter hyperintensities on brain imaging. B4GALNT1 encodes β-1,4-N-acetyl-galactosaminyl transferase 1 (B4GALNT1), involved in ganglioside biosynthesis. These findings confirm the increasing interest of lipid metabolism in HSPs. Interestingly, although the catabolism of gangliosides is implicated in a variety of neurological diseases, SPG26 is only the second human disease involving defects of their biosynthesis. PMID:23746551

  1. Dominant transmission of de novo KIF1A motor domain variant underlying pure spastic paraplegia.

    PubMed

    Ylikallio, Emil; Kim, Doyoun; Isohanni, Pirjo; Auranen, Mari; Kim, Eunjoon; Lönnqvist, Tuula; Tyynismaa, Henna

    2015-10-01

    Variants in family 1 kinesin (KIF1A), which encodes a kinesin axonal motor protein, have been described to cause variable neurological manifestations. Recessive missense variants have led to spastic paraplegia, and recessive truncations to sensory and autonomic neuropathy. De novo missense variants cause developmental delay or intellectual disability, cerebellar atrophy and variable spasticity. We describe a family with father-to-son transmission of de novo variant in the KIF1A motor domain, in a phenotype of pure spastic paraplegia. Structural modeling of the predicted p.(Ser69Leu) amino acid change suggested that it impairs the stable binding of ATP to the KIF1A protein. Our study reports the first dominantly inherited KIF1A variant and expands the spectrum of phenotypes caused by heterozygous KIF1A motor domain variants to include pure spastic paraplegia. We conclude that KIF1A should be considered a candidate gene for hereditary paraplegias regardless of inheritance pattern. PMID:25585697

  2. 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

  3. 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

  4. A study of posterior column function in familial spastic paraplegia.

    PubMed Central

    Dimitrijevic, M R; Lenman, J A; Prevec, T; Wheatly, K

    1982-01-01

    A family is described in which affected members have clinical features consistent with the late onset form of Strümpell's Familial Spastic Paraplegia which is of dominant inheritance. Abnormalities in cortical somatosensory to peroneal nerve stimulation were found in all affected members of the family and in several who were clinically unaffected. In some cases responses were better defined at slow rates of stimulation. Peripheral nerve conduction velocity was normal. These changes are consistent with previous findings of degeneration in the posterior columns at necroscopy and with a dying back process in the first sensory neuron. Clinically unaffected members of the family with abnormalities in the somatosensory response may represent asymptomatic heterozygotes. PMID:7062069

  5. 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

  6. [Ossification of ligamentum flavum unmasked by acute paraplegia].

    PubMed

    Rivierez, M; Vally, P

    2001-12-01

    A 30-year-old black man presented sudden-onset paraplegia during a foot-ball match, after a movement of hyperextension of the trunk. Moreover, the patient exhibited an hypoesthesia below the T11 level, with sphincter disturbances. The MRI and the CT-scan showed a stenosis of the spinal canal related to an ossification of hypertrophied ligamenta flava from T10 to T12. Intramedullary abnormal signals on MRI images were compatible with a spinal cord hemorrhage. A laminectomy with removal of abnormal ligamenta flava was carried out, and their endochondral ossification was confirmed by pathological examination. Two months later, the patient was able to walk alone and exhibited a mild spasticity associated to sensory disturbances of lower limbs. Ossification of ligamenta flava is usually observed in Japanese patients, sometimes in Caucasians, more rarely in black people. Its mechanism is unclear except when associated with metabolic or endocrine diseases. The patients usually present with clinical features of chronic spinal cord compression. Our case seems to be the first one disclosed by an acute spinal cord injury on ossified ligamenta flava. In this patient, because of remaining adjacent ossified ligamenta flava and the development on postoperative MRI of an intramedullary cavity, a long-term clinical and radiological follow-up is particularly necessary. PMID:11915618

  7. 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

  8. 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

  9. Strumpell's pure familial spastic paraplegia: case study and review of the literature.

    PubMed Central

    Holmes, G L; Shaywitz, B A

    1977-01-01

    A family with pure Strumpell's familial paraplegia is presented. There were 11 afflicted members involving three generations. The mode of inheritance was dominant, the onset in the first decade, and in this family the disease was mild. Literature data from 104 families with 536 members dating from 1880 are tabulated. This report confirms others regarding mode of inheritance, age of onset, distribution between sexes, and disease manifestations. However, contrary to other reports, we found the dominant and recessive form of pure Strumpell's familial spastic paraplegia to be similar in severity. There are now clinical and pathological data supporting the separation of pure Strumpell's familial spastic paraplegia from the other heredodegenerative diseases of the nervous system. PMID:591968

  10. 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

  11. 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.

  12. Paraplegia after contrast media application: a transient or devastating rare complication? Case report.

    PubMed

    Mielke, Dorothee; Kallenberg, Kai; Hartmann, Marius; Rohde, Veit

    2016-05-01

    The authors report the case of a 76-year-old man with a spinal dural arteriovenous fistula. The patient suffered from sudden repeated reversible paraplegia after spinal digital subtraction angiography as well as CT angiography. Neurotoxicity of contrast media (CM) is the most probable cause for this repeated short-lasting paraplegia. Intolerance to toxicity of CM to the vulnerable spinal cord is rare, and probably depends on the individual patient. This phenomenon is transient and can occur after both intraarterial and intravenous CM application. PMID:26544597

  13. 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

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

    ERIC Educational Resources Information Center

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

    2008-01-01

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

  15. 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"…

  16. Striatal Dopaminergic Functioning in Patients with Sporadic and Hereditary Spastic Paraplegias with Parkinsonism

    PubMed Central

    Kim, Ji Seon; Kim, Jong Min; Kim, Yu Kyeong; Kim, Sang Eun; Yun, Ji Young

    2013-01-01

    Sporadic spastic paraplegia (SSP) and hereditary spastic paraplegia (HSP) belong to a clinical and genetically heterogeneous group of disorders characterized by progressive spasticity and weakness in the lower extremities. The symptoms are associated with pyramidal tract dysfunction and degeneration of the corticospinal tracts. Parkinsonism is uncommon in SSP/HSP patients. However, both disorders are associated with damage to the nigrostriatal dopaminergic system. In the present study, the clinical features of patients with SSP/HSP were investigated, and nigrostriatal dopaminergic binding potential was assessed using dopamine transporter (DAT) single-photon emission computer tomography (SPECT). Nine patients with spastic paraplegia participated in the present study. The subjects underwent DAT SPECT using the agent [2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino]ethanethiolato (3-)-N2,N20,S2,S20]oxo-[IR-(exo-exo)])-[99mTc]technetium ([99mTc]TRODAT-1). The [99mTc]TRODAT-1 SPECT images of five patients appeared normal, whereas the images of four patients revealed reduced striatal ligand uptake. Among the four patients with reduced uptake, two had parkinsonism, and one exhibited periodic limb movements and restless leg syndrome. Our DAT SPECT imaging study shows that reduced DAT density may be observed in patients with parkinsonism. The results of the present study offer an explanation for the spectrum of spastic paraplegia symptoms and the progression of the disorder. PMID:24265532

  17. Paraplegia as the presenting manifestation of extramedullary megakaryoblastic transformation of previously undiagnosed chronic myelogenous leukemia.

    PubMed

    Bryant, Barbara J; Alperin, Jack B; Elghetany, M Tarek

    2007-02-01

    Extramedullary tumors, also known as granulocytic sarcomas (GS), occur most frequently in acute myelogenous leukemia (AML). They may signal the onset of the accelerated phase of chronic myelogenous leukemia (CML) or the blastic transformation of a myeloproliferative disorder. Occasionally, a GS may be the presenting sign of undiagnosed AML, and rarely the presenting sign of undiagnosed CML or aleukemic leukemia. Paraplegia due to a spinal cord GS is an extremely rare presentation of undiagnosed leukemia. This is the first case report of paraplegia as the presenting manifestation of extramedullary megakaryoblastic transformation of previously undiagnosed CML. A 53-year-old woman reported back pain for 6 days, rapidly progressing to paraplegia. Physical examination noted a large abdominal mass and flaccid paralysis in both lower extremities. Spinal MRI revealed a T4-T6 vertebral mass causing spinal stenosis and cord compression. Tumor debulking and laminectomy were performed emergently. The tumor consisted of noncohesive blast cells. The CBC revealed a leukocyte count of 238,300/microl and a differential consistent with CML. Reexamination of the patient found that the abdominal mass was a giant spleen. Further immunohistochemical studies of the tumor were consistent with extramedullary acute megakaryoblastic blast transformation of CML. Although extramedullary blast crises herald the accelerated phases in approximately 10% of CML cases, megakaryoblastic blast transformation of CML accounts for less than 3% of these cases. The combination of acute paraplegia and megakaryoblastic transformation in a previously undiagnosed patient with CML is extremely rare and may pose a diagnostic dilemma. PMID:17019692

  18. 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 ...

  19. The serum lipoprotein profile in veterans with paraplegia: the relationship to nutritional factors and body mass index.

    PubMed

    Zlotolow, S P; Levy, E; Bauman, W A

    1992-07-01

    Individuals with spinal cord injury have a shortened life expectancy, with coronary heart disease as a leading cause of death. Identifying potentially reversible risk factors would be expected to be of value in the long-term care of the person with a spinal cord injury. We addressed the relationships among diet, body mass index, and serum lipid levels in 28 veterans with paraplegia compared to 52 age-matched ambulatory veteran controls. There are no significant differences in body mass index or in total caloric, saturated fat, or cholesterol intake between those with paraplegia and the control group. The serum HDL cholesterol level is significantly lower in those with paraplegia compared to the control group (35 +/- 2 vs 49 +/- 2 mg/dL). There are no significant differences noted in serum total cholesterol, LDL cholesterol, or triglycerides between the groups. Total caloric intake decreases significantly with age in the control subjects but not in the subjects with paraplegia. Inverse correlations are found between serum HDL cholesterol and serum triglycerides levels both in those with paraplegia (r = -0.54, p less than 0.005) and in the controls (r = -0.42, p less than 0.001). In our group of subjects with paraplegia, serum lipid levels appear to be independent of dietary intake and body weight. PMID:1500941

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

    PubMed Central

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

    2013-01-01

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

  1. 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

  2. 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.

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

    PubMed

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

    2013-08-01

    In this review we focus on Charcot-Marie-Tooth (CMT) neuropathies and hereditary spastic paraplegias (HSPs). Although these diseases differ in whether they primarily affect the peripheral or central nervous system, both are genetically determined, progressive, long axonopathies that affect motor and sensory pathways. This commonality suggests that there might be similarities in the molecular pathology underlying these conditions, and here we compare the molecular genetics and cellular pathology of the two groups. PMID:22285450

  4. 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

  5. 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

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

    PubMed Central

    Caballero Oteyza, Andrés; Battaloğlu, Esra; Ocek, Levent; Lindig, Tobias; Reichbauer, Jennifer; Rebelo, Adriana P.; Gonzalez, Michael A.; Zorlu, Yasar; Ozes, Burcak; Timmann, Dagmar; Bender, Benjamin; Woehlke, Günther; Züchner, Stephan; Schöls, 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

  7. 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

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

    PubMed

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

    2014-09-15

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

  9. 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

  10. Hereditary "pure" spastic paraplegia: a clinical and genetic study of 22 families.

    PubMed Central

    Harding, A E

    1981-01-01

    In 22 families with the "pure" form of hereditary spastic paraplegia inheritance was autosomal dominant in 19 and autosomal recessive in three. Examination of intrafamilial correlation of age of onset in the dominant cases suggested that the disorder is genetically heterogeneous. Two forms of dominant hereditary spastic paraplegia were identified: one with an age of onset mostly below 35 years (type I), and the other onset usually over 35 years (type II). In the type I cases, delay in walking was not infrequent and spasticity of the lower limbs was more marked than weakness. The disorder was very slowly progressive and was extremely variable in terms of severity. Sixteen per cent of the patients aged over 20 years were asymptomatic but clinically affected. In the type II group muscle weakness, urinary symptoms and sensory loss were more marked. This form of the disease evolved more rapidly. In the three families demonstrating autosomal recessive inheritance the clinical features were very similar to those of the dominant cases. Biological fitness of patients from both the dominant groups was not impaired and no definite evidence of new mutation was observed. A cumulative frequency curve of age of onset in the type I group was constructed with suggested that an asymptomatic child of an affected parent has a 20% chance of developing the disease at the age of 25 years; the risk is probably even less if the child is clinically normal. PMID:7310405

  11. 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

  12. 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…

  13. 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.

  14. 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

  15. 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

  16. 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

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

    PubMed Central

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

    2014-01-01

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

  18. Mutations in CAPN1 Cause Autosomal-Recessive Hereditary Spastic Paraplegia.

    PubMed

    Gan-Or, Ziv; Bouslam, Naima; Birouk, Nazha; Lissouba, Alexandra; Chambers, Daniel B; Vérièpe, Julie; Androschuck, Alaura; Laurent, Sandra B; Rochefort, Daniel; Spiegelman, Dan; Dionne-Laporte, Alexandre; Szuto, Anna; Liao, Meijiang; Figlewicz, Denise A; Bouhouche, Ahmed; Benomar, Ali; Yahyaoui, Mohamed; Ouazzani, Reda; Yoon, Grace; Dupré, Nicolas; Suchowersky, Oksana; Bolduc, Francois V; Parker, J Alex; Dion, Patrick A; Drapeau, Pierre; Rouleau, Guy A; Bencheikh, Bouchra Ouled Amar

    2016-05-01

    Hereditary spastic paraplegia (HSP) is a genetically and clinically heterogeneous disease characterized by spasticity and weakness of the lower limbs with or without additional neurological symptoms. Although more than 70 genes and genetic loci have been implicated in HSP, many families remain genetically undiagnosed, suggesting that other genetic causes of HSP are still to be identified. HSP can be inherited in an autosomal-dominant, autosomal-recessive, or X-linked manner. In the current study, we performed whole-exome sequencing to analyze a total of nine affected individuals in three families with autosomal-recessive HSP. Rare homozygous and compound-heterozygous nonsense, missense, frameshift, and splice-site mutations in CAPN1 were identified in all affected individuals, and sequencing in additional family members confirmed the segregation of these mutations with the disease (spastic paraplegia 76 [SPG76]). CAPN1 encodes calpain 1, a protease that is widely present in the CNS. Calpain 1 is involved in synaptic plasticity, synaptic restructuring, and axon maturation and maintenance. Three models of calpain 1 deficiency were further studied. In Caenorhabditis elegans, loss of calpain 1 function resulted in neuronal and axonal dysfunction and degeneration. Similarly, loss-of-function of the Drosophila melanogaster ortholog calpain B caused locomotor defects and axonal anomalies. Knockdown of calpain 1a, a CAPN1 ortholog in Danio rerio, resulted in abnormal branchiomotor neuron migration and disorganized acetylated-tubulin axonal networks in the brain. The identification of mutations in CAPN1 in HSP expands our understanding of the disease causes and potential mechanisms. PMID:27153400

  19. 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

  20. 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; Schüle, Rebecca; Schöls, 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

  1. 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

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

    PubMed Central

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

    2016-01-01

    Background Hereditary spastic paraplegias (HSP) are a composite and genetically heterogeneous group of conditions mainly expressed by the impairment of the central motor system (“pure” forms). The involvement of other components of the central nervous system or of other systems is described in the “complicate” forms. The definition of an investigation protocol capable, by assembling clinical and paraclinical indicators to fully represent the extent of the motor system impairment, would help both the clinical handling of these conditions and contribute to our understanding of their pathogenesis. Methods We applied a clinical and paraclinical protocol which included tools exploring motor and non motor functioning, neurophysiology and MRI to a composite cohort of 70 molecularly defined HSP patients aged 3 to 65, to define for each indicator its significance in detailing the presence and the severity of the pathology. Results Clinically increased deep tendon reflexes and lower limb (LL) weakness are constant findings in all patients. The “complicated” forms are characterized by peripheral motor impairment, cognitive and cerebellar involvement. The Spastic Paraplegia Rating Scale efficiently reflects the severity of functional problems and correlates with disease duration. Neurophysiology consistently documents the impairment of the central motor pathway to the LLs. Nevertheless, the upper extremities and sensory system involvement is a frequent finding. MRI diffusion tensor imaging (DTI) highlighted a significant alteration of FA and MD. Combining the sampling of the various portion of the cortico-spinal tract (CST) DTI consistently discriminated patients from controls. Conclusion We propose a graded clinical and paraclinical protocol for HSP phenotype definition, indicating for each tool the discriminative and descriptive capacity. Our protocol applied to 9 different forms of HSP showed that the functional impairment often extends beyond the CST. The novel DTI approach may add significant elements in disease recognition, staging and mapping. PMID:27077743

  3. 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

  4. 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

  5. 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

  6. 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

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

    PubMed Central

    Féron, F.; Cochrane, J.; Bassingthwaighte, L.; Bayliss, C.; Davies, W.; Fronek, P.; Gray, C.; Kerr, G.; Licina, P.; Nowitzke, A.; Perry, C.; Silburn, P.A.S.; Urquhart, S.; Geraghty, T.

    2008-01-01

    Olfactory ensheathing cells show promise in preclinical animal models as a cell transplantation therapy for repair of the injured spinal cord. This is a report of a clinical trial of autologous transplantation of olfactory ensheathing cells into the spinal cord in six patients with complete, thoracic paraplegia. We previously reported on the methods of surgery and transplantation and the safety aspects of the trial 1 year after transplantation. Here we address the overall design of the trial and the safety of the procedure, assessed during a period of 3 years following the transplantation surgery. All patients were assessed at entry into the trial and regularly during the period of the trial. Clinical assessments included medical, psychosocial, radiological and neurological, as well as specialized tests of neurological and functional deficits (standard American Spinal Injury Association and Functional Independence Measure assessments). Quantitative test included neurophysiological tests of sensory and motor function below the level of injury. The trial was a Phase I/IIa design whose main aim was to test the feasibility and safety of transplantation of autologous olfactory ensheathing cells into the injured spinal cord in human paraplegia. The design included a control group who did not receive surgery, otherwise closely matched to the transplant recipient group. This group acted as a control for the assessors, who were blind to the treatment status of the patients. The control group also provided the opportunity for preliminary assessment of the efficacy of the transplantation. There were no adverse findings 3 years after autologous transplantation of olfactory ensheathing cells into spinal cords injured at least 2 years prior to transplantation. The magnetic resonance images (MRIs) at 3 years showed no change from preoperative MRIs or intervening MRIs at 1 and 2 years, with no evidence of any tumour of introduced cells and no development of post-traumatic syringomyelia or other adverse radiological findings. There were no significant functional changes in any patients and no neuropathic pain. In one transplant recipient, there was an improvement over 3 segments in light touch and pin prick sensitivity bilaterally, anteriorly and posteriorly. We conclude that transplantation of autologous olfactory ensheathing cells into the injured spinal cord is feasible and is safe up to 3 years of post-implantation, however, this conclusion should be considered preliminary because of the small number of trial patients. PMID:18689435

  8. 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

  9. 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.

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

    PubMed

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

    2016-06-01

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

  11. 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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2016-06-01

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

  14. 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

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

    PubMed Central

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

    2015-01-01

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

  16. 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

  17. [Familial spastic paraplegia with severe amyotrophy of the hands. (Silver syndrome?)].

    PubMed

    Feki, I; Miladi, M I; Elleuch, N; Boukhris, A; Stévanin, G; Brice, A; Mhiri, C

    2007-04-01

    Familial spastic paraplegia (FSP) with severe muscular atrophy of hands and feet is exceptional. Autosomal dominant forms were initially described by Silver in 1966. We report two cases, from the same Tunisian family, presenting FSP with severe amyotrophy of the hands. A brother and his sister, aged respectively 37 and 36 years old, presented practically the same clinical picture. Their parents were cousins. The female patient was hospitalized. Both patients developed gait disorders around the age of three years. Muscular atrophy of the hands arose much later, around the age of 20 years. The neurological examination disclosed a spastic gait with distal amyotrophy, severe in the hands and moderate in the feet. Sensitivity was preserved and there was no fasciculation. The spinal cord and cerebral MRI was normal. Electromyography (EMG) showed a neurogenic pattern in the distal muscles. Stimulation of the median, ulnar and sciatica nerves was ineffective. The somatosensory evoked potentials (EP) were delayed (upper limb) or desynchronised (lower limb). The auditory and visual EP were normal. The cerebrospinal fluid contained 1 mononuclear cell/mm3 and 10 mg protein/100 ml. Abnormalities of the cranio-vertebral junction, Arnold-Chiari malformation, syringomyelia and familial juvenile amyotrophic lateral sclerosis (ALS) were excluded and the diagnosis of Silver's syndrome was evoked. PMID:17452950

  18. 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, 3–4 decades after onset of gait impairment. Other relevant features during the disease were urinary and fecal incontinence, obesity and psychosis. Our study of 18 Dutch SPG11-patients shows the potential serious long-term consequences of SPG11 including a possibly restricted life span. PMID:23443022

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

    PubMed Central

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

    2013-01-01

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

  20. Hereditary spastic paraplegia: Novel mutations and expansion of the phenotype variability in SPG56.

    PubMed

    Masciullo, M; Tessa, A; Perazza, S; Santorelli, F M; Perna, A; Silvestri, G

    2016-05-01

    We describe a novel sporadic case of SPG56, a rare complicated form of HSP, that expands the clinical and molecular spectrum of the disease, being associated to novel mutations in CYP2U1 and showing as novel feature dorsal hydromyelia at spinal cord MRI. The patient presented an early-onset, slowly progressive paraparesis associated with mild mental retardation. Neurological assessments included the Spastic Paraplegia Rating Scale (SPRS), Mental Deterioration Battery (MDB), and Wechsler Adult Intelligence Scale (WAIS), neurophysiological and neuroimaging studies. Targeted next-generation sequencing panels for the whole set of genes associated with HSP were performed in the probands and her relatives. Neuroimaging studies showed dorsal hydromyelia but no brain MRI abnormalities. Targeted next-generation identified two novel mutations: the c.5C > A/p.S2* on the maternal allele in compound heterozygosity with the paternally-inherited c.1288+5G > C in CYP2U1. Both mutations predict early protein truncation and a loss of function. So far, only few SPG56 cases have been reported. This case, expands and further characterize the clinical and molecular spectrum of SPG56. In this regard, in consideration of the putative gene function in neurodevelopment, we suggest a causal association between CYP2U1 mutations and hydromyelia in our patient. PMID:26936192

  1. 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

  2. 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

  3. 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

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

    PubMed Central

    Lee, Sang-Hyo; Jeun, Sin-Soo

    2016-01-01

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

  5. 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.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-02-01

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

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

    PubMed

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

    2010-04-01

    The aim of this paper is to show the feasibility of the use of functional electrical stimulation (FES) applied to the lower back muscles for pressure sores prevention in paraplegia. The hypothesis under study is that FES induces a change in the pressure distribution on the contact area during sitting. Tests were conducted on a paraplegic subject (T5), sitting on a standard wheelchair and cushion. Trunk extensors (mainly the erector spinae) were stimulated using surface electrodes placed on the skin. A pressure mapping system was used to measure the pressure on the sitting surface in four situations: (a) no stimulation; (b) stimulation on one side of the spine only; (c) stimulation on both sides, at different levels; and (d) stimulation at the same level on both sides, during pressure-relief manoeuvres. A session of prolonged stimulation was also conducted. The experimental results show that the stimulation of the erector spinae on one side of the spine can induce a trunk rotation on the sagittal plane, which causes a change in the pressure distribution. A decrease of pressure on the side opposite to the stimulation was recorded. The phenomenon is intensified when different levels of stimulation are applied to the two sides, and such change can be sustained for a considerable time (around 5 minutes). The stimulation did not induce changes during pressure-relief manoeuvres. Finally, from this research we can conclude that the stimulation of the trunk extensors can be a useful tool for pressure sores prevention, and can potentially be used in a routine for pressure sores prevention based on periodical weight shifts. PMID:20170355

  9. The extent of axonal loss in the long tracts in hereditary spastic paraplegia.

    PubMed

    Deluca, G C; Ebers, G C; Esiri, M M

    2004-12-01

    Hereditary spastic paraplegia (HSP) comprises a group of inherited neurodegenerative disorders with the shared characteristics of progressive weakness and spasticity predominantly affecting the lower limbs. Limited pathological accounts have described a 'dying back' axonal degeneration in this disease. However, the distribution and extent of axonal loss has not been elucidated in a quantitative way. We have studied post-mortem material from six HSP patients and 32 controls in detail. The population of axons was examined quantitatively in the corticospinal tracts from the medulla to the lumbar spinal cord and the sensory tracts from the lumbar to upper cervical spinal cord. Myelin and axon-stained sections were employed to estimate the notional area and axonal density, respectively, of both tracts. Our results indicate that in the corticospinal tracts there is a significant reduction in area and axonal density at all levels investigated in HSP compared to controls. In the corticospinal tracts, the ratio of medulla and lumbar total axonal number was significantly greater in HSP cases compared to controls suggesting more pronounced axonal loss in the distal neuraxis in HSP than in controls. The sensory tracts in HSP, in contrast, showed a significant reduction in area and axonal density only in the upper regions of the spinal cord. Similar to the corticospinal tracts, the ratio of lumbar and upper cervical cord total axonal number in the sensory tracts was increased in HSP cases compared to controls. These findings are consistent with a length-dependent 'dying back' axonopathy. Nerve fibre loss was not size-selective with both small and large diameter fibres affected. In HSP, axonal loss is widespread and symmetrical and its extent tract-specific. The characterization of the nature of axonal loss in HSP, where this is a primary phenomenon, may help the interpretation of axonal loss in conditions such as multiple sclerosis where the sequence of events is less clear. PMID:15540998

  10. Further evidence for a fourth gene causing X-linked pure spastic paraplegia.

    PubMed

    Starling, A; Rocco, P; Cambi, F; Hobson, G M; Passos Bueno, M R; Zatz, M

    2002-08-01

    X-linked hereditary spastic paraplegias (HSPs) present with two distinct phenotypes: pure and complicated. The pure form is characterized by slowly progressive weakness and spasticity of the lower limbs, whereas the complicated forms have additional features (optic neuropathy, retinopathy, extrapyramidal disturbance, dementia, epilepsy, ataxia, ichthyosis, mental retardation, and deafness). Three X-linked loci have been identified for the complicated HSP, while mutations in the proteolipid gene (PLP) (locus SPG2) were implicated in both pure and complicated forms. The absence of identified mutations in the PLP gene in families with both complicated and pure HSP, linked to the SPG2 locus, suggests the existence of another gene in close proximity. We had previously reported a large pedigree with an X-linked form of pure HSP affecting 24 males [Zatz et al., 1976: J Med Genet 13:217-222]. Here, we present the results of linkage analysis in 19 members of this Brazilian family with markers in or near the PLP locus. Positive LOD scores were obtained with markers at the PLP locus (Zmax = 2.41 at Theta = 0); however, no mutation was found in the coding region of PLP, the intron-exon boundaries, or part of the promoter region. The possibility of a duplication of the PLP gene was also excluded. These results suggest either that there is another X-linked gene in close proximity to the PLP gene or that a novel mutation in the noncoding regions of the PLP gene may cause the disease in this family. PMID:12210342

  11. 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.

  12. 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

  13. 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

  14. 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

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

    PubMed Central

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

    2013-01-01

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

  16. 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

  17. 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

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

    PubMed

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

    2015-11-15

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

  19. 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

  20. 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

  1. 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 (Aβ) 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 Aβ 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 Aβ to Tau-dependent toxicity remains a matter of debate.Using primary neurons exposed to oligomeric forms of Aβ, we have found that Tau becomes mislocalized (missorted) into the somatodendritic compartment. Missorting of Tau correlates with loss of microtubules and downstream consequences such as loss of mature spines, loss of synaptic activity, and mislocalization of mitochondria.In this cascade, missorting of Tau induces mislocalization of TTLL6 (Tubulin-Tyrosine-Ligase-Like 6) into the dendrites. TTLL6 induces polyglutamylation of microtubules, which acts as a trigger for spastin mediated severing of dendritic microtubules. Loss of microtubules makes cells unable to maintain transport of mitochondria, which in turn results in synaptic dysfunction and loss of mature spines. These pathological changes are absent in TauKO derived primary neurons. Thus, Tau mediated mislocalization of TTLL6 and spastin activation reveals a pathological gain of function for Tau and spastin in this cellular model system of AD.In contrast, in hereditary spastic paraplegia (HSP) caused by mutations of the gene encoding spastin (spg4 alias SPAST), spastin function in terms of microtubule severing is decreased at least for the gene product of the mutated allele, resulting in overstable microtubules in disease model systems. Whether total spastin severing activity or microtubule stability in human disease is also affected is not yet clear. No human disease has been associated so far with the long-chain polyglutamylation enzyme TTLL6, or the other TTLLs (1,5,11) possibly involved.Here we review the findings supporting a role for Tau, spastin and TTLL6 in AD and other tauopathies, HSP and neurodegeneration, and summarize possible therapeutic approaches for AD and HSP. PMID:26691836

  2. Gait evaluation of a novel hip constraint orthosis with implication for walking in paraplegia.

    PubMed

    Audu, Musa L; To, Curtis S; Kobetic, Rudi; Triolo, Ronald J

    2010-12-01

    The aim of this study was to determine the effects of a newly developed reciprocal gait orthosis (RGO) with a variable constraint hip mechanism (VCHM) on the kinematics and kinetics of normal gait. The VCHM was compared with the isocentric reciprocating gait orthosis (IRGO) for walking after paraplegia. Both the VCHM and the IRGO were evaluated with able-bodied volunteers with the hip reciprocating mechanisms coupled and uncoupled. The VCHM was further evaluated with context-dependent coupling based on a finite-state control algorithm utilizing information from brace-mounted sensors. Walking performance for each brace condition was also compared to normal walking without an orthosis. Without the hip controller, the VCHM affected the kinematics of the hip joint in a similar manner as the IRGO, regardless of whether the hip reciprocator was coupled or uncoupled. With the controller active, hip kinematics with the VCHM were closer to normal gait than with the IRGO or any other condition tested (Intraclass correlation coefficient, ICC=0.96). The effects of the braces on the knee and ankle angles were not as prominent as their effects on the hip angles. In terms of kinetics, the VCHM with controller active allowed the generation of joint moments that were closer to normal (ICC=0.80) than the IRGO with hips coupled (ICC= 0.68). There was no statistically significant difference between the various conditions tested in terms of step-length and no statistically significant difference in the preferred walking speed between the IRGO and normal walking, whether or not the hips were coupled. However, there was a 25% reduction in walking speed with the VCHM when compared to normal, and the relative magnitudes of the EMG activity of three muscles (tibialis anterior, quadriceps, and hamstrings) were also higher with the VCHM than with either the IRGO or normal gait, likely due to the additional weight of the mechanism. Overall, the VCHM with controller active provided smooth control of the hip joints via context-dependent coupling and allowed for increased hip flexion relative to the IRGO. The results suggest that the VCHM with controlled joint coupling may eventually be a valuable component of a hybrid system combining functional electrical stimulation (FES) with orthotics. PMID:20378478

  3. 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

  4. 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

  5. Solitary plasmacytoma of the thoracic vertebra presenting with sudden paraplegia and back pain: a pathologic case report.

    PubMed

    Terada, Tadashi

    2011-03-01

    Solitary plasmacytoma (SPC) accounts for 5% of plasma cell neoplasm. SPC of the spine is relatively rare, and SPC presenting with sudden paraplegia is very rare. A 53 year-old woman was admitted to our hospital complaining of sudden severe paraplegia and back pain. Emergency MRI revealed a tumor of the thoracic vertebra no. 10 (Th10). Pressure fracture of the Th10 was also recognized. The tumor was not osteolytic and invasion was recognized around the Th10. The tumor directly compressed the spinal cord. An excision of the tumor was performed under the clinical diagnosis of metastatic carcinoma. Pathologtically, the tumor consisted of plasmacytoid atypical cells with hyperchromatic nuclei. Histochemically, the tumor cells showed pyroninophilia. Immunohistochemically, the tumor cells were positive for λ-light chain, but negative for cytokeratin, epithelial mermbrane antigen, vimentin, CD45, CD20, CD45RO, κ-light chain, α-heavy chain, λ-heavy chain, μ-heavy chain, δ-heavy chain, ε-heavy chain, IgA, IgG, IgM, synaptophysin, chromogranin, S100 protein, desmin, α-smooth muscle antigen, myoglobin, and p53 protein. The Ki-67 labeling was 73%. The author diagnosed the tumor as SPC with λ-light chain disease. After the diagnosis, whole body CT and MRI revealed no other tumors. Blood and serum test revealed no significant changes; no M-protein was recognized. However, voided urine test revealed λ-light chain protein. The patient underwent fixation operation of TH10, and received radiation (50 Gray) and chemotherapy. No recurrence or transformation into myeloma occurred at the present time 25 months after the first manifestation. The present study indicated that pathological examination is an only clue to the diagnosis of SPC of the vertebra bone. PMID:20676811

  6. 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

  7. Molecular spectrum of the SPAST, ATL1 and REEP1 gene mutations associated with the most common hereditary spastic paraplegias in a group of Polish patients.

    PubMed

    Elert-Dobkowska, Ewelina; Stepniak, Iwona; Krysa, Wioletta; Rajkiewicz, Marta; Rakowicz, Maria; Sobanska, Anna; Rudzinska, Monika; Wasielewska, Anna; Pilch, Jacek; Kubalska, Jolanta; Lipczynska-Lojkowska, Wanda; Kulczycki, Jerzy; Kurdziel, Katarzyna; Sikorska, Agata; Beetz, Christian; Zaremba, Jacek; Sulek, Anna

    2015-12-15

    Hereditary spastic paraplegias (HSPs) consist of a heterogeneous group of genetically determined neurodegenerative disorders. Progressive lower extremity weakness and spasticity are the prominent features of HSPs resulting from retrograde axonal degeneration of the corticospinal tracts. Three genetic types, SPG3 (ATL1), SPG4 (SPAST) and SPG31 (REEP1), appear predominantly and may account for up to 50% of autosomal dominant hereditary spastic paraplegias (AD-HSPs). Here, we present the results of genetic testing of the three mentioned SPG genetic types in a group of 216 unrelated Polish patients affected with spastic paraplegia. Molecular evaluation was performed by multiplex ligation-dependent probe amplification (MLPA) and DNA sequencing. Nineteen novel mutations: 13 in SPAST, 4 in ATL1 and 2 in REEP1, were identified among overall 50 different mutations detected in 57 families. Genetic analysis resulted in the identification of molecular defects in 54% of familial and 8.4% of isolated cases. Our research expanded the causative mutations spectrum of the three most common genetic forms of HSPs found in a large cohort of probands originating from the Central Europe. PMID:26671083

  8. 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.

  9. 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

  10. 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 48 years 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 40 years, and neither hypogonadism nor prominent cognitive impairment are obligatory features. PMID:24742043

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

    PubMed Central

    Sundarapandian, Rajkumar Jayachandran; Surulivel, Vignesh Jayabalan

    2015-01-01

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

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

    PubMed

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

    2016-04-01

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

  13. Brazilian family with pure autosomal dominant spastic paraplegia maps to 8q: analysis of muscle beta 1 syntrophin.

    PubMed

    Rocco, P; Vainzof, M; Froehner, S C; Peters, M F; Marie, S K; Passos-Bueno, M R; Zatz, M

    2000-05-15

    The autosomal dominant hereditary spastic paraplegias (AD-HSP) are a heterogeneous group of degenerative disorders of the central motor system, characterized by progressive spasticity of the lower limbs. Five loci for pure AD-HSP have been identified to date: SPG3 at 14q, SPG4 at 2p, SPG6 at 15q, SPG8 at 8q, and more recently SPG10 at 12q. We have analyzed a Brazilian family with 16 affected individuals by pure AD-HSP who developed progressive gait disturbance with onset at age 18-26 years. Linkage analysis performed with 13 relatives (6 affected and 7 normal) excluded SPG3, SPG4, and SPG6 as candidate regions. However, positive LOD scores were obtained with markers flanking the candidate region for the SPG8 locus [maximum two point Lod score (Zmax) = 3.3 at theta = 0 for D8S1804]. In this region lies the syntrophin beta 1 gene (SNT2B1), a widely expressed dystrophin-associated protein and therefore a good positional and functional candidate for this disease. Immunohistochemical and Western Blot (WB) studies showed that the distribution, expression, and apparent molecular weight of the beta 1 syntrophin protein were comparable to those of normal control individuals. Therefore, it is unlikely that defects in this protein are related to SPG8, at least in the present family. PMID:10797436

  14. An analysis of exome sequencing for diagnostic testing of the genes associated with muscle disease and spastic paraplegia.

    PubMed

    Dias, Cristina; Sincan, Murat; Cherukuri, Praveen F; Rupps, Rosemarie; Huang, Yan; Briemberg, Hannah; Selby, Kathryn; Mullikin, James C; Markello, Thomas C; Adams, David R; Gahl, William A; Boerkoel, Cornelius F

    2012-04-01

    In this study, we assess exome sequencing (ES) as a diagnostic alternative for genetically heterogeneous disorders. Because ES readily identified a previously reported homozygous mutation in the CAPN3 gene for an individual with an undiagnosed limb girdle muscular dystrophy, we evaluated ES as a generalizable clinical diagnostic tool by assessing the targeting efficiency and sequencing coverage of 88 genes associated with muscle disease (MD) and spastic paraplegia (SPG). We used three exome-capture kits on 125 individuals. Exons constituting each gene were defined using the UCSC and CCDS databases. The three exome-capture kits targeted 47-92% of bases within the UCSC-defined exons and 97-99% of bases within the CCDS-defined exons. An average of 61.2-99.5% and 19.1-99.5% of targeted bases per gene were sequenced to 20X coverage within the CCDS-defined MD and SPG coding exons, respectively. Greater than 95-99% of targeted known mutation positions were sequenced to ≥1X coverage and 55-87% to ≥20X coverage in every exome. We conclude, therefore, that ES is a rapid and efficient first-tier method to screen for mutations, particularly within the CCDS annotated exons, although its application requires disclosure of the extent of coverage for each targeted gene and supplementation with second-tier Sanger sequencing for full coverage. PMID:22311686

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

    SciTech Connect

    Robay, Dimitri; Patel, Heema; Simpson, Michael A.; Brown, Nigel A.; Crosby, Andrew H. . E-mail: acrosby@sgul.ac.uk

    2006-09-10

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

  16. 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

  17. Late-onset spastic paraplegia type 10 (SPG10) family presenting with bulbar symptoms and fasciculations mimicking amyotrophic lateral sclerosis.

    PubMed

    Kaji, Seiji; Kawarai, Toshitaka; Miyamoto, Ryosuke; Nodera, Hiroyuki; Pedace, Lucia; Orlacchio, Antonio; Izumi, Yuishin; Takahashi, Ryosuke; Kaji, Ryuji

    2016-05-15

    Pathogenic mutations in the KIF5A-SPG10 gene, encoding the kinesin HC5A, can be associated with autosomal dominant hereditary spastic paraplegia (ADHSP). It accounts for about 10% of the complicated forms of ADHSP. Peripheral neuropathy, distal upper limb amyotrophy, and cognitive decline are the most common additional clinical features. We examined a 66-year-old Japanese woman manifesting gait disturbance and spastic dysarthria for 6years with positive family history. She showed evidence of upper and lower motor neuron involvement and fasciculations, thus mimicking amyotrophic lateral sclerosis (ALS). Genetic analysis revealed a heterozygous variant in KIF5A (c.484C>T, p.Arg162Trp) in 2 symptomatic members. The mutation was also identified in 4 asymptomatic members, including 2 elderly members aged over 78years. Electromyography in the 2 symptomatic members revealed evidence of lower motor neuron involvement and fasciculation potentials in distal muscles. This report describes the first known Asian family with a KIF5A mutation and broadens the clinical and electrophysiological spectrum associated with KIF5A-SPG10 mutations. Given that our cases showed pseudobulbar palsy, fasciculation and altered penetrance, KIF5A-SPG10 might well be considered as a differential diagnosis of sporadic ALS. PMID:27084214

  18. 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

  19. 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

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

    PubMed Central

    Słabicki, Mikołaj; Theis, Mirko; Krastev, Dragomir B.; Samsonov, Sergey; Mundwiller, Emeline; Junqueira, Magno; Paszkowski-Rogacz, Maciej; Teyra, Joan; Heninger, Anne-Kristin; Poser, Ina; Prieur, Fabienne; Truchetto, Jérémy; Confavreux, Christian; Marelli, Cécilia; 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

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

    PubMed

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

    2014-08-01

    Autosomal-dominant hereditary spastic paraplegia (AD-HSP) is a crippling neurodegenerative disease for which effective treatment or cure remains unknown. Victims experience progressive mobility loss due to degeneration of the longest axons in the spinal cord. Over half of AD-HSP cases arise from loss-of-function mutations in spastin, which encodes a microtubule-severing AAA ATPase. In Drosophila models of AD-HSP, larvae lacking Spastin exhibit abnormal motor neuron morphology and function, and most die as pupae. Adult survivors display impaired mobility, reminiscent of the human disease. Here, we show that rearing pupae or adults at reduced temperature (18°C), compared with the standard temperature of 24°C, improves the survival and mobility of adult spastin mutants but leaves wild-type flies unaffected. Flies expressing human spastin with pathogenic mutations are similarly rescued. Additionally, larval cooling partially rescues the larval synaptic phenotype. Cooling thus alleviates known spastin phenotypes for each developmental stage at which it is administered and, notably, is effective even in mature adults. We find further that cold treatment rescues larval synaptic defects in flies with mutations in Flower (a protein with no known relation to Spastin) and mobility defects in flies lacking Kat60-L1, another microtubule-severing protein enriched in the CNS. Together, these data support the hypothesis that the beneficial effects of cold extend beyond specific alleviation of Spastin dysfunction, to at least a subset of cellular and behavioral neuronal defects. Mild hypothermia, a common neuroprotective technique in clinical treatment of acute anoxia, might thus hold additional promise as a therapeutic approach for AD-HSP and, potentially, for other neurodegenerative diseases. PMID:24906373

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

    PubMed Central

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

    2014-01-01

    Autosomal-dominant hereditary spastic paraplegia (AD-HSP) is a crippling neurodegenerative disease for which effective treatment or cure remains unknown. Victims experience progressive mobility loss due to degeneration of the longest axons in the spinal cord. Over half of AD-HSP cases arise from loss-of-function mutations in spastin, which encodes a microtubule-severing AAA ATPase. In Drosophila models of AD-HSP, larvae lacking Spastin exhibit abnormal motor neuron morphology and function, and most die as pupae. Adult survivors display impaired mobility, reminiscent of the human disease. Here, we show that rearing pupae or adults at reduced temperature (18°C), compared with the standard temperature of 24°C, improves the survival and mobility of adult spastin mutants but leaves wild-type flies unaffected. Flies expressing human spastin with pathogenic mutations are similarly rescued. Additionally, larval cooling partially rescues the larval synaptic phenotype. Cooling thus alleviates known spastin phenotypes for each developmental stage at which it is administered and, notably, is effective even in mature adults. We find further that cold treatment rescues larval synaptic defects in flies with mutations in Flower (a protein with no known relation to Spastin) and mobility defects in flies lacking Kat60-L1, another microtubule-severing protein enriched in the CNS. Together, these data support the hypothesis that the beneficial effects of cold extend beyond specific alleviation of Spastin dysfunction, to at least a subset of cellular and behavioral neuronal defects. Mild hypothermia, a common neuroprotective technique in clinical treatment of acute anoxia, might thus hold additional promise as a therapeutic approach for AD-HSP and, potentially, for other neurodegenerative diseases. PMID:24906373

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

    PubMed

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

    2016-06-01

    The conventional methods of treatment of pressure ulcers (PUs) by serial debridement and daily dressings require prolonged hospitalisation, associated with considerable morbidity. There is, however, recent evidence to suggest that negative pressure wound therapy (NPWT) accelerates healing. The commercial devices for NPWT are costly, cumbersome, and electricity dependent. We compared PU wound healing in traumatic paraplegia patients by conventional dressing and by an innovative negative pressure device (NPD). In this prospective, non-randomised trial, 48 traumatic paraplegia patients with PUs of stages 3 and 4 were recruited. Patients were divided into two groups: group A (n = 24) received NPWT with our NPD, and group B (n = 24) received conventional methods of dressing. All patients were followed up for 9 weeks. At week 9, all patients on NPD showed a statistically significant improvement in PU healing in terms of slough clearance, granulation tissue formation, wound discharge and culture. A significant reduction in wound size and ulcer depth was observed in NPD as compared with conventional methods at all follow-up time points (P = 0·0001). NPWT by the innovative device heals PUs at a significantly higher rate than conventional treatment. The device is safe, easy to apply and cost-effective. PMID:24894079

  4. Reticulon-like-1, the Drosophila orthologue of the hereditary spastic paraplegia gene reticulon 2, is required for organization of endoplasmic reticulum and of distal motor axons.

    PubMed

    O'Sullivan, Niamh C; Jahn, Thomas R; Reid, Evan; O'Kane, Cahir J

    2012-08-01

    Several causative genes for hereditary spastic paraplegia encode proteins with intramembrane hairpin loops that contribute to the curvature of the endoplasmic reticulum (ER), but the relevance of this function to axonal degeneration is not understood. One of these genes is reticulon2. In contrast to mammals, Drosophila has only one widely expressed reticulon orthologue, Rtnl1, and we therefore used Drosophila to test its importance for ER organization and axonal function. Rtnl1 distribution overlapped with that of the ER, but in contrast to the rough ER, was enriched in axons. The loss of Rtnl1 led to the expansion of the rough or sheet ER in larval epidermis and elevated levels of ER stress. It also caused abnormalities specifically within distal portions of longer motor axons and in their presynaptic terminals, including disruption of the smooth ER (SER), the microtubule cytoskeleton and mitochondria. In contrast, proximal axon portions appeared unaffected. Our results provide direct evidence for reticulon function in the organization of the SER in distal longer axons, and support a model in which spastic paraplegia can be caused by impairment of axonal the SER. Our data provide a route to further understanding of both the role of the SER in axons and the pathological consequences of the impairment of this compartment. PMID:22543973

  5. 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.

  6. Paraplegia in women.

    PubMed

    Kiwerski, J; Ahmad, S H

    1983-06-01

    In the period 1965-80, 125 women were treated because of paralysis or paresis of the lower extremities resulting from spinal trauma. In this report the causes of trauma, as well as the clinical and functional treatment of this group are discussed. The most frequent causes of trauma were falls from heights, from a tree, a ladder, a horse-cart as well as suicidal jumps and road accidents. It was ascertained that the results of treatment of spinal cord injuries in the upper thoracic segment are worse than in its lower part. These results do not differ from men with similar degrees and neurological levels of spinal cord injury. On the other hand the duration of treatment is longer in women than in men with the same degree of spinal cord lesion, amounting on the average to 17.4 weeks. PMID:6877854

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

    PubMed Central

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

    2016-01-01

    Background: Spinal cord injury (SCI) is not likely to recover by current therapeutic modalities. Stem cell (SC) therapy (SCT) has promising results in regenerative medicine. We present our experience of co-infusion of autologous adipose tissue derived mesenchymal SC differentiated neuronal cells (N-Ad-MSC) and hematopoietic SCs (HSCs) in a set of patients with posttraumatic paraplegia. Materials and Methods: Ten patients with posttraumatic paraplegia of mean age 3.42 years were volunteered for SCT. Their mean age was 28 years, and they had variable associated complications. They were subjected to adipose tissue resection for in vitro generation of N-Ad-MSC and bone marrow aspiration for generation of HSC. Generated SCs were infused into the cerebrospinal fluid (CSF) below injury site in all patients. Results: Total mean quantum of SC infused was 4.04 ml with a mean nucleated cell count of 4.5 × 104/μL and mean CD34+ of 0.35%, CD45−/90+ and CD45−/73+ of 41.4%, and 10.04%, respectively. All of them expressed transcription factors beta-3 tubulin and glial fibrillary acid protein. No untoward effect of SCT was noted. Variable and sustained improvement in Hauser's index and American Spinal Injury Association score was noted in all patients over a mean follow-up of 2.95 years. Mean injury duration was 3.42 years against the period of approximately 1-year required for natural recovery, suggesting a positive role of SCs. Conclusion: Co-infusion of N-Ad-MSC and HSC in CSF is safe and viable therapeutic approach for SCIs. PMID:27110548

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

    PubMed

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

    2016-01-01

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

  9. 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

  10. 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

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

    PubMed Central

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

    2015-01-01

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

  12. 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

  13. 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

  14. 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

  15. 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 ...

  16. Genetics Home Reference: spastic paraplegia type 2

    MedlinePlus

    ... F, Mimault C, Isabelle V, Courtois V, Giraud G, Dastugue B, Boespflug-Tanguy O. Genotype-phenotype correlation in inherited brain myelination defects due to proteolipid protein gene mutations. Clinical European Network on Brain Dysmyelinating ...

  17. Genetics Home Reference: spastic paraplegia type 15

    MedlinePlus

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

  18. The value of sport as a recreation in paraplegia.

    PubMed

    Schneider, G

    1966-08-01

    On an afternoon in 1944, an able-bodied man attempted to move about in a wheel chair and, using the curved handle of a walking stick as a mallet, to hit a ball and chase after it, at the same time endeavouring to prevent his opponent in a wheel chair from counteracting his movements. The man was Dr. Ludwig Guttmann; the activity was later to become wheel-chair polo and from his simple experiment was born the idea of competitive team sport for paraplegics. Two decades later in Tokyo, paralyzed men and women from twenty-three nations competed in sports demanding of their patiently trained bodies skill, strength, speed and endurance. This was the occasion of the 1964 International Games for the Paralyzed. Paraplegic sport is a success story and the history of its growth of great interest. PMID:25023754

  19. Genetics Home Reference: spastic paraplegia type 3A

    MedlinePlus

    ... Claeys KG, Deconinck T, Litvinenko I, Jordanova A, Auer-Grumbach M, Haberlova J, Löfgren A, Smeyers G, ... Jan 31. [Epub ahead of print] Leonardis L, Auer-Grumbach M, Papić L, Zidar J. The N355K ...

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

    PubMed Central

    Ganesh, Shankar; Mishra, Chittaranjan

    2016-01-01

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

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

    PubMed

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

    2006-12-01

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

  2. 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

  3. 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

  4. 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

  5. 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

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

    PubMed Central

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

    1986-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2006-12-01

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

  8. Sensor-based hip control with hybrid neuroprosthesis for walking in paraplegia.

    PubMed

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

    2014-01-01

    The objectives of this study were to test whether a hybrid neuroprosthesis (HNP) with an exoskeletal variable-constraint hip mechanism (VCHM) combined with a functional neuromuscular stimulation (FNS) controller can maintain upright posture with less upper-limb support and improve gait speed as compared with walking with either an isocentric reciprocating gait orthosis (IRGO) or FNS only. The results show that walking with the HNP significantly reduced forward lean in FNS-only walking and the maximum upper-limb forces by 42% and 19% as compared with the IRGO and FNS-only gait, respectively. Walking speed increased significantly with VCHM as compared with 1:1 reciprocal coupling and by 15% when using the sensor-based FNS controller as compared with HNP with fixed baseline stimulation without the controller active. PMID:24933721

  9. 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

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

    ERIC Educational Resources Information Center

    Davis, Kay

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

  11. 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

  12. 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

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

    PubMed Central

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

    2013-01-01

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

  14. 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…

  15. 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

  16. Potent suppression of stretch reflex activity after systemic or spinal delivery of Tizanidine in rats with spinal ischemia-induced chronic spastic paraplegia

    PubMed Central

    Fuchigami, Tatsuya; Kakinohana, Osamu; Hefferan, Michael P.; Lukacova, Nadezda; Marsala, Silvia; Sugahara, Kazuhiro; Yaksh, Tony L.; Marsala, Martin

    2011-01-01

    Background Spasticity and rigidity are serious complications associated with spinal traumatic or ischemic injury. Clinical studies show that Tizanidine (Tiz) is an effective anti-spasticity agent, however, the mechanism of this effect is still not clear. Tiz binds not only to α2-adrenoreceptors (AR) but also to imidazoline (I) receptors. Both receptor systems (AR+I) are present in the spinal cord interneurons and α-motoneurons. The aim of the present study was to evaluate the therapeutic potency of systematically or spinally (intrathecally) delivered Tiz on stretch reflex activity (SRA) in animals with ischemic spasticity, and to delineate supraspinal or spinal sites of Tiz action. Methods Animals were exposed to 10 min of spinal ischemia to induce an increase in SRA. Increase in SRA was identified by simultaneous increase in recorded EMG activity and ankle resistance measured during computer-controlled ankle dorsiflexion (40°/3 sec) in fully awake animals. Animals with increased SRA were divided into several experimental subgroups and treated as follows: i) Tiz administered systemically at the dose of 1 mg kg-1, or intrathecally (IT) at 10 μg or 50 μg delivered as a single dose; ii) Treatment with systemic Tiz was followed by the systemic injection of vehicle, or by non-selective AR antagonist without affinity for imidazoline receptors; Yohimbine (Yoh), α2A AR antagonist; BRL44408 (BRL), α2B AR antagonist; ARC239 (ARC), non-selective AR and I1 receptor antagonist; Efaroxan (Efa), or non-selective AR and I2 receptor antagonist; Idazoxan (Ida); iii) Treatment with IT Tiz was followed by the IT injection of selective α2A AR antagonist; Atipamezole (Ati). In a separate group of spastic animals the effect of systemic Tiz treatment (1 mg/kg) or isoflurane anesthesia on H-reflex activity was also studied. Results Systemic and/or IT treatment with Tiz significantly suppressed SRA. This Tiz-mediated anti-SRA effect was reversed by BRL (5 mg kg-1), Efa (1 mg kg-1) and Ida (1 mg kg-1). No reversal was seen after Yoh (3 mg kg-1) or ARC (5 mg kg-1) treatment. Anti-SRA induced by IT Tiz (50 μg) was reversed by IT injection of Ati (50 μg). Significant suppression of H-reflex was measured after systemic Tiz treatment (1mg/kg) or isoflurane (2%) anesthesia, respectively. Immunofluoresecene staining of spinal cord sections taken from animals with spasticity showed upregulation of α-2A receptor in activated astrocytes. Conclusions These data suggest that α2A AR and I receptors, but not α2B AR primarily mediate the Tiz-induced anti-spasticity effect. This effect involves spinal and potentially supraspinal sites and likely targets α2A receptor present on spinal neurons, primary afferents and activated astrocytes Further studies using highly selective antagonists are needed to elucidate the involvement of specific subtypes of the AR and imidazoline receptors in the anti-spasticity effect seen after Tiz treatment. PMID:21871540

  17. 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

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

    PubMed

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

    2010-02-01

    Spinal epidural angiolipoma is a rare tumor revealed by a slowly progressive paraplegia. We reported a case of a 44-year-old female and point out the peculiar pattern of this lesion characterized by the prominence of the vascular component over the lipomatous component. Recognition of this entity is important because this is a benign and curable cause of paraplegia. PMID:20223352

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

    PubMed

    Mahbubul Huq, A H; Nigro, M A

    2000-10-01

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

  20. Primary Lateral Sclerosis

    MedlinePlus

    ... When symptoms begin, PLS may be mistaken for amyotrophic lateral sclerosis (ALS) or spastic paraplegia. Most neurologists follow an affected ... www.sp-foundation.org Tel: 877-773-4483 ALS Association 1275 K Street, N.W. Suite 250 ...

  1. 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 ...

  2. Genetics Home Reference: Troyer syndrome

    MedlinePlus

    ... materials from the cell surface into the cell (endocytosis). Spartin is found in a wide range of ... the diagnosis or management of Troyer syndrome: Gene Review: Gene Review: Hereditary Spastic Paraplegia Overview Gene Review: ...

  3. Peripheral nerve involvement in spinal cord injury: an electromyographic study.

    PubMed

    Laurence, T N; Pugel, A V; Teasdall, R D

    1978-07-01

    This electromyographic study was undertaken to assess the peripheral nervous system in patients with various types of paraplegia. Twelve patients were studied. In 8 patients the paraplegia was of the spastic type while 4 had flaccid paraplegia. Electromyographic abnormalities consisting of denervation potentials, slowed conduction and inexcitability of nerve were demonstrated in the lower limbs of all patients. These findings suggest a diffuse neuropathy of unknown cause, although local pressure palsies may have occurred in some patients. Because this involvement was more apparent in the flaccid group of paraplegic patients as compared with the spastic one, it is concluded that the peripheral nervous system plays an important role in determining the type of paraplegia that develops following complete spinal cord lesions. PMID:687037

  4. Planned Staged Repair of Thoracoabdominal Aortic Aneurysms to Minimize Spinal Cord Injury

    PubMed Central

    Luozzo, Gabriele Di; Wilderman, Michael; Pawale, Amit; McCullough, Jock; Griepp, Randall B.

    2015-01-01

    Management of thoracoabdominal aortic aneurysms (TAA) can lead to spinal cord injury. A variety of clinical adjuncts have proven to decrease the incidence of paraplegia; however, at least 10% patients remain at risk of developing paraplegia. Experimentally and in sporadic clinical experiences, the staged repair of TAAs can lead to better neurologic outcomes. We present two clinical cases with extensive TAA in which a deliberate staged repair leads to excellent neurologic outcomes. PMID:27175369

  5. 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.

  6. 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 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

  7. Increased susceptibility to ventricular arrhythmias is associated with changes in Ca2+ regulatory proteins in paraplegic rats.

    PubMed

    Rodenbaugh, David W; Collins, Heidi L; Nowacek, Dustin G; DiCarlo, Stephen E

    2003-12-01

    Paraplegia may increase susceptibility to ventricular arrhythmias by altering the autonomic control of the heart. Altered cardiac autonomic control has been documented to change the expression of genes that encode cardiac Ca2+ regulatory proteins. Therefore, we tested the hypothesis that paraplegia alters cardiac electrophysiology with concomitant changes in Ca2+ regulatory proteins in a manner that increases the susceptibility to ventricular arrhythmias. To test this hypothesis, intact (n = 10) and paraplegic (n = 6) male Wistar rats were chronically instrumented to measure atrioventricular (AV) interval, sinus cycle length, sinus node recovery time (SNRT), SNRT corrected for spontaneous sinus cycle (cSNRT), Wenckebach cycle length (WCL), and the electrical stimulation threshold to induce ventricular arrhythmias. In addition, relative protein abundance and mRNA expression for sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA), phospholamban, and the Na/Ca exchanger were determined in intact (n = 8) and paraplegic (n = 8) rats. Paraplegia significantly (P < 0.05) reduced AV interval (-25%), sinus cycle length (-24%), SNRT (-28%), cSNRT (-53%), WCL (-19%), and the electrical stimulation threshold to induce ventricular arrhythmia (-48%). Paraplegia significantly increased the relative protein abundances of SERCA (45%) and the Na/Ca exchanger (40%) and decreased phospholamban levels (-28%). In contrast, only the relative mRNA expression of the Na/Ca exchanger was increased (25%) in paraplegic rats. These data demonstrate that paraplegia enhances cardiac electrophysiological properties and alters Ca2+ regulatory proteins in a manner that increases susceptibility to ventricular arrhythmias. PMID:12881214

  8. 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

  9. 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

  10. [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

  11. 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

  12. 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).…

  13. 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,…

  14. 5 CFR 831.1209 - Termination of disability annuity because of restoration to earning capacity.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... disabilities include blindness, paraplegia, multiple sclerosis, and cerebral hemorrhage. Claims involving... standards that appear in the Social Security Administration's regulations at 20 CFR 404.1041(d). (2) Any... applies only to restoration to earning capacity decisions. In cases involving use of either of the...

  15. 5 CFR 831.1209 - Termination of disability annuity because of restoration to earning capacity.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... disabilities include blindness, paraplegia, multiple sclerosis, and cerebral hemorrhage. Claims involving... standards that appear in the Social Security Administration's regulations at 20 CFR 404.1041(d). (2) Any... applies only to restoration to earning capacity decisions. In cases involving use of either of the...

  16. 5 CFR 831.1209 - Termination of disability annuity because of restoration to earning capacity.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... disabilities include blindness, paraplegia, multiple sclerosis, and cerebral hemorrhage. Claims involving... standards that appear in the Social Security Administration's regulations at 20 CFR 404.1041(d). (2) Any... applies only to restoration to earning capacity decisions. In cases involving use of either of the...

  17. Seppuku: a modern approach to an ancient injury.

    PubMed

    Richardson, A J; Tevlin, R; Larkin, J O; Beddy, D

    2013-01-01

    A 67 year-old man with paraplegia and depression presented with self-inflicted evisceration and small bowel injury. Damage control surgery was undertaken at emergency laparotomy with definitive anastomosis performed at second-look laparotomy following 24 hours resuscitation in ICU. He had an uncomplicated post-operative course and was discharged to an inpatient psychiatric unit. PMID:24218749

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

    PubMed

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

    1975-01-01

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

  19. 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

  20. 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

  1. Spinal anaesthesia for caesarean section in the presence of respiratory failure and spinal metastases from a soft tissue clear cell sarcoma.

    PubMed

    Miskovic, A M; Dob, D P

    2013-07-01

    Spinal metastases occur in up to 70% of all patients with cancer. However, only 10% are symptomatic. Before considering central neuraxial blockade in patients with malignancy, a history of back pain should be excluded. Anaesthetists should be aware that intrathecal and epidural injections could cause paraplegia if metastases are impinging on the spinal cord. Failure to achieve adequate sensory anaesthesia after central neuraxial blockade or presentation with postoperative paraplegia may indicate the presence of asymptomatic vertebral canal metastases. In this report, the anaesthetic management of a patient with respiratory failure and spinal metastases from a soft tissue sarcoma, requiring caesarean section is described. Sensory anaesthesia extending above a level of imminent cord compression was achieved despite loss of cerebrospinal fluid signal on magnetic resonance imaging. PMID:23809016

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

    PubMed Central

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

    1990-01-01

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

  3. Traumatic cervical epidural hematoma in an infant.

    PubMed

    Rangarajan, Vithal; Mavani, Sandip B; Nadkarni, Trimurti D; Goel, Atul H

    2013-01-01

    An 8-month-old male infant had presented with a history of a fall from the crib a fortnight ago. He had developed progressive weakness of both lower limbs. On examination, the infant had spastic paraplegia. Magnetic resonance (MR) imaging of the cervical spine showed an epidural hematoma extending from the fourth cervical (C4) to the first dorsal (D1) vertebral level with cord compression. The patient had no bleeding disorder on investigation. He underwent cervical laminoplasty at C6 and C7 levels. The epidural hematoma was evacuated. The cervical cord started pulsating immediately. Postoperatively, the patient's paraplegia improved dramatically in 48 hours. According to the author's literature search, only seven cases of post-traumatic epidural hematoma have been reported in pediatric patients, and our patient is the youngest. The present case report discusses the etiopathology, presentation, and management of this rare case. PMID:24381456

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. Spinal Cord Lesion: Effects of and Perspectives for Treatment

    PubMed Central

    Dietz, V.

    2001-01-01

    Following central motor lesions, two forms of adaptation can be observed which lead to improved mobility: (1) the development of spastic muscle tone, and (2) the activation of spinal locomotor centers induced by specific treadmill training. Tension development during spastic gait is different from that during normal gait and appears to be independent of exaggerated monosynaptic stretch reflexes. Exaggerated stretch reflexes are associated with an absence or reduction of functionally essential polysynaptic reflexes. When supraspinal control of spinal reflexes is impaired, the inhibition of monosynaptic reflexes is missing in addition to a reduced facilitation of polysynaptic reflexes. Therefore, overall leg muscle activity becomes reduced and less well modulated in patients with spasticity. Electrophysiologicai and histological studies have shown that a transformation of motor units takes place following central motor lesions with the consequence that regulation of muscle tone is achieved at a lower level of neuronal organization which in turn enables the patient to walk. Based on observations of the locomotor capacity of the spinal cat, recent studies have indicated that spinal locomotor centers can be activated and trained in patients with complete or incomplete paraplegia when the body is partially unloaded. However, the level of electromyographic activity in the gastrocnemius (the main antigravity muscle during gait) is considerably lower in the patients compared to healthy subjects. During the course of a daily locomotor training program, the amplitude of gastrocnemius, electromyographic activity increases significantly during the stance phase, while inappropriate tibialis anterior activation decreases. Patients with incomplete paraplegia benefit from such training programs such that their walking ability on a stationary surface improves. The pathophysiology and functional significance of spastic muscle tone and the effects of treadmill training on the locomotor pattern underlying new attempts to improve the mobility of patients with paraplegia are reviewed. PMID:11530890

  11. 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

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

    PubMed Central

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

    2016-01-01

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

  13. Demographic Trends of Patients with Compressive Myelopathy in a Developing Asian Country

    PubMed Central

    Kumar, Vishal; Kumar, Avinash; Bahadur, Raj

    2016-01-01

    Study Design Prospective case series. Purpose To analyze the demographic picture of the patients suffering from compression myelopathy due to various spinal problems. Overview of Literature: There is a lack of literature depicting demographic picture of such patients with spinal injuries as most of the articles have shown the epidemiology of spinal cord injuries either managed conservatively or operatively. None have focused on the patients with compressive myelopathy requiring surgeries. Methods Patients with spinal pathologies with a neurological deficit due to compressive myelopathy requiring surgical decompression of dorsal and thoracolumbar region were studied. The different kinds of etiologies, the demographic profiles involved, the involvement of various regions of spine in each of the etiologies, sex distribution of different etiologies, association of age and sex with the occurrence of paraplegia, and association of thoracolumbar junction (TLJ) involvement by age and sex were studied. This study addressed the dorsal and TLJ till L2 vertebrae surgically treated by anterior transthoracic transpleural approach. Results With regard to gender, 75% of the females and 67.3% of the males were paraplegic but there was no relationship between gender and the occurrence of paraplegia (p >0.05). There was also no association between TLJ involvement and the age and sex of the patients (p >0.05). Seventy percent of the patients were paraplegic with a mean age of 38.90 years and 30% were paraparetic with a mean age of 43.43 years. Male to female ratio stood at 4.43:1. Conclusions Traumatic spine in females is increasing. The occurrence of paraplegia and involvement of TLJ is not affected by the age and the sex of the patients. Deep epidemiological understanding of spinal pathologies can lead to a better appreciation of the potential impact of health care management strategies and health policies to prevent and minimize their consequences considering limited worldwide reports on the same. PMID:27114774

  14. 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 .

  15. [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

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

    PubMed

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

    2011-01-01

    Cerebrovascular accidents (CVA) and spinal cord injuries (SCI) are the most common causes of paralysis and paresis with reported prevalence of 12,000 cases per million and 800 cases per million, respectively. Disabilities that follow CVA (hemiplegia) or SCI (paraplegia, tetraplegia) severely impair motor functions (e.g., standing, walking, reaching and grasping) and prevent the affected individuals from healthy-like, full and autonomous participation in daily activities. Our research focuses on the development of a new virtual reality (VR) system combined with wearable neurorobotics (NR), motor-neuroprosthetics (MNP) and brain neuro-machine interface (BNMI) to overcome the major limitations of current rehabilitation solutions. PMID:21335782

  17. 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.

  18. Leg Swelling Caused by Heterotopic Ossification Mimicking Deep Vein Thrombosis in a Paraplegic Patient

    PubMed Central

    Bang, Jin Hyuk; Lee, Ho Jun

    2015-01-01

    Leg swelling in patients with paraplegia due to spinal cord injury (SCI) occurs for various reasons, including heterotopic ossification (HO), deep vein thrombosis (DVT), fracture, or cellulitis. The clinical presentations of these conditions may overlap in part or in whole and it may occasionally be difficult to distinguish. Of these conditions, DVT and subsequent pulmonary embolism remain significant causes of morbidity and mortality in patients with SCI. Therefore, a prompt diagnostic work-up, particularly for DVT, is essential in patients with SCI, who present with leg swelling. Here, we report a case of leg swelling in a paraplegic patient, resulting from HO mimicking DVT and discuss the differential diagnosis. PMID:27169085

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

    PubMed

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

    2016-04-01

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

  20. Mitochondrial quality control: a matter of life and death for neurons

    PubMed Central

    Rugarli, Elena I; Langer, Thomas

    2012-01-01

    Neuronal survival critically depends on the integrity and functionality of mitochondria. A hierarchical system of cellular surveillance mechanisms protects mitochondria against stress, monitors mitochondrial damage and ensures the selective removal of dysfunctional mitochondrial proteins or organelles. Mitochondrial proteases emerge as central regulators that coordinate different quality control (QC) pathways within an interconnected network of mechanisms. A failure of this system causes neuronal loss in a steadily increasing number of neurodegenerative disorders, which include Parkinson's disease, spinocerebellar ataxia, spastic paraplegia and peripheral neuropathies. Here, we will discuss the role of the mitochondrial QC network for neuronal survival and neurodegeneration. PMID:22354038

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

    PubMed

    Silverthorn, K G; Gillespie, W J

    1986-02-12

    The presentation and outcome of 61 cases of nontuberculous spinal osteomyelitis were reviewed. Although the commonest presentation was subacute, with back pain predominating, 10% had septicaemia and 7% paraperesis or paraplegia. Most infections were caudal to the fourth thoracic vertebra. One third were associated with preceding urinary, respiratory, dental or abdominal sepsis. Staphylococcus aureus was the infecting organism in 85% of isolates. Delay in diagnosis was frequent. There were four deaths, and seven individuals remained severely disabled: outcome was otherwise satisfactory. An algorithm for the investigation and management of this uncommon but serious condition is proposed. PMID:3456113

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

    PubMed

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

    2016-04-01

    In this study, a novel parvovirus (strain swine/Zsana3/2013/HUN, KT965075) was detected in domestic pigs and genetically characterized by viral metagenomics and PCR methods. The novel parvovirus was distantly related to the human bufaviruses and was detected in 19 (90.5 %) of the 21 and five (33.3 %) of the 15 faecal samples collected from animals with and without cases of posterior paraplegia of unknown etiology from five affected farms and one control farm in Hungary, respectively. Swine/Zsana3/2013/HUN is highly prevalent in domestic pigs and potentially represents a novel parvovirus species in the subfamily Parvovirinae. PMID:26733298

  3. 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

  4. 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

  5. Exome sequencing reveals a novel missense mutation in the KIAA0196 gene in a Japanese patient with SPG8.

    PubMed

    Ichinose, Yuta; Koh, Kishin; Fukumoto, Megumi; Yamashiro, Nobuo; Kobayashi, Fumikazu; Miwa, Michiaki; Nagasaka, Takamura; Shindo, Kazumasa; Ishiura, Hiroyuki; Tsuji, Shoji; Takiyama, Dr Yoshihisa

    2016-05-01

    Exome sequencing revealed a novel missense mutation (c.2152G>A, p.E713K) in the KIAA0196 gene in a Japanese patient with SPG8. To date, only 10 mutations in the KIAA0196 gene have been reported in the world. We describe the clinical and genetic findings in our patient with SPG8, which is a rare dominant hereditary spastic paraplegia. Notably, our patient showed mild upper limb ataxia, which is a relatively atypical symptom of SPG8. Thus, our patient showed a wide clinical spectrum of SPG8. PMID:26967522

  6. 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

  7. Telangiectatic osteosarcoma of the spine: a case report

    PubMed Central

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

    2008-01-01

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

  8. Postoperative early hemolytic anemia due to inverted teflon felt strip after emergency repair for type A dissection.

    PubMed

    Hata, M; Yoshitake, I; Wakui, S; Unosawa, S; Hata, H; Shiono, M

    2012-10-01

    A 39-year-old man underwent emergency surgery for type A acute aortic dissection complicated by paraplegia. However, hemolytic anemia increased significantly due to severe stenosis of the proximal anastomosis one month after surgery. He finally underwent a redo procedure 4 months after the initial operation whereupon it was verified that half of the inner felt strip used for proximal stump fixation had turned up and was protruding into the inner lumen. We report here on a rare case of survival of postoperative early hemolytic anemia due to severe graft stenosis caused by an inverted inner Teflon felt strip without any extra vascular compression. PMID:21766281

  9. 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

  10. [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

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

    PubMed Central

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

    2014-01-01

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

  12. 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

  13. 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.

  14. Spinal Hydatid Disease: A Case Series

    PubMed Central

    Prabhakar, Mukund M; Acharya, Apurv J; Modi, Dhaval R; Jadav, Bhavin

    2005-01-01

    Background: Over the past 10 years, 4 cases of spinal hydatid disease (3 men, 1 woman) were diagnosed and treated at our institution, with an average follow-up of 4 years. Hydatid disease of the spine is a rare condition with a poor prognosis that presents diagnostic and therapeutic challenges. Methods: The patients were evaluated clinically, using the latest imaging modalities available in our institution. Decompressive surgeries were performed and the diagnosis was confirmed by histopathologic examination. All patients received long-term antihelminthic therapy with 400 mg of albendazole 3 times daily for 1 year. Results: After surgery, all patients improved; however, over time, recurrence and residual disease were observed. Two patients had complete neurologic recovery at follow-up at 2 to 3 years, although there were radiographic signs of recurrence. The other 2 patients did not achieve complete neurologic recovery despite anterior decompression; they developed recurrent disease and the neurologic status deteriorated to spastic paraplegia. All patients refused further surgeries for recurrences and 2 patients died of complications of paraplegia. Conclusion: Diagnosis was challenging, eradication was difficult, and hydatid disease recurred in all 4 patients. In our experience, morbidity and mortality were high and prognosis was poor. PMID:16869090

  15. Pneumomediastinum, subcutaneous emphysema, and tracheal tear in the early postoperative period of spinal surgery in a paraplegic achondroplastic dwarf.

    PubMed

    Kahraman, Sinan; Enercan, Meriç; Demirhan, Ozkan; Sengül, Türker; Dalar, Levent; Hamzaoğlu, Azmi

    2013-01-01

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

  16. 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

  17. 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

  18. Non-compressive myelopathy: clinical and radiological study.

    PubMed

    Prabhakar, S; Syal, P; Singh, P; Lal, V; Khandelwal, N; Das, C P

    1999-12-01

    Fifty seven patients (42 males and 15 females) with non-compressive myelopathy were studied from 1997 to 1999. Acute transverse myelitis (ATM) was the commonest (31) followed by Vit B12 deficiency myelopathy (8), primary progressive multiple sclerosis (5), hereditary spastic paraplegia (3), tropical spastic paraplegia (2), subacute necrotising myelitis (1), radiation myelitis (1), syphilitic myelitis (1) and herpes zoster myelitis (1). 4 cases remained unclassified. In the ATM group, mean age was 30.35 years, antecedent event was observed in 41.9% case, 25 cases had symmetrical involvement and most of the cases had severe deficit at onset. CSF study carried out in 23 patients of ATM revealed rise in proteins (mean 147.95mg%, range 20-1200 mg/dL) and pleocytosis (mean 20.78/cumm, range 0-200 mm3). Oligoclonal band (OCB) was present in 28% of cases of ATM. The most common abnormality detected was a multisegment hyperintense lesion on T2W images, that occupied the central area on cross section. In 6 patients hyperintense signal was eccentric in location. MRI was normal in 4 cases of ATM. Thus ATM is the leading cause of non-compressive myelopathy. Clinical features combined with MRI findings are helpful in defining the cause of ATM. PMID:10625902

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

    PubMed

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

    2014-01-01

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

  20. Successful management of a giant spinal arteriovenous malformation with multiple communications between primitive arterial and venous structures by embolization: report of a case.

    PubMed

    Kuga, T; Esato, K; Zempo, N; Fujioka, K; Harada, M; Furutani, A; Akiyama, N; Toyota, S; Fujita, Y

    1996-01-01

    A 47-year-old woman was admitted to our hospital with a giant spinal arteriovenous malformation (AVM) causing heart failure and thoracic myelopathy. Angiography revealed that the spinal AVM had multiple feeding vessels branching from the 5th through 12th intercostal arteries. The drainage vein flowed to the azygos vein and superior vena cava. The AVM destroyed the 7th thoracic vertebra. The cardiac output was 16.7l/min and the shunt ratio was 64% before treatment. Embolization with cyanoacrylate was performed because the operation was considered to be associated with a significant risk of paraplegia and organ ischemia. The cardiac output decreased to 11.6l/min and the shunt ratio was reduced to 32%. After embolization the patient demonstrated no symptoms of either heart failure or sensory deficits. During embolization, provocative tests using sodium amytal and lidocaine with magnetic stimulation were also performed. The above findings suggest that provocative tests and magnetic stimulation are useful to predict paraplegia, which could result from embolization while, in addition, embolization is considered to be a useful treatment for multiple shunt and nidus in this region. PMID:8883257

  1. Obstetric outcomes in women who sustained a spinal cord injury during pregnancy.

    TOXLINE Toxicology Bibliographic Information

    Engel S; Ferrara G

    2013-02-01

    STUDY DESIGN: Case report.SETTING: Prince of Wales Spinal Cord Injuries Unit, Sydney, Australia.METHODS: Interrogation of our unit database identified only two women who became spinal cord injured while pregnant; their medical records were reviewed and an unstructured follow-up telephone interview conducted 6 years after discharge. Case 1: CC sustained a fracture dislocation with paraplegia at the sixth thoracic level (T6) in a motorbike accident while she was pregnant, 12-week gestational age (GA). Profound shock and hypoxia complicated the injury and recurrent urinary tract infections complicated the rest of her pregnancy. A baby with arthrogryposis multiplex congenita was delivered at full term. Severe cerebral palsy (CP) and deafness were present at follow-up 6 years later. Case 2: A 33-year-old multigravida, 27 weeks GA, developed sudden, spontaneous onset of paraplegia (T3 ASIA B) due to an extradural haematoma, which was evacuated on the day of admission. Systolic blood pressure was maintained above 90 mm Hg during and after surgery. A normal, healthy boy was delivered by caesarean section at 40 weeks GA and remained so at 6 years.CONCLUSION: Traumatic spinal cord injury (SCI) with its attendant multiple potential insults to the developing foetus results in a high risk of foetal loss and malformation particularly in the first trimester. However, if the injury occurs later in pregnancy and if blood pressure and oxygenation are maintained, the risk of foetal loss and abnormality may be substantially reduced.

  2. Progressive correction of severe spinal deformities with halo-gravity traction.

    PubMed

    Bouchoucha, Sami; Khelifi, Anis; Saied, Walid; Ammar, Chokri; Nessib, Mohamed Nebil; Ben Ghachem, Maher

    2011-08-01

    Treatment of rigid and severe spinal deformities is challenging and risky. Preoperative halo-gravity traction can be used to progressively reduce the deformity before spinal fusion. The aim of this study was to evaluate the effectiveness of halo-gravity traction for the correction of severe spinal deformities. Fifteen patients were reviewed retrospectively. Their mean age at the beginning of traction was 13.5 years. The mean duration of traction was 64 days. The main curve in the coronal plane improved from +/- 95 degrees to +/- 67 degrees, a gain of +/- 28 degrees (range 0 degrees-50 degrees) or +/- 30%. The curve in the sagittal plane improved from +/- 96 degrees to +/- 78 degrees, a gain of +/- 18 degrees (range 0 degrees-45 degrees) or +/- 19%. Other authors report gains up to 46% and 43%, respectively in the coronal and in the sagittal plane, but this might be due to different conditions, techniques, and evaluations. One patient with a pre-existing neurological deficit developed paraplegia. According to the literature congenital curves with associated kyphosis are exposed to paraplegia. Halo-gravity traction is effective and is usually tolerated better than other techniques of traction using the halo device. PMID:21954764

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

    PubMed Central

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

    2014-01-01

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

  4. Spartin regulates synaptic growth and neuronal survival by inhibiting BMP-mediated microtubule stabilization.

    PubMed

    Nahm, Minyeop; Lee, Min-Jung; Parkinson, William; Lee, Mihye; Kim, Haeran; Kim, Yoon-Jung; Kim, Sungdae; Cho, Yi Sul; Min, Byung-Moo; Bae, Yong Chul; Broadie, Kendal; Lee, Seungbok

    2013-02-20

    Troyer syndrome is a hereditary spastic paraplegia caused by human spartin (SPG20) gene mutations. We have generated a Drosophila disease model showing that Spartin functions presynaptically with endocytic adaptor Eps15 to regulate synaptic growth and function. Spartin inhibits bone morphogenetic protein (BMP) signaling by promoting endocytic degradation of BMP receptor wishful thinking (Wit). Drosophila fragile X mental retardation protein (dFMRP) and Futsch/MAP1B are downstream effectors of Spartin and BMP signaling in regulating microtubule stability and synaptic growth. Loss of Spartin or elevation of BMP signaling induces age-dependent progressive defects resembling hereditary spastic paraplegias, including motor dysfunction and brain neurodegeneration. Null spartin phenotypes are prevented by administration of the microtubule-destabilizing drug vinblastine. Together, these results demonstrate that Spartin regulates both synaptic development and neuronal survival by controlling microtubule stability via the BMP-dFMRP-Futsch pathway, suggesting that impaired regulation of microtubule stability is a core pathogenic component in Troyer syndrome. PMID:23439121

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

    PubMed

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

    2014-05-01

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

  6. 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

  7. 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

  8. DARS-associated leukoencephalopathy can mimic a steroid-responsive neuroinflammatory disorder

    PubMed Central

    Toro, Camilo; Kister, Ilya; Latif, Kartikasalwah Abd; Leventer, Richard; Pizzino, Amy; Simons, Cas; Abbink, Truus E.M.; Taft, Ryan J.; van der Knaap, Marjo S.; Vanderver, Adeline

    2015-01-01

    Objective: To describe the expanding clinical spectrum of a recently described hereditary leukoencephalopathy, hypomyelination with brainstem and spinal cord involvement and leg spasticity, which is caused by mutations in the aspartyl tRNA-synthetase encoding gene DARS, including patients with an adolescent onset. Methods: Three patients with mutations in DARS were identified by combining MRI pattern recognition and genetic analysis. Results: One patient had the typical infantile presentation, but 2 patients with onset in late adolescence had a disease mimicking an acquired inflammatory CNS disorder. Adolescent-onset patients presented with subacute spastic paraplegia and had positive response to steroids. They had only minor focal supratentorial white matter abnormalities, but identical spinal cord changes involving dorsal columns and corticospinal tracts. Clinical presentation included subacute spastic paraplegia with partial improvement on steroids. Conclusions: Focal T2 hyperintense white matter changes on brain MRI in combination with spinal cord signal abnormalities usually suggest acquired inflammatory conditions such as multiple sclerosis, especially in the context of relapsing course and a positive response to steroid treatment. Adolescents with mutations in DARS can present with a comparable clinical picture, broadening the clinical spectrum of hypomyelination with brainstem and spinal cord involvement and leg spasticity. PMID:25527264

  9. 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

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

    PubMed Central

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

    2016-01-01

    The hereditary spastic paraplegias (HSPs) are genetic conditions in which there is progressive axonal degeneration in the corticospinal tract. Autosomal dominant mutations, including nonsense, frameshift and missense changes, in the gene encoding the microtubule severing ATPase spastin are the most common cause of HSP in North America and northern Europe. In this study we report quantitative gait analysis using a motorized treadmill system, carried out on mice knocked-in for a disease-associated mutation affecting a critical residue in the Walker A motif of the spastin ATPase domain. At 4 months and at one year of age homozygous mutant mice had a number of abnormal gait parameters, including in stride length and stride duration, compared to heterozygous and wild-type littermates. Gait parameters in heterozygous animals did not differ from wild-type littermates. We conclude that quantitative gait analysis using the DigiGait system sensitively detects motor abnormalities in a hereditary spastic paraplegia model, and would be a useful method for analyzing the effects of pharmacological treatments for HSP. PMID:27019090

  11. 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.

  12. 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

  13. 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

  14. Syphilitic myelopathy.

    PubMed

    Silber, M H

    1989-10-01

    Whether the clinical pattern of neurosyphilis has changed since the introduction of penicillin is controversial. This study describes the clinical, laboratory and radiological features of nine patients with syphilitic myelopathy, to assess whether the disease pattern has changed in this subgroup. Four patterns based on clinical course and radiological findings were identified: three patients presented with subacute paraparesis, four with prodromal backache and/or mild leg weakness followed by sudden paraplegia, one patient developed slowly progressive weakness over 4 years and one patient who progressed over one month was shown to have dural thickening on myelography. All patients showed CSF pleocytosis with positive CSF VDRL in seven patients. Despite therapy the prognosis for recovery was not good. Compared with pre-penicillin era studies, the clinical pattern has not significantly changed. Greater alertness to the diagnosis might result in earlier therapy and thus possibly lead to improved prognosis. PMID:2583718

  15. Posterior Trans-Dural Repair of Iatrogenic Spinal Cord Herniation after Resection of Ossification of Posterior Longitudinal Ligament

    PubMed Central

    Kim, Hong-Ki; Kim, Ki-Jeong; Jahng, Tae-Ahn; Kim, Hyun-Jib

    2016-01-01

    Iatrogenic spinal cord herniation is a rare complication following spinal surgery. We introduce a posterior trans-dural repair technique used in a case of thoracic spinal cord herniation through a ventral dural defect following resection of ossification of the posterior longitudinal ligament (OPLL) in the cervicothoracic spine. A 51-year-old female was suffering from paraplegia after laminectomy alone for cervicothoracic OPLL. Magnetic resonance imaging revealed a severely compressed spinal cord with pseudomeningocele identified postoperatively. Cerebrospinal fluid leak and iatrogenic spinal cord herniation persisted despite several operations with duroplasty and sealing agent. Finally, the problems were treated by repair of the ventral dural defect with posterior trans-dural duroplasty. Several months after surgery, the patient could walk independently. This surgical technique can be applied to treat ventral dural defect and spinal cord herniation. PMID:27114779

  16. 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.

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

    PubMed

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

    2016-06-01

    A 22-year-old man presented with a sudden backache and paraplegia (ASIA = B). Magnetic resonance imaging showed an anterior pan-spinal epidural haematoma. Digital subtraction angiography was performed and ruled out an underlying vascular malformation but showed an active contrast media leakage into the T-4 ventral epidural space with a pattern of pseudo-aneurysm. A rupture of a T-4 retrocorporeal artery was considered as the aetiology, possibly caused by a haemorrhagic sub-adventitial dissection. Treatment consisted in the embolisation of both the pseudo-aneurysm and the parent artery with liquid acrylic glue, followed by neurosurgical decompression in emergency. The patient had totally recovered (ASIA = E) by the 10-month clinical follow-up. PMID:27106842

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

    PubMed

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

    2015-05-01

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

  19. A review of the neurological and neurosurgical implications of tuberculosis in children.

    PubMed

    Vadivelu, Sudhakar; Effendi, Sabih; Starke, Jeffrey R; Luerssen, Thomas G; Jea, Andrew

    2013-12-01

    Tuberculous involvement of the central nervous system (CNS) and vertebral column is the most lethal and disabling form of tuberculosis (TB). Several factors contribute to poor outcome, including cerebrovascular involvement with ischemia, hydrocephalus, direct parenchymal injury and formation of abscess and inflammation in the brain and spinal cord, hyponatremia, seizures, and delayed diagnosis. Spinal spondylitis from TB and associated spinal deformity is the leading cause of paraplegia in developing countries. The evidence for supportive treatment of TB infection of the CNS is limited, leading to substantial differences in management protocols. Many of the treatment approaches used in TB infection of the CNS have been extrapolated from treatment of other acute neurological disorders such as bacterial meningitis and traumatic brain injury. We review data from the available literature and highlight questions relating to the neurological and neurosurgical care of children with TB infection of the CNS and vertebral column. PMID:23847176

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

    PubMed

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

    2015-01-01

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

  1. Spontaneous ventral spinal epidural hematoma in a child: A case report and review of literature.

    PubMed

    Ratre, Shailendra; Yadav, Yadram; Choudhary, Sushma; Parihar, Vijay

    2016-01-01

    Spontaneous spinal epidural hematoma is very uncommon cause of spinal cord compression. It is extremely rare in children and is mostly located in dorsal epidural space. Ventral spontaneous spinal epidural hematoma (SSEH) is even rarer, with only four previous reports in childrens. We are reporting fifth such case in a 14 year old male child. He presented with history of sudden onset weakness and sensory loss in both lower limbs with bladder bowel involvment since 15 days. There was no history of trauma or bleeding diasthesis. On clinical examination he had spastic paraplegia. Magnetic resonance imaging (MRI) of dorsal spine was suggestive of ventral spinal epidural hematoma extending from first to sixth dorsal vertebrae. Laminectomy of fourth and fifth dorsal vertebrae and complete evacuation of hematoma was done on the same day of admission. Postoperatively the neurological status was same. PMID:27114667

  2. [Absconding of a patient from an acute psychiatric ward. Whom do the courts hold liable?].

    PubMed

    Fähndrich, Erdmann; Munk, Ingrid

    2010-03-01

    An involuntarily admitted patient absconds from a mental health hospital, which works on the open-door-system. Two days after leaving, he falls from a balcony on the fifth floor of a residential building and injures himself severely (paraplegia). The court case concerning damages and responsibility for paying the costs of the medical treatment eventually reaches the Kammergericht, the highest court of the state of Berlin. The main question in each trial was whether the hospital had violated its duty and was responsible for the accident and the resulting severe injuries. Relying on the hospital's documentation, the courts noted that closing the door of a ward is actually only one of the various possibilities of preventing absconding. The Kammergericht accepted the arguments of the hospital that prevention of absconding can also be achieved by intensive personal care and that security measures should not disturb the therapeutic alliance with the patient. PMID:20183774

  3. 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

  4. 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

  5. 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

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

    SciTech Connect

    Die-Smulders, C.E.M. de; Engelen, J.J.M.; Schrander-Stumpel, C.T.R.M.

    1995-11-20

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

  8. 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

  9. 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

  10. Neuroprosthetic applications of electrical stimulation.

    PubMed

    Grill, W M; Kirsch, R F

    2000-01-01

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

  11. 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

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

    PubMed

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

    2015-01-01

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

  13. 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

  14. 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.

  15. 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

  16. Safety belt education using visual crash images and low-cost incentives.

    PubMed

    Bross, M H; Spellicy, M J

    1994-03-01

    Automobile safety belt use among teen-agers remains low despite high crash morbidity and mortality. This article describes a model of a community-based safety belt promotional program. Ten public high schools, with student club and administrative support, were selected from across Mississippi. Safety belt assemblies, which created vivid crash images, were conducted using police officers, ambulance personnel, people with paraplegia, football players, and others. Low-cost incentives were awarded to buckled students over a 10-week period. Implementation of the program resulted in a mean increase of 21% in male safety belt use and 17% in female safety belt use. Concepts used in the program are reproducible, at minimal cost, by using personnel found in most communities. PMID:7515131

  17. Acupuncture for back pain, knee pain and insomnia in transverse myelitis - a case report.

    PubMed

    Vaghela, Sonia A; Donnellan, Clare P

    2008-09-01

    This case report describes the use of acupuncture for back pain, knee pain and insomnia in a 49 year old woman with a recent diagnosis of transverse myelitis with paraplegia, sensory disturbance, and bladder and bowel dysfunction. She was receiving intensive in-patient multi-disciplinary rehabilitation but was struggling to participate fully due to pain and poor sleep quality. She received a course of acupuncture in addition to standard care and reported substantial benefits including reduction in pain, improved sleep and mood, and reduction in daytime fatigue. Effective symptom control allowed this patient to participate more fully in her rehabilitation programme. Reduction of knee pain and sleep disturbance was maintained until discharge, 15 weeks after the last acupuncture treatment. This case report suggests that acupuncture may be an option to consider for other patients with pain or sleep disturbance that is interfering with their rehabilitation programme. PMID:18818565

  18. 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

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

    PubMed

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

    2015-10-01

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

  20. [An autopsy case of intracranial T cell type malignant lymphoma with fluctuating neuropsychological symptoms].

    PubMed

    Oda, M; Udaka, F; Fujisawa, M; Izumi, Y; Kameyama, M

    1999-07-01

    A 59-year-old man was admitted to the hospital due to leg edema. He had multiple sclerosis-like episodes of transient diplopia at the age of 36 years and spastic paraplegia at the age of 38. After admission he showed various fluctuating neuropsychological symptoms (disorientation, hallucination, apraxia, aphasia) and cranial nerve palsy. Magnetic resonance imaging revealed abnormal signal intensity in the right thalamus and deep white matter. The patient was diagnosed as having malignant lymphoma and treated with steroid therapy and chemotherapy. Although partial improvement of clinical findings was observed, recurrent cerebral hemorrhage followed. Autopsy findings revealed perivascular infiltration of T cells in the brain, spinal cord and other general organs. PMID:10548914

  1. 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

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

    PubMed Central

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

    2015-01-01

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

  3. 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

  4. Graded Control of Microtubule Severing by Tubulin Glutamylation.

    PubMed

    Valenstein, Max L; Roll-Mecak, Antonina

    2016-02-25

    Microtubule-severing enzymes are critical for the biogenesis and maintenance of complex microtubule arrays in axons, spindles, and cilia where tubulin detyrosination, acetylation, and glutamylation are abundant. These modifications exhibit stereotyped patterns suggesting spatial and temporal control of microtubule functions. Using human-engineered and differentially modified microtubules we find that glutamylation is the main regulator of the hereditary spastic paraplegia microtubule severing enzyme spastin. Glutamylation acts as a rheostat and tunes microtubule severing as a function of glutamate number added per tubulin. Unexpectedly, glutamylation is a non-linear biphasic tuner and becomes inhibitory beyond a threshold. Furthermore, the inhibitory effect of localized glutamylation propagates across neighboring microtubules, modulating severing in trans. Our work provides the first quantitative evidence for a graded response to a tubulin posttranslational modification and a biochemical link between tubulin glutamylation and complex architectures of microtubule arrays such as those in neurons where spastin deficiency causes disease. PMID:26875866

  5. 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

  6. The first report of fetal alcohol effect in a 12 year-old child in Korea.

    PubMed

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

    2009-03-01

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

  7. Gowers and Osler: good friends 'all through'.

    PubMed

    Boes, C J

    2016-12-01

    William Gowers and William Osler first met in 1878, and Osler visited Gowers often when in London. Osler dedicated his book On Chorea and Choreiform Affections to Gowers in 1894, addressing himself as Gowers' sincere friend. Two warm letters between Osler and Gowers exist in the Osler Library Archives, highlighting their strong friendship, and Gowers' son Ernest wrote Osler a letter after the death of his father. Referring to the relationship between William Osler and William Gowers, he noted that Osler had indeed been a good friend to him all through. Osler wrote and edited the first edition of his textbook from 1890 through early 1892, and was influenced by Gowers' Manual of Diseases of the Nervous System. In 1913, Osler commented that Gowers had ataxic paraplegia. Macdonald Critchley disagreed, and felt that Gowers had generalised cerebrovascular degeneration. Osler and Gowers were close friends, and this friendship was mutually beneficial. PMID:27092371

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

    PubMed

    Cooper, Robin

    2016-04-01

    Treating lymphoedema in patients with critical arterial disease can be contraindicated. This case study describes current methods of managing lymphoedema in a patient with arterial disease and leg ulcers. The patient, a 65-year-old male, had paraplegia and lower-limb lymphoedema with leg ulceration for 18 years, as well as arterial disease. The patient was referred to the lymphoedema/vascular service in 2013. Duplex ultrasound indicated superficial femoral occlusion. The arterial disease was treated with an angiogram and angioplasty, and when the blood supply was improved, the lymphoedema was treated. Emphasis was placed on self-care and reducing the need for community nurse involvement. Selfcare included compression bandaging, use of FarrowWrap, low-level light therapy, and ulcer dressings. Outcomes were measured using a telemedicine software programme. The patient's lymphoedema was reduced, leg ulcers healed, and quality of life transformed. PMID:27046424

  9. [Neuromuscular dysfunction of the lower urinary tract dysfunction beyond spinal cord injury and multiple sclerosis. A challenge for urologists].

    PubMed

    Reitz, A; Fisang, C; Müller, S C

    2008-09-01

    Neurogenic bladder subsequent to paraplegia serves as a paradigm when classifying the type of disorder analogous to the level of paralysis. In cases of multiple sclerosis micturition symptoms already present a manifold picture that changes in the clinical course. Rarer neurological disorders, on the other hand, such as infantile cerebral palsy, Parkinson's disease, multisystem atrophy, Alzheimer's disease, cerebrovascular disorders, Guillain-Barré syndrome, AIDS, herpes zoster, systemic lupus erythematosus, and herniated lumbar disc, often cause uncertainty with regard to necessary diagnostic tests and treatment.This review considers the available knowledge about voiding disorders and urinary incontinence associated with specific neurologic and neuromuscular diseases and provides recommendations for diagnostic work-up and pragmatic therapy. PMID:18679645

  10. 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

  11. 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 Nϵ-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

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

    PubMed Central

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

    2014-01-01

    Hereditary spastic paraplegias (HSPs) are neurodegenerative motor neuron diseases characterized by progressive age-dependent loss of corticospinal motor tract function. Although the genetic basis is partly understood, only a fraction of cases can receive a genetic diagnosis, and a global view of HSP is lacking. By using whole-exome sequencing in combination with network analysis, we identified 18 previously unknown putative HSP genes and validated nearly all of these genes functionally or genetically. The pathways highlighted by these mutations link HSP to cellular transport, nucleotide metabolism, and synapse and axon development. Network analysis revealed a host of further candidate genes, of which three were mutated in our cohort. Our analysis links HSP to other neurodegenerative disorders and can facilitate gene discovery and mechanistic understanding of disease. PMID:24482476

  13. Hybrid orthosis system with a variable hip coupling mechanism.

    PubMed

    To, C S; Kobetic, R; Triolo, R J

    2006-01-01

    Existing reciprocating gait orthoses, to help restore gait to individuals with paraplegia, have a fixed 1:1 hip flexion/extension coupling ratios (FECR), limiting stride length and gait speed. The purpose of this study was to develop a hip reciprocating mechanism for the hybrid orthosis system that is capable of variable hip FECR. The design of the new variable hip reciprocating mechanism incorporates a hydraulic system which utilizes solenoid valves to control coupling between cylinders linked to each hip joint of the orthosis. A specific set of valves are pulsed to achieve continual variable hip coupling. It was shown that piston velocity was inversely proportional to pulse width and also dependent on pulsing frequency. Internal losses in the hydraulic hip reciprocating mechanism occur primarily in the cylinders. Feedback control will be achieved with a dual layer gait event detector consisting of a fuzzy inference system and a set of supervisory rules. PMID:17946991

  14. [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

  15. 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

  16. [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

  17. Urgent resection of a giant left atrial appendage aneurysm and mitral valve replacement in a complex case of Hurler-Scheie syndrome.

    PubMed

    Brazier, Andrew; Hasan, Ragheb; Jenkins, Petra; Hoschtitzky, Andreas

    2015-01-01

    Hurler-Scheie syndrome is a rare lysosomal storage disease affecting the cardiovascular system. Besides the cardiac manifestations, it presents with complications from abnormal proteoglycan deposition in soft tissues in many locations, resulting in joint contractures, paraplegia, impaired vision, airway narrowing and restrictive lung function, to name a few. There are very few reports of surgical management of valvular heart disease due to mucopolysaccharidosis (MPS). We describe the successful management of a patient with an extremely challenging case of mitral valve stenosis and a giant left atrial appendage aneurysm due to MPS type 1 (Hurler-Scheie syndrome). The patient underwent mitral valve replacement and excision of the giant left atrial appendage aneurysm; a similar case has not been previously reported. PMID:26546621

  18. 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.

  19. Adaptor protein complexes and intracellular transport

    PubMed Central

    Park, Sang Yoon; Guo, Xiaoli

    2014-01-01

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

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

    PubMed

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

    2016-05-01

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

  1. 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.

  2. Spontaneous ventral spinal epidural hematoma in a child: A case report and review of literature

    PubMed Central

    Ratre, Shailendra; Yadav, Yadram; Choudhary, Sushma; Parihar, Vijay

    2016-01-01

    Spontaneous spinal epidural hematoma is very uncommon cause of spinal cord compression. It is extremely rare in children and is mostly located in dorsal epidural space. Ventral spontaneous spinal epidural hematoma (SSEH) is even rarer, with only four previous reports in childrens. We are reporting fifth such case in a 14 year old male child. He presented with history of sudden onset weakness and sensory loss in both lower limbs with bladder bowel involvment since 15 days. There was no history of trauma or bleeding diasthesis. On clinical examination he had spastic paraplegia. Magnetic resonance imaging (MRI) of dorsal spine was suggestive of ventral spinal epidural hematoma extending from first to sixth dorsal vertebrae. Laminectomy of fourth and fifth dorsal vertebrae and complete evacuation of hematoma was done on the same day of admission. Postoperatively the neurological status was same. PMID:27114667

  3. 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

  4. Coexistence of Spinal Intramedullary Tuberculoma and Multiple Intracranial Tuberculomas

    PubMed Central

    Lee, Dong-Yoon; Kim, Sang-Pyo

    2015-01-01

    Spinal intramedullary tuberculoma remains a very rare entity of central nervous system tuberculosis. This is the same with the coexistence of spinal intramedullary and intracranial tuberculomas that remains extremely rare with less than 20 cases reported at present. Authors describe this uncommon case by analyzing a 65-year-old female patient who had past history of kidney transplantation due to stage 5 chronic kidney disease and pulmonary tuberculosis on medication. The patient experiences progressive paraplegia and numbness on both lower extremities. Magnetic resonance imaging demonstrated an intramedullary mass at T9-10 level and multiple intracranial enhancing nodules. Microsurgical resection of spinal intramedullary mass was performed and the lesion was histopathologically confirmed as Mycobacterium tuberculosis. Efficient diagnosis and management of this rare disease are reviewed along with previously reported cases. PMID:26217392

  5. 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

  6. Idiopathic Thoracic Spontaneous Spinal Epidural Hematoma

    PubMed Central

    Aycan, Abdurrahman; Ozdemir, Seymen; Gonullu, Edip; Bozkına, Cemal

    2016-01-01

    A 33-year-old male patient experienced temporary sensory loss and weakness in the right lower extremity one month prior to admission. The patient was admitted to a private clinic with a three-day history of acute onset of sensory loss and weakness in both lower extremities and was treated and followed up with a prediagnosis of transverse myelitis and the Guillain-Barre syndrome (GBS). The patient was subsequently transferred to our clinic and the neurologic examination revealed paraplegia in both lower extremities, positive bilateral Babinski signs, and hypesthesia below the T10 dermatome with saddle anesthesia. The patient had urinary incontinence and thoracic magnetic resonance imaging (MRI) showed an image of a mass compressing the medulla. PMID:27088028

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

    PubMed

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

    2012-09-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    Rothschild, B; Behnam, S

    2005-01-01

    Objective: To assess diagnostic implications of abnormalities of the pedal digital tufts and to identify features to facilitate distinguishing of spondyloarthropathy and leprosy. Background: Better criteria for distinguishing between these disorders are necessary if their character, natural history, and evolution are to be understood. Methods: Pedal x rays of 91 consecutive patients with diabetes, 21 alcoholic patients, 100 with spondyloarthropathy, 8 with scleroderma, and 137 with leprosy, and 188 defleshed skeletons of individuals with alcoholism, syphilis, cerebrovascular disease, and paraplegia from the Terry and Hamman-Todd collections were examined for evidence of osseous and articular pathologies. Digital tuft abnormalities were divided into irregularity, divot, flattening, resorption, whittling, and fragmentation. Results: Tuft divots were more common in alcoholics than in diabetic, and were more common in both than in the other groups studied. Tuft flattening was limited to alcoholic and neurosyphilis groups. Tuft whittling was especially prominent among individuals with spondyloarthropathy, contrasted with leprosy and diabetes. Aligned fractures were more common in diabetics than individuals with leprosy. Misaligned fractures were limited to individuals with leprosy and neurosyphilis. Leprosy and spondyloarthropathy were complicated by phalangeal and metatarsal whittling more commonly than other diseases studied. Background pedal abnormalities, derived from individuals with cardiovascular syphilis, cerebrovascular accidents, and paraplegia, was limited to abnormal divots only. Conclusions: Pedal digital tufts undergo a variety of pathological alterations useful in the recognition of disorders traditionally considered neuropathic in aetiology and in distinguishing differential considerations. Tuft flattening appears specific for alcoholism and neurosyphilis, and misaligned fractures seem specific for neurosyphilis and leprosy, providing differential assistance related to spondyloarthropathy. Conversely, periosteal reaction distinguishes spondyloarthropathy from leprosy. PMID:15647437

  10. Four-limb muscle motor evoked potential and optimized somatosensory evoked potential monitoring with decussation assessment: results in 206 thoracolumbar spine surgeries

    PubMed Central

    Al Zayed, Zayed; Al Saddigi, Abdulmoneam

    2007-01-01

    The objective of this study was to improve upon leg somatosensory-evoked potential (SEP) monitoring that halves paraplegia risk but can be slow, miss or falsely imply motor injury and omits arm and decussation assessment. We applied four-limb transcranial muscle motor-evoked potential (MEP) and optimized peripheral/cortical SEP monitoring with decussation assessment in 206 thoracolumbar spine surgeries under propofol/opioid anesthesia. SEPs were optimized to minimal averaging time that determined feedback intervals between MEP/SEP sets. Generalized changes defined systemic alterations. Focal decrements (MEP disappearance and/or clear SEP reduction) defined neural compromise and prompted intervention. They were transient (quickly resolved) or protracted (>40 min). Arm and leg MEP/SEP monitorability was 100% and 98/97% (due to neurological pathology). Decussation assessment disclosed sensorimotor non-decussation requiring ipsilateral monitoring in six scoliosis surgeries (2.9%). Feedback intervals were 1–3 min. Systemic changes never produced injury regardless of degree. They were gradual, commonly included MEP/SEP fade and sometimes required large stimulus increments to maintain MEPs or produced >50% SEP reductions. Focal decrements were abrupt; their positive predictive value for injury was 100% when protracted and 13% when transient. Six transient arm decrements predicted one temporary radial nerve injury; five suggested arm neural injury prevention (2.4%). There were 15 leg decrements: six MEP-only, four MEP before SEP, three simultaneous and two SEP-only. Five were protracted, predicting four temporary cord injuries (three motor, one Brown–Sequard) and one temporary radiculopathy. Ten were transient, predicting one temporary sensory cord injury; nine suggested cord injury prevention (4.4%). Two radiculopathies and one temporary delayed paraparesis were unpredicted. The methods are reliable, provide technical/systemic control, adapt to non-decussation and improve spinal cord and arm neural protection. SEP optimization speeds feedback and MEPs should further reduce paraplegia risk. Radiculopathy and delayed paraparesis can evade prediction. PMID:17638028

  11. Is Level of Injury a Determinant of Quality of Life Among Individuals with Spinal Cord Injury? 
A Tertiary Rehabilitation Center Report

    PubMed Central

    Tavakoli, Seyed Amir Hossein; Kavian, Mohammad; Bakhsh, Samira Chai; Ghajarzadeh, Mahsa; Hamedan, Maryam Shabany; Ghazwin, Manijeh Yazdanshenas; Latifi, Sahar

    2016-01-01

    Objectives The role of injury-related variables in determining health-related quality of life (HRQOL) among Iranian persons with spinal cord injury (SCI) has not yet been fully described. In this study, we compared HRQOL between individuals with injury at cervical level and those with injury at thoracolumbar sections and evaluated the discriminating value of injury level as a determinant of HRQOL among Iranian people with SCI. Methods Individuals with SCI, who were referred to Brain and Spinal Cord Injury Research Center, were invited to participate in this investigation. HRQOL was assessed using the Short Form (SF-36) questionnaire to determine the quality of life (QOL) in eight domains: physical functioning (PF), role limitation due to physical problems (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role limitation due to emotional problems (RE), and mental health (MH). Results Ninety patients with paraplegia and 94 quadriplegic patients participated in this investigation. The mean score of PF domain was significantly lower in patients with injury at cervical level (p < 0.0001). There was no significant difference in other domains of SF-36 between subjects with paraplegia and quadriplegia (p = 0.670, 0.700, 0.910, 0.710, 0.730, 0.290 and 0.850 for RP, RE, VT, MH, SF, BP and GH, respectively). Similarly, the mean physical component summary (PCS) score was significantly higher among individuals with injury at thoracolumbar sections (p < 0.0001). The mean mental component summary (MCS) score did not differ between the two groups (p = 0.720). Conclusions Patients with SCI at the cervical level have similar mental health compared to those with injury at thoracolumbar sections, which shows proper mental adaptability in quadriplegic individuals. Injury level can be used as a major determinant of the physical component of QOL among people with SCI. PMID:27168921

  12. 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

  13. 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

  14. Two novel CYP7B1 mutations in Italian families with SPG5: a clinical and genetic study.

    PubMed

    Criscuolo, Chiara; Filla, Alessandro; Coppola, Giovanni; Rinaldi, Carlo; Carbone, Rosa; Pinto, Stefano; Wang, Qing; de Leva, Maria Fulvia; Salvatore, Elena; Banfi, Sandro; Brunetti, Arturo; Quarantelli, Mario; Geschwind, Daniel H; Pappatà, Sabina; De Michele, Giuseppe

    2009-08-01

    Hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurodegenerative disorders characterized by progressive weakness and spasticity in the lower limbs. Spasticity may occur in isolation (''pure'' HSP) or may be accompanied by other features. Although autosomal recessive HSPs usually have clinically complex phenotypes, mutations within a few genes underlie pure forms. Recently the gene (CYP7B1) responsible for SPG5, a pure recessive HSP, has been identified. The six CYP7B1 coding exons were analysed in four Italian families. Complete clinical assessment was performed in all patients. Blood CYP7B1 mRNA levels were assessed in three patients and six controls. Brain MRI and (18)F-fluoro-deoxy-glucose positron emission tomography (PET) scan were conducted in three patients. Two novel homozygous mutations were identified. Both result in a frameshift and the introduction of a premature stop codon at the C-terminal of the protein. Patients have reduced blood CYP7B1 mRNA levels, suggesting nonsense mediated RNA decay. Although clinical assessment showed a pure form of spastic paraplegia, MRI demonstrated white matter abnormalities in three patients and PET scan revealed cerebellar hypometabolism in one. Based on the results, we report the first Italian families with SPG5 molecular characterization and describe two novel truncating mutations in CYP7B1. The recessive character, the truncating nature of the mutations, and the reduced peripheral blood CYP7B1 mRNA levels suggest that the development of the disease is associated with a loss of function. SPG5 is considered a pure form of HSP, but MRI and PET findings in our patients suggest that SPG5 phenotype may be broader than the pure presentation. PMID:19363635

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2001-06-01

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

  17. 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

  18. 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

  19. Spontaneous thoracic spinal subarachnoid hemorrhage diagnosed with brain computed tomography.

    PubMed

    Sasaji, Tatsuro; Shinagawa, Kiyotsugu; Matsuya, Shigetsune

    2013-01-01

    Spontaneous thoracic spinal subarachnoid hemorrhage is rare, and thus no useful radiological findings for preoperative diagnosis have been reported. We experienced a patient with spontaneous thoracic spinal subarachnoid hemorrhage. A 37-year-old female presented with sudden-onset paraplegia and numbness in the trunk and bilateral lower extremities. The patient had no past history of trauma, lumbar puncture and bleeding disorder. T2-weighted sagittal magnetic resonance imaging (MRI) of the cervical and thoracic spines showed a mass occupied in the ventral space of spinal cord that was dorsally shifted. The mass extended from C6 to Th6 levels, with its largest size at Th2 level. Thoracic spine T2-weighted sagittal and axial MRI showed that the mass compressed spinal cord and was located in the intradural space. There was no spinal cord tumor and no spinal vascular malformation around the mass. Brain computed tomography (CT) showed a high-density area in the subarachnoid space, indicating the possibility of subarachnoid hemorrhage. Brain MRI showed no ruptured aneurysm. The patient was diagnosed as a spontaneous thoracic spinal subarachnoid hemorrhage and emergency surgery was selected. We performed right-side hemilaminectomy at Th1-Th6 and opened dura mater and arachnoid membrane. Hematoma was found in the ventral space of spinal cord and was removed. One year after surgery, numbness in the trunk and bilateral lower extremities had disappeared but paraplegia remained unchanged. Thoracic spine T2-weighted MRI confirmed no hematoma but showed a newly formed intradural cyst. Preoperative combination of brain CT and thoracic MRI is useful to diagnose thoracic spinal subarachnoid hemorrhage. PMID:24131866

  20. 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, Frédéric; Laforêt, 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

  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. 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

  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. The effect of ageing in spinal cord injured humans on the blood pressure and heart rate responses during fatiguing isometric exercise.

    PubMed

    Petrofsky, Jerrold Scott; Laymon, Michael

    2002-04-01

    Groups of 50 healthy male controls and 50 subjects suffering from paraplegia (aged 20-65 years) were examined as to the inter-relationships between age, paraplegia and the strength, endurance, blood pressure and heart rate responses to fatiguing isometric exercise. Contractions were maintained in both groups under voluntary effort and through a contraction induced by electrical stimulation in the paraplegic group. All contractions were maintained to fatigue at a tension of 40% of the maximal muscle strength in either the handgrip or quadriceps muscles. Muscle strength of the handgrip was higher in the paraplegic subjects than in the controls, averaging 589 N and 463 N, respectively for the two groups. In contrast, quadriceps leg extension strength averaged 696 N in the controls and 190 N in the paraplegic groups; for both groups, ageing was associated with a reduction in muscle strength. While leg endurance was less in the paraplegic group than the control group, handgrip endurance was similar in the two groups, endurance increasing with ageing in both the controls and paraplegics. Both systolic and diastolic blood pressures increased at rest in paraplegic and control subjects with age. The magnitude of the pressor response to exercise also increased with age. This was true during both voluntary exercise and exercise induced through electrical stimulation in the paraplegic groups. The heart rate response (change in heart rate during exercise) to a fatiguing isometric handgrip contraction decreased by about 50% between the ages of 20 and 60 years in both the controls and paraplegics for isometric handgrip exercise. In contrast, heart rate changed little with age during contractions of the quadriceps muscle in paraplegics which were induced by electrical stimulation. PMID:11944094

  6. 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 γ-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 15–20% 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

  7. Thoracoabdominal Aneurysm Repair: Results With 337 Operations Performed Over a 15-Year Interval

    PubMed Central

    Cambria, Richard P.; Clouse, W. Darrin; Davison, J. Kenneth; Dunn, Peter F.; Corey, Michael; Dorer, David

    2002-01-01

    Objective To review perioperative results and late survival after thoracoabdominal aneurysm repair (TAA), in particular to assess the impact over time of epidural cooling (EC) on spinal cord ischemic complications (SCI). Summary Background Data A variety of operative approaches and protective adjuncts have been used in TAA to minimize the major complications of perioperative death and SCI. There is no consensus with respect to the optimal approach. Methods From January 1987 to November 2001, 337 consecutive TAA repairs were performed by a single surgeon. Clinical features included prior aortic grafts in 97 (28.8%) and emergent operation in 82 (24.6%), including rupture in 46 (13.6%) and dissection in 63 (19%). Operative management consisted of a clamp/sew technique with adjuncts in 93%. EC (since July 1993) to prevent SCI was used in 194 (57.6%) repairs. Variables associated with the end points of operative mortality and postoperative SCI were assessed with the Fisher exact test and logistic regression; late survival was estimated with the Kaplan-Meier method. Results Operative mortality was 8.3% and was associated with nonelective operation, intraoperative hypotension, total transfusion requirement, and the postoperative complications of paraplegia, renal failure, and pulmonary insufficiency. Postoperative renal failure and transfusion requirement were independent correlates of mortality. SCI of any severity occurred in 38 of 334 (11.4%) operative survivors, with 22/38 (6.6% of cohort) sustaining total paraplegia. EC reduced the risk of SCI in patients with types I–III TAA (10.6% vs. 19.8%, P = .04). Independent correlates of SCI over the entire study interval included types I/II TAA, rupture, cross-clamp duration, sacrifice of T9–L1 intercostal vessels, and intraoperative hypotension. Late survival rates at 2 and 5 years were 81.2 ± 3% and 67.2 ± 5%. Conclusions EC has decreased the risk of SCI after TAA repair. Decreasing the substantial proportion (nearly 25%) of patients requiring nonelective operation will improve results. Late survival is equal to that after routine AAA repair, indicating that the considerable resource expenditure required for TAA repair is worthwhile. PMID:12368676

  8. Functional assessment of patients with spinal cord injury: measured by the motor score and the Functional Independence Measure.

    PubMed

    Ota, T; Akaboshi, K; Nagata, M; Sonoda, S; Domen, K; Seki, M; Chino, N

    1996-09-01

    There is some information about the Functional Independence Measure (FIM) score of patients with spinal cord injury (SCI), but there are a few publications dealing with the relationship between the FIM score and the motor score of the American Spinal Injury Association (ASIA). We have studied the relationship of all FIM items with the motor score, and reviewed the disability of patients with spinal cord injury in greater detail. The purpose of this study was to describe the characteristics of impairment and disability in patients with SCI, using the FIM and motor score of the ASIA. The subjects were 100 inpatients with SCI (Frankel A, B). Neurological level, days from the onset, and the FIM were examined. In addition to these items, the ASIA motor scores were calculated for 22 tetraplegic patients. We investigated the relationships among these various respects. We also examined the changes of the physical items of the FIM score (physical FIM) over time for 18 patients. The mean FIM scores of those with tetraplegia with C4, C5, C6, C7, C8 lesions, and those with paraplegia with above T5 levels, and those below T6 were 35, 61, 82, 90, 116, 114 and 114 respectively. The FIM score reached the plateau in approximately 10 months, 6 months and 3 months post-injury, in tetraplegia, paraplegia above T5 and that below T6 respectively. The FIM scores in C6 patients were widely distributed from 56 to 104. On the other hand, the ASIA motor score could subdivide C6 patients and related well to the FIM score. The mean FIM scores for each neurological level were similar to those previously reported, thus they appeared to be plateau scores. With regard to the motor score, we feel that it could reflect the disability of the patients better than considering the neurological levels alone. Also considering the changes in the physical FIM score over time within a year from the onset of the injury, there were differences in the ADL improvement patterns among patients with different neurological levels. It appears that timing of the highest physical FIM improvement for each neurological level can exist. Thus it is important not to delay the start of the rehabilitation of patients with spinal cord injury in proper time. PMID:8883187

  9. 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

  10. Brain-computer interface controlled robotic gait orthosis

    PubMed Central

    2013-01-01

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

  11. 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

  12. 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

  13. Thoracolumbar intradural disc herniation in eight dogs: clinical, low-field magnetic resonance imaging, and computed tomographic myelography findings.

    PubMed

    Tamura, Shinji; Doi, Shoko; Tamura, Yumiko; Takahashi, Kuniaki; Enomoto, Hirokazu; Ozawa, Tsuyoshi; Uchida, Kazuyuki

    2015-01-01

    Intradural disc herniation is a rarely reported cause of neurologic deficits in dogs and few published studies have described comparative imaging characteristics. The purpose of this retrospective cross sectional study was to describe clinical and imaging findings in a group of dogs with confirmed thoracolumbar intradural disc herniation. Included dogs were referred to one of four clinics, had acute mono/paraparesis or paraplegia, had low field magnetic resonance imaging (MRI) and/or computed tomographic myelography, and were diagnosed with thoracolumbar intradural disc herniation during surgery. Eight dogs met inclusion criteria. The prevalence of thoracolumbar intradural disc herniation amongst the total population of dogs that developed a thoracolumbar intervertebral disc herniation and that were treated with a surgical procedure was 0.5%. Five dogs were examined using low-field MRI. Lesions that were suspected to be intervertebral disc herniations were observed; however, there were no specific findings indicating that the nucleus pulposus had penetrated into the subarachnoid space or into the spinal cord parenchyma. Thus, the dogs were misdiagnosed as having a conventional intervertebral disc herniation. An intradural extramedullary disc herniation (three cases) or intramedullary disc herniation (two cases) was confirmed during surgery. By using computed tomographic myelography (CTM) for the remaining three dogs, an intradural extramedullary mass surrounded by an accumulation of contrast medium was observed and confirmed during surgery. Findings from this small sample of eight dogs indicated that CTM may be more sensitive for diagnosing canine thoracolumbar intradural disc herniation than low-field MRI. PMID:25263808

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-01-01

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

  16. 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

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

    PubMed

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

    2015-01-01

    Assistive and rehabilitative powered exoskeletons for spinal cord injury (SCI) and stroke subjects have recently reached the clinic. Proper tension and joint alignment are critical to ensuring safety. Challenges still exist in adjustment and fitting, with most current systems depending on personnel experience for appropriate individual fastening. Paraplegia and tetraplegia patients using these devices have impaired sensation and cannot signal if straps are uncomfortable or painful. Excessive pressure and blood-flow restriction can lead to skin ulcers, necrotic tissue and infections. Tension must be just enough to prevent slipping and maintain posture. Research in pressure dynamics is extensive for wheelchairs and mattresses, but little research has been done on exoskeleton straps. We present a system to monitor pressure exerted by physical human-machine interfaces and provide data about levels of skin/body pressure in fastening straps. The system consists of sensing arrays, signal processing hardware with wireless transmission, and an interactive GUI. For validation, a lower-body powered exoskeleton carrying the full weight of users was used. Experimental trials were conducted with one SCI and one able-bodied subject. The system can help prevent skin injuries related to excessive pressure in mobility-impaired patients using powered exoskeletons, supporting functionality, independence and better overall quality of life. PMID:25690551

  18. Recent Clinical Experience With Left Heart Bypass Using a Centrifugal Pump for Repair of Traumatic Aortic Transection

    PubMed Central

    Szwerc, Michael F.; Benckart, Daniel H.; Lin, Jeffrey C.; Johnnides, Christopher G.; Magovern, James A.; Magovern, George J.; Magovern, George J.

    1999-01-01

    Objective To analyze the indications, results, and limitations of using left atrial to femoral artery (LA-FA) bypass to provide distal perfusion during repair of traumatic aortic injuries. Summary Background Data There is no consensus about the best method for repair of traumatic aortic transection. Distal aortic perfusion with LA-FA bypass and a centrifugal pump has been the authors’ preferred technique for injuries to the aortic isthmus and descending thoracic aorta. Methods From 1988 to 1998, the authors operated on 30 patients with traumatic aortic transection using LA-FA bypass. The mean age of the group was 36 ± 2 years. The mechanism of injury was from a motor vehicle accident in 97% of the cases. Distal aortic perfusion was maintained at 50 to 75 mm Hg with flow rates of 1.5 and 3 L/min. The mean aortic cross-clamp time was 38 ± 2 minutes, and the mean bypass time was 49 ± 2 minutes. Results No complications related to cannulation, arterial thromboembolism, renal failure, mesenteric ischemia, or hepatic insufficiency occurred. There were no cases of postoperative paraplegia and no deaths. Conclusion Left atrial to femoral artery bypass is a safe, simple, and effective adjunct to the repair of traumatic injuries to the thoracic aorta. Active distal aortic perfusion preserves spinal cord, mesenteric, and renal blood flow and eliminates the potential catastrophic consequence of spinal cord ischemia from an unexpectedly prolonged aortic cross-clamp time. PMID:10522718

  19. 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

  20. 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

  1. Periodically Relieving Ischial Sitting Load to Decrease the Risk of Pressure Ulcers

    PubMed Central

    Makhsous, Mohsen; Rowles, Diane M.; Rymer, William Z.; Bankard, James; Nam, Ellis K.; Chen, David; Lin, Fang

    2010-01-01

    Objective To investigate the relieving effect on interface pressure of an alternate sitting protocol involving a sitting posture that reduces ischial support. Design Repeated measures in 2 protocols on 3 groups of subjects. Setting Laboratory. Participants Twenty able-bodied persons, 20 persons with paraplegia, and 20 persons with tetraplegia. Interventions Two 1-hour protocols were used: alternate and normal plus pushup. In the alternate protocol, sitting posture was alternated every 10 minutes between normal (sitting upright with ischial support) and with partially removed ischial support (WO-BPS) postures; in the normal plus pushup protocol, sitting was in normal posture with pushups (lifting the subject off the seat) performed every 20 minutes. Main Outcome Measure Interface pressure on seat and backrest. Results In WO-BPS posture, the concentrated interface pressure observed around the ischia in normal posture was significantly repositioned to the thighs. By cyclically repositioning the interface pressure, the alternate protocol was superior to the normal plus pushup protocol in terms of a significantly lower average interface pressure over the buttocks. Conclusions A sitting protocol periodically reducing the ischial support helps lower the sitting load on the buttocks, especially the area close to ischial tuberosities. PMID:17601466

  2. Effects of Krankcycle Training on Performance and Body Composition in Wheelchair Users

    PubMed Central

    Čichoň, Rostislav; Maszczyk, Adam; Stastny, Petr; Uhlíř, Petr; Petr, Miroslav; Doubrava, Ondřej; Mostowik, Aleksandra; Gołaś, Artur; Cieszczyk, Paweł; Żmijewski, 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

  3. 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

  4. Spinal cord blood flow measured by /sup 14/C-iodoantipyrine autoradiography during and after graded spinal cord compression in rats

    SciTech Connect

    Holtz, A.; Nystroem, B.G.; Gerdin, B.

    1989-05-01

    The relations between degree of thoracic spinal cord compression causing myelographic block, reversible paraparesis, and extinction of the sensory evoked potential on one hand, and spinal cord blood flow on the other, were investigated. This was done in rats using the blocking weight-technique and /sup 14/C-iodoantipyrine autoradiography. A load of 9 g caused myelographic block. Five minutes of compression with that load caused a reduction of spinal cord blood flow to about 25%, but 5 and 60 minutes after the compression spinal cord blood flow was restored to 60% of the pretrauma value. A load of 35 g for 5 minutes caused transient paraparesis. Recovery to about 30% was observed 5 and 60 minutes thereafter. During compression at a load of 55 g, which caused almost total extinction of sensory evoked potential and irreversible paraplegia, spinal cord blood flow under the load ceased. The results indicate that myelographic block occurs at a load which does not cause irreversible paraparesis and that a load which permits sensory evoked potential to be elicited results in potentially salvageable damage.

  5. 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

  6. 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

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

    PubMed

    Hübner, Christian A; Kurth, Ingo

    2014-12-01

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

  8. 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

  9. 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

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

    PubMed Central

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

    2013-01-01

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

  11. 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

  12. SPG20 protein spartin associates with cardiolipin via its plant-related senescence domain and regulates mitochondrial Ca2+ homeostasis.

    PubMed

    Joshi, Dinesh C; Bakowska, Joanna C

    2011-01-01

    Hereditary spastic paraplegias (HSPs) are a group of neurological disorders characterized clinically by spasticity of lower limbs and pathologically by degeneration of the corticospinal tract. Troyer syndrome is an autosomal recessive HSP caused by a frameshift mutation in the spartin (SPG20) gene. Previously, we established that this mutation results in a lack of expression of the truncated mutant spartin protein. Spartin is involved in many cellular processes and associates with several intracellular organelles, including mitochondria. Spartin contains a conserved plant-related senescence domain at its C-terminus. However, neither the function of this domain nor the roles of spartin in mitochondrial physiology are currently known. In this study, we determined that the plant-related senescence domain of spartin interacts with cardiolipin but not with two other major mitochondrial phospholipids, phosphatidylcholine and phosphatidylethanolamine. We also found that knockdown of spartin by small interfering RNA in a human neuroblastoma cell line resulted in depolarization of the mitochondrial membrane. In addition, depletion of spartin resulted in a significant decrease in both mitochondrial calcium uptake and mitochondrial membrane potential in cells treated with thapsigargin. Our results suggest that impairment of mitochondrial calcium uptake might contribute to the neurodegeneration of long corticospinal axons and the pathophysiology of Troyer syndrome. PMID:21559443

  13. 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

  14. 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

  15. The Kinase Inhibitory Region of SOCS-1 is Sufficient to Inhibit T-helper 17 and other Immune Functions in Experimental Allergic Encephalomyelitis

    PubMed Central

    Jager, Lindsey D.; Dabelic, Rea; Waiboci, Lilian W.; Lau, Kenneth; Haider, Mohammad S.; Ahmed, Chulbul M. I.; Larkin, Joseph; David, Samuel; Johnson, Howard M.

    2010-01-01

    Suppressors of cytokine signaling (SOCS) negatively regulate the immune response, primarily by interfering with the JAK/STAT pathway. We have developed a small peptide corresponding to the kinase inhibitory region (KIR) sequence of SOCS-1, SOCS1-KIR, which inhibits kinase activity by binding to the activation loop of tyrosine kinases such as JAK2 and TYK2. Treatment of SJL/J mice with SOCS1-KIR beginning 12 days post-immunization with myelin basic protein (MBP) resulted in minimal symptoms of EAE, while most control treated mice developed paraplegia. SOCS1-KIR treatment suppressed interleukin-17A (IL-17A) production by MBP-specific lymphocytes, as well as MBP-induced lymphocyte proliferation. When treated with IL-23, a key cytokine in the terminal differentiation of IL-17-producing cells, MBP-sensitized cells produced IL-17A and IFNγ; SOCS1-KIR was able to inhibit the production of these cytokines. SOCS1-KIR also blocked IL-23 and IL-17A activation of STAT3. There is a deficiency of SOCS-1 and SOCS-3 mRNA expression in CD4+ T cells that infiltrate the CNS, reflecting a deficiency in regulation. Consistent with therapeutic efficacy, SOCS1-KIR reversed the cellular infiltration of the CNS that is associated with EAE. We have shown here that a SOCS-1 like effect can be obtained with a small functional region of the SOCS-1 protein that is easily produced. PMID:21131060

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. Neurobrucellosis presenting as an intra-medullary spinal cord abscess

    PubMed Central

    Vajramani, Girish V; Nagmoti, Mahantesh B; Patil, Chidanand S

    2005-01-01

    Background Of the diverse presentation of neurobrucellosis, intra-medullary spinal cord abscess is extremely rare. Only four other cases have been reported so far. We present a case of spinal cord intra-medullary abscess due to Brucella melitensis. Case presentation A forty-year-old female presented with progressive weakness of both lower limb with urinary incontinence of 6 months duration. She was febrile. Neurological examination revealed flaccid areflexic paraplegia with T10 below sensory impairment including perianal region. An intramedullary mass was diagnosed on Magnetic Resonance Image (MRI) scan extending from T12 to L2. At surgery, a large abscess was encountered at the conus medullaris, from which Brucella melitensis was grown on culture. She was started on streptomycin and doxycycline for 1 month, followed by rifampicin and doxycycline for 1 month. At 2-year follow-up, she had recovered only partially and continued to have impaired bladder function. Conclusion Neurobrucellosis, if not treated early, can result in severe neurological morbidity and sequale, which may be irreversible. Hence it is important to consider the possibility of neurobrucellosis in endemic region and treat aggressively. PMID:16168059

  1. A New Mutation in Gjc2 Associated with Subclinical Leukodystrophy

    PubMed Central

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

    2014-01-01

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

  2. Cortical activation during visual illusory walking in persons with spinal cord injury: A pilot study

    PubMed Central

    Eick, John; Richardson, Elizabeth J.

    2014-01-01

    Objective To determine the location of cortical activation during a visual illusion walking paradigm, a recently proposed treatment for spinal cord injury (SCI)-related neuropathic pain, in persons with SCI compared to able-bodied controls. Design Pilot experimental fMRI trial. Setting Outpatient rehabilitation clinic. Participants Three persons with paraplegia and five able bodied participants were included in this study. Interventions Not applicable. Main Outcome Measures Cortical activation as measured by blood oxygenation-level dependent (BOLD) method of fMRI. Results During visually illusory walking, there was significant activation in the somatosensory cortex among those with SCI. In contrast, able-bodied participants showed little to no significant activation in this area, but rather, in the frontal and pre-motor areas. Conclusions Treatment modalities for SCI-related neuropathic pain that are based on sensory input paradigms such as virtual or visual illusory walking may work by targeting somatosensory cortex, an area that has been previously found to functionally reorganize following SCI. PMID:25461820

  3. The retromer complex – endosomal protein recycling and beyond

    PubMed Central

    Seaman, Matthew N. J.

    2012-01-01

    Summary The retromer complex is a vital element of the endosomal protein sorting machinery that is conserved across all eukaryotes. Retromer is most closely associated with the endosome-to-Golgi retrieval pathway and is necessary to maintain an active pool of hydrolase receptors in the trans-Golgi network. Recent progress in studies of retromer have identified new retromer-interacting proteins, including the WASH complex and cargo such as the Wntless/MIG-14 protein, which now extends the role of retromer beyond the endosome-to-Golgi pathway and has revealed that retromer is required for aspects of endosome-to-plasma membrane sorting and regulation of signalling events. The interactions between the retromer complex and other macromolecular protein complexes now show how endosomal protein sorting is coordinated with actin assembly and movement along microtubules, and place retromer squarely at the centre of a complex set of protein machinery that governs endosomal protein sorting. Dysregulation of retromer-mediated endosomal protein sorting leads to various pathologies, including neurodegenerative diseases such as Alzheimer disease and spastic paraplegia and the mechanisms underlying these pathologies are starting to be understood. In this Commentary, I will highlight recent advances in the understanding of retromer-mediated endosomal protein sorting and discuss how retromer contributes to a diverse set of physiological processes. PMID:23148298

  4. 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

  5. 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

  6. The acute abdomen in spinal cord injury individuals.

    PubMed

    Bar-On, Z; Ohry, A

    1995-12-01

    A review of 1300 patients with spinal cord injury (SCI), over a period of 14 years, revealed 12 patients with an 'acute abdomen'. Seven events occurred during the initial admission, ranging from 10 days to 9 months from injury, and five during readmission of 'chronic' SCI patients. Four were in the acute stage 10-30 days from injury, all with peptic ulcer perforations. The remainder had either an intestinal obstruction, appendicitis or peritonitis. All of the neurological levels were above T6 except for one patient who had a low level paraplegia. The classical signs of an 'acute abdomen' may be missing in such patients thus delaying diagnosis by 1-4 days. The most important signs were autonomic dysreflexia, referred shoulder tip pain, abdominal pain, abdominal distension, increased spasticity and abdominal pain with nausea and vomiting. Less importance was given to the classical signs of abdominal tenderness, abdominal muscle rigidity, rebound, fever and of leukocytosis. Prompt diagnosis and treatment will minimise morbidity and mortality. PMID:8927409

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

    PubMed

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

    2015-05-01

    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

  8. 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

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

    PubMed Central

    2011-01-01

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

  10. 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

  11. 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

  12. 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.

  13. 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

  14. Fishing for causes and cures of motor neuron disorders.

    PubMed

    Patten, Shunmoogum A; Armstrong, Gary A B; Lissouba, Alexandra; Kabashi, Edor; Parker, J Alex; Drapeau, Pierre

    2014-07-01

    Motor neuron disorders (MNDs) are a clinically heterogeneous group of neurological diseases characterized by progressive degeneration of motor neurons, and share some common pathological pathways. Despite remarkable advances in our understanding of these diseases, no curative treatment for MNDs exists. To better understand the pathogenesis of MNDs and to help develop new treatments, the establishment of animal models that can be studied efficiently and thoroughly is paramount. The zebrafish (Danio rerio) is increasingly becoming a valuable model for studying human diseases and in screening for potential therapeutics. In this Review, we highlight recent progress in using zebrafish to study the pathology of the most common MNDs: spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS) and hereditary spastic paraplegia (HSP). These studies indicate the power of zebrafish as a model to study the consequences of disease-related genes, because zebrafish homologues of human genes have conserved functions with respect to the aetiology of MNDs. Zebrafish also complement other animal models for the study of pathological mechanisms of MNDs and are particularly advantageous for the screening of compounds with therapeutic potential. We present an overview of their potential usefulness in MND drug discovery, which is just beginning and holds much promise for future therapeutic development. PMID:24973750

  15. Spatacsin and spastizin act in the same pathway required for proper spinal motor neuron axon outgrowth in zebrafish.

    PubMed

    Martin, Elodie; Yanicostas, Constantin; Rastetter, Agnès; Alavi Naini, Seyedeh Maryam; Maouedj, Alissia; Kabashi, Edor; Rivaud-Péchoux, Sophie; Brice, Alexis; Stevanin, Giovanni; Soussi-Yanicostas, Nadia

    2012-12-01

    Hereditary spastic paraplegias (HSPs) are rare neurological conditions caused by degeneration of the long axons of the cerebrospinal tracts, leading to locomotor impairment and additional neurological symptoms. There are more than 40 different causative genes, 24 of which have been identified, including SPG11 and SPG15 mutated in complex clinical forms. Since the vast majority of the causative mutations lead to loss of function of the corresponding proteins, we made use of morpholino-oligonucleotide (MO)-mediated gene knock-down to generate zebrafish models of both SPG11 and SPG15 and determine how invalidation of the causative genes (zspg11 and zspg15) during development might contribute to the disease. Micro-injection of MOs targeting each gene caused locomotor impairment and abnormal branching of spinal cord motor neurons at the neuromuscular junction. More severe phenotypes with abnormal tail developments were also seen. Moreover, partial depletion of both proteins at sub-phenotypic levels resulted in the same phenotypes, suggesting for the first time, in vivo, a genetic interaction between these genes. In conclusion, the zebrafish orthologues of the SPG11 and SPG15 genes are important for proper development of the axons of spinal motor neurons and likely act in a common pathway to promote their proper path finding towards the neuromuscular junction. PMID:22801083

  16. Als2 mRNA splicing variants detected in KO mice rescue severe motor dysfunction phenotype in Als2 knock-down zebrafish.

    PubMed

    Gros-Louis, Francois; Kriz, Jasna; Kabashi, Edor; McDearmid, Jonathan; Millecamps, Stéphanie; Urushitani, Makoto; Lin, Li; Dion, Patrick; Zhu, Qinzhang; Drapeau, Pierre; Julien, Jean-Pierre; Rouleau, Guy A

    2008-09-01

    Recessive ALS2 mutations are linked to three related but slightly different neurodegenerative disorders: amyotrophic lateral sclerosis, hereditary spastic paraplegia and primary lateral sclerosis. To investigate the function of the ALS2 encoded protein, we generated Als2 knock-out (KO) mice and zAls2 knock-down zebrafish. The Als2(-/-) mice lacking exon 2 and part of exon 3 developed mild signs of neurodegeneration compatible with axonal transport deficiency. In contrast, zAls2 knock-down zebrafish had severe developmental abnormalities, swimming deficits and motor neuron perturbation. We identified, by RT-PCR, northern and western blotting novel Als2 transcripts in mouse central nervous system. These Als2 transcripts were present in Als2 null mice as well as in wild-type littermates and some rescued the zebrafish phenotype. Thus, we speculate that the newly identified Als2 mRNA species prevent the Als2 KO mice from developing severe neurodegenerative disease and might also regulate the severity of the motor neurons phenotype observed in ALS2 patients. PMID:18558633

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

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

    PubMed Central

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

    2014-01-01

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

  3. 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

  4. 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

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

    PubMed Central

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

    2015-01-01

    Human PNPLA6 gene encodes Neuropathy Target Esterase protein (NTE). PNPLA6 gene mutations cause hereditary spastic paraplegia (SPG39 HSP), Gordon-Holmes syndrome, Boucher-Neuhäuser syndromes, Laurence-Moon syndrome, and Oliver-McFarlane syndrome. Mutations in the Drosophila NTE homolog swiss cheese (sws) cause early-onset, progressive behavioral defects and neurodegeneration characterized by vacuole formation. We investigated sws5 flies and show for the first time that this allele causes progressive vacuolar formation in the brain and progressive deterioration of negative geotaxis speed and endurance. We demonstrate that inducible, neuron-specific expression of full-length human wildtype NTE reduces vacuole formation and substantially rescues mobility. Indeed, neuron-specific expression of wildtype human NTE is capable of rescuing mobility defects after 10 days of adult life at 29°C, when significant degeneration has already occurred, and significantly extends longevity of mutants at 25°C. These results raise the exciting possibility that late induction of NTE function may reduce or ameliorate neurodegeneration in humans even after symptoms begin. In addition, these results highlight the utility of negative geotaxis endurance as a new assay for longitudinal tracking of degenerative phenotypes in Drosophila. PMID:26671664

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

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

    PubMed Central

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

    2016-01-01

    Peripersonal space (PPS) is the space surrounding us within which we interact with objects. PPS may be modulated by actions (e.g. when using tools) or sense of ownership (e.g. over a rubber hand). Indeed, intense and/or prolonged use of a tool may induce a sense of ownership over it. Conversely, inducing ownership over a rubber hand may activate brain regions involved in motor control. However, the extent to which PPS is modulated by action-dependent or ownership-dependent mechanisms remains unclear. Here, we explored the PPS around the feet and the sense of ownership over lower limbs in people with Paraplegia following Complete spinal cord Lesions (PCL) and in healthy subjects. PCL people can move their upper body but have lost all sensory-motor functions in their lower body (e.g. lower limbs). We tested whether PPS alterations reflect the topographical representations of various body parts. We found that the PPS around the feet was impaired in PCL who however had a normal representation of the PPS around the hands. Significantly, passive mobilization of paraplegic limbs restored the PPS around the feet suggesting that activating action representations in PCL brings about short-term changes of PPS that may thus be more plastic than previously believed. PMID:27049439

  13. 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

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

    PubMed

    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

  15. 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

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

    PubMed

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

    2016-01-01

    Peripersonal space (PPS) is the space surrounding us within which we interact with objects. PPS may be modulated by actions (e.g. when using tools) or sense of ownership (e.g. over a rubber hand). Indeed, intense and/or prolonged use of a tool may induce a sense of ownership over it. Conversely, inducing ownership over a rubber hand may activate brain regions involved in motor control. However, the extent to which PPS is modulated by action-dependent or ownership-dependent mechanisms remains unclear. Here, we explored the PPS around the feet and the sense of ownership over lower limbs in people with Paraplegia following Complete spinal cord Lesions (PCL) and in healthy subjects. PCL people can move their upper body but have lost all sensory-motor functions in their lower body (e.g. lower limbs). We tested whether PPS alterations reflect the topographical representations of various body parts. We found that the PPS around the feet was impaired in PCL who however had a normal representation of the PPS around the hands. Significantly, passive mobilization of paraplegic limbs restored the PPS around the feet suggesting that activating action representations in PCL brings about short-term changes of PPS that may thus be more plastic than previously believed. PMID:27049439

  17. Structural and dynamic basis of human cytochrome P450 7B1: a survey of substrate selectivity and major active site access channels.

    PubMed

    Cui, Ying-Lu; Zhang, Ji-Long; Zheng, Qing-Chuan; Niu, Rui-Juan; Xu, Yu; Zhang, Hong-Xing; Sun, Chia-Chung

    2013-01-01

    Cytochrome P450 (CYP) 7B1 is a steroid cytochrome P450 7α-hydroxylase that has been linked directly with bile salt synthesis and hereditary spastic paraplegia type 5 (SPG5). The enzyme provides the primary metabolic route for neurosteroids dehydroepiandrosterone (DHEA), cholesterol derivatives 25-hydroxycholesterol (25-HOChol), and other steroids such as 5α-androstane-3β,17β-diol (anediol), and 5α-androstene-3β,17β-diol (enediol). A series of investigations including homology modeling, molecular dynamics (MD), and automatic docking, combined with the results of previous experimental site-directed mutagenesis studies and access channels analysis, have identified the structural features relevant to the substrate selectivity of CYP7B1. The results clearly identify the dominant access channels and critical residues responsible for ligand binding. Both binding free energy analysis and total interaction energy analysis are consistent with the experimental conclusion that 25-HOChol is the best substrate. According to 20 ns MD simulations, the Phe cluster residues that lie above the active site, particularly Phe489, are proposed to merge the active site with the adjacent channel to the surface and accommodate substrate binding in a reasonable orientation. The investigation of CYP7B1-substrate binding modes provides detailed insights into the poorly understood structural features of human CYP7B1 at the atomic level, and will be valuable information for drug development and protein engineering. PMID:23180418

  18. 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

  19. 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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-06-01

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

  2. 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

  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. 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

  5. Constructs of human neuropathy target esterase catalytic domain containing mutations related to motor neuron disease have altered enzymatic properties.

    PubMed

    Hein, Nichole D; Stuckey, Jeanne A; Rainier, Shirley R; Fink, John K; Richardson, Rudy J

    2010-07-01

    Neuropathy target esterase (NTE) is a phospholipase/lysophospholipase associated with organophosphorus (OP) compound-induced delayed neurotoxicity (OPIDN). Distal degeneration of motor axons occurs in both OPIDN and the hereditary spastic paraplegias (HSPs). Recently, mutations within the esterase domain of NTE were identified in patients with a novel type of HSP (SPG39) designated NTE-related motor neuron disease (NTE-MND). Two of these mutations, arginine 890 to histidine (R890H) and methionine 1012 to valine (M1012V), were created in human recombinant NTE catalytic domain (NEST) to measure possible changes in catalytic properties. These mutated enzymes had decreased specific activities for hydrolysis of the artificial substrate, phenyl valerate. In addition, the M1012V mutant exhibited a reduced bimolecular rate constant of inhibition (k(i)) for all three inhibitors tested: mipafox, diisopropylphosphorofluoridate, and chlorpyrifos oxon. Finally, while both mutated enzymes inhibited by OP compounds exhibited altered time-dependent loss of their ability to be reactivated by nucleophiles (aging), more pronounced effects were seen with the M1012V mutant. Taken together, the results from specific activity, inhibition, and aging experiments suggest that the mutations found in association with NTE-MND have functional correlates in altered enzymological properties of NTE. PMID:20382209

  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. 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

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

    PubMed

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

    2014-03-01

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

  9. Non-Parkinson movement disorders

    PubMed Central

    2013-01-01

    Summary Solutions to the major riddles in movement disorders are appearing at a breathtaking pace: 1) loss-of-function mutations in PRRT2, which encodes a cell surface protein expressed in neurons, have been found in many patients with paroxysmal kinesigenic dyskinesias; 2) mutations in CIZ1, which encodes a protein involved in cell-cycle control at the G1-S checkpoint, have been identified in a small percentage of patients with cervical dystonia; and 3) finally, after many years of genetics and identification of more than 25 disease-associated genes, cellular studies related to the pathobiology of hereditary spastic paraplegia are converging on defects in modeling the endoplasmic reticulum and membrane trafficking. On the treatment front, the distinctive syndromes of faciobrachial dystonic seizures with anti-LRI1 antibodies and anti-N-methyl-d-aspartic acid encephalitis with orobuccolingual dyskinesias are becoming increasingly recognized by clinicians as imminently treatable conditions. Also on the treatment front, the first phase I trial of MRI-guided high-intensity focused ultrasound for essential tremor has been completed and intraoperative MRI is currently being used to place electrodes in the brains of patients with medically intractable dystonia. Definitive etiologies and efficacious treatments for non–Parkinson disease movement disorders are no longer wishful thinking. PMID:23634381

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. Inbreeding levels in Northeast Brazil: Strategies for the prospecting of new genetic disorders.

    PubMed

    Santos, Silvana; Kok, Fernando; Weller, Mathias; de Paiva, Francisco Rennan Lopes; Otto, Paulo A

    2010-04-01

    A new autosomal recessive genetic condition, the SPOAN syndrome (an acronym for spastic paraplegia, optic atrophy and neuropathy syndrome), was recently discovered in an isolated region of the State of Rio Grande do Norte in Northeast Brazil, in a population that was identified by the IBGE (Brazilian Institute of Geography and Statistics) as belonging to the Brazilian communities with the highest rates of "deficiencies" (Neri, 2003), a term used to describe diseases, malformations, and handicaps in general. This prompted us to conduct a study of consanguinity levels in five of its municipal districts by directly interviewing their inhabitants. Information on 7,639 couples (corresponding to about 40% of the whole population of the studied districts) was obtained. The research disclosed the existence of very high frequencies of consanguineous marriages, which varied from about 9% to 32%, suggesting the presence of a direct association between genetic diseases such as the SPOAN syndrome, genetic drift and inbreeding levels. This fact calls for the introduction of educational programs for the local populations, as well as for further studies aiming to identify and characterize other genetic conditions. Epidemiological strategies developed to collect inbreeding data, with the collaboration of health systems available in the region, might be very successful in the prospecting of genetic disorders. PMID:21637472

  16. Inbreeding levels in Northeast Brazil: Strategies for the prospecting of new genetic disorders

    PubMed Central

    2010-01-01

    A new autosomal recessive genetic condition, the SPOAN syndrome (an acronym for spastic paraplegia, optic atrophy and neuropathy syndrome), was recently discovered in an isolated region of the State of Rio Grande do Norte in Northeast Brazil, in a population that was identified by the IBGE (Brazilian Institute of Geography and Statistics) as belonging to the Brazilian communities with the highest rates of “deficiencies” (Neri, 2003), a term used to describe diseases, malformations, and handicaps in general. This prompted us to conduct a study of consanguinity levels in five of its municipal districts by directly interviewing their inhabitants. Information on 7,639 couples (corresponding to about 40% of the whole population of the studied districts) was obtained. The research disclosed the existence of very high frequencies of consanguineous marriages, which varied from about 9% to 32%, suggesting the presence of a direct association between genetic diseases such as the SPOAN syndrome, genetic drift and inbreeding levels. This fact calls for the introduction of educational programs for the local populations, as well as for further studies aiming to identify and characterize other genetic conditions. Epidemiological strategies developed to collect inbreeding data, with the collaboration of health systems available in the region, might be very successful in the prospecting of genetic disorders. PMID:21637472

  17. Clinical variability and female penetrance in X-linked familial FTD/ALS caused by a P506S mutation in UBQLN2.

    PubMed

    Vengoechea, Jaime; David, Marjorie P; Yaghi, Shadi R; Carpenter, Lori; Rudnicki, Stacy A

    2013-12-01

    Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disease leading to progressive paralysis that is generally fatal. Only 10% of cases are familial, a subset of which overlaps with frontotemporal dementia (FTD). Up to half of ALS patients have cognitive impairment, with 15% meeting the criteria for FTD. Clinical sequencing of UBQLN2 in a family with X-linked FTD/ALS with suspected incomplete penetrance, manifesting in both genders, revealed a P506S mutation in. Affected individuals were diagnosed with various conditions including hereditary spastic paraplegia (HSP), bulbar palsy and multiple sclerosis. The mutation in UBQLN2 was first identified in a 35-year-old female who presented with one year of progressive dysarthria, dyspnea, dysphagia, and cognitive decline. EMG suggested early motor neuron disease with prominent bulbar involvement. Her cognition declined rapidly and she developed extremity weakness. Her brother, initially diagnosed with HSP, and her second cousin, with primary lateral sclerosis, also have a P506S mutation in UBQLN2. In conclusion, the P506S mutation in UBQLN2 can affect both males and females and displays great phenotypic variability within the same family. Females can potentially have a more severe and rapidly progressive presentation than their male relatives. Additionally, the P506S mutation can also cause an FTD phenotype. PMID:23944734

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

    PubMed

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

    2014-08-13

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

  19. 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

  20. 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

  1. Case Report: Myelodysplastic syndrome- associated myeloid sarcoma: an unusual clinical presentation of a rare disease

    PubMed Central

    Horvath, Emoke; Demian, Smaranda; Nagy, Elod

    2016-01-01

    Myeloid sarcoma results from the extramedullary homing and proliferation of immature myeloid precursors. We present the timeline, events and diagnostic pitfalls related to a 66 year-old male patient’s case, admitted to the Hematology Clinic for pancytopenia, fever, weight loss and fatigue. The severe cytopenia and the few blasts observed in his blood smear indicated a bone marrow biopsy. The bone marrow showed hypercellularity and multilineage dysplasia with the presence of 15% myeloblasts. After the biopsy, he promptly developed paraplegia and nuclear magnetic resonance revealed an epidural tumour which was then resected.In the epidural tumour mass blast-like, round cells were observed with a complex immunophenotype, characterized by myeloperoxidase, CD117, CD15, CD99, leucocyte common antigen positivity and a high Ki-67 proliferation index. Considering the main differential diagnostic issues, the final diagnosis was stated as myelodysplastic syndrome-associated myeloid sarcoma. The prognosis was unfavourable, the bone marrow was quickly invaded by proliferating blast cells, and despite chemotherapy attempts, the patient died. PMID:27019694

  2. 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

  3. 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.

  4. 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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2012-01-01

    Spastin is a hexameric ring AAA ATPase that severs microtubules. To see whether the ring complex funnels the energy of multiple ATP hydrolysis events to the site of mechanical action, we investigate here the cooperativity of spastin. Several lines of evidence indicate that interactions among two subunits dominate the cooperative behavior: (i) the ATPase activity shows a sigmoidal dependence on the ATP concentration; (ii) ATPγS 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

  7. 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

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

    PubMed Central

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

    2014-01-01

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

  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. 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

  11. Intradural extramedullary primary hydatid cyst of the spine: a case report and review of literature.

    PubMed

    Lotfinia, Iraj; Sayyahmelli, Sima; Mahdkhah, Ata; Shoja, M M

    2013-05-01

    Primary intradural extramedullary hydatid cyst is a rare form of parasitic infection, causing focal neurological signs, commonly observed in sheep-raising areas of the world. We report a rare case of intradural, extramedullary spinal cyst, which we had misdiagnosis in the first surgery, because of rarity of the case. A 55-year-old man presented to our hospital in August 2008. He was admitted to our clinic because of lumbar pain of increasing severity and progressive difficulty with walking and stiffness of both lower limbs, which had lasted for 1 month. On the basis of imaging results, arachnoid cyst of the lumbar spine was diagnosed. Due to rapid progression of the patient's symptoms toward spastic paraplegia, he underwent an emergency surgical decompression procedure. The patient underwent exploratory surgery using a posterior approach. A L1-L2 laminectomy was performed. After opening the dura, an intradural extramedullary cystic mass was determined. The surgical specimen measured 6 × 2 cm and was described as a whitish, pearl-like, semitranslucent, cystic material, which was thought to be parasitic. Surgery has to be followed by albendazole therapy. PMID:22706667

  12. 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

  13. October 1942: a strange epidemic paralysis in Saval, Verona, Italy. Revision and diagnosis 50 years later of tri-ortho-cresyl phosphate poisoning.

    PubMed

    Tosi, L; Righetti, C; Adami, L; Zanette, G

    1994-07-01

    In the autumn of 1942 a strange epidemic paralysis started in Saval, at that time a country area but now part of the city of Verona. The epidemic went on for several months and affected 41 people, all working as owners or labourers on the same farm. Some of the farm animals (chickens, horses, cattle, pigs) also became ill. About 20 patients were admitted to the nearby city hospital. The outbreak was diagnosed as polyneuritis with a probable viral cause. Fifty years later, seven people with sequelae of the disease were examined. The most severe cases present a spastic paraplegia and lower leg muscle atrophy without sensory impairment, resembling an amyotrophic lateral sclerosis "frozen" for 50 years. The clinical syndrome can now be attributed confidently to organophosphate induced delayed polyneuropathy. All the epidemiological data obtained from the survivors were evaluated and a careful review of the literature was made. Contamination of the ground from a rubbish dump near the farmyard would explain the epidemiology of the Saval outbreak. PMID:8021666

  14. Metabolic changes in the thalamus after spinal cord injury followed by proton MR spectroscopy.

    PubMed

    Likavcanová, Katarína; Urdzíková, Lucia; Hájek, Milan; Syková, Eva

    2008-03-01

    Our study followed the changes in thalamic nuclei metabolism, hindlimb sensitivity to thermal stimulation, and locomotor function after spinal cord injury (SCI). MR spectroscopy (MRS) was used to examine the thalamic nuclei of rats 1 day before and 1, 3, 6, and 15 days after SCI or sham surgery. All animals were tested before MRS measurements for motor performance and thermal sensitivity. SCI induced by balloon compression caused complete paraplegia from the first to third day, followed by partial functional recovery during the second week. MRS revealed an increase in N-acetylaspartate (NAA) concentration in the thalamic nuclei on the first day after SCI, which decreased by the third day. The data also showed an increase in inositol (Ins), glutamate, and creatine (Cr) concentrations on the third day postinjury; the Ins concentration remained elevated on the sixth day. In sham-operated animals an increase in NAA concentration was observed on the sixth and fifteenth days after surgery and an increase in Cr concentration on the third day. A positive correlation between Ins concentration and hindlimb sensitivity in both SCI and sham-operated animals suggests changes in glial activity, while changes in NAA levels may indicate the response of thalamic neuronal cells to injury. PMID:18219631

  15. 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

  16. 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

  17. 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

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

    PubMed

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

    2016-06-01

    In tort lawsuits, plaintiffs may seek damages for loss of enjoyment of life, so-called hedonic loss, which occurred as a result of an accident or injury. In 2 studies, we examined how people judge others' adaptation and hedonic loss after an injury. Laypeople's forecasts of hedonic loss are relevant to concerns about whether jurors appropriately compensate plaintiffs. Longitudinal data of subjective well-being (e.g., Binder & Coad, 2013) show that hedonic loss is domain-specific: Many physical impairments (e.g., strokes) inflict less hedonic loss than many persistent yet invisible ailments (e.g., mental illness and conditions that cause chronic pain). We used vignette methodology to determine whether laypeople (n = 68 community members and 65 students in Study 1; 87 community members and 93 students in Study 2) and rehabilitation professionals (n = 47 in Study 2) were aware of this fact. In Study 1, participants' ratings of hedonic loss subsequent to a physical injury and a comparably severe psychological impairment did not differ. In Study 2, ratings of short- and long-term hedonic loss stemming from paraplegia and chronic back pain showed that neither laypeople nor professionals understood that hedonic loss is domain-specific. These findings imply that observers may forecast a future for people who suffered serious physical injuries as grimmer than it is likely to be, and a future for people who experience chronic pain and psychological disorders as rosier than is likely. (PsycINFO Database Record PMID:26914859

  19. 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

  20. October 1942: a strange epidemic paralysis in Saval, Verona, Italy. Revision and diagnosis 50 years later of tri-ortho-cresyl phosphate poisoning.

    PubMed Central

    Tosi, L; Righetti, C; Adami, L; Zanette, G

    1994-01-01

    In the autumn of 1942 a strange epidemic paralysis started in Saval, at that time a country area but now part of the city of Verona. The epidemic went on for several months and affected 41 people, all working as owners or labourers on the same farm. Some of the farm animals (chickens, horses, cattle, pigs) also became ill. About 20 patients were admitted to the nearby city hospital. The outbreak was diagnosed as polyneuritis with a probable viral cause. Fifty years later, seven people with sequelae of the disease were examined. The most severe cases present a spastic paraplegia and lower leg muscle atrophy without sensory impairment, resembling an amyotrophic lateral sclerosis "frozen" for 50 years. The clinical syndrome can now be attributed confidently to organophosphate induced delayed polyneuropathy. All the epidemiological data obtained from the survivors were evaluated and a careful review of the literature was made. Contamination of the ground from a rubbish dump near the farmyard would explain the epidemiology of the Saval outbreak. PMID:8021666

  1. 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

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

    PubMed Central

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

    2009-01-01

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

  3. 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

  4. 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

  5. The AIDS dementia complex: I. Clinical features.

    PubMed

    Navia, B A; Jordan, B D; Price, R W

    1986-06-01

    Of 70 autopsied patients with the acquired immune deficiency syndrome (AIDS), 46 suffered progressive dementia that was frequently accompanied by motor and behavioral dysfunction. Impaired memory and concentration with psychomotor slowing represented the most common early presentation of this disorder, but in nearly one half of the patients either motor or behavioral changes predominated. Early motor deficits commonly included ataxia, leg weakness, tremor, and loss of fine-motor coordination, while behavioral disturbances were manifested most commonly as apathy or withdrawal, but occasionally as a frank organic psychosis. The course of the disease was steadily progressive in most patients, and at times was punctuated by an abrupt acceleration. However, in 20% of patients a more protracted indolent course was observed. In the most advanced stage of this disease, patients exhibited a stereotyped picture of severe dementia, mutism, incontinence, paraplegia, and in some cases, myoclonus. The high incidence and unique clinical presentation of this AIDS dementia complex is consistent with the emerging concept that this complication is due to direct brain infection by the retrovirus that causes AIDS. PMID:3729308

  6. 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

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

    PubMed Central

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

    2015-01-01

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

  8. Combination of icotinib, surgery, and internal-radiotherapy of a patient with lung cancer severely metastasized to the vertebrae bones with EGFR mutation: a case report

    PubMed Central

    Qu, Li-Li; Qin, Hai-Feng; Gao, Hong-Jun; Liu, Xiao-Qing

    2015-01-01

    A 48-year-old Chinese female was referred to us regarding EGFR-mutated advanced non-small cell lung cancer, and metastasis to left scapula and vertebrae bones which caused pathological fracture at T8 and T10 thoracic vertebrae. An aggressive combined therapy with icotinib, vertebrae operation, and radioactive particle implantation and immunotherapy was proposed to prevent paraplegia, relieve pain, and control the overall and local tumor lesions. No postoperative symptoms were seen after surgery, and the pain was significantly relieved. Icotinib merited a 31-month partial response with grade 1 diarrhea as its drug-related adverse event. High dose of icotinib was administered after pelvis lesion progression for 3 months with good tolerance. Combination therapy of icotinib, surgery, and internal radiation for metastases of the vertebrae bones from non-small cell lung cancer seems to be a very promising technique both for sufficient pain relief and for local control of the tumor, vertebrae operation can be an encouraging option for patients with EFGR positive mutation and good prognosis indicator. PMID:26082644

  9. 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

  10. 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

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

    PubMed

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

    2016-01-01

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

  12. 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

  13. 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

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

    PubMed

    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

  15. 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

  16. Clinical and pathologic features of Aicardi-Goutières syndrome due to an IFIH1 mutation: A pediatric case report.

    PubMed

    Marguet, Florent; Laquerrière, Annie; Goldenberg, Alice; Guerrot, Anne-Marie; Quenez, Olivier; Flahaut, Philippe; Vanhulle, Catherine; Dumant-Forest, Clémentine; Charbonnier, Françoise; Vezain, Myriam; Bekri, Soumeya; Tournier, Isabelle; Frébourg, Thierry; Nicolas, Gaël

    2016-05-01

    We describe the case of a young patient with calcifying encephalopathy, born to asymptomatic parents. An extensive hypothesis-driven etiological assessment was performed and failed to detect the precise etiology during many years. We therefore decided to perform whole exome sequencing of the child-unaffected parents trio. A de novo pathogenic variant in the IFIH1 gene which has recently been shown to cause autosomal dominant forms of Aicardi-Goutières syndrome was identified. This child presented with a severe form with neonatal thrombocytopenia and hepatomegaly, the latter having been detected during late gestation. Although first milestones were uneventful, he progressively lost motor skills from the age of 12 months and developed severe spastic paraplegia. Brain imaging revealed white matter abnormalities and extensive calcifications. He also presented atypical skin lesions, different from chilblains. His medical history was marked by two episodes of acute pancreatitis. We provide herein the results of pathological examination including detailed description of the neuropathological hallmarks. To our knowledge, this the first detailed clinico-pathological description of a patient with an IFIH1 pathogenic variant. © 2016 Wiley Periodicals, Inc. PMID:26833990

  17. Gonadotropin-releasing hormone treatment improves locomotor activity, urinary function and neurofilament protein expression after spinal cord injury in ovariectomized rats.

    PubMed

    Calderón-Vallejo, Denisse; Quintanar, J Luis

    2012-05-01

    It was reported that the hypothalamic decapeptide, gonadotropin-releasing hormone (GnRH) produces neurotrophic effects and that the spinal cord possesses GnRH receptors. The aim of the present study was to determine whether administration of GnRH improves locomotor activity, urinary function and neurofilament (NFs) protein expression after spinal cord injury (SCI) in ovariectomized rats. SCI was induced by balloon inflation model resulting in paraplegia. Locomotion was evaluated according to the Basso, Beattie, and Bresnahan Scale. Rats were subjected to bladder compression, twice daily until bladder reflex was established. NFs of 68, 160 and 200 kDa from spinal cords were analyzed by electrophoresis. GnRH (60 μg/kg) or physiologic NaCl solution was administered at 1 day after SCI and then daily for 15 days and the functional evaluation was realized for 5 weeks. Our results indicate that locomotor activity, restoration of urinary dysfunction and NFs expression of 160 and 200 kDa were improved in SCI animals given GnRH compared to those without treatment. These findings suggest that GnRH acts as a neurotrophic factor and may be used as a potential therapeutic agent for treatment of SCI. PMID:22480691

  18. [Disseminated cryptococcosis in an immunocompetent patient].

    PubMed

    Elkhihal, B; Hasnaoui, A; Ghfir, I; Moustachi, A; Aoufi, S; Lyagoubi, M

    2015-09-01

    Disseminated cryptococcosis is a serious opportunistic fungal infection caused by a yeast-encapsulated fungus of the genus Cryptococcus neoformans. It occurs most often in patients with a significant deficit of cellular immunity and preferentially affects the central nervous system. The skin and the lungs are the most commonly affected sites outside the neuro-subarachnoid location. We report the case of a patient apparently immunocompetent who had a disseminated cryptococcosis. The disease started with the multiple purplish skin lesions, large umbilicated on the face, groin, forearm and leg with progressively increasing volume. This symptomatology had evolved in the context of weight loss and poor general condition. The diagnosis was established by the presence of cryptococcal at the skin biopsy and cerebrospinal fluid. Research of immunosuppression common pathologies were negative. Treatment was initiated based on amphotericin B for 40 days. The patient's condition deteriorates onset of paraplegia and swallowing disorders causing death in an array of cachexia. This observation points out that disseminated cryptococcosis can occur in an immunocompetent patient. The skin lesions may be the first sign of the disease. PMID:26227506

  19. 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

  20. Development of a novel type of shoe to improve the efficiency of knee-ankle-foot orthoses with a medial single hip joint (Primewalk orthoses): a novel type of shoe for Primewalk orthosis.

    PubMed

    Suzuki, Toru; Sonoda, Shigeru; Saitoh, Eiichi; Murata, Motonori; Uno, Akihito; Shimizu, Yasuhiro; Misawa, Kayo; Kotake, Tomomitsu

    2005-12-01

    The purpose of the study was to develop and evaluate a new heel cushion in shoes for use with knee-ankle-foot orthoses having a medial single hip joint (Primewalk orthoses) in order to improve walking velocity and efficiency. Primewalk orthoses and shoes were made for a 24-year-old man having paraplegia with flaccid paresis (level T-7; grade A, ASIA impairment scale) of 2 years' duration. Walking exercises were assigned. Shoes were modified with the sole made of hard rubber and the addition of soft rubber heel cushions. The walking speed, centre of foot pressure during walking, and ground reaction force were evaluated. The patient also subjectively assessed the devices. The modifications to the shoes resulted in a 1.94-fold increase in walking speed (8.6 to 16.7 m/min), a 1.87-fold increase in step length (16.7 to 31.3 cm) and a 54.8% decrease in the physiological cost index (7.7 to 3.48 beats/min). The centre of foot pressure during walking was found to deviate towards the lateral margin of the foot. The horizontal rotation of the pelvis increased simultaneously. The patient reported increased amplitude of flail motion of the trunk and decreased burden to the upper limbs. It was concluded that the modified new heel cushion of the shoe provided freedom to the lower legs and thereby increased walking efficiency. PMID:16466159

  1. Early Experiences with the Endovascular Repair of Ruptured Descending Thoracic Aortic Aneurysm

    PubMed Central

    Choi, Jae-Sung; Oh, Se Jin; Sung, Yong Won; Moon, Hyun Jong; Lee, Jung Sang

    2016-01-01

    Background The aim of this study was to report our early experiences with the endovascular repair of ruptured descending thoracic aortic aneurysms (rDTAAs), which are a rare and life-threatening condition. Methods Among 42 patients who underwent thoracic endovascular aortic repair (TEVAR) between October 2010 and September 2015, five patients (11.9%) suffered an rDTAA. Results The mean age was 72.4±5.1 years, and all patients were male. Hemoptysis and hemothorax were present in three (60%) and two (40%) patients, respectively. Hypovolemic shock was noted in three patients who underwent emergency operations. A hybrid operation was performed in three patients. The mean operative time was 269.8±72.3 minutes. The mean total length of aortic coverage was 186.0±49.2 mm. No 30-day mortality occurred. Stroke, delirium, and atrial fibrillation were observed in one patient each. Paraplegia did not occur. Endoleak was found in two patients (40%), one of whom underwent an early and successful reintervention. During the mean follow-up period of 16.8±14.8 months, two patients died; one cause of death was a persistent type 1 endoleak and the other cause was unknown. Conclusion TEVAR for rDTAA was associated with favorable early mortality and morbidity outcomes. However, early reintervention should be considered if persistent endoleak occurs. PMID:27064672

  2. 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

  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. Severe and irreversible myelopathy after concurrent systemic and intrathecal nucleoside analogue treatment for refractory diffuse large B-cell lymphoma: A case report and review of the literature.

    PubMed

    Alsdorf, Winfried H; Schmitz, Michael; Schieferdecker, Aneta; Dierlamm, Judith; Bokemeyer, Carsten; Binder, Mascha

    2016-06-01

    We report a patient with refractory diffuse large B-cell lymphoma who developed irreversible, severe spinal neurotoxicity after concurrent treatment with intrathecal and systemic cytarabine. Shortly after concomitant administration of intrathecal triple therapy (MTX, dexamethasone and cytarabine) and high-dose systemic cytarabin (R-DHAP protocol) the patient lost control of bowel and bladder function and developed an ascending, irreversible paraplegia. Infectious or neoplastic diseases of the spinal cord were ruled out. A magnetic resonance imaging scan of the spine resulted in a diagnosis of toxic myelitis. Previously observed cases of spinal neurotoxicity after cytarabine treatment are reviewed as well as current guidelines for the use of intrathecal chemotherapy in high-grade non-Hodgkin lymphoma. In summary, severe spinal neurotoxicity of intrathecal chemotherapy is a rare side-effect, however several studies suggest that the neurotoxicity of cytarabine is significantly enhanced by concurrent intrathecal and high-dose systemic administration. Simultaneous high-dose systemic and intrathecal chemotherapy with cytarabine should therefore be avoided. PMID:25655468

  5. The effects of ER morphology on synaptic structure and function in Drosophila melanogaster.

    PubMed

    Summerville, James B; Faust, Joseph F; Fan, Ethan; Pendin, Diana; Daga, Andrea; Formella, Joseph; Stern, Michael; McNew, James A

    2016-04-15

    Hereditary spastic paraplegia (HSP) is a set of genetic diseases caused by mutations in one of 72 genes that results in age-dependent corticospinal axon degeneration accompanied by spasticity and paralysis. Two genes implicated in HSPs encode proteins that regulate endoplasmic reticulum (ER) morphology. Atlastin 1 (ATL1, also known as SPG3A) encodes an ER membrane fusion GTPase and reticulon 2 (RTN2, also known as SPG12) helps shape ER tube formation. Here, we use a new fluorescent ER marker to show that the ER within wild-typeDrosophilamotor nerve terminals forms a network of tubules that is fragmented and made diffuse upon loss of the atlastin 1 orthologatlatlorRtnl1loss decreases evoked transmitter release and increases arborization. Similar to other HSP proteins, Atl inhibits bone morphogenetic protein (BMP) signaling, and loss ofatlcauses age-dependent locomotor deficits in adults. These results demonstrate a crucial role for ER in neuronal function, and identify mechanistic links between ER morphology, neuronal function, BMP signaling and adult behavior. PMID:26906425

  6. 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

  7. Inborn errors of metabolism in the biosynthesis and remodelling of phospholipids.

    PubMed

    Wortmann, Saskia B; Espeel, Marc; Almeida, Ligia; Reimer, Annette; Bosboom, Dennis; Roels, Frank; de Brouwer, Arjan P M; Wevers, Ron A

    2015-01-01

    Since the proposal to define a separate subgroup of inborn errors of metabolism involved in the biosynthesis and remodelling of phospholipids, sphingolipids and long chain fatty acids in 2013, this group is rapidly expanding. This review focuses on the disorders involved in the biosynthesis of phospholipids. Phospholipids are involved in uncountable cellular processes, e.g. as structural components of membranes, by taking part in vesicle and mitochondrial fusion and fission or signal transduction. Here we provide an overview on both pathophysiology and the extremely heterogeneous clinical presentations of the disorders reported so far (Sengers syndrome (due to mutations in AGK), MEGDEL syndrome (or SERAC defect, SERAC1), Barth syndrome (or TAZ defect, TAZ), congenital muscular dystrophy due to CHKB deficiency (CHKB). Boucher-Neuhäuser/Gordon Holmes syndrome (PNPLA6), PHARC syndrome (ABHD12), hereditary spastic paraplegia type 28, 54 and 56 (HSP28, DDHD1; HSP54, DDHD2; HSP56, CYP2U1), Lenz Majewski syndrome (PTDSS1), spondylometaphyseal dysplasia with cone-rod dystrophy (PCYT1A), atypical haemolytic-uremic syndrome due to DGKE deficiency (DGKE). PMID:25178427

  8. 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

  9. 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.

  10. 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.

  11. Prediction of limb lean tissue mass from bioimpedance spectroscopy in persons with chronic spinal cord injury

    PubMed Central

    Cirnigliaro, Christopher M.; La Fountaine, Michael F.; Emmons, Racine; Kirshblum, Steven C.; Asselin, Pierre; Spungen, Ann M.; Bauman, William A.

    2013-01-01

    Background Bioimpedance spectroscopy (BIS) is a non-invasive, simple, and inexpensive modality that uses 256 frequencies to determine the extracellular volume impedance (ECVRe) and intracellular volume impedance (ICVRi) in the total body and regional compartments. As such, it may have utility as a surrogate measure to assess lean tissue mass (LTM). Objective To compare the relationship between LTM from dual-energy X-ray absorptiometry (DXA) and BIS impedance values in spinal cord injury (SCI) and able-bodied (AB) control subjects using a cross-sectional research design. Methods In 60 subjects (30 AB and 30 SCI), a total body DXA scan was used to obtain total body and leg LTM. BIS was performed to measure the impedance quotient of the ECVRe and ICVRi in the total body and limbs. Results BIS-derived ECVRe yielded a model for LTM in paraplegia, tetraplegia, and control for the right leg (RL) (R2 = 0.75, standard errors of estimation (SEE) = 1.02 kg, P < 0.0001; R2 = 0.65, SEE = 0.91 kg, P = 0.0006; and R2 = 0.54, SEE = 1.31 kg, P < 0.0001, respectively) and left leg (LL) (R2 = 0.76, SEE = 1.06 kg, P < 0.0001; R2 = 0.64, SEE = 0.83 kg, P = 0.0006; and R2 = 0.54, SEE = 1.34 kg, P < 0.0001, respectively). The ICVRi was similarly predictive of LTM in paraplegia, tetraplegia, and AB controls for the RL (R2 = 0.85, SEE = 1.31 kg, P < 0.0001; R2 = 0.52, SEE = 0.95 kg, P = 0.003; and R2 = 0.398, SEE = 1.46 kg, P = 0.0003, respectively) and LL (R2 = 0.62, SEE = 1.32 kg, P = 0.0003; R2 = 0.57, SEE = 0.91 kg, P = 0.002; and R2 = 0.42, SEE = 1.31 kg, P = 0.0001, respectively). Conclusion Findings demonstrate that the BIS-derived impedance quotients for ECVRe and ICVRi may be used as surrogate markers to track changes in leg LTM in persons with SCI. PMID:23941792

  12. ALS5/SPG11/KIAA1840 mutations cause autosomal recessive axonal Charcot-Marie-Tooth disease.

    PubMed

    Montecchiani, Celeste; Pedace, Lucia; Lo Giudice, Temistocle; Casella, Antonella; Mearini, Marzia; Gaudiello, Fabrizio; Pedroso, José L; Terracciano, Chiara; Caltagirone, Carlo; Massa, Roberto; St George-Hyslop, Peter H; Barsottini, Orlando G P; Kawarai, Toshitaka; Orlacchio, Antonio

    2016-01-01

    Charcot-Marie-Tooth disease is a group of hereditary peripheral neuropathies that share clinical characteristics of progressive distal muscle weakness and atrophy, foot deformities, distal sensory loss, as well as diminished tendon reflexes. Hundreds of causative DNA changes have been found, but much of the genetic basis of the disease is still unexplained. Mutations in the ALS5/SPG11/KIAA1840 gene are a frequent cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum and peripheral axonal neuropathy, and account for ∼ 40% of autosomal recessive juvenile amyotrophic lateral sclerosis. The overlap of axonal Charcot-Marie-Tooth disease with both diseases, as well as the common autosomal recessive inheritance pattern of thin corpus callosum and axonal Charcot-Marie-Tooth disease in three related patients, prompted us to analyse the ALS5/SPG11/KIAA1840 gene in affected individuals with autosomal recessive axonal Charcot-Marie-Tooth disease. We investigated 28 unrelated families with autosomal recessive axonal Charcot-Marie-Tooth disease defined by clinical, electrophysiological, as well as pathological evaluation. Besides, we screened for all the known genes related to axonal autosomal recessive Charcot-Marie-Tooth disease (CMT2A2/HMSN2A2/MFN2, CMT2B1/LMNA, CMT2B2/MED25, CMT2B5/NEFL, ARCMT2F/dHMN2B/HSPB1, CMT2K/GDAP1, CMT2P/LRSAM1, CMT2R/TRIM2, CMT2S/IGHMBP2, CMT2T/HSJ1, CMTRID/COX6A1, ARAN-NM/HINT and GAN/GAN), for the genes related to autosomal recessive hereditary spastic paraplegia with thin corpus callosum and axonal peripheral neuropathy (SPG7/PGN, SPG15/ZFYVE26, SPG21/ACP33, SPG35/FA2H, SPG46/GBA2, SPG55/C12orf65 and SPG56/CYP2U1), as well as for the causative gene of peripheral neuropathy with or without agenesis of the corpus callosum (SLC12A6). Mitochondrial disorders related to Charcot-Marie-Tooth disease type 2 were also excluded by sequencing POLG and TYMP genes. An additional locus for autosomal recessive Charcot-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. PMID:26556829

  13. Elements of academic productivity: a comparison of PM&R units versus other clinical science units.

    PubMed

    Davidoff, G N; Ditunno, J F; Findley, T W; Goldberg, G F; Hazel, S

    1991-10-01

    In early 1989, the Research Committee of the American Academy of Physical Medicine and Rehabilitation (AAPM&R) established a subcommittee to develop methods to monitor academic progress in physical medicine and rehabilitation (PM&R) units in the US. To develop an indirect baseline of academic productivity in PM&R, the rates and types of publications by PM&R researchers were assessed in eight peer review medical journals. The journals selected consisted of all issues of the following (published in calendar years 1987 to 1989): Archives of Physical Medicine and Rehabilitation, American Journal of Physical Medicine and Rehabilitation, Physical Therapy, Archives of Neurology, Pain, Stroke, Paraplegia, and Arthritis & Rheumatism. The sampling frame consisted of 3,553 journal articles. Affiliation with a PM&R unit or other clinical science unit (other unit), extramural funding sources, and type of manuscript (eg, case report or scientific investigation) were identified and coded. Sixteen percent of all articles were authored by members of PM&R units. The prevalence of scientific reports written by other unit authors (71%) was comparable to that written by PM&R authors (67%) (chi 2[3] = 5.54; p less than .20). There was a greater prevalence of funding by the US Department of Education of studies written by PM&R authors (10%) than of studies written by members of other units (2%) (chi 2[1] = 79.4; p less than .0001). Reports authored by members of other units had a greater prevalence rate of funding from all other sources--federal and private (47% vs 33%; chi 2[1] = 41.2; p less than .0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1929803

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

    PubMed Central

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

    2014-01-01

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

  15. Sports-related spinal cord injury in Japan (from the nationwide spinal cord injury registry between 1990 and 1992).

    PubMed

    Katoh, S; Shingu, H; Ikata, T; Iwatsubo, E

    1996-07-01

    The Injury Prevention Committee of the Japan Medical Society of Paraplegia (JMSoP) conducted a nationwide epidemiological survey on spinal cord injury (SCI) using postal questionnaires for 3 years periods from 1990 to 1992, and the annual incidence of the spinal cord injury was estimated as 40.2 per million. From this registry, we investigated SCI related to sports activities. In 3 years, 528 patients were registered and 374 of them had neurological deficits. The incidence was 1.95 per million per annum. Mean age at injury was 28.5 years (10-77), and 88.1% of the patients were males. Diving was the commonest cause of SCI (21.6%), which was followed by skiing (13.4%), football including rugby, American football and soccer (12.7%), sky sports (7.0%), judo (6.8%) and gymnastics (6.6%). Mean age at injury was higher than 30 years in skiing (38.6 years) and sky sports (38.2 years). Cervical injury was predominant in all but sky sports and accounted for 83.5% of SCI. Motor complete paralysis was reported in 35.0% of the patients. Bony injury was observed in 55.9% of the patients; most of the patients who sustained the SCI in diving and sky sports had bony injury, and no bony injury was detected in more than a half of the patients who sustained injuries in skiing, judo or gymnastics. Although the percentage of sports-related SCI was small in the present study as compared to the data from previous reports, it is not difficult to imagine the increase in the number of sports-related SCI. We have launched an injury prevention campaign and are planning to conduct a similar study in future to evaluate the effect of the campaign as well as the changes in the incidence and pattern of SCI. PMID:8963997

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

    PubMed

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

    2015-12-15

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

  17. Clinical and epidemiological characterisation of Burkitt's lymphoma: an eight-year case study at Komfo Anokye Teaching Hospital, Ghana.

    PubMed

    Owusu, L; Yeboah, F A; Osei-Akoto, A; Rettig, T; Arthur, F K N

    2010-01-01

    Endemic Burkitt's lymphoma (BL) is a juvenile malignant neoplasm of B-lymphocyte origin, markedly affected by climate, vegetation and geographical location. This real country-based, cross-sectional, retrospective study reviews all out-patient clinical records of patients histologically and/or clinically diagnosed with BL from January, 2000 to December, 2007 at the Komfo Anokye Teaching Hospital, Ghana, a country within the malaria and lymphoma belts of the world. The aim of the study is to clinically and epidemiologically characterise all cases of BL over an eight-year period to ascertain the most common form of BL demographically prevalent. A mean age of 6.9 +/- 2.7 (range: 1-16) was observed. Males generally dominated in incidence (M:F=1.43:1, P<0.001) and significantly with facial presentation (P<0.05). Females weakly dominated in abdominal tumour presentation (P>0.05). The age range 4-8 years was the high risk range (P<0.001) for both sexes. Males were affected early in life (4-7 years) compared to their female counterparts (6-11 years). Of the 551 cases reviewed, 48.3%, 32.7%, 15.8% and 3.3% involved the face, abdomen, combined facial and abdominal and either facial or abdominal with central nervous system (CNS) involvement (usually paraplegia), respectively. An intriguing observation was evident between facial and combined facial and abdominal cases which exhibited reversed trends in incidence. Three regions within the forest zone showed significantly higher (P<0.001) incidences compared to the seven cohorts from the coastal and savannah agro-ecological zones of Ghana. No region was explicitly associated with any particular clinical presentation. The study has shown that although BL can present with demographic patterns in prevalence within a given geographical location, no clinical characterisation is associated with such patterns. PMID:20373676

  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 7.3±6 years. The most common injury was paraplegia. Most of the patients have moderate QOL (54.7 %). The results showed a significant relationship between QOL and marital status and employment status (P < 0.05). Also, results showed a significant relationship between QOL and education levels (P = 0.002), age (P = 0.001), and duration of illness (P = 0.001).The highest and lowest scores were 64 ± 7.1 and 36 ± 5.3 for understanding General Health (GH) and role physical, respectively. Conclusions: The results show that patients with SCI have a moderate health-related QOL Determining the QOL is needed to focus on the strengths and weaknesses of patients with spinal cord injuries. Planning principles is recommended in order to reform the disability. PMID:26557639

  19. 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.

  20. A pharmacogenetic study of docetaxel and thalidomide in patients with castration-resistant prostate cancer using the DMET genotyping platform.

    PubMed

    Deeken, J F; Cormier, T; Price, D K; Sissung, T M; Steinberg, S M; Tran, K; Liewehr, D J; Dahut, W L; Miao, X; Figg, W D

    2010-06-01

    The anticancer agent docetaxel shows significant inter-individual variation in its pharmacokinetic and toxicity profile. Thalidomide is an active anticancer agent and also shows wide pharmacological variation. Past pharmacogenetic research has not explained this variation. Patients with prostate cancer enrolled in a randomized phase II trial using docetaxel and thalidomide versus docetaxel alone were genotyped using the Affymetrix DMET 1.0 platform, which tests for 1256 genetic variations in 170 drug disposition genes. Genetic polymorphisms were analyzed for associations with clinical response and toxicity. In all, 10 single-nucleotide polymorphisms (SNPs) in three genes were potentially associated with response to therapy: peroxisome proliferator-activated receptor-delta (PPAR-delta), sulfotransferase family, cytosolic, 1C, member 2 (SULT1C2) and carbohydrate (chondroitin 6) sulfotransferase 3 (CHST3). In addition, 11 SNPs in eight genes were associated with toxicities to treatment: spastic paraplegia 7 (pure and complicated autosomal recessive) (SPG7), CHST3, cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6), N-acetyltransferase 2 (arylamine N-acetyltransferase) (NAT2), ATP-binding cassette, sub-family C (CFTR/MRP), member 6 (ABCC6), ATPase, Cu++ transporting, alpha polypeptide (ATP7A), cytochrome P450, family 4, subfamily B, polypeptide 1 (CYP4B1) and solute carrier family 10 (sodium/bile acid cotransporter family), member 2 (SLC10A2). Genotyping results between drug metabolizing enzymes and transporters (DMET) and direct sequencing showed >96% of concordance. These findings highlight the role that non-CYP450 metabolizing enzymes and transporters may have in the pharmacology of docetaxel and thalidomide. PMID:20038957

  1. Inflammogenesis of Secondary Spinal Cord Injury

    PubMed Central

    Anwar, M. Akhtar; Al Shehabi, Tuqa S.; Eid, Ali H.

    2016-01-01

    Spinal cord injury (SCI) and spinal infarction lead to neurological complications and eventually to paraplegia or quadriplegia. These extremely debilitating conditions are major contributors to morbidity. Our understanding of SCI has certainly increased during the last decade, but remains far from clear. SCI consists of two defined phases: the initial impact causes primary injury, which is followed by a prolonged secondary injury consisting of evolving sub-phases that may last for years. The underlying pathophysiological mechanisms driving this condition are complex. Derangement of the vasculature is a notable feature of the pathology of SCI. In particular, an important component of SCI is the ischemia-reperfusion injury (IRI) that leads to endothelial dysfunction and changes in vascular permeability. Indeed, together with endothelial cell damage and failure in homeostasis, ischemia reperfusion injury triggers full-blown inflammatory cascades arising from activation of residential innate immune cells (microglia and astrocytes) and infiltrating leukocytes (neutrophils and macrophages). These inflammatory cells release neurotoxins (proinflammatory cytokines and chemokines, free radicals, excitotoxic amino acids, nitric oxide (NO)), all of which partake in axonal and neuronal deficit. Therefore, our review considers the recent advances in SCI mechanisms, whereby it becomes clear that SCI is a heterogeneous condition. Hence, this leads towards evidence of a restorative approach based on monotherapy with multiple targets or combinatorial treatment. Moreover, from evaluation of the existing literature, it appears that there is an urgent requirement for multi-centered, randomized trials for a large patient population. These clinical studies would offer an opportunity in stratifying SCI patients at high risk and selecting appropriate, optimal therapeutic regimens for personalized medicine. PMID:27147970

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

    PubMed Central

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

    2008-01-01

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

  3. 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

  4. 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

  5. β-Glucosidase 2 (GBA2) Activity and Imino Sugar Pharmacology*

    PubMed Central

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

    2013-01-01

    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 (kinact). 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

  6. 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

  7. 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.

  8. Frozen elephant trunk surgery—the Bologna’s experience

    PubMed Central

    Pantaleo, Antonio; Murana, Giacomo; Pellicciari, Giovanni; Castrovinci, Sebastiano; Berretta, Paolo; Folesani, Gianluca; Di Bartolomeo, Roberto

    2013-01-01

    Background Different approaches are available to treat patients with complex and extensive diseases of the thoracic aorta. This study aims to report and comment on our experience with the frozen elephant trunk (FET) technique. Methods Between January 2007 and July 2012, 122 patients (male: 86.9%; mean age: 61 years) underwent extensive thoracic aorta surgery using the FET approach with an E-vita open prosthesis. The most frequent indications for surgery included residual type A chronic dissection (45.9%), extensive degenerative aneurysm of the thoracic aorta (27%), and type A acute aortic dissection (7.4%). Sixty-nine patients had already undergone cardiac/aortic interventions through a median sternotomy. A total of 60 associated procedures were performed, with 76.6% on the aortic root. Selective antegrade cerebral perfusion and moderate hypothermia were used in all cases. Results Overall, hospital mortality was 15.2%. Post-operatively, 7.4% and 9.0% of patients were complicated by permanent neurologic dysfunction and spinal cord injury, respectively. For the surviving patients, 1- and 3-year freedom from all-cause mortality was (91.7±2.8)% and (79.1±6.1)%, respectively. 1- and 3-year freedom from re-intervention was (83.1±3.5)% and (74.1±4.3)%, respectively. Conclusions In our experience, FET surgery allowed treatment of complex patients with extensive thoracic aortic diseases with satisfactory short- and mid-term results. Acute and chronic dissections represent interesting subsets for FET application. While further larger and longer-term studies are required to show the survival benefits of the FET technique versus other types of management, new strategies for spinal cord injury (paraplegia/paraparesis) reduction should also be researched. PMID:24109567

  9. Mycoplasma-induced minimally conscious state.

    PubMed

    Horvath, Thomas; Fischer, Urs; Müller, Lionel; Ott, Sebastian; Bassetti, Claudio L; Wiest, Roland; Sendi, Parham; Schefold, Joerg C

    2016-01-01

    Mycoplasma pneumoniae (M. pneumoniae) frequently causes community-acquired respiratory tract infection and often presents as atypical pneumonia. Following airborne infection and a long incubation period, affected patients mostly suffer from mild or even asymptomatic and self-limiting disease. In particular in school-aged children, M. pneumoniae is associated with a wide range of extrapulmonary manifestations including central nervous system (CNS) disease. In contrast to children, severe CNS manifestations are rarely observed in adults. We report a case of a 37 year-old previously healthy immunocompetent adult with fulminant M. pneumoniae-induced progressive encephalomyelitis who was initially able to walk to the emergency department. A few hours later, she required controlled mechanical ventilation for ascending transverse spinal cord syndrome, including complete lower extremity paraplegia. Severe M. pneumoniae-induced encephalomyelitis was postulated, and antimicrobial, anti-inflammatory and immunosuppressive therapy was applied on the intensive care unit. Despite early and targeted therapy using four different immunosuppressive strategies, clinical success was limited. In our patient, locked-in syndrome developed followed by persistent minimally conscious state. The neurological status was unchanged until day 230 of follow-up. Our case underlines that severe M. pneumoniae- related encephalomyelitis must not only be considered in children, but also in adults. Moreover, it can be fulminant and fatal in adults. Our case enhances the debate for an optimal antimicrobial agent with activity beyond the blood-brain barrier. Furthermore, it may underline the difficulty in clinical decision making regarding early antimicrobial treatment in M. pneumoniae disease, which is commonly self-limited. PMID:27026840

  10. The Collateral Network Concept: A Reassessment of the Anatomy of Spinal Cord Perfusion

    PubMed Central

    Etz, Christian D.; Kari, Fabian A.; Mueller, Christoph S.; Silovitz, Daniel; Brenner, Robert; Lin, Hung-Mo; Griepp, Randall B.

    2010-01-01

    OBJECTIVE Prevention of paraplegia following repair of thoracoabdominal aortic aneurysms (TAAA) requires understanding the anatomy and physiology of the blood supply to the spinal cord. Recent laboratory studies and clinical observations suggest that a robust collateral network must exist to explain preservation of spinal cord perfusion when segmental vessels are interrupted. An anatomical study was undertaken. METHODS Twelve juvenile Yorkshire pigs underwent aortic cannulation and infusion of a low-viscosity acrylic resin at physiological pressures. After curing of the resin and digestion of all organic tissue, the anatomy of the blood supply to the spinal cord was studied grossly and using light and electron microscopy. RESULTS All vascular structures ≥ 8μm in diameter were preserved. Thoracic and lumbar segmental arteries (SAs) give rise not only to the anterior spinal artery (ASA), but to an extensive paraspinous network feeding the erector spinae, iliopsoas, and associated muscles. The ASA, mean diameter 134±20 μm, is connected at multiple points to repetitive circular epidural arteries with mean diameters of 150±26 μm. The capacity of the paraspinous muscular network is 25-fold the capacity of the circular epidural arterial network and ASA combined. Extensive arterial collateralization is apparent between the intraspinal and paraspinous networks, and within each network. Only 75% of all SAs provide direct ASA-supplying branches. CONCLUSIONS The ASA is only one component of an extensive paraspinous and intraspinal collateral vascular network. This network provides an anatomic explanation of the physiological resiliency of spinal cord perfusion when SAs are sacrificed during TAAA repair. PMID:21419903

  11. 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

  12. Alteration of Basilar Artery Rho-Kinase and Soluble Guanylyl Cyclase Protein Expression in a Rat Model of Cerebral Vasospasm following Subarachnoid Hemorrhage

    PubMed Central

    Wang, Chih-Jen; Lee, Pei-Yu; Wu, Bin-Nan; Wu, Shu-Chuan; Loh, Joon-Khim; Tsai, Hung-Pei; Kassell, Neal F.; Kwan, Aij-Lie

    2014-01-01

    Background and Purpose. The vasoconstrictor endothelin-1 (ET-1) has been implicated in the pathogenesis of cerebral vasospasm following subarachnoid hemorrhage (SAH). Previous results showed that CGS 26303, an endothelin converting enzyme (ECE) inhibitor, effectively prevented and reversed arterial narrowing in animal models of SAH. In the present study, we assessed the effect of CGS 26303 on neurological deficits in SAH rats. The involvement of vasoactive pathways downstream of ET-1 signaling in SAH was also investigated. Methods. Sprague-Dawley rats were divided into five groups (n = 6/group): (1) normal control, (2) SAH, (3) SAH+vehicle, (4) SAH+CGS 26303 (prevention), and (5) SAH+CGS 26303 (reversal). SAH was induced by injecting autologous blood into cisterna magna. CGS 26303 (10 mg/kg) was injected intravenously at 1 and 24 hr after the initiation of SAH in the prevention and reversal protocols, respectively. Behavioral changes were assessed at 48 hr after SAH. Protein expression was analyzed by Western blots. Results. Deficits in motor function were obvious in the SAH rats, and CGS 26303 significantly improved the rate of paraplegia. Expressions of rho-kinase-II and membrane-bound protein kinase C-δ and rhoA were significantly increased, while those of soluble guanylyl cyclase α1 and β1 as well as protein kinase G were significantly decreased in the basilar artery of SAH rats. Treatment with CGS 26303 nearly normalized these effects. Conclusions. These results demonstrate that the rhoA/rho-kinase and sGC/cGMP/PKG pathways play pivotal roles in cerebral vasospasm after SAH. It also shows that ECE inhibition is an effective strategy for the treatment of this disease. PMID:24982890

  13. 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

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

    PubMed Central

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

    2011-01-01

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

  15. Serum level of serotonin during rest and during exercise in paraplegic patients.

    PubMed

    Steinberg, L L; Sposito, M M; Lauro, F A; Tufik, S; Mello, M T; Naffah-Mazzacoratti, M G; Cavalheiro, E A; Silva, A C

    1998-01-01

    The purpose of this study was to evaluate the serum level of serotonin (5-HT) during rest and response to exercise in subjects with spinal cord injury (SCI) with different levels of physical activity. Twenty-five male subjects with traumatic paraplegia, the neurological levels being between T1 and T12, volunteered for the study. They were divided into two groups matched for age, weight and time since injury, according to the level of physical activity: 14 inactive and 11 subjects regularly involved in sports activity and considered active. They all performed a maximal spiroergometric test with an arm crank ergometer. Two samples of blood were collected for 5-HT determination, during rest (PRE) and immediately after exercise test (POST). Serum 5-HT concentration was measured by high performance liquid chromatography using electrochemical detection (HPLC-ED). The results showed that peak oxygen uptake (VO2peak) was higher in the active group (27.08 +/- 2.60 vs 18.89 +/- 5.58 mL.kg-1.min-1, P < 0.001). There were no significant differences between the inactive and active groups for the 5-HT PRE (respectively 176.96 and 193.73 ng.mL - 1, P > 0.05) or POST values (275.44 vs 311.05 ng.mL-1, P > 0.05). Both groups showed an increment in 5-HT after maximal exercise, but only in the active group it reached statistical significance (Wilcoxon test, P < 0.02). Our results show that chronic paraplegic individuals have normal resting serum serotonin levels and normal response to exercise. The relationship between training status, mood elevation and 5-HT in SCI could not be established in the present study, and further investigation is needed to clarify this issue. PMID:9471132

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

    PubMed Central

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

    2014-01-01

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

  17. Effectiveness of intense, activity-based physical therapy for individuals with spinal cord injury in promoting motor and sensory recovery: Is olfactory mucosa autograft a factor?

    PubMed Central

    Larson, Cathy A.; Dension, Paula M.

    2013-01-01

    Background/objectives Rehabilitation for individuals with spinal cord injury (SCI) is expanding to include intense, activity-based, out-patient physical therapy (PT). The study's primary purposes were to (i) examine the effectiveness of intense PT in promoting motor and sensory recovery in individuals with SCI and (ii) compare recovery for individuals who had an olfactory mucosa autograft (OMA) with individuals who did not have the OMA while both groups participated in the intense PT program. Methods Prospective, non-randomized, non-blinded, intervention study. Using the American Spinal Injury Association examination, motor and sensory scores for 23 (7 OMA, 6 matched control and 10 other) participants were recorded. Results Mean therapy dosage was 137.3 total hours. The participants’ total, upper and lower extremity motor scores improved significantly while sensory scores did not improve during the first 60 days and from initial to discharge examination. Incomplete SCI or paraplegia was associated with greater motor recovery. Five of 14 participants converted from motor-complete to motor-incomplete SCI. Individuals who had the OMA and participated in intense PT did not have greater sensory or greater magnitude or rate of motor recovery as compared with participants who had intense PT alone. Conclusion This study provides encouraging evidence as to the effectiveness of intense PT for individuals with SCI. Future research is needed to identify the optimal therapy dosage and specific therapeutic activities required to generate clinically meaningful recovery for individuals with SCI including those who elect to undergo a neural recovery/regenerative surgical procedure and those that elect intense therapy alone. PMID:23433335

  18. 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

  19. 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

  20. 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

  1. The safety and efficacy of bariatric surgery for obese, wheelchair bound patients

    PubMed Central

    Williams, GJ; Georgiou, PA; Cocker, DM; Bonanomi, G; Smellie, J; Efthimiou, E

    2014-01-01

    Introduction The aim of this study was to evaluate outcomes of bariatric surgery performed in order to improve mobility in patients with severe mobility limitations. Methods Patients with severe mobility impairment (wheelchair bound) who underwent laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic adjustable gastric banding (LAGB) surgery to improve their mobility were included in this study. Patients were identified between July 2009 and October 2011 using an electronic prospective bariatric database. Mobility was assessed by questionnaire during clinic follow-up appointments. Results Fifteen patients (11 female, 4 male) with a mean age of 48 years (range: 26–71 years) and a mean body mass index of 46kg/m2 (range: 33–54kg/m2) were included. Seven patients (47%) underwent LAGB and eight (53%) LRYGB. The aetiologies of mobility impairment included advanced osteoarthritis (n=6), spinal conditions (n=4), severe bilateral leg oedema and ulceration (n=2), advanced rheumatoid arthritis (n=2) and traumatic paraplegia (n=1). The mean length of hospital stay was 3.8 days. There was no mortality. One patient was lost to follow-up. Of the remaining 14 patients, the mean excess weight loss percentage at a mean of 18.5 months postoperatively was 48% (68% for LRYGB, 20 months; 29% for LAGB, 17 months). Ten patients reported improved mobility. Reduced pain, improved independence and ability to transfer were most commonly cited. Four patients reported no improvement in mobility (three LAGB patients, one LRYGB patient). Conclusions Bariatric surgery can safely improve mobility and quality of life in obese patients with severe mobility impairment. Our paper supports the idea that severe mobility impairment should be considered an indication for bariatric surgery in selected patients. LRYGB demonstrated better weight loss and mobility improvement than LAGB. Larger studies are required to establish robust selection criteria for surgery in this group. PMID:24992422

  2. Modern concepts of therapy and management of spinal cord injuries.

    PubMed

    Woolsey, R M

    1988-01-01

    Trauma is the most common cause of spinal cord-related disability. There are approximately 52 new spinal cord injuries per million population per year in the U.S., and about 200,000 persons with post-traumatic paraplegia or quadriplegia require continuing medical care in this country at the present time. Management of the spinal cord-injured patient commences at the moment of injury and continues throughout the entire lifetime of the patient. While there is considerable consensus regarding the management of some problems related to traumatic myelopathy, other treatment concerns, mainly related to spinal fractures, are highly controversial, with a plethora of strongly held opinions, frequently supported by meager factual evidence or none at all. It is not generally recognized that whatever treatment the patient receives during the first days or weeks following injury is of considerably less importance, from a lifelong perspective, than that which occurs over subsequent months. Skillful physical rehabilitation to maximize the functional usefulness of remaining neurological function permits the return of most spinal cord-injured patients to their family and community able to function as an independent person. Paraplegic and quadriplegic patients acquire health risks unique to their condition, mainly related to pressure sore liability and altered bladder function, which requires continual, meticulous attention from the patient and his physician. The sudden transition from being an unimpaired to a permanently paralyzed person is a cataclysmic emotional experience. Unless psychic rehabilitation is undertaken in tandem with physical rehabilitation, a spinal cord-injured patient is likely to become an unhappy social recluse or denizen of a chronic care facility, rather than an independent productive member of his community. Centers dedicated to comprehensive spinal cord care have become generally available and provide optimal care for traumatic myelopathy. PMID:3063393

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

    PubMed Central

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

    2015-01-01

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

  4. Endovascular management of chronic post-dissection aneurysms

    PubMed Central

    Oikonomou, Kyriakos; Katsargyris, Athanasios; Ritter, Wolfgang; Spinelli, Domenico; Seto, Yuki

    2014-01-01

    Open repair is still the gold standard in acute type A dissection. Endovascular repair is advocated for complicated acute type B dissections. Recent evidence also supports the role of endovascular repair in a larger proportion of uncomplicated acute type B dissections. The role of endovascular repair in chronic post-dissection aneurysms, however, is still unclear. Most commonly, post-dissection aneurysms involve the thoracoabdominal aorta, making the use of fenestrated/branched stent-grafts to achieve complete aneurysm exclusion mandatory. These fenestrated/branched stent-grafts have been used with success in atherosclerotic thoracoabdominal aortic aneurysms (TAAAs). In chronic post-dissection aneurysms, however, additional technical challenges arise. The usually narrow true lumen makes the use of branches more tedious and overall planning difficult. A second technical challenge relates to the fact that visceral branches can also originate from the false lumen. In such cases, perforation of the stiff chronic dissection flap is required to obtain access to the vessel. During the period January 2010 to November 2013, 17 patients (13 males, mean age 65±7.8 years) with chronic thoracoabdominal aneurismal degeneration following acute dissection were treated in our department with the use of fenestrated/branched stent-grafts. Technical success was achieved in all cases (100%). Perioperative mortality was two (11.8%) patients. One patient died due to multiple organ failure and one due to cardiac failure. No case of paraplegia was observed. During a 12-month median follow-up (range, 4-28 months) no aneurysm-related deaths were observed. Reintervention was required in three cases to repair a type Ib endoleak from a side branch. Endovascular treatment with fenestrated/branched stent-grafts is feasible for chronic post-dissection aneurysms. Standard thoracic stent-grafting is an option in a minority of patients, when the aneurysm is limited to the thoracic segment. Fenestrated and branched devices can successfully be used for aneurysms extending to the thoracoabdominal aorta. PMID:24967171

  5. 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.

  6. Long-term outcomes of the bronchial artery embolization are diagnosis dependent

    PubMed Central

    Pathak, Vikas; Stavas, Joseph M; Ford, Hubert J; Austin, Charles A; Aris, Robert M

    2016-01-01

    Background: Bronchial artery embolization (BAE) is an established, safe, and effective procedure for the treatment of hemoptysis but long-term outcomes of the BAE have never been investigated before. Objectives: To retrospectively analyze long-term outcomes of the BAE. Materials and Methods: A retrospective chart analysis was done from the hospital central database for all patients undergoing the BAE over a consecutive 14-year period (January 2000-February 2014). A total of 58 patients were identified from the database. Eight patients were excluded due to the lack of follow-up. Data such as patient demographics, reason for hemoptysis, medical imaging results, bronchoscopy findings, recurrence rates, and morbidity/mortality rates after the BAE were collected. Results: Eighty three embolizations were performed in 50 patients. The median follow-up was of 2.2 years. Cystic fibrosis (CF) bronchiectasis was the most common etiology (21/50), followed by non-CF bronchiectasis (9/50). Cavitary lung disease occurred in 12/50 patients, an additional 4/50 had cancer (primary lung and metastatic), and one patient had antineutrophil cytoplasmic antibody (ANCA) vasculitis. In three patients the etiology was unknown. Postprocedural complications occurred in 5/83 (6%) patients, two patients with two major complications - stroke (one) and paraplegia (one) - and three patients with minor complications - chest pain (two) and bronchial artery dissection (one). A total of 15/50 patients died during the follow-up. Three patients died of hemoptysis, and the remaining deaths were unrelated to the procedure or hemoptysis. Twenty four patients had recurrent hemoptysis. A Kaplan-Meier analysis revealed an excellent long-term survival that was 85% at 10 years. Conclusions: The BAE is a safe and effective procedure with excellent overall long-term survival. PMID:26933299

  7. 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

  8. 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

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

    PubMed Central

    Oza, Chintan S.

    2015-01-01

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

  10. 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

  11. Mutations in B4GALNT1 (GM2 synthase) underlie a new disorder of ganglioside biosynthesis

    PubMed Central

    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; Hurles, Matthew E.

    2013-01-01

    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

  12. Spinal deformity in children treated for neuroblastoma

    SciTech Connect

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

    1981-02-01

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

  13. Skin thickness on bony prominences measured by ultrasonography in patients with spinal cord injury

    PubMed Central

    Yalcin, Elif; Akyuz, Mufit; Onder, Burcu; Unalan, Halil; Degirmenci, Ibrahim

    2013-01-01

    Objective The detailed assessment of soft tissues over bony prominences and identification of methods of predicting pressure sores would improve the quality of care for patients with spinal cord injury (SCI). Comparing skin thicknesses on bony prominences in patients with SCI to those in healthy individuals will represent, to our knowledge, the first study aimed at determining whether differences in skin thicknesses between these groups can be detected by ultrasound. Design In both patients and controls, skin thicknesses on the sites at risk for pressure ulcers – sacrum, greater trochanter, and ischium – were evaluated using high-frequency ultrasound. The waist was also evaluated by the same method for control as it was considered to be a pressure-free region. Participants Thirty-two patients with complete thoracic SCI and 34 able-bodied individuals. Results The skin was significantly thinner over the sacrum and ischial tuberosity in individuals with SCI compared with healthy individuals. No significant differences were observed in skin thicknesses over the greater trochanter or the waist between the two groups. Conclusions Protecting skin integrity in patients with paraplegia is challenging due to many contributing factors, such as prolonged pressure, frictional/shearing forces, and poor nutrition. Thinning of the skin can increase the risk of soft tissue damage, leading to pressure ulcers. The significant differences in skin thickness at the sacrum and ischium provide the basis for establishing the early signs of pressure damage. Measuring skin thickness by ultrasound is a reliable non-invasive method that could be a promising tool for predicting pressure ulcers. PMID:23809593

  14. 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

  15. 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

  16. CNS myelination and PLP gene dosage.

    PubMed

    Woodward, K; Malcolm, S

    2001-08-01

    The phenomenon of gene dosage effects demonstrates that the mechanisms of some genetic diseases are best recognised at the genomic level. Classical gene mutation screening approaches utilising PCR are unsuccessful in unravelling the basis of disease because the gene sequence is unaltered and only the copy number is different. Techniques for detecting DNA dosage are required. Examples of haploinsufficiency and gene deletions are well documented, but increased gene dosage is also an important genetic mechanism in disorders involving myelin proteins in the central (CNS) and peripheral nervous system (PNS). Here we review the dosage effects and mutations of the proteolipid protein (PLP) gene that causes Pelizaeus-Merzbacher disease (PMD) and spastic paraplegia Type 2 (SPG2) disorders of CNS myelination. Similarities are drawn with the peripheral neuropathies Charcot-Marie-Tooth disease Type 1 (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) that are also caused by dosage effects and mutations in a single myelin protein gene (peripheral myelin protein 22, PMP-22). We compare the different mutational mechanisms in man and analogous mouse models that suggest a function for PLP beyond its structural role in myelin. We focus on the increased dosage of the PLP gene that is the major cause of PMD and results from a submicroscopic duplication of Xq22. Other clinical phenotypes may arise from gene dosage imbalance with the potential effect of submicroscopic duplications and deletions of the genome being underestimated. Genome sequencing may identify intrinsic structural properties of the DNA with greater susceptibility to these rearrangements and thereby reflect structural changes in the genome. PMID:11535114

  17. Thoracic Nerve Root Schwannoma Filling the Spinal Canal Almost Entirely Without any Neurological Deficits

    PubMed Central

    Godlewski, Bartosz; Klauz, Grzegorz; Czepko, Ryszard

    2016-01-01

    Introduction Spinal tumours may be classified in three groups: 1) extradural, 2) intradural extramedullary and 3) intramedullary spinal cord tumours. Intradural extramedullary tumours arise from the leptomeninges or nerve roots and include schwannomas. A schwannoma is usually a firm grey-whitish tumour growing near a nerve trunk or ramus. It can be separated from the nerve without damaging neural tissue. Schwannomas are usually solitary tumours. Case Presentation We present the case of a 37-year-old male who underwent surgery for a tumour in the upper thoracic segment of the spinal canal. Although the tumour filled the spinal canal almost entirely, the patient did not manifest any neurological deficits. During the surgery, the tumour was removed completely. A histological examination confirmed a benign schwannoma lesion (WHO G1). Conclusions The question whether doctors are keen to order more diagnostic investigations (including both laboratory and imaging studies) than are necessary is often asked in clinical practice. The cost factor is also important. Not every patient with back pain is referred for an MRI study in the absence of characteristic neurological signs. The case of our patient, however, speaks in favour of early referral for such diagnostic modalities. Appropriate imaging studies, even in patients presenting with no neurological deficits, may help detect pathologies than can lead to severe disability. A spinal canal tumour filling the spinal canal almost entirely and displacing the spinal cord could cause spinal cord damage at any time with all the dire consequences such as paraplegia and loss of the ability to walk. PMID:27110539

  18. 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

  19. 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

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

    PubMed Central

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

    2014-01-01

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