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. Genetics Home Reference: spastic paraplegia type 8

    MedlinePlus

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

  3. Hereditary Spastic Paraplegia

    MedlinePlus

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

  4. Genetics Home Reference: spastic paraplegia type 2

    MedlinePlus

    ... Hereditary spastic paraplegias are divided into two types: pure and complex. The pure types involve the lower limbs. The complex types ... paraplegia type 2 can occur in either the pure or complex form. People with the pure form ...

  5. 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.

  6. 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

  7. Genetics Home Reference: spastic paraplegia type 11

    MedlinePlus

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

  8. 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

  9. Non-traumatic paraplegia in northern Tanzania.

    PubMed Central

    Scrimgeour, E M

    1981-01-01

    A retrospective study of all 100 cases of non-traumatic (medical) paraplegia admitted to a large hospital in northern Tanzania over an eight-year period was undertaken; 15 of the patients were examined. Patients' ages ranged from 2 to 80 years (mean 31), and 67 were male. Seventy-one lived under 85 km (53 miles) from the hospital, and the average period from onset of symptoms of paraplegia to admission to the referral hospital was ten weeks. Tuberculosis was the most frequent cause of paraplegia (54%), followed by neoplasia (13%) and schistosomiasis, (6%). No cases of nutritional myelopathy were diagnosed. In 12 cases a diagnosis could not be established. The average period spent in hospital was 11 weeks, and 35 patients made a good recovery and were ambulant at discharge. PMID:6793199

  10. Painless Aortic Dissection Presenting as Paraplegia

    PubMed Central

    Colak, Necmettin; Nazli, Yunus; Alpay, Mehmet Fatih; Akkaya, Ismail Olgun; Cakir, Omer

    2012-01-01

    Acute dissection of the aorta can be life-threatening. As a presenting manifestation of aortic dissection, neurologic complications such as paraplegia are rare. Herein, we report the case of a 51-year-old man who presented with sudden-onset paraplegia and ischemia of the legs, with no chest or back pain. His medical history included coronary artery bypass grafting. Physical examination revealed pulseless lower extremities, and computed tomography showed aortic dissection from the ascending aorta to the common iliac arteries bilaterally. A lumbar catheter was inserted for cerebrospinal fluid drainage, and axillary arterial cannulation was established. With the use of cardiopulmonary bypass, the aortic dissection was corrected, and the previous coronary artery grafts were reattached. The surgery restored spinal and lower-extremity perfusion, and the patient walked unaided from the hospital upon his discharge 5 days later. Although acute aortic dissection presenting as paraplegia is rare, it should be considered in patients who have pulseless femoral arteries bilaterally and sudden-onset paraplegia, despite no pain in the chest or back. Prompt diagnosis and intervention can prevent morbidity and death. PMID:22740752

  11. Acute Aortic Occlusion Presenting as Flaccid Paraplegia

    PubMed Central

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

    2015-01-01

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

  12. 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

  13. 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

  14. Paraplegia due to Acute Aortic Coarctation and Occlusion

    PubMed Central

    Park, Chang-Bum; Kim, Min-Ki; Kim, Sang-Hyun

    2014-01-01

    Coarctation and occlusion of the aorta is a rare condition that typically presents with hypertension or cardiac failure. However, neuropathy or myelopathy may be the presenting features of the condition when an intraspinal subarachnoid hemorrhage has compressed the spinal cord causing ischemia. We report two cases of middle-aged males who developed acute non-traumatic paraplegia. Undiagnosed congenital abnormalities, such as aortic coarctation and occlusion, should be considered for patients presenting with nontraumatic paraplegia in the absence of other identifiable causes. Our cases suggest that spinal cord ischemia resulting from acute spinal subarachnoid hemorrhage and can cause paraplegia, and that clinicians must carefully examine patients presenting with nontraumatic paraplegia because misdiagnosis can delay initiation of the appropriate treatment. PMID:24851152

  15. Molecular aspects of hereditary spastic paraplegia.

    PubMed

    Noreau, Anne; Dion, Patrick A; Rouleau, Guy A

    2014-07-01

    Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by progressive lower limbs spasticity and weakness. What was first thought to be a small group of rare Mendelian disorder has now become a large group that includes many complex syndromes. While large families with defined modes of inheritance were used for the initial HSP gene discovery, new sequencing technologies have recently allowed the study of small families, with the identification of many new disease causative genes. These discoveries are slowly leading to a better understanding of the molecular mechanisms underlying HSP with the identification of precise disease pathways. These insights may lead to new therapeutic strategies for what is a group of largely untreatable diseases. This review looks at the key players involved in HSP and where they act in their specific pathways. PMID:24631291

  16. Acute Paraplegia due to Thoracic Hematomyelia.

    PubMed

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

    2016-01-01

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

  17. Acute Paraplegia due to Thoracic Hematomyelia

    PubMed Central

    Celik, Bahattin; Canbek, Ihsan; Karavelioğlu, Ergun

    2016-01-01

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

  18. Type A aortic dissection presenting with isolated paraplegia.

    PubMed

    Tsiouris, Athanasios; Morgan, Jeffrey A; Paone, Gaetano

    2012-12-01

    Acute type A thoracic aortic dissections most commonly present with sudden onset of severe chest and/or back pain. We summarize the case of a patient with an acute type A dissection who presented with acute, painless paraplegia caused by malperfusion of the artery of Adamkiewicz. Although an uncommon cause of acute paraplegia, type A dissections should be included in the differential diagnosis. PMID:23262048

  19. Genetic and phenotypic characterization of complex hereditary spastic paraplegia.

    PubMed

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

    2016-07-01

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

  20. Genetic and phenotypic characterization of complex hereditary spastic paraplegia

    PubMed Central

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

    2016-01-01

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

  1. 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

  2. Spinal cord ischemia resulting in paraplegia following extrapleural pneumonectomy.

    PubMed

    Ural, Kelly; Jakob, Kyle; Lato, Scott; Gilly, George; Landreneau, Rodney

    2014-08-01

    A patient undergoing radical extrapleural pneumonectomy for epithelioid malignant mesothelioma developed acute paraplegia postoperatively related to long-segment spinal cord ischemia. The usual area of concern for this complication is the T9 to T12 area where the artery of Adamkiewicz is most likely to originate. In this patient, there was ligation of only upper thoracic, ipsilateral segmental arteries from the T3 to T6 level, yet he still developed paraplegia. Our hypothesis is variant mid-thoracic vascular anatomy. Previously unreported, to our knowledge, this should be understood as a rare complication of this surgery. PMID:25091760

  3. Migrated Disc at Cervicothoracic Junction Presenting as Acute Paraplegia

    PubMed Central

    Mahore, Amit; Agarwal, Monit; Tikeykar, Vishakha

    2015-01-01

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

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

    PubMed

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

    2015-06-01

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

  5. Clinical features and management of hereditary spastic paraplegia.

    PubMed

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

    2014-03-01

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

  6. Hybrid Treatment of Acute Abdominal Aortic Thrombosis Presenting with Paraplegia.

    PubMed

    Azzarone, Matteo; De Troia, Alessandro; Iazzolino, Luigi; Nabulsi, Bilal; Tecchio, Tiziano

    2016-05-01

    Acute thrombotic or embolic occlusion of the abdominal aorta is a rare vascular emergency associated with high morbidity and mortality rates. Classically, the clinical presentation is a severe peripheral ischemia with bilateral leg pain as the predominant feature. Aortic occlusion presenting as an isolated acute onset of paraplegia due to spinal cord ischemia is very rare and requires improved awareness to prevent adverse outcomes associated with delayed diagnosis. We report the case of a 54-year-old man who presented with sudden paraplegia due to the thrombotic occlusion of the infrarenal aorta involving the first segment of the common iliac arteries on both sides; emergent transperitoneal aorto iliac thrombectomy combined with the endovascular iliac kissing-stent technique were performed achieving perioperative complete regression of the symptoms. PMID:26968371

  7. 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

  8. 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

  9. Alteration of ganglioside biosynthesis responsible for complex hereditary spastic paraplegia.

    PubMed

    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

    2013-07-11

    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

  10. Neuroarthropathy of the Wrist in Paraplegia: A Case Report

    PubMed Central

    Shem, Kazuko L

    2006-01-01

    Background/Objective: Neuroarthropathy, also known as Charcot joint, is most commonly seen in the spine and other weight-bearing joints in individuals with spinal cord injury (SCI). It is rarely seen in the joints of the upper extremities because the pathophysiology of the neuroarthropathy is thought to be significant repetitive trauma such as with weight bearing in an insensate joint. Methods: Case report of neuroarthropathy in the wrist of a 46-year-old man with a 30-year history of T4 paraplegia caused by ependymoma. Results: The patient recently developed a nonpainful swelling in the left wrist, which had decreased sensation since the time of his initial SCI. Radiological evaluation showed marked degenerative changes consistent with neuroarthropathy. A magnetic resonance image of the spine showed spinal cord atrophy at the cervicothoracic junction. Conclusions: This case shows an unusual presentation of a neuroarthropathy in a wrist in an individual with functional paraplegia. Because the treatment options for neuroarthropathy in the upper extremity in individuals with SCI are limited, early diagnosis is crucial to implement conservative management before significant destruction of the joint occurs. PMID:17044396

  11. 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

  12. 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

  13. 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

  14. Acute myelopathy with sudden paraplegia as the sole manifestation of meningococcal meningitis.

    PubMed

    Ibrahim, Wanis H; Elalamy, Osama R; Doiphode, Sanjay H; Mobyaed, Hassan; Darweesh, Adham

    2010-01-01

    Acute myelopathy with sudden paraplegia is a very rare manifestation of meningococcal meningitis, with only a few cases reported in the literature. In almost all previously reported cases, other clinical manifestations of meningitis, such as fever, headache, and neck stiffness preceded acute myelopathy. In this paper, we report a case of acute myelopathy with sudden paraplegia as the sole manifestation of meningococcal meningitis, in the absence of other clinical manifestations of meningitis. PMID:21483588

  15. Acute myelopathy with sudden paraplegia as the sole manifestation of meningococcal meningitis

    PubMed Central

    Ibrahim, Wanis H.; Elalamy, Osama R.; Doiphode, Sanjay H.; Mobyaed, Hassan; Darweesh, Adham

    2010-01-01

    Acute myelopathy with sudden paraplegia is a very rare manifestation of meningococcal meningitis, with only a few cases reported in the literature. In almost all previously reported cases, other clinical manifestations of meningitis, such as fever, headache, and neck stiffness preceded acute myelopathy. In this paper, we report a case of acute myelopathy with sudden paraplegia as the sole manifestation of meningococcal meningitis, in the absence of other clinical manifestations of meningitis. PMID:21483588

  16. 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

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

    PubMed

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

    2016-03-01

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

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

    PubMed

    Zhao, Jiali; Hedera, Peter

    2015-01-01

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

  19. 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

  20. 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

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

    PubMed

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

    2015-12-01

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

  2. 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

  3. 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.

  4. 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

  5. Medicolegal Corner: When minimally invasive thoracic surgery leads to paraplegia.

    PubMed

    Epstein, Nancy E

    2014-01-01

    A patient with mild cervical myelopathy due to multilevel ossification of the posterior longitudinal ligament (OPLL) initially underwent a cervical C3-T1 laminectomy with C2-T2 fusion utilizing lateral mass screws. The patient's new postoperative right upper extremity paresis largely resolved within several postoperative months. However, approximately 6 months later, the patient developed increased paraparesis attributed to thoracic OPLL and Ossification of the yellow ligament (OYL) at the T2-T5 and T10-T11 levels. The patient underwent simultaneous minimally invasive (MIS) unilateral MetRx approaches to both regions. Postoperatively, the patient was paraplegic and never recovered function. Multiple mistakes led to permanent paraplegia due to MIS MetRx decompressions for T2-T5 and T10-11 OPLL/OYL in this patient. First, both thoracic procedures should have been performed "open" utilizing a full laminectomy rather than MIS; adequate visualization would have likely averted inadvertent cord injury, and the resultant CSF leak. Second, the surgeon should have used an operating microscope. Third, the operation should have been monitored with somatosensory evoked potentials (SEP), motor evoked potentials (MEP), and EMG (electromyography). Fourth, preoperatively the patient should have received a 1-gram dose of Solumedrol for cord "protection". Fifth, applying Gelfoam as part of the CSF leak repair is contraindicated (e.g. due to swelling in confined spaces- see insert). Sixth, if the patient had not stopped Excedrin prior to the surgery, the surgery should have been delayed to avoid the increased perioperative risk of bleeding/hematoma. PMID:24843811

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

    ERIC Educational Resources Information Center

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

    2008-01-01

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

  7. A Patient with Splenic Marginal Zone Lymphoma Presenting with Spastic Paraplegia as the Initial Symptom

    PubMed Central

    Wada, Yuko; Nishimura, Yo; Hashimoto, Kimio

    2011-01-01

    In this report, we describe the case of a patient with splenic marginal zone lymphoma (SMZL) who presented with spastic paraplegia as the initial symptom. A 42-year-old male developed progressive spastic paraplegia over 4 months. His neurologic examination revealed paraplegia with pyramidal syndrome, hypoesthesia below the T1 level, and anal hypotonia. Magnetic resonance imaging (MRI) of the spinal cord revealed an extensive high-intensity signal in T2-weighted sequences and swelling involving the thoracic region and conus medullaris. A laboratory test revealed presence of the serum M component. Abdominal computed tomography images showed moderate splenomegaly. Abnormal lymphocytes of B-cell lineage markers (CD19+, CD20+, and CD25+; surface immunoglobulin κ expression; IgD+ and IgM+) were found in the peripheral blood, cerebrospinal fluid, bone marrow and spleen. Splenectomy confirmed the SMZL diagnosis. After the completion of chemotherapy, the patient was in complete remission, and spinal MRI findings were normal. Intramedullary spinal cord involvement in SMZL is extremely rare, and, to the best of our knowledge, this is the first case of SMZL with intramedullary spinal cord involvement associated with clinical and radiologic signs without the involvement of cerebral structures. Spastic paraplegia can be the initial presentation of SMZL. PMID:21468362

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

    PubMed

    Ville, I; Ravaud, J F

    1998-04-01

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

  9. 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

  10. A rare hyperextension injury in thoracic spine presenting with delayed paraplegia.

    PubMed

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

    2013-06-01

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

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

    PubMed Central

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

    2009-01-01

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

  12. [Acute paraplegia and intramedullary cavitation in a patient with pulmonary tuberculosis].

    PubMed

    Schapira, M; Presas, J L; Speiser, E; Klimovsky, S; Barro, A; Nogués, M

    1992-01-01

    This 42-year-old male patient voluntarily discontinued treatment for lung TBC and twenty days later developed acute paraplegia. Magnetic resonance imaging (MRI) demonstrated a large intramedullary cavity extending from T2 to the conus medullaris. Having resumed anti-TBC treatment, the patient progressed favourably, despite any change in cavity size. Tuberculous meningitis may be complicated by the appearance of intramedullary cavities by two distinct mechanisms: 1) adhesive arachnoiditis at the skull base with obstruction of Luschka and Magendie foramina, followed by hydrocephalus and hydromyelia; and 2) spinal cord arachnoiditis with the development of arachnoidal and intramedullary cysts. In either case, symptoms are of late presentation. To the best of our knowledge, this is the first report in the literature of lung tuberculosis associated with syringomyelia but without basal arachnoiditis. Acute clinical presentation with paraplegia is exceptional. PMID:1340906

  13. 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

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

    PubMed

    Sayasathid, Jarun; Somboonna, Naraporn; Numchaisiri, Chun

    2006-12-01

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

  15. Paraplegia due to intervertebral disc lesions: a review of 57 operated cases.

    PubMed

    Ravichandran, G; Frankel, H L

    1981-01-01

    In a review of 57 cases of paraplegia due to surgically confirmed disc protrusion (representing 0.9 per cent of all admissions to the National Spinal Injuries Centre), seven were in the cervical, 31 in the dorsal and 19 in the lumbar regions. Patients with dorsal disc protrusions treated by laminectomy had the worst neurological outcome. A recent decline in the incidence of neurological dysfunction following disc excision is noted and its probable causes discussed. PMID:7254892

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

    PubMed

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

    2014-11-01

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

  17. Medical-surgical treatment of progressive tuberculous (Pott's) paraplegia in Gabon.

    PubMed

    Loembe, P M

    1995-10-01

    The present study deals with the results of the medical-surgical treatment of 22 patients with Pott's tetraplegia or paraplegia. Seventeen had progressive tetraplegia-paraplegia which failed to respond solely to medical treatment. On admission, four patients exhibited an acute onset tetraplegia-paraplegia, and one had a 'spinal tumour syndrome'. In addition to antituberculous therapy, seven patients had anterior spinal surgery, consisting of four corporectomies, two anterior debridments and grafting, and one debridment alone. Moreover, one patient had a posterior interbody fusion, four had laminotomies, and 10 had laminectomies. The causes of the spinal cord or cauda equina compression, as was determined at operation, were extradural abscess in eight patients, bony compressions in 11, arachnoiditis in two, and posterior neural arch tuberculosis in one patient. Neurological recovery began between 10 and 21 days postoperatively. The mean length of follow-up was 42.36 months (range 8-144 months). Fourteen patients were found to be functionally and neurologically normal at follow-up examinations (63%). Eighty-two percent recovered sufficiently to walk unaided. Two patients were left paralysed and unable to walk. Two patients were able to get about on crutches. The onset of objective improvement soon after surgical decompression suggests a causal effect. It was concluded that early neural decompression and spinal stabilisation provided the maximum potential for neurological recovery. PMID:8848312

  18. Acute-onset nontraumatic paraplegia in childhood: fibrocartilaginous embolism or acute myelitis?

    PubMed

    Davis, G A; Klug, G L

    2000-09-01

    Fibrocartilaginous embolus causing acute spinal cord infarction is a rare cause of acute-onset paraplegia or quadriplegia. Few cases of survivors have been reported in the neurosurgical literature, with most reports involving postmortem or biopsy findings. There is little information on MRI findings in such patients. We present the youngest patient ever reported, and discuss the important differences between fibrocartilaginous embolus and acute myelitis of childhood. A 6-year-old girl with a history of back pain presented with sudden-onset nontraumatic paraplegia, with a clinical anterior spinal artery syndrome. Initial MRI scan revealed intervertebral disc disease at L1-2 and an incidental thoracic syrinx, but no cause for her acute-onset paraplegia was identified. Cerebrospinal fluid and other investigations were all negative. Sequential MRI scans revealed development of spinal cord expansion from T10 to the conus medullaris, with increased cord signal in the anterior aspect of the spinal cord. The intervertebral disc disease was unchanged. The imaging and clinical findings were caused by fibrocartilaginous embolus, which meant there was no need for spinal cord biopsy. The report describes the clinical and imaging criteria for diagnosis of fibrocartilaginous embolus, highlighting the case for avoiding an unnecessary biopsy. The clinical pattern in the paediatric group is discussed, with features differentiating it from acute myelitis of childhood. PMID:11048627

  19. Influence of neurological level of injury in bones, muscles, and fat in paraplegia.

    PubMed

    Dionyssiotis, Yannis; Lyritis, George P; Papaioannou, Nikolaos; Papagelopoulos, Panagiotis; Thomaides, Thomas

    2009-01-01

    To investigate the influence of the neurological level of injury in bone mineral content (BMC) and mechanical properties, lean mass (LM), and fat mass (FM) among paraplegics with a similar duration of paralysis (DOP), we separated 30 paraplegics into group A (15 men, high-level paraplegia) and group B (15 men, low-level paraplegia) and compared them with group C (33 men, nondisabled). In all subjects, we measured stress-strain index (SSI) at 14% (SSI(2)) and 38% (SSI(3)) of the tibia length and the difference between them using peripheral quantitative computed tomography (XCT 3000 [Stratec Medizintechnik, Pforzheim, Germany]) and lower-limb BMC, LM, and FM (g) using whole-body dual-energy X-ray absorptiometry (Norland XR-36 [Norland Medical Systems, Inc; Fort Atkinson, Wisconsin]). Bone strength parameters, BMC, and LM were statistically decreased, but we found no difference in paraplegic FM compared with group C. We found a correlation between the DOP and the difference between SSI 3 and SSI 2 in group B (r = 0.53, p = 0.03 and r = 0.5, p = 0.04, respectively). We correlated DOP with FM in group A's lower limbs (r = 0.5, p = 0.05). Because of the nonsignificant DOP, the groups with paraplegia act differently in tibia mechanical properties and lower-limb body composition. PMID:20157860

  20. 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

  1. Anterior spinal artery syndrome: reversible paraplegia after minimally invasive spine surgery.

    PubMed

    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

  2. Paraplegia caused by giant intradural herniation of a lumbar disk after combined spinal-epidural anesthesia in total hip arthroplasty.

    PubMed

    Sawai, Toshiyuki; Nakahira, Junko; Minami, Toshiaki

    2016-08-01

    Total paraplegia after epidural or spinal anesthesia is extremely rare. We herein report a case of total paraplegia caused by a giant intradural herniation of a lumbar disk at the L3-L4 level after total hip arthroplasty for coxarthrosis. The patient had no preoperative neurologic abnormalities. Intraoperative anesthetic management involved combined spinal-epidural anesthesia at the L3-L4 level with continuous intravenous propofol administration. Postoperatively, the patient complained of numbness and total paraplegia of the lower extremities. Magnetic resonance imaging showed a giant herniation of a lumbar disk compressing the spinal cord at the L3-L4 level. The intradural herniation was surgically treated, and the patient's symptoms completely resolved. PMID:27290969

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2013-01-01

    Objective To test a strategy for minimizing ischemic spinal cord injury (SCI) following extensive thoracoabdominal aneurysm (TAAA) repair, we occluded a small number of segmental arteries (SAs) endovascularly one week before simulated aneurysm repair in an experimental model. Methods 30 juvenile Yorkshire pigs (25.2±1.7kg) were randomized into three groups. All SAs—intercostal and lumbar—were sacrificed by a combination of surgical ligation of the lumbar SAs and occlusion of intercostal SAs with thoracic endovascular stent grafting (TEVAR). 7–10 days before this simulated TAAA replacement, SAs in the lower thoracic/upper lumbar region were occluded using embolization coils: 1.5±0.5 SAs in Group 1 (T13/L1), and 4.5±0.5 in Group 2 (T11-L3). No SAs were coiled in the controls. Hind limb function was evaluated blindly from daily videotapes using a modified Tarlov score: 0=paraplegia; 9=full recovery. After sacrifice, each segment of spinal cord was graded histologically using the 9-point Kleinman score: 0=normal, 8=complete necrosis. Results Hind limb function remained normal after coil embolization. After simulated TAAA repair, paraplegia occurred in 6/10 control pigs, but only 2/10 pigs in Group 1: no pigs in Group 2 had SCI. Tarlov scores were significantly better in Group 2 (Control vs 1 p=0.06; Control vs 2 p= 0.0002; 1 vs 2 p=0.05). A dramatic reduction in histologic damage—most prominently in the coiled region—was seen when SAs were embolized before simulated TAAA repair. Conclusions Endovascular coiling of 2–4 SAs prevents paraplegia in an experimental model of extensive hybrid TAAA repair, and helps protect the spinal cord from ischemic histopathological injury. A clinical trial in a selected patient population at high risk for postoperative SCI may be appropriate. PMID:24220154

  5. [Incomplete paraplegia after delayed diagnostics of motor function deficits. Severe malpractice?].

    PubMed

    Regauer, M; Neu, J

    2013-03-01

    A 72-year-old female patient was transferred to a rehabilitation centre after surgical stabilization of a subtrochanteric femoral fracture. However, adequate mobilization was not possible there and 5 days after transfer deficits in the motor function of both lower extremities were documented for the first time and an initial paraplegia was diagnosed the following day by a neurologist. Magnetic resonance imaging (MRI) revealed the suspicion of an unstable fracture of the seventh thoracic vertebral body 8 days after the initial symptoms, which was confirmed by computed tomography after another 3 days. Surgical decompression and stabilization were performed at a department for neurosurgery 4 days later but incomplete paraplegia persisted permanently. The patient complained about insufficient diagnostic measures at the rehabilitation centre. The expert opinion concluded that it would have been mandatory to investigate the matter of the newly occurring neurological symptoms immediately but this had only been performed after undue delay, which had to be interpreted as a case of medical malpractice. The expert pointed out that it was not possible to provide clear evidence that emergent diagnosis and surgery would have enabled a significantly better outcome.The arbitration board ascertained a lack of examination and argued that prompt and adequate diagnostic measures would have revealed the relevant pathological finding and thus surgery would have been performed immediately. According to the reversal of evidence in favor of the patient it could be assumed that no permanent neurological damage existed when the first neurological symptoms occurred and that emergent surgery at least had the potential to prevent permanent paraplegia. This opinion of the arbitration board is supported by numerous references in the literature. PMID:23478903

  6. A psychological study of spinal cord injured patients involved in the Madras Paraplegia Project.

    PubMed

    Somasundaram, O; Balakrishnan, S; Ravindran, O S; Shanmugasundaram, T K

    1992-11-01

    The psychological features of spinal cord injured (SCI) patients involved in the Madras Paraplegia Project are described. Three hundred and twenty-eight patients were studied. Based on personality tests, 11% were extroverts, 14% were introverts and 76% were neither extroverts nor introverts. Twenty-four percent of the subjects were neurotic, 11% had a depressive illness, and 26% had pathological anxiety. The study has highlighted the psychological status of SCI patients, and the usefulness of a psychiatric team in the multidisciplinary care of such patients. This is probably the first large psychological study of SCI patients from a developing country. PMID:1484733

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

    PubMed

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

    2014-07-01

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

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

    PubMed

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

    2000-08-01

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

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

    PubMed Central

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

    2015-01-01

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

  10. [Molecular genetics study of hereditary spastic paraplegia accompanied by distal amyotrophy-an update].

    PubMed

    Wang, Zhen-zhen; Cen, Zhi-dong; Luo, Wei

    2013-08-01

    Hereditary spastic paraplegia(HSP or SPG) is a clinically and genetically heterogeneous group of neurodegenerative diseases characterized by progressive spasticity, weakness of lower limbs, and pathologically by retrograde axonal degeneration of corticospinal tracts and posterior spinal tracts. Presence of additional features allows differentiation between simple and complex forms of the disease. Genetically, 16 loci for HSP accompanied by distal amyotrophy have been mapped, for which 13 genes have been identified. With the identification of causative genes, the molecular mechanism of this disease is gradually elucidated. PMID:23926010

  11. Subarachnoid Fluid Lactate and Paraplegia after Descending Aorta Aneurysmectomy: Two Compared Case Reports

    PubMed Central

    Malossini, Silvia Eleonora; Pellegrino, Francesco; Cancellieri, Franco

    2013-01-01

    We report a comparison of two cases regarding subjects who underwent thoracoabdominal aorta aneurysmectomy. During the procedure we monitored cerebrospinal fluid lactate concentration. One patient experienced postoperative paraplegia and his cerebrospinal fluid lactate concentration was much higher than that in the other case, whose postoperative outcome was uneventful. Consequently we consider that monitoring the lactate concentration in cerebrospinal fluid during thoracic aorta surgical procedures may be a helpful tool to predict the ischemic spine-cord injury allowing for trying to recover it precociously. PMID:24198975

  12. 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

  13. 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

  14. Effect of increased load on scapular kinematics during manual wheelchair propulsion in individuals with paraplegia and tetraplegia.

    PubMed

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

    2012-04-01

    Repetitive loading of the upper extremity musculature during activities like wheelchair propulsion can lead to fatigue of surrounding musculature causing irregular segment kinematics. The goal of this study was to determine the effect of increase in load on the kinematics of the scapula in users with paraplegia and tetraplegia. Data were collected on 18 participants (11 with paraplegia and 7 with tetraplegia) using an electromagnetic motion tracking system (100Hz) and force sensing pushrim (200Hz). The participants propelled under no load and loaded conditions at their customary propulsion velocity. On average a 60N increase in force was elicited with the experimental protocol. Users with tetraplegia showed significant increases (p<.05) in the rate of change of scapular angles in the upward/downward rotation and the retraction/protraction direction under the loaded conditions, whereas users with paraplegia only showed difference in the retraction/protraction rotation direction. Overall both user populations moved towards position of increased downward rotation, anterior tilt and protraction with increase in load hence increasing the risk of impingement. This experiment adds depth to our understanding of dynamic scapular kinematics during wheelchair propulsion under different loading conditions and differences in scapular control between users with paraplegia and tetraplegia. PMID:21782267

  15. 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…

  16. Acute painful paraplegia in a 49-year-old man with allergic asthma.

    PubMed

    Sorino, Claudio; Agati, Sergio; Milani, Giuseppe; Maspero, Annarosa

    2014-01-01

    We present a case of a 49-year-old man, with a 10-year history of bronchial asthma and nasal polyposis, who developed acutely painful paraplegia and paresthesias. Laboratory data showed elevated blood creatine kinase levels and myoglobinuria, which were diagnostic for rhabdomyolysis but only partially explained the neurological deficit. Electrophysiological studies revealed a sensorimotor neuropathy of multiple mononeuritis type. The patient also had leucocytosis with marked eosinophilia and antineutrophil cytoplasmic autoantibodies. Bronchial biopsies showed inflammatory infiltrates with a prevalence of eosinophils. All these findings led us to diagnose eosinophilic granulomatosis with polyangiitis, a systemic vasculitis with almost constant respiratory tract involvement and good response to corticosteroid treatment. This can also affect other organs including the nervous system, while muscular involvement is unusual. Some diseases deserve attention in differential diagnosis. Histology can support the diagnosis which remains essentially clinical. Steroid sparing agents/immunosuppressants are suggested for extensive disease. PMID:24980994

  17. Delayed paraplegia following infrarenal abdominal aortic endograft placement: case report and literature review.

    PubMed

    Fortes, Daniel L; Atkins, B Zane; Chiou, Andy C

    2004-03-01

    The treatment of abdominal aortic aneurysms (AAAs) has changed over the past 12 years, with increased numbers of endovascular procedures being performed. Early morbidity is decreased following endovascular abdominal aortic aneurysm repair (EVAR) compared with open repair, and long-term studies of EVAR have focused on freedom from death, rupture, and conversion to open repair. Other less commonly encountered complications of EVAR are rarely reported. For instance, spinal cord ischemia (SCI) is a devastating complication infrequently seen after open AAA repair. This report discusses a case of delayed paraplegia after EVAR and reviews the pertinent literature. The incidence of SCI after EVAR is similar to open repair, but the mechanisms may be different. Atheroembolization and occlusion of pelvic inflow appear to be the predominant etiologies for SCI after EVAR. Careful consideration of the potential for SCI should be made in elderly patients undergoing EVAR, particularly if difficult arterial anatomy is present. PMID:15248644

  18. 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

  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. 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

  1. 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

  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

  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. 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

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

    PubMed

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

    1991-04-01

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

  6. Novel De Novo Mutations in KIF1A as a Cause of Hereditary Spastic Paraplegia With Progressive Central Nervous System Involvement.

    PubMed

    Hotchkiss, Leslie; Donkervoort, Sandra; Leach, Meganne E; Mohassel, Payam; Bharucha-Goebel, Diana X; Bradley, Nathaniel; Nguyen, David; Hu, Ying; Gurgel-Giannetti, Juliana; Bönnemann, Carsten G

    2016-08-01

    Hereditary spastic paraplegias are a clinically and genetically heterogeneous group of disorders characterized by lower extremity spasticity and weakness. Recently, the first de novo mutations in KIF1A were identified in patients with an early-onset severe form of complicated hereditary spastic paraplegia. We report two additional patients with novel de novo mutations in KIF1A, hereby expanding the genetic spectrum of KIF1A-related hereditary spastic paraplegia. Both children presented with spastic paraplegia and additional findings of optic nerve atrophy, structural brain abnormalities, peripheral neuropathy, cognitive/language impairment, and never achieved ambulation. In particular, we highlight the progressive nature of cerebellar involvement as captured on sequential magnetic resonance images (MRIs), thus linking the neurodegenerative and spastic paraplegia phenotypes. Exome sequencing in patient 1 and patient 2 identified novel heterozygous missense mutations in KIF1A at c.902G>A (p.R307Q) and c.595G>A (p.G199 R), respectively. Therefore, our report contributes to expanding the genotypic and phenotypic spectrum of hereditary spastic paraplegia caused by mutations in KIF1A. PMID:27034427

  7. 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

  8. Enhancing Stance Phase Propulsion during Level Walking by Combining FES with a Powered Exoskeleton for Persons with Paraplegia*

    PubMed Central

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

    2013-01-01

    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 hamstrings activated by 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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2004-09-01

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

  11. Electrophysiological characterisation of motor and sensory tracts in patients with hereditary spastic paraplegia (HSP)

    PubMed Central

    2013-01-01

    Background Hereditary spastic paraplegias (HSPs) are characterised by lower limb spasticity due to degeneration of the corticospinal tract. We set out for an electrophysiological characterisation of motor and sensory tracts in patients with HSP. Methods We clinically and electrophysiologically examined a cohort of 128 patients with genetically confirmed or clinically probable HSP. Motor evoked potentials (MEPs) to arms and legs, somato-sensory evoked potentials of median and tibial nerves, and nerve conduction studies of tibial, ulnar, sural, and radial nerves were assessed. Results Whereas all patients showed clinical signs of spastic paraparesis, MEPs were normal in 27% of patients and revealed a broad spectrum with axonal or demyelinating features in the others. This heterogeneity can at least in part be explained by different underlying genotypes, hinting for distinct pathomechanisms in HSP subtypes. In the largest subgroup, SPG4, an axonal type of damage was evident. Comprehensive electrophysiological testing disclosed a more widespread affection of long fibre tracts involving peripheral nerves and the sensory system in 40%, respectively. Electrophysiological abnormalities correlated with the severity of clinical symptoms. Conclusions Whereas HSP is primarily considered as an upper motoneuron disorder, our data suggest a more widespread affection of motor and sensory tracts in the central and peripheral nervous system as a common finding in HSP. The distribution patterns of electrophysiological abnormalities were associated with distinct HSP genotypes and could reflect different underlying pathomechanisms. Electrophysiological measures are independent of symptomatic treatment and may therefore serve as a reliable biomarker in upcoming HSP trials. PMID:24107482

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

    PubMed

    Kannan, Karthik Kailash; Sundarapandian, Rajkumar Jayachandran; Surulivel, Vignesh Jayabalan

    2015-03-01

    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

  13. [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

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

    PubMed

    Gagliano, R G; Costanzi, J J

    1976-04-01

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

  15. Analysis of CYP7B1 in non-consanguineous cases of hereditary spastic paraplegia.

    PubMed

    Schüle, Rebecca; Brandt, Elisabeth; Karle, Kathrin N; Tsaousidou, Maria; Klebe, Stephan; Klimpe, Sven; Auer-Grumbach, Michaela; Crosby, Andrew H; Hübner, Christian A; Schöls, Ludger; Deufel, Thomas; Beetz, Christian

    2009-04-01

    Hereditary spastic paraplegia (HSP) is a neurodegenerative condition defined clinically by lower limb spasticity and weakness. Homozygous mutations in CYP7B1 have been identified in several consanguineous families that represented HSP type 5 (SPG5), one of the many genetic forms of the disease. We used direct sequencing and multiplex ligation-dependent probe amplification to screen for CYP7B1 alterations in apparently sporadic HSP patients (n = 12) as well as index patients from non-consanguineous families with recessive (n = 8) and dominant (n = 8) transmission of HSP. One sporadic patient showing HSP as well as optic atrophy carried a homozygous nonsense mutation. Compound heterozygosity was observed in a recessive family with a clinically pure phenotype. A heterozygous missense change segregated in a small dominant family. We also found a significant association of a known coding polymorphism with cerebellar signs complicating a primary HSP phenotype. Our findings suggest CYP7B1 alterations to represent a rather frequent cause of HSP that should be considered in patients with various clinical presentations. PMID:18855023

  16. Optimal control of FES-assisted standing up in paraplegia using genetic algorithms.

    PubMed

    Davoodi, R; Andrews, B J

    1999-11-01

    A practical system for Functional Electrical Stimulation (FES) assisted standing up in paraplegia should involve only a minimum of manual set up and tuning. An improved tuning method, using a genetic algorithm (GA) is proposed and demonstrated using computer simulation. Specifically, the GA adjusts the parameters of fuzzy logic (FL) and gain-scheduling proportional integral derivative (GS-PID) controllers that electrically stimulate the hip and knee musculature during the sit-stand maneuver. These new GA designed controllers were found to be effective in coordinating volitional and FES control according to formulated criteria. The latter was based on the deviations from a desired trajectory of the knee and hip joints and the magnitude of the voluntary upper body forces. The magnitude of the average arm forces were slightly higher when compared with the open-loop maximal stimulation of the hip and knee musculature; however, the terminal knee velocities were significantly reduced to less than 10 degrees /s. For practical implementation, the number of trials required to optimize the FL and GS-PID controllers can be reduced by a proposed pre-training procedure using a computer model scaled to the individual. The GA designed controllers remain near optimal provided the model-subject mismatch is small. PMID:10699563

  17. Mutations in BICD2 Cause Dominant Congenital Spinal Muscular Atrophy and Hereditary Spastic Paraplegia

    PubMed Central

    Oates, Emily C.; Rossor, Alexander M.; Hafezparast, Majid; Gonzalez, Michael; Speziani, Fiorella; MacArthur, Daniel G.; Lek, Monkol; Cottenie, Ellen; Scoto, Mariacristina; Foley, A. Reghan; Hurles, Matthew; Houlden, Henry; Greensmith, Linda; Auer-Grumbach, Michaela; Pieber, Thomas R.; Strom, Tim M.; Schule, Rebecca; Herrmann, David N.; Sowden, Janet E.; Acsadi, Gyula; Menezes, Manoj P.; Clarke, Nigel F.; Züchner, Stephan; Muntoni, Francesco; North, Kathryn N.; Reilly, Mary M.

    2013-01-01

    Dominant congenital spinal muscular atrophy (DCSMA) is a disorder of developing anterior horn cells and shows lower-limb predominance and clinical overlap with hereditary spastic paraplegia (HSP), a lower-limb-predominant disorder of corticospinal motor neurons. We have identified four mutations in bicaudal D homolog 2 (Drosophila) (BICD2) in six kindreds affected by DCSMA, DCSMA with upper motor neuron features, or HSP. BICD2 encodes BICD2, a key adaptor protein that interacts with the dynein-dynactin motor complex, which facilitates trafficking of cellular cargos that are critical to motor neuron development and maintenance. We demonstrate that mutations resulting in amino acid substitutions in two binding regions of BICD2 increase its binding affinity for the cytoplasmic dynein-dynactin complex, which might result in the perturbation of BICD2-dynein-dynactin-mediated trafficking, and impair neurite outgrowth. These findings provide insight into the mechanism underlying both the static and the slowly progressive clinical features and the motor neuron pathology that characterize BICD2-associated diseases, and underscore the importance of the dynein-dynactin transport pathway in the development and survival of both lower and upper motor neurons. PMID:23664120

  18. 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

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

    PubMed

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

    2014-10-14

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

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

    PubMed Central

    Al, Behçet; 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. Severe adhesive arachnoiditis resulting in progressive paraplegia following obstetric spinal anaesthesia: a case report and review.

    PubMed

    Killeen, T; Kamat, A; Walsh, D; Parker, A; Aliashkevich, A

    2012-12-01

    A 27-year-old woman developed severe adhesive arachnoiditis after an obstetric spinal anaesthetic with bupivacaine and fentanyl, complicated by back pain and headache. No other precipitating cause could be identified. She presented one week postpartum with communicating hydrocephalus and syringomyelia and underwent ventriculoperitoneal shunting and foramen magnum decompression. Two months later, she developed rapid, progressive paraplegia and sphincter dysfunction. Attempted treatments included exploratory laminectomy, external drainage of the syrinx and intravenous steroids, but these were unsuccessful and the patient remains significantly disabled 21 months later. We discuss the pathophysiology of adhesive arachnoiditis following central neuraxial anaesthesia and possible causative factors, including contamination of the injectate, intrathecal blood and local anaesthetic neurotoxicity, with reference to other published cases. In the absence of more conclusive data, practitioners of central neuraxial anaesthesia can only continue to ensure meticulous, aseptic, atraumatic technique and avoid all potential sources of contamination. It seems appropriate to discuss with patients the possibility of delayed, permanent neurological deficit while taking informed consent. PMID:23061983

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

    PubMed

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

    1986-07-01

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

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

    PubMed Central

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

    1986-01-01

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

  10. 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

  11. Pharmacologic rescue of axon growth defects in a human iPSC model of hereditary spastic paraplegia SPG3A.

    PubMed

    Zhu, Peng-Peng; Denton, Kyle R; Pierson, Tyler Mark; Li, Xue-Jun; Blackstone, Craig

    2014-11-01

    Hereditary spastic paraplegias are a large, diverse group of neurological disorders (SPG1-71) with the unifying feature of prominent lower extremity spasticity, owing to a length-dependent axonopathy of corticospinal motor neurons. The most common early-onset form of pure, autosomal dominant hereditary spastic paraplegia is caused by mutation in the ATL1 gene encoding the atlastin-1 GTPase, which mediates homotypic fusion of ER tubules to form the polygonal ER network. We have identified a p.Pro342Ser mutation in a young girl with pure SPG3A. This residue is in a critical hinge region of atlastin-1 between its GTPase and assembly domains, and it is conserved in all known eukaryotic atlastin orthologs. We produced induced pluripotent stem cells from skin fibroblasts and differentiated these into forebrain neurons to generate a human neuronal model for SPG3A. Axons of these SPG3A neurons showed impaired growth, recapitulating axonal defects in atlastin-1-depleted rat cortical neurons and impaired root hair growth in loss-of-function mutants of the ATL1 ortholog rhd3 in the plant Arabidopsis. Both the microtubule cytoskeleton and tubular ER are important for mitochondrial distribution and function within cells, and SPG3A neurons showed alterations in mitochondrial motility. Even so, it is not clear whether this change is involved in disease pathogenesis. The SPG3A axon growth defects could be rescued with microtubule-binding agents, emphasizing the importance of tubular ER interactions with the microtubule cytoskeleton in hereditary spastic paraplegia pathogenesis. The prominent alterations in axon growth in SPG3A neurons may represent a particularly attractive target for suppression in screens for novel pharmacologic agents. PMID:24908668

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

    PubMed

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

    2016-04-01

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

  13. 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

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

    PubMed Central

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

    2015-01-01

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

  15. A series of Greek children with pure hereditary spastic paraplegia: clinical features and genetic findings.

    PubMed

    Polymeris, Alexandros A; Tessa, Alessandra; Anagnostopoulou, Katherine; Rubegni, Anna; Galatolo, Daniele; Dinopoulos, Argirios; Gika, Artemis D; Youroukos, Sotiris; Skouteli, Eleni; Santorelli, Filippo M; Pons, Roser

    2016-08-01

    Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous group of neurodegenerative disorders mainly characterized by progressive spasticity of the lower limbs. Adult case series dominate the literature, and there have been only a few studies in children. The purpose of this study is to describe our experience with pediatric HSP in Greece. We report the clinical and genetic findings in our patients and aim to offer insights into the diagnostic difficulties of childhood-onset disease. A series of 15 Greek children affected by pure HSP underwent extensive diagnostic investigations. Molecular analysis included whole exome sequencing (WES) or consecutive screening of candidate genes ATL1, SPAST, REEP1, and CYP7B1. WES performed in three cases yielded previously reported mutations in ATL1 and CYP7B1, and a variant c.397C>T of unknown significance in SPG7. Candidate gene screening performed in the remaining patients identified previously reported mutations in ATL1 (2), SPAST (2), and REEP1 (1), and two novel mutations, c.1636G>A and c.1413+3_6delAAGT, in SPAST. In six cases, the mutations were inherited from their parents, while in three cases, the mutations were apparently de novo. Our data confirm the genetic heterogeneity of childhood-onset pure HSP, with SPG4/SPAST and SPG3A/ATL1 being the most frequent forms. De novo occurrence of HSP does not seem to be uncommon. Candidate gene studies guided by diagnostic algorithms and WES seem both to be reasonable genetic testing strategies. PMID:27260292

  16. 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.

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

    PubMed Central

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

    2009-01-01

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

  18. 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

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

    PubMed

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

    1989-06-01

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

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

    PubMed

    Zietek, P; Dobiecki, K

    2015-01-01

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

  1. Burn from car seat heater in a man with paraplegia: case report

    PubMed Central

    Benjamin, Cheryl; Gittler, Michelle; Lee, Ray

    2011-01-01

    Objective/background Heated car seats are a common feature in newer automobiles. They are increasingly being recognized as potential hazards as there have been multiple reports of significant burns to its users. The potential for harm is considerably increased in those with impaired sensation with the possibility of a devastating injury. Methods Case report and literature review. Results A 26-year-old male with a T8 ASIA A paraplegia presented to the outpatient clinic for management of a hip burn. Two weeks prior to his visit he was driving a 2004 Jeep Cherokee for approximately 30 minutes. He was unaware that the driver's side seat warmer was set on high. He denied that his seat belt was in direct contact with the skin of his right hip. He presented to an acute care hospital that evening with a hip burn where he was prescribed silver sulfadiazine cream and instructed to apply it until his scheduled follow-up clinic visit. In clinic, the hip wound was unstageable with approximately 95% eschar. A dressing of bismuth tribromophenate in petrolatum was applied to the wound and he was instructed to change the dressing daily. This was later changed to an antimicrobial alginate dressing. The ulcer eventually healed. Conclusions This case illustrates the significant risk of car seat heaters in individuals with spinal cord injuries or neurological impairment who have decreased sensation. Additionally, it highlights an atypical area of potential for burn. Furthermore, it emphasizes the need for a heightened awareness for this unique and dangerous situation. PMID:21756574

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

    PubMed Central

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

    2013-01-01

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

  3. 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

  4. 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

  5. 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

  6. Non-traumatic acute paraplegia associated with a CT-guided needle biopsy in a silicotic nodule: A case report

    PubMed Central

    XU, LIYING; DING, XUN; LIAO, MEIYAN

    2016-01-01

    The present study reports the case of an adult patient with non-traumatic acute paraplegia following a computed tomography (CT)-guided automated cutting needle biopsy (ACNB). Multiple nodules and masses were revealed on performing chest radiography and CT on a 45-year-old man. In order to make a pathological diagnosis, a CT-guided biopsy using an automatic cutting needle was performed. However, 10 min after the biopsy, a weakness of the lower extremities occurred, and the patient collapsed to the ground, albeit with clear consciousness. Spinal magnetic resonance imaging (MRI) performed subsequently revealed no abnormal findings in the spinal cord. An MRI performed 24 h later, however, revealed swelling of the thoracic spinal cord and a high-signal-intensity lesion in T2-weighted images at the level of T7, T8 and T9. The patient subsequently received hyperbaric oxygen therapy for a few days, and rehabilitative treatment over the course of a few weeks. At 6 months following the biopsy, the patient was unable to walk, although the patient could stand for 10 min and defecate independently. Currently, the patient remains active in daily life, in spite of confinement to a wheelchair. The present case study was reported to raise the awareness of the possibility of spinal cord ischemia and acute paraplegia following a CT-guided ACNB of the lungs. The mechanism underlying spinal cord ischemia remains to be fully elucidated, although is thought to be multifactorial, involving air embolism. PMID:26998303

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

    PubMed

    Klebe, S; Stevanin, G; Depienne, C

    2015-01-01

    Hereditary spastic paraplegias (HSPs) are genetically determined neurodegenerative disorders characterized by progressive weakness and spasticity of lower limbs, and are among the most clinically and genetically heterogeneous human diseases. All modes of inheritance have been described, and the recent technological revolution in molecular genetics has led to the identification of 76 different spastic gait disease-loci with 59 corresponding spastic paraplegia genes. Autosomal recessive HSP are usually associated with diverse additional features (referred to as complicated forms), contrary to autosomal dominant HSP, which are mostly pure. However, the identification of additional mutations and families has considerably enlarged the clinical spectra, and has revealed a huge clinical variability for almost all HSP; complicated forms have also been described for primary pure HSP subtypes, adding further complexity to the genotype-phenotype correlations. In addition, the introduction of next generation sequencing in clinical practice has revealed a genetic and phenotypic overlap with other neurodegenerative disorders (amyotrophic lateral sclerosis, neuropathies, cerebellar ataxias, etc.) and neurodevelopmental disorders, including intellectual disability. This review aims to describe the most recent advances in the field and to provide genotype-phenotype correlations that could help clinical diagnoses of this heterogeneous group of disorders. PMID:26008818

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

    PubMed

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

    2015-12-15

    We identified a novel homozygous mutation in the splice site donor (SSD) of intron 30 (c.5866+1G>A) in consanguineous Japanese SPG11 siblings showing late-onset spastic paraplegia using the whole-exome sequencing. Phenotypic variability was observed, including age-at-onset, dysarthria and pes cavus. Coding DNA sequencing revealed that the mutation affected the recognition of the constitutive SSD of intron 30, splicing upstream onto a nearby cryptic SSD in exon 30. The use of constitutive splice sites of intron 29 was confirmed by sequencing. The mutant transcripts are mostly subject to degradation by the nonsense-mediated mRNA decay system. SPG11 transcripts, escaping from the nonsense-mediated mRNA decay pathway, would generate a truncated protein (p.Tyr1900Phefs5X) containing the first 1899 amino acids and followed by 4 aberrant amino acids. This study showed a successful clinical application of whole-exome sequencing in spastic paraplegia and demonstrated a further evidence of allelic heterogeneity in SPG11. The confirmation of aberrant transcript by splice site mutation is a prerequisite for a more precise molecular diagnosis. PMID:26671123

  9. Role of kinesin-1 in the pathogenesis of SPG10, a rare form of hereditary spastic paraplegia.

    PubMed

    Kawaguchi, Kenji

    2013-08-01

    Molecular protein motors play key roles in processes such as intracellular cargo transport and brain wiring, and failure of function can give rise to serious diseases. Kinesin-1, a member of the kinesin superfamily (also known as KIFs) is a two-headed motor protein that uses energy derived from ATP hydrolysis to transport diverse types of intracellular cargo toward the plus-ends of microtubules within axons. Recent studies at the level of a single molecule have provided extensive knowledge on how kinesin-1 moves along microtubules. Further elucidation of kinesin-1 movement may shed light on its influence on axon generation, thereby leading to therapies for diseases such as spastic paraplegia type 10 (SPG10), the subject of this review. SPG10 is an autosomal dominant form of hereditary spastic paraplegia caused by mutations in KIF5A, which encodes one of the isoforms of kinesin-1 (KIF5A, KIF5B, and KIF5C). Although little is known about the cargo of KIF5A, a recent study revealed an axonal transport defect of mitochondria in a KIF5A (-/-) mouse model. This review discusses the consensus moving model of kinesin-1 and the pathogenicity of SPG10 caused by defective KIF5A function. PMID:22785106

  10. 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

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

    PubMed Central

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

    2015-01-01

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

  12. 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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    1976-03-01

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

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

    PubMed

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

    1995-05-01

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

  16. 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.

  17. Delving into the complexity of hereditary spastic paraplegias: how unexpected phenotypes and inheritance modes are revolutionizing their nosology.

    PubMed

    Tesson, Christelle; Koht, Jeanette; Stevanin, Giovanni

    2015-06-01

    Hereditary spastic paraplegias (HSP) are rare neurodegenerative diseases sharing the degeneration of the corticospinal tracts as the main pathological characteristic. They are considered one of the most heterogeneous neurological disorders. All modes of inheritance have been described for the 84 different loci and 67 known causative genes implicated up to now. Recent advances in molecular genetics have revealed clinico-genetic heterogeneity of these disorders including their clinical and genetic overlap with other diseases of the nervous system. The systematic analysis of a large set of genes, including exome sequencing, is unmasking unusual phenotypes or inheritance modes associated with mutations in HSP genes and related genes involved in various neurological diseases. A new nosology may emerge after integration and understanding of these new data to replace the current classification. Collectively, functions of the known genes implicate the disturbance of intracellular membrane dynamics and trafficking as the consequence of alterations of cytoskeletal dynamics, lipid metabolism and organelle structures, which represent in fact a relatively small number of cellular processes that could help to find common curative approaches, which are still lacking. PMID:25758904

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2016-09-01

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

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

    PubMed

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

    2014-03-01

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

  1. 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

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

    PubMed Central

    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.

    2012-01-01

    In this study we assess exome sequencing (ES) as a diagnostic alternative for genetically heterogeneous disorders. Since 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

  3. 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

  4. 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

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

    PubMed

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

    2013-06-01

    In 1983, Fitzsimmons et al. reported four brothers with an unrecognized disorder characterized by intellectual disability, spastic paraplegia, and palmo-plantar hyperkeratosis (OMIM 309500). In this report, we describe a family in which two males, maternal half-brothers, had learning disabilities. Both patients also showed spasticity in the lower limbs and palmo-plantar hyperkeratosis. The mother of the affected boys had learning difficulties but did not show any dermatological symptoms. This report confirms that the association of features reported by Fitzsimmons et al. is a distinct entity and further suggests an X-linked mode of inheritance. PMID:23613454

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

    PubMed Central

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

    1995-01-01

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

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

    PubMed

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

    2014-01-01

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

  8. 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

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

    PubMed

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

    2011-06-10

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

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

    PubMed Central

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

    2014-01-01

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

  11. 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

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

    PubMed

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

    2015-09-11

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

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

    PubMed

    Bonnefoy-Mazure, A; Turcot, K; Kaelin, A; De Coulon, G; Armand, S

    2013-01-01

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

  14. 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

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

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2008-01-01

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

  17. 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

  18. Energy Cost of Lower Body Dressing, Pop-Over Transfers, and Manual Wheelchair Propulsion in People with Paraplegia Due to Motor-Complete Spinal Cord Injury

    PubMed Central

    McCormick, Zachary; Liem, Brian; Jacobs, Geneva; Hwang, Peter; Hornby, Thomas George; Rydberg, Leslie; Roth, Elliot J.

    2015-01-01

    Background: Energy required for able-bodied individuals to perform common activities is well documented, whereas energy associated with daily activities among people with spinal cord injury (SCI) is less understood. Objective: To determine energy expended during several basic physical tasks specific to individuals with paraplegia due to motor-complete SCI. Methods: Sixteen adults with motor-complete SCI below T2 level and duration of paraplegia greater than 3 months were included. Oxygen consumption (VO2), caloric expenditure, and heart rate were measured at rest and while participants performed lower body dressing (LBD), pop-over transfers (POTs), and manual wheelchair propulsion (MWP) at a self-selected pace. These data were used to calculate energy expenditure in standard metabolic equivalents (METs), as defined by 1 MET = 3.5 mL O2/kg/min, and in SCI METs using the conversion 1 SCI MET = 2.7 mL O2/kg/min. Results: VO2 at rest was 3.0 ± 0.9 mL O2/kg/min, which equated to 0.9 ± 0.3 standard METs and 1.1 ± 0.4 SCI METs in energy expenditure. LBD required 3.2 ± 0.7 METs and 4.1 ± 0.9 SCI METs; POTs required 3.4 ± 1.0 METs and 4.5 ± 1.3 SCI METs; and MWP required 2.4 ± 0.6 METs and 3.1 ± 0.7 SCI METs. Conclusion: Resting VO2 for adults with motor-complete paraplegia is 3.0 mL O2/kg/min, which is lower than standard resting VO2 in able-bodied individuals. Progressively more energy is required to perform MWP, LBD, and POTs, respectively. Use of the standard METs formula may underestimate the level of intensity an individual with SCI uses to perform physical activities. PMID:26364283

  19. 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

  20. Hypokalemic paraplegia in pregnancy.

    PubMed

    Kulkarni, Maitri; Tv, Srividya; Gopal, N

    2014-06-01

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

  1. Erectile mechanism in paraplegia.

    PubMed

    Courtois, F J; Macdougall, J C; Sachs, B D

    1993-04-01

    Erection is generally viewed as a reflex mechanism that can receive higher CNS influences. Paraplegic men who have lost reflex activity from the genital area are, therefore, treated as irreversibly impotent. However, the innervation of the male reproductive system suggests that two neural pathways innervate the genitals. In theory, the second (thoracic-lumbar) pathway should compensate for the loss of the first (sacral) pathway in cases of low spinal lesions. Clinical practice, however, ignores the TL pathway as a basis for treatment of spinal cord-injured men. This study used an animal model to demonstrate that the TL pathway could mediate penile responses in paraplegic rats. Eighty-five percent (85%) of spinal animals showed penile responses following hypothalamic (MPOA) stimulation despite a complete loss of peripheral erectile reflexes. These results not only have important implications from a clinical perspective, they further document the physiology of erection and support the view that erection is not a primary parasympathetic activity, but probably results from a sequence of sympathetic processes. PMID:8511177

  2. 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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2015-01-01

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

  5. KIF1A missense mutations in SPG30, an autosomal recessive spastic paraplegia: distinct phenotypes according to the nature of the mutations

    PubMed Central

    Klebe, Stephan; Lossos, Alexander; Azzedine, Hamid; Mundwiller, Emeline; Sheffer, Ruth; Gaussen, Marion; Marelli, Cecilia; Nawara, Magdalena; Carpentier, Wassila; Meyer, Vincent; Rastetter, Agnès; Martin, Elodie; Bouteiller, Delphine; Orlando, Laurent; Gyapay, Gabor; El-Hachimi, Khalid H; Zimmerman, Batel; Gamliel, Moriya; Misk, Adel; Lerer, Israela; Brice, Alexis; Durr, Alexandra; Stevanin, Giovanni

    2012-01-01

    The hereditary spastic paraplegias (HSPs) are a clinically and genetically heterogeneous group of neurodegenerative diseases characterised by progressive spasticity in the lower limbs. The nosology of autosomal recessive forms is complex as most mapped loci have been identified in only one or a few families and account for only a small percentage of patients. We used next-generation sequencing focused on the SPG30 chromosomal region on chromosome 2q37.3 in two patients from the original linked family. In addition, wide genome scan and candidate gene analysis were performed in a second family of Palestinian origin. We identified a single homozygous mutation, p.R350G, that was found to cosegregate with the disease in the SPG30 kindred and was absent in 970 control chromosomes while affecting a strongly conserved amino acid at the end of the motor domain of KIF1A. Homozygosity and linkage mapping followed by mutation screening of KIF1A allowed us to identify a second mutation, p.A255V, in the second family. Comparison of the clinical features with the nature of the mutations of all reported KIF1A families, including those reported recently with hereditary sensory and autonomic neuropathy, suggests phenotype–genotype correlations that may help to understand the mechanisms involved in motor neuron degeneration. We have shown that mutations in the KIF1A gene are responsible for SPG30 in two autosomal recessive HSP families. In published families, the nature of the KIF1A mutations seems to be of good predictor of the underlying phenotype and vice versa. PMID:22258533

  6. 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

  7. 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 ...

  8. Genetics Home Reference: spastic paraplegia type 4

    MedlinePlus

    ... rigid, hollow fibers that make up the cell's structural framework (the cytoskeleton). Microtubules are also involved in ... on PubMed Central Roll-Mecak A, Vale RD. Structural basis of microtubule severing by the hereditary spastic ...

  9. Genetics Home Reference: spastic paraplegia type 31

    MedlinePlus

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

  10. 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 ...

  11. Paraplegia following lumbosacral steroid epidural injections.

    PubMed

    AbdeleRahman, Kader Tawfiq; Rakocevic, Goran

    2014-09-01

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

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

    PubMed

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

    2012-12-01

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

  13. Spinal cord infarction: a rare cause of paraplegia

    PubMed Central

    Patel, Sonali; Naidoo, Khimara; Thomas, Peter

    2014-01-01

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

  14. Genetics Home Reference: spastic paraplegia type 3A

    MedlinePlus

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

  15. 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

  16. Multi-focal histiocytosis X of bone in two adjacent vertebrae causing paraplegia.

    PubMed

    Turgut, M; Gurçay, O

    1992-03-01

    This report describes a case of multi-focal histiocytosis X of bone in two adjacent vertebrae that caused a spinal cord compression. This case was treated radically with combined surgery and postoperative radiotherapy (RT). PMID:1550511

  17. 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

  18. 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

  19. 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

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

    NASA Astrophysics Data System (ADS)

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

    2006-12-01

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

  1. 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

  2. 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…

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

    PubMed

    Bodaleo, Felipe J; Gonzalez-Billault, Christian

    2016-01-01

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

  4. 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

  5. Paraneoplastic Syndrome in Splenic Marginal Zone Lymphoma: A Rare Phenomenon of Paraplegia as an Atypical Presenting Manifestation

    PubMed Central

    Schering, Jessica; Donthireddy, Vijayalakshmi

    2016-01-01

    We describe a case presenting complaint of complete lower body paraparesis, which was discovered to have splenic marginal zone lymphoma (SMZL). While paraneoplastic syndromes are more common in tumors, such as small cell lung cancer, very few reports exist on this condition with SMZL. We describe such a rare entity with a clinical course spanning twenty-four months after diagnosis. PMID:27293921

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

    PubMed

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

    1980-08-01

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

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

    PubMed Central

    Bodaleo, Felipe J.; Gonzalez-Billault, Christian

    2016-01-01

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

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

    PubMed

    Ekelem, Andrew; Murray, Spencer; Goldfarb, Michael

    2015-08-01

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

  9. 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

  10. 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

  11. 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…

  12. 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

  13. Transverse myelopathy occurring with intrathecal administration of methotrexate and cytarabine chemotherapy: A case report

    PubMed Central

    PAN, YING; WANG, CHUNHUAI; WANG, HUIPING; TAO, QIANSHAN; XIONG, SHUDAO; ZHAI, ZHIMIN

    2016-01-01

    Paraplegia following spinal injury is a rare complication subsequent to the administration of intrathecal chemotherapy; however, it is also one of the rare clinical features of central nervous system leukemia (CNSL). Distinguishing between the two is extremely important. The present study reports the case of a 46-year-old man who was diagnosed with acute lymphoblastic leukemia and subsequently achieved remission in the blood and bone marrow following the initial course of chemotherapy. However, the patient developed a sudden onset of paraplegia and urinary retention due to spinal cord infiltration of leukemia cells following the administration of intrathecal methotrexate and cytarabine. The paraplegia was initially reversible. However, a few weeks later, the patient developed irreversible paraplegia due to a complication of the intrathecal administration of chemotherapy (methotrexate and cytarabine arabinoside). The patient gave up further treatment in May 2013 and succumbed to the disease in June 2013. PMID:27313742

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

    MedlinePlus

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

  15. 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

  16. 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.

  17. Recurrent de novo c.316G>A mutation in NIPA1 hotspot.

    PubMed

    Hedera, Peter

    2013-12-15

    Mutations in the NIPA1 cause autosomal dominant form of hereditary spastic paraplegia. Allelic heterogeneity of known NIPA1 mutations is quite limited and the most common mutation is c.316G>A resulting in p.G106R protein change. Here we report the first direct evidence of de novo c.316G>A mutation in the same hotspot of the gene in two unrelated patients who had otherwise a prototypical NIPA1-associated phenotype with a severe form of uncomplicated spastic paraplegia. De novo nature of these mutations was confirmed by sequencing both sets of clinically unaffected parents and confirmation of paternity. We also discuss likely molecular mechanisms accounting for recurrent mutations in this segment of the gene. Apparently sporadic patients without a positive family history of hereditary spastic paraplegia need to be also evaluated for possible disease-causing mutations in genes that are inherited in an autosomal dominant fashion. PMID:24075313

  18. Spinal cord injury rehabilitation outcome: the impact of age.

    PubMed

    Yarkony, G M; Roth, E J; Heinemann, A W; Lovell, L L

    1988-01-01

    The effect of age on self-care and mobility skill performance after spinal cord injury was studied using a 15-task modified Barthel Index (MBI) to score functional abilities for 708 patients aged 6 through 88 years. Analysis of covariance showed no relationship between age and discharge MBI score; however, patients with paraplegia, incomplete lesions, and greater admission functional ratings had greater discharge functional scores than did those with quadriplegia, complete lesions, and lower admission scores, respectively. Advancing age was associated with increased dependence in only seven functional skills (bathing, upper and lower body dressing, stair climbing, and transfers to chair, toilet and bath) and only for patients with complete paraplegia. Other MBI component tasks and patients with complete quadriplegia, incomplete paraplegia and incomplete quadriplegia demonstrated no relationship between age and skill performance. Results of this study support the practice of providing comprehensive rehabilitation services to all patients following spinal cord injury regardless of age. PMID:3335882

  19. Paraplegic Neurodeficit Management Post Endovascular Graft: A Rare Case of Aortic Dissection

    PubMed Central

    Kanse, Vilas Yadavarao; Chongtham, Dhanaraj Singh; Nemichandra, S C; Salam, Kenny Singh

    2013-01-01

    Acute aortic dissection is a catastrophic episode that usually presents as a sudden, painful, ripping sensation in the chest or back. It is associated with neurologic sequelae in as many as one-third of patients. We report a case of aortic dissection, presenting as acute paraplegia. A 50-year-old patient presented to us with chief complaints of paraplegia and back pain. On examination, strength was 5/5 in both upper extremities and 0/5 in both lower extremities. Deep tendon reflexes were absent in her legs. CT angiogram of aorta Aortic Dissection Stanford type B / De-Bakey type –III. Patient was treated with endovascular graft for aortic dissection, paraplegia recovered completely. PMID:24298506

  20. Neurologic Complication Following Spinal Epidural Anesthesia in a Patient with Spinal Intradural Extramedullary Tumor

    PubMed Central

    Kim, Sung Hoon; Son, Dong Wuk; Lee, Sang Won

    2010-01-01

    Paraplegia following spinal epidural anesthesia is extremely rare. Various lesions for neurologic complications have been documented in the literature. We report a 66-year-old female who developed paraplegia after left knee surgery for osteoarthritis under spinal epidural anesthesia. In the recovery room, paraplegia and numbness below T4 vertebra was checked. A magnetic resonance image (MRI) scan showed a spinal thoracic intradural extramedullary (IDEM) tumor. After extirpation of the tumor, the motor weakness improved to the grade of 3/5. If a neurologic deficit following spinal epidural anesthesia does not resolve, a MRI should be performed without delay to accurately diagnose the cause of the deficit and optimal treatment should be rendered for the causative lesion. PMID:21430985

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  3. Malignant Rhabdoid Tumor of the Kidney and Spine in an Infant

    PubMed Central

    Park, Sejun; Seo, Jae-Hee; Park, Jun Bum

    2014-01-01

    Rhabdoid tumor of the kidney (RTK) is a rare malignancy in infancy. Central nervous system involvement in RTK is already known. However, solitary spinal metastasis in RTK has been hardly reported. The authors report a case of metastatic RTK to spine causing paraplegia in an 8-month-old girl. Since the patient was young, the diagnosis of spine metastasis was delayed until paraplegia was seen after radical nephrectomy. Thorough neurological examination should be performed for early diagnosis of spinal metastasis in young patients with RTK. If there are any abnormal signs in neurologic examination, magnetic resonance images of brain and spine are recommended. PMID:24570822

  4. 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

  5. [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

  6. 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

  7. 78 FR 12264 - Criteria for a Catastrophically Disabled Determination for Purposes of Enrollment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-22

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

  8. 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,…

  9. 34 CFR 373.4 - What definitions apply?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  10. 34 CFR 350.5 - What definitions apply?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

  11. 34 CFR 373.4 - What definitions apply?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

  12. 34 CFR 373.4 - What definitions apply?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

  13. 34 CFR 377.5 - What definitions apply?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  14. 34 CFR 350.5 - What definitions apply?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

  15. 34 CFR 377.5 - What definitions apply?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

  16. 34 CFR 377.5 - What definitions apply?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

  17. 34 CFR 350.5 - What definitions apply?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  18. 34 CFR 377.5 - What definitions apply?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

  19. 16 CFR 1116.2 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

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

  20. 34 CFR 373.4 - What definitions apply?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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

  1. Comparison of Heart Rate Response to Tennis Activity between Persons with and without Spinal Cord Injuries: Implications for a Training Threshold

    ERIC Educational Resources Information Center

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

    2009-01-01

    The purpose of this study was to evaluate the ability of individuals with spinal cord injury (SCI) to reach a training threshold during on-court sport activity. Monitors collected heart rate (HR) data every 5 s for 11 wheelchair tennis players (WCT) with low paraplegia and 11 able-bodied controls matched on experience and skill level (ABT).…

  2. 16 CFR 1116.2 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

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

  3. 34 CFR 350.5 - What definitions apply?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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

  4. 34 CFR 350.5 - What definitions apply?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

  5. 16 CFR 1116.2 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

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

  6. 16 CFR 1116.2 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

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

  7. 34 CFR 377.5 - What definitions apply?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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

  8. 16 CFR 1116.2 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

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

  9. 34 CFR 373.4 - What definitions apply?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

  10. Neurologic Complications in Percutaneous Nephrolithotomy

    PubMed Central

    Basiri, Abbas; Soltani, Mohammad Hossein; Kamranmanesh, Mohammadreza; Tabibi, Ali; Mohsen Ziaee, Seyed Amir; Nouralizadeh, Akbar; Sharifiaghdas, Farzaneh; Poorzamani, Mahtab; Gharaei, Babak; Ozhand, Ardalan; Lashay, Alireza; Ahanian, Ali; Aminsharifi, Alireza; Sichani, Mehrdad Mohammadi; Asl-Zare, Mohammad; Ali Beigi, Faramarz Mohammad; Najjaran, Vahid; Abedinzadeh, Mehdi

    2013-01-01

    Purpose Percutaneous nephrolithotomy (PCNL) has been the preferred procedure for the removal of large renal stones in Iran since 1990. Recently, we encountered a series of devastating neurologic complications during PCNL, including paraplegia and hemiplegia. There are several reports of neurologic complications following PCNL owing to paradoxical air emboli, but there are no reports of paraplegia following PCNL. Materials and Methods We retrospectively reviewed the medical records of patients who had undergone PCNL in 13 different endourologic centers and retrieved data related to neurologic complications after PCNL, including coma, paraplegia, hemiplegia, and quadriplegia. Results The total number of PCNL procedures in these 13 centers was 30,666. Among these procedures, 11 cases were complicated by neurologic events, and four of these cases experienced paraplegia. All events happened with the patient in the prone position with the use of general anesthesia and in the presence of air injection. There were no reports of neurologic complications in PCNL procedures performed with the patient under general anesthesia and in the prone position and with contrast injection. Conclusions It can be assumed that using room air to opacify the collecting system played a major role in the occurrence of these complications. Likewise, the prone position and general anesthesia may predispose to these events in the presence of air injection. PMID:23526482

  11. 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

  12. 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

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

    PubMed

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

    2012-03-01

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

  14. Thoracic spinal trauma and associated injuries: should early spinal decompression be considered?

    PubMed

    Petitjean, M E; Mousselard, H; Pointillart, V; Lassie, P; Senegas, J; Dabadie, P

    1995-08-01

    The relative benefits of conservative or surgical treatment in thoracic spinal trauma are still controversial. Owing to its anatomic relations, thoracic spinal trauma is specific regarding neurologic prognosis, the high incidence of associated injuries, and surgical management. Over a 30-month period, 49 patients sustained thoracic spinal trauma with neurologic impairment. The authors review population characteristics, associated injuries, and surgical management, and underline the high incidence of associated injuries, in particular, blunt chest trauma. In their opinion, early spinal decompression has no indication in complete paraplegia. Concerning partial paraplegia, early surgery may enhance neurologic recovery. Nevertheless, they suggest three main criteria in deciding whether or not to perform surgery early: the existence of residual spinal compression, the degree of neurologic impairment, and the presence of potential hemorrhagic lesions or blunt chest trauma, especially pulmonary contusion. PMID:7674409

  15. Prosthetic ambulation in a paraplegic patient with a transfemoral amputation and radial nerve palsy.

    PubMed

    Shin, J C; Park, C; Kim, D Y; Choi, Y S; Kim, Y K; Seong, Y J

    2000-08-01

    Great importance and caution should be placed on prosthetic fitting for a paraplegic patient with an anesthetic residual limb if functional ambulation is to be achieved. The combination of paraplegia with a transfemoral amputation and radial nerve palsy is a complex injury that makes the rehabilitation process difficult. This article describes a case of L2 paraplegia with a transfemoral amputation and radial nerve palsy on the right side. Following the rehabilitation course, the patient independently walked using a walker at indoor level with a transfemoral prosthesis with ischial containment socket, polycentric knee assembly, endoskeletal shank and multiaxis foot assembly and a knee ankle foot orthosis on the sound side. The difficulties of fitting a functional prosthesis to an insensate limb and the rehabilitation stages leading to functional ambulation are reviewed. PMID:10992814

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

    PubMed

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

    2016-04-01

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

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

    PubMed

    Madorsky, J G; Madorsky, A G

    1988-03-01

    In the past, physicians prohibited patients with neuromuscular disease or disability from participating in scuba diving. This report highlights the opportunities that self-contained underwater breathing apparatus (scuba) affords to physically handicapped individuals, to move without assistive devices in a gravity-free environment. The experience of a person with T10 paraplegia is used to illustrate the applicability of a new system of evaluation, training, and certification for scuba diving to patients with a wide variety of disabilities, such as paraplegia, quadriplegia, amputation, cerebral palsy, and poliomyelitis. This review also discusses equipment needs, potential risks, and safety precautions. Physicians are encouraged to support those handicapped individuals who choose to explore the submerged two thirds of our planet for its recreational as well as its potential vocational opportunities. PMID:3348724

  18. [Unilateral, paramedian spinal contusion after athletic injury with complete recovery].

    PubMed

    Ebert, B; Badke, A

    1995-03-01

    The acute injury of the spinal column and the spinal cord asks for immediate diagnostic techniques and adequate therapeutical intensive care in order to secure the possibility of a maximum of neurologic recovery. An impact trauma of the spinal cord in sports accidents can cause an incomplete paraplegia. In some cases, morphologic lesions of the myelon cannot be detected. We present an exceptional and striking case of a 15-year old young woman who suffered from a contusio spinalis after high jump with the clinical signs of an incomplete, sensomotoric paraplegia which showed a strictly unilateral and paramedian border at the right side of her body for about two weeks. Additionally, the diagnostic possibilities of physical examination, magnetic resonance imaging, computed tomography and neurophysiologic diagnostic techniques in detecting spinal cord injuries are demonstrated. PMID:7778020

  19. 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

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

    PubMed Central

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

    2016-01-01

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

  1. Imaging diagnosis--Spontaneous subperiosteal vertebral hemorrhage in a greyhound.

    PubMed

    Theobald, Anita; Dennis, Ruth; Beltran, Elsa

    2014-01-01

    A 4-year-old, spayed female greyhound dog was presented with an acute onset of paraplegia. There was no known history of trauma or coagulopathy. Spinal cord compression was identified on MRI. Intra-operative evaluation revealed the presence of a large subperiosteal hematoma and a smaller epidural hematoma. To the authors' knowledge, this is the first report of a spinal subperiosteal hematoma diagnosed antemortem through MRI, with surgical exploration and successful treatment in a dog. PMID:23815130

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

    PubMed Central

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

    2014-01-01

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

  3. 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

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

    PubMed Central

    Khare, Shailendra; Sharma, Vijay

    2013-01-01

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

  5. 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

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

    PubMed

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

    2013-05-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  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

  11. 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

  12. 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

  13. 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

  14. The effects of 4-aminopyridine on neurological deficits in chronic cases of traumatic spinal cord injury in dogs: a phase I clinical trial.

    PubMed

    Blight, A R; Toombs, J P; Bauer, M S; Widmer, W R

    1991-01-01

    A Phase I trial of 4-aminopyridine (4-AP) was carried out in 39 dogs referred to the veterinary teaching hospital with naturally occurring traumatic paraplegia or paraparesis. The rationale for the study was provided by the observation that 4-AP restores conduction in demyelinated nerve fibers in experimental spinal cord injury. Most injuries (77%) resulted from degenerative disk disease, occurring at or near the thoracolumbar junction, and producing chronic, complete paraplegia. Neurological examination of each dog was recorded on videotape before and at intervals after administration of 4-AP. The drug was administered systemically in total doses between 0.5 and 1 mg/kg body weight. Three areas of neurological status changed significantly at 15-45 minutes following administration of 4-AP: (a) striking improvements in hindlimb placing occurred in 18 animals; (b) increased awareness of painful stimuli to the hindlimb in 10 animals; (c) partial recovery of the cutaneus trunci muscle reflex of the back skin in 9 animals. These effects reversed within a few hours of administration. Other animals (36%) showed no change in neurological signs except a slight enhancement of hindlimb reflex tone. Significant side effects were seen in 6 dogs receiving higher intravenous doses, with elevation of body temperature and apparent anxiety, leading to mild seizures in 3 of the animals. These seizures were controlled with diazepam. The results indicate that conduction block may contribute significantly to functional deficits in closed-cord injuries and that potassium channel blockade may prove to be a valid, if limited approach to therapeutic intervention in chronic paraplegia and paraparesis. PMID:1870134

  15. Outcome of extensive descending aorta repair adopting present concepts of spinal cord preservatio.

    PubMed

    Park, K H; Lim, C; Kim, T H; Park, I; Jung, Y

    2012-11-01

    AIM: Preoperative radiological identification of the Adamkiewicz artery and intraoperative neurologic monitoring are known to be helpful for preventing paraplegia after thoracoabdominal aorta replacement. To answer whether they should be used routinely, we investigated the incidence of spinal cord ischemia after extensive descending aortic repair without using such modalities. METHODS: We retrospectively reviewed the outcome of 95 patients who underwent extensive descending thoracic (DTA) or thoracoabdominal aorta (TAA) repair without the Adamkiewicz artery identification or neurologic monitoring from 2006 through 2010. Spinal cord protection strategy consisted of distal aortic perfusion, cerebrospinal fluid drainage, mild hypothermia, and maintenance of hypertension (systolic≥120mmHg) through the second postoperative day. A few segmental arteries were empirically selected for reimplantation based on the size and the amount of backbleeding; overall 1.4 per patient, 0.3 for DTA, 1.4 for type I, 2.4 for type II, 0.9 for type III, and 0 for type IV TAA. RESULTS: Two patients died early after surgery. All the remaining patients awoke without paraplegia or paraparesis. Delayed deficit occurred in 7 patients (7.4%) after hypotensive events caused by sedation, bleeding, respiratory distress, or cardiac dysfunction. Three patients (3.2%) became permanently paraplegic and the other four recovered completely within 48 hours after cerebrospinal fluid drainage and elevation of systemic blood pressure. CONCLUSION: Even without the Adamkiewicz artery identification and neuromonitoring, the incidence of immediate paraplegia could be kept low by applying the strategy based on the modern concept of cord perfusion. The relatively high incidence of delayed deficit suggests the importance of postoperative hemodynamic management and prevention of cardiopulmonary complications. PMID:23138604

  16. Modification of a Standard Thoracoabdominal Incision to Preserve Collaterals to Adamkiewicz Artery.

    PubMed

    Takahara, Shingo; Kanda, Keisuke; Kawatsu, Satoshi; Yoshioka, Ichiro; Fujiwara, Hidenori; Adachi, Osamu; Akiyama, Masatoshi; Kumagai, Kiichiro; Kawamoto, Shunsuke; Ota, Hideki; Saiki, Yoshikatsu

    2016-09-01

    We report a case of a 35-year-old male who underwent thoracoabdominal aortic repair of a chronic dissecting aortic aneurysm, Crawford extent II. Preoperative computed tomography showed thrombosis of almost all intercostal arteries. Precise diagnostic assessment demonstrated the Adamkiewicz artery originating from the left lateral thoracic artery and subscapular artery, which would have been at risk after using a standard Stoney's incision, thus potentially causing paraplegia or paraparesis due to spinal cord ischemia. We modified the lateral thoracic incision anteriorly and successfully preserved the collateral arteries without impairing the spinal cord function. PMID:27549554

  17. Lidocaine 5% Medicated Plaster for Spinal Neuropathic Pain.

    PubMed

    Freo, Ulderico; Ambrosio, Francesco; Furnari, Maurizio; Ori, Carlo

    2016-06-01

    Spinal cord injuries frequently determine central pain symptoms that are difficult to control. The authors present the case of a 67-year-old suffering from a pleural mesothelioma. During the disease course, he developed a paraplegia syndrome from mesothelioma compression of the spinal cord at T4-T5 level. Following spinal decompression surgery, the patient presented an intense at-level, superficial neuropathic pain syndrome with allodynia and hyperalgesia. After systemic pharmacological therapies had failed, treatment with lidocaine 5% plaster was initiated. The superficial neuropathic symptoms almost completely disappeared within a few days. The lidocaine topical treatment was continued for months with durable analgesic effect. PMID:27018847

  18. Acute traumatic cord injury associated with ossified ligamentum flavum.

    PubMed

    Kow, Chien Yew; Chan, Patrick; Etherington, Greg; Rosenfeld, Jeffrey V

    2016-08-01

    Ossification of the ligamentum flavum (OLF) is an uncommon condition, which usually occurs amongst people of Asian descent, and most commonly in the thoracic spine region. Whilst often asymptomatic, OLF can cause spinal canal stenosis, with patients presenting with back pain, posterior cord syndrome or myelopathy. We present a rare case of acute spinal cord injury associated with OLF after a kite surfing accident, with the resulting paraplegia partially improved after decompression was performed. The prevalence, presentation and management of OLF are also discussed. PMID:27052256

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

    PubMed

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

    2014-04-01

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

  20. 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

  1. 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

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

    PubMed

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

    2016-01-01

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

  3. Primary extradural hydatid cyst extended to paraspinal muscles

    PubMed Central

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

    2012-01-01

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

  4. [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

  5. SLE presenting as multiple hemorrhagic complications.

    PubMed

    Abdulla, M C; Alungal, J; Hashim, S; Ali, M M; Musambil, M

    2015-09-01

    A 24 year old female with hereditary spastic paraplegia presented with intermittent headache for one year. She also had lower abdominal pain and vomiting for two months. She was pale, had icterus and mild splenomegaly. On diagnostic evaluation she was found to have hemolytic anemia, thrombocytopenia and bilateral adrenal, subdural, soft tissue (scalp and orbit) hemorrhages due to systemic lupus erythematosus (SLE). However, antiphospholipid syndrome (APS) antibodies were negative. Bilateral adrenal hemorrhage without associated APS is a rare phenomenon in SLE. We describe a case of SLE presenting with sequence of rare hemorrhagic complications in concert. PMID:25716420

  6. 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.

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

    PubMed

    Kangude, Abhijit; Burgstahler, Brett; Durfee, William

    2010-01-01

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

  9. 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

  10. Extensive spinal epidural hematoma: a rare complication of aortic coarctation.

    PubMed

    Zizka, J; Eliás, P; Michl, A; Harrer, J; Cesák, T; Herman, A

    2001-01-01

    Development of collateral circulation belongs among the typical signs of aortic coarctation. Cerebral or spinal artery aneurysm formation with increased risk of subarachnoid hemorrhage represent the most common neurovascular complication of this disease. We report a case of a 20-year-old sportsman who developed acute non-traumatic paraplegia as a result of extensive spinal epidural hemorrhage from collateral vessels accompanying aortic coarctation which was unrecognized up to that time. To the best of our knowledge, acute spinal epidural hematoma as a complication of aortic coarctation has not been previously reported. PMID:11471620

  11. Spinal cord metastasis in small cell carcinoma of the lung

    SciTech Connect

    Holoye, P.; Libnoch, J.; Cox, J.; Kun, L.; Byhardt, R.; Almagro, U.; McCelland, S.; Chintapali, K.

    1984-03-01

    Among 50 patients with small cell bronchogenic carcinoma who were placed on a protocol of combined chemotherapy and radiation therapy, seven patients developed recurrence in the spinal cord. Five cases terminated in paraplegia and death. One patient with pontine recurrence recovered with local radiation therapy. One patient, diagnosed early, responded to local radiation therapy and is ambulatory. Methods of diagnosis were myelogram, computerized axial tomography, cerebro spinal fluid, chemistry and cytologies. The poor prognosis and the difficulty of diagnosis suggest that prophylactic therapy of the entire cranio-spinal axis should be evaluated.

  12. “The Flipping Bullet” with Associated Intramedullary Dystrophic Calcification: An Unusual Cause for Migratory Myelopathy and Radiculopathy

    PubMed Central

    Hunt, Christopher H; McKenzie, Gavin A; Diehn, Felix E; Morris, Jonathan M; Wood, Christopher P

    2012-01-01

    We report the case of a 24 year old male who had a retained bullet within his thoracic spine from a gunshot wound resulting in paraplegia. After 7 months he began experiencing painful dysesthesias at his sensory level. Repeat imaging demonstrated migration of the bullet as well as the development of intramedullary dystrophic calcification associated with the bullet. This case demonstrates not only the ability for retained bullets to migrate within the spinal canal but also demonstrates they can lead to remote symptoms due to the development of dystrophic calcification. PMID:22942925

  13. [The experience in employing reciprocal gait orthoses].

    PubMed

    Radło, W; Miklaszewski, K; Gasińska, M; Michno, P

    1999-01-01

    The paper presents the experience of the authors in employing reciprocal gait orthoses in a group of 23 patients age 3-25 years (mean age 7.8 years). The orthoses were indicated in patients with flaccid paresis (17 children with myelodysplasia and 3 patients with traumatic paraplegia) and with arthrogryposis (3 patients). The follow-up period was 6 months to 5 years (mean 2.4 years). The authors discuss the principles of construction and operation of reciprocal gait orthoses and types of patients in whom they are recommended. The principles of learning walking and using the orthosis are also presented. PMID:10367535

  14. 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

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

    PubMed

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

    2004-06-24

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

  16. 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.

  17. Evaluation of spinal cord ischemia with a retrievable stent graft is useful for determining the type of repair for a case of patch aneurysm.

    PubMed

    Akasaka, Junetsu; Takase, Kei; Tabayashi, Koichi

    2014-07-01

    Patch aneurysms after thoracoabdominal aortic aneurysm repair are a serious late complication. We treated a patient with patch aneurysm (originating at the artery of Adamkiewicz) involving a portion of an implanted graft from a previous operation. First, thoracic endovascular aneurysm repair was planned. A retrievable stent graft was inserted, and motor-evoked potentials were monitored to evaluate spinal cord ischemia. Significant changes in the motor-evoked potentials were observed, and permanent stent graft placement was abandoned. Later, open surgery was performed. The patient showed no postoperative paraplegia and was discharged in good condition. PMID:24333526

  18. 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

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

    PubMed Central

    Neto, Frederico Ribeiro; Lopes, Guilherme Henrique

    2011-01-01

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

  20. 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

  1. Kung-Fu: synthesis of wheelchair sport and self-protection.

    PubMed

    Madorsky, J G; Scanlon, J R; Smith, B

    1989-06-01

    As persons with disabilities enter the mainstream of society, and as the incidence of violent crime in society rises, disabled persons become victims of violent crime more frequently. It is vital for citizens with significant physical limitations to take precautionary steps for their own safety. Martial arts offer time-honored methods of self-protection for members of society who are physically disadvantaged. The case history of a young man with paraplegia is used to illustrate the potential of Kung-Fu as a sport and as a method of training for self-protection and survival. PMID:2730312

  2. Remote spinal epidural haematoma after spinal anaesthesia presenting with a ‘spinal lucid interval’

    PubMed Central

    Madhugiri, Venkatesh S; Singh, Manish; Sasidharan, Gopalakrishnan M; Kumar, V R Roopesh

    2012-01-01

    An obstetric patient who had no significant risk factors developed a spinal epidural haematoma remote from the site of needle puncture (for administration of spinal anaesthesia). The clinical deficits were manifest after recovery from the motor blockade had started a phenomenon that we have termed as a ‘spinal lucid interval’. The patient developed flaccid paraplegia with a sharp sensory level and urinary retention. The patient underwent emergency laminectomy and evacuation of the haematoma. She gradually recovered near normal power and was ambulant independently and had normal sphincter function at follow-up. PMID:23109417

  3. Spastin subcellular localization is regulated through usage of different translation start sites and active export from the nucleus

    SciTech Connect

    Claudiani, Pamela; Riano, Elena; Errico, Alessia; Andolfi, Gennaro; Rugarli, Elena I. . E-mail: rugarli@tigem.it

    2005-10-01

    Most cases of autosomal-dominant hereditary spastic paraplegia are linked to mutations in SPG4 encoding spastin, a protein involved in microtubule dynamics and membrane trafficking. In pyramidal neurons of the motor cortex and in immortalized motor neurons, spastin is localized to the synaptic terminals and growth cones. However, in other neurons and in proliferating cells spastin is prevalently nuclear. The mechanisms that determine targeting of spastin to the nucleus or the cytoplasm are unknown. We show here that the SPG4 mRNA is able to direct synthesis of two spastin isoforms, 68 and 60 kDa, respectively, through usage of two different translational start sites. Both isoforms are imported into the nucleus, but the 68-kDa isoform contains two nuclear export signals that efficiently drive export to the cytoplasm. Nuclear export is leptomycin-B sensitive. The cytoplasmic 68-kDa spastin isoform is more abundant in the brain and the spinal cord than in other tissues. Our data indicate that spastin function is modulated through usage of alternative translational start sites and active nuclear import and export, and open new perspectives for the pathogenesis of hereditary spastic paraplegia.

  4. Endovascular treatment of blunt traumatic thoracic aortic injury.

    PubMed

    Nicolaou, Georghios

    2009-06-01

    Blunt traumatic thoracic aortic injury (BTTAI) is a lethal injury associated with a prehospital mortality of 80% to 90%. Patients arriving in the emergency room and considered appropriate to undergo emergency open surgical repair still have a mortality rate of 15% to 30% because of severe associated injuries. Conventional open surgical repair requires a left thoracotomy, single lung ventilation, aortic-cross clamping and unclamping, with or without the adjunct use of partial or full cardiopulmonary bypass and systemic heparinization. All this leads to significant physiological stress and surgical trauma resulting in perioperative complications such as major blood loss, coagulopathy, myocardial infarction, stroke, respiratory failure, renal failure, bowel infarction, and paraplegia. Despite advances in anesthesia, critical care medicine, and surgical techniques, a recent meta-analysis showed no definite improvement in operative mortality over the past decade, following open surgical repair in patients with BTTAI. Endovascular repair of BTTAI does not require a thoracotomy, single lung ventilation, aorticcross clamping and unclamping, or systemic heparinization. As a result, endovascular repair of BTTAI has emerged as an effective, minimally invasive treatment alternative, especially in patients with severe concomitant injuries, which may be prohibitive to open surgical repair. Recent published studies have shown that endovascular repair of BTTAI is associated with lower morbidity, mortality, stroke, and paraplegia/paraparesis rates, when compared with open surgical repair of BTTAI. PMID:19617250

  5. A test of the 1992 International Standards for Neurological and Functional Classification of Spinal Cord Injury.

    PubMed

    Cohen, M E; Ditunno, J F; Donovan, W H; Maynard, F M

    1998-08-01

    This study was designed to test the 1992 International Standards for Neurological and Functional Classification of Spinal Cord Injury. One hundred and six professionals in the field of spinal cord injury attending an instructional course at the 1994 ASIA Meeting participated in the test. Participants completed a pretest and posttest in which they classified two patients who had a spinal cord injury (one with complete tetraplegia and one with incomplete paraplegia) by sensory and motor levels, zone of partial preservation (ZPP), ASIA Impairment Scale and completeness of injury. Between tests, three members of the ASIA Standards Executive Committee gave presentations on the neurological assessment, scoring, scaling and classification of spinal cord injury and a video of the actual examinations of the two cases was viewed. Percent 'correct' (as defined by the ASIA Standards Committee) was calculated for sensory and motor levels, ZPP, ASIA Impairment and completeness. Overall, the analyses showed that participants had very little difficulty in correctly classifying the patient with complete tetraplegia. Pretests scores ranged from 72% (left motor level) to 96% (complete injury), posttest scores from 73% (left motor level) to 100% correct (complete injury). For the patient with incomplete paraplegia (Case 2), scores were considerably lower. Pretest scores ranged from 16% (right motor level) to 95% correct (incomplete injury); posttest scores from 21% (right motor level) to 97% correct (incomplete injury). The results showed that further revisions of the 1992 Standards and more training is needed to ensure accurate classification of spinal cord injury. PMID:9713924

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

    PubMed Central

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

    2015-01-01

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

  7. 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

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

    PubMed Central

    Manvikar, Laxmi P.; Adhye, Bharati A.

    2012-01-01

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

  9. Time course of diffusion weighted image and apparent diffusion coefficient in acute spinal cord infarction: A case report and review of the literature.

    PubMed

    Takeshita, Sho; Ogata, Toshiyasu; Mera, Hidekazu; Tsugawa, Jun; Fukae, Jiro; Tsuboi, Yoshio

    2016-05-31

    An 80-year-old woman was admitted to our hospital with acute onset of flaccid paraplegia and sensory and urinary disturbances that developed soon after acute pain in her lower back and leg. Neurological examination revealed, severe flaccid paraplegia, bladder and rectal disturbances and dissociated sensory loss below the level of L1 spinal cord segment. MR imaging with T2 weighted imaging (T2WI) and diffusion weighted imaging (DWI) on day 2 showed hyper signal intensity in the spinal cord at the vertebral level of L1 while initial apparent diffusion coefficient (ADC) showed decreased signal intensity in the lesion. We diagnosed spinal cord infarction, and anticoagulant and neuroprotective agents were administrated. Serial MRI findings revealed that the DWI signal of the lesion attenuated with time, and pseudo-normalization of the ADC occurred approximately 1 month after onset. These findings were similar to those seen in brain infarction. Our patient demonstrated serial MRI changes of spinal cord infarction showing anterior spinal cord syndrome. PMID:27098903

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

    PubMed

    Miyamoto, Shinji

    2016-07-01

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

  11. Fractures of the thoraco-lumbar spine.

    PubMed

    Lifeso, R M; Arabie, K M; Kadhi, S K

    1985-08-01

    A personal prospective study of 98 consecutive patients presenting with neurological impairment and fractures or dislocations between the 9th thoracic and 2nd lumbar vertebrae bodies. Fifty-three patients underwent Harrington instrumentation, and 45 patients were treated recumbently. Neurological improvement was much better following Harrington rods in the complete paraplegia group but there was no difference in neurological recovery between the two groups in those with incomplete paraplegia. Forty-two patients who had been stabilised with Harrington rods underwent post-operative myelography or tomography to assess the adequacy of spinal decompression. The best results were in patients with adequate neural canal decompression. In 21 cases decompression had not been adequate, usually due to a stereotyped pattern in which the postero-superior aspect of the fractured body remained in the neural canal. All 21 underwent anterior decompression at an average of five months post injury. All the incomplete anterior decompression at an average of five months post injury. All the incomplete paraplegics (nine patients) regained the ability to walk, three of the 12 complete paraplegics improved and regained the ability to walk with bilateral ankle-foot orthoses. Neurological improvement was dependent upon the adequacy of spinal cord decompression and not upon Harrington rods. per se. Harrington rods alone were not adequate to decompress the spinal canal in 50 per cent of cases. The best results after anterior decompression occurred where neural compression was caused by a minimally displaced wedge fracture distal to T12. PMID:4047711

  12. 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

  13. Comparing deficits following excitotoxic and contusion injuries in the thoracic and lumbar spinal cord of the adult rat.

    PubMed

    Magnuson, D S; Trinder, T C; Zhang, Y P; Burke, D; Morassutti, D J; Shields, C B

    1999-03-01

    The majority of human spinal cord injuries involve gray matter loss from the cervical or lumbar enlargements. However, the deficits that arise from gray matter damage are largely masked by the severe deficits due to associated white matter damage. We have developed a model to examine gray matter-specific deficits and therapeutic strategies that uses intraspinal injections of the excitotoxin kainic acid into the T9 and L2 regions of the spinal cord. The resulting deficits have been compared to those from standard contusion injuries at the same levels. Injuries were assessed histologically and functional deficits were determined using the Basso, Beattie, and Bresnahan (BBB) 21-point open field locomotor scale and transcranial magnetic motor evoked potentials (tcMMEPs). Kainic acid injections into T9 resulted in substantial gray matter damage; however, BBB scores and tcMMEP response latencies were not different from those of controls. In contrast, kainic acid injections into L2 resulted in paraplegia with BBB scores similar to those following contusion injuries at either T9 or L2, without affecting tcMMEP response latencies. These observations demonstrate that gray matter loss can result in significant functional deficits, including paraplegia, in the absence of a disruption of major descending pathways. PMID:10192790

  14. SPG7 mutations explain a significant proportion of French Canadian spastic ataxia cases.

    PubMed

    Choquet, Karine; Tétreault, Martine; Yang, Sharon; La Piana, Roberta; Dicaire, Marie-Josée; Vanstone, Megan R; Mathieu, Jean; Bouchard, Jean-Pierre; Rioux, Marie-France; Rouleau, Guy A; Boycott, Kym M; Majewski, Jacek; Brais, Bernard

    2016-07-01

    Hereditary cerebellar ataxias and hereditary spastic paraplegias are clinically and genetically heterogeneous and often overlapping neurological disorders. Mutations in SPG7 cause the autosomal recessive spastic paraplegia type 7 (SPG7), but recent studies indicate that they are also one of the most common causes of recessive cerebellar ataxia. In Quebec, a significant number of patients affected with cerebellar ataxia and spasticity remain without a molecular diagnosis. We performed whole-exome sequencing in three French Canadian (FC) patients affected with spastic ataxia and uncovered compound heterozygous variants in SPG7 in all three. Sanger sequencing of SPG7 exons and exon/intron boundaries was used to screen additional patients. In total, we identified recessive variants in SPG7 in 22 FC patients belonging to 12 families (38.7% of the families screened), including two novel variants. The p.(Ala510Val) variant was the most common in our cohort. Cerebellar features, including ataxia, were more pronounced than spasticity in this cohort. These results strongly suggest that variants affecting the function of SPG7 are the fourth most common form of recessive ataxia in FC patients. Thus, we propose that SPG7 mutations explain a significant proportion of FC spastic ataxia cases and that this gene should be considered in unresolved patients. PMID:26626314

  15. 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.

  16. 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

  17. Mechanisms and prevention of anterior spinal artery syndrome following abdominal aortic surgery.

    PubMed

    Aydin, A

    2015-01-01

    Paraplegia or paraparesis occurring as a complication of thoracic or thoracoabdominal aortic aneurysm repair is a well known phenomenon, but the vast majority of elective abdominal aortic aneurysm repairs are performed without serious neurological complications. Nevertheless, there have been many reported cases of spinal cord ischaemia following the elective repair of abdominal aortic aneurysms (AAA); giving rise to paraplegia, sphincter incontinence and, often, dissociated sensory loss. According to the classification made by Gloviczki et al. (1991), this presentation is classified as type II spinal cord ischaemia, more commonly referred to as anterior spinal artery syndrome (ASAS). It is the most common neurological complication occurring following abdominal aortic surgery with an incidence of 0.1-0.2%. Several aetiological factors, including intra-operative hypotension, embolisation and prolonged aortic crossclamping, have been suggested to cause anterior spinal artery syndrome, but the principal cause has almost always been identified as an alteration in the blood supply to the spinal cord. A review of the literature on the anatomy of the vascular supply of the spinal cord highlights the significance of the anterior spinal artery as well as placing additional emphasis on the great radicular artery of Adamkiewicz (arteria radicularis magna) and the pelvic collateral circulation. Although there have been reported cases of spontaneous recovery, complete recovery is uncommon and awareness and prevention remains the mainstay of treatment. However, being so tragically unpredictable and random, spinal cord ischaemia after abdominal aortic operations appears to be an unpreventable event. PMID:25757179

  18. Spartin Regulates Synaptic Growth and Neuronal Survival by Inhibiting BMP-Mediated Microtubule Stabilization

    PubMed Central

    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

    2013-01-01

    SUMMARY 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

  19. 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

  20. 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

  1. Diffusion tensor imaging observation in Pott's spine with or without neurological deficit

    PubMed Central

    Abbas, Sohail; Jain, Anil Kumar; Saini, Namita Singh; Kumar, Sudhir; Mukunth, Rajagopalan; Kumar, Jaswant; Kumar, Pawan; Kaur, Prabhjot

    2015-01-01

    Background: Diffusion tensor imaging (DTI) is based upon the phenomenon of water diffusion known as “Brownian motion.” DTI can detect changes in compressed spinal cord earlier than magnetic resonance imaging and is more sensitive to subtle pathological changes of the spinal cord. DTI observation in compressed and noncompressed spinal cord in tuberculosis (TB) spine is not described. This study presents observations in Pott's spine patients with or without neural deficit. Materials and Methods: Thirty consecutive cases of TB spine with mean age of 32.1 years of either sexes with paradiscal lesion, with/without paraplegia divided into two groups: Group A: (n = 15) without paraplegia and group B: (n = 15) with paraplegia were evaluated by DTI. The average fractional anisotropy (FA) and mean diffusivity (MD) values were calculated at 3 different sites, above the lesion (SOL)/normal, at the lesion and below SOL for both groups and mean was compared. Visual impression of tractography was done to document changes in spinal tracts. Results: The mean canal encroachment in group A was 39.60% and group B 44.4% (insignificant). Group A mean FA values above SOL, at the lesion and below SOL were 0.608 ± 0.09, 0.554 ± 0.14, and 0.501 ± 0.16 respectively. For group B mean FA values above SOL, at the lesion and below SOL were 0.628 ± 0.09, 0.614 ± 0.12 and 0.487 ± 0.15 respectively. There was a significant difference in mean FA above the SOL as compared to the mean FA at and below SOL. P value above versus below the SOL was statistically significant for both groups (0.04), but P value for at versus below the SOL (0.01) was statistically significant only in group B. On tractography, disruption of fiber tract at SOL was found in 14/15 (93.3%) cases of group A and 14/15 cases (93.3%) of group B (6/6 grade 4, 3/3 grade 3 and 5/6 grade 2 paraplegic cases). Conclusion: The FA and MD above the lesion were same as reported for healthy volunteer hence can be taken as control. FA

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

    PubMed

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

    1998-05-01

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

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

    PubMed Central

    2014-01-01

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

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

    PubMed

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

    1994-08-01

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

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

    PubMed Central

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

    2012-01-01

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

  6. Behr's syndrome and 3-methylglutaconic aciduria.

    PubMed

    Sheffer, R N; Zlotogora, J; Elpeleg, O N; Raz, J; Ben-Ezra, D

    1992-10-15

    We examined three patients from two families of Jewish-Iraqi origin who had progressive reduction of visual acuity and childhood onset of bilateral optic nerve atrophy without additional retinal abnormalities. They had neurologic symptoms compatible with Behr's syndrome. Neurologic signs included increased tendon reflexes, a positive Babinski sign, progressive spastic paraplegia, dysarthria, head nodding, and horizontal nystagmus. Neurologic involvement varied between affected siblings. The patients excreted excessive amounts of 3-methylglutaconic acid and 3-methylglutaric acid in their urine. We compared the characteristic ophthalmic features and the spectrum of neurologic signs encountered in this recently delineated autosomal recessive clinical entity with those of previously described entities associated with 3-methylglutaconic aciduria. Patients with early-onset optic atrophy should be examined for neurologic signs and screened for organic aciduria. A detailed ophthalmic examination is important in patients with neurologic abnormalities compatible with Behr's syndrome. PMID:1384336

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

    PubMed

    Gray, Kendra M; Derosa, Angela

    2013-12-01

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

  8. 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

  9. 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

  10. 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

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

    PubMed

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

    2015-09-01

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

  12. Bilateral oculomotor nerve palsy in Guillain-Barre syndrome.

    PubMed

    Burina, Adnan; Sinanović, Osman; Smajlović, Dzevdet; Vidović, Mirjana

    2008-01-01

    Guillain-Barre syndrome (GBS) is an acquired immune-mediated inflammatory disorder of the peripheral nervous system. GBS is also called acute idiopathic polyradiculoneuritis. Cranial nerves are affected in over 50% of all cases, with the facial nerves being affected the most. Otherwise, oculomotor nerves affection is rare and might occur in about 10% of cases. In this case report we present 61 years old female with GBS (acute motor and sensory axonal neuropathy subtype) associated with bilateral oculomotor nerve palsy. At the admittance in the neurological status were flaccid paraplegia, tendon reflexes absent at legs and reduced at arms, sensory disturbances in a distal (stocking-glove) distribution and bilateral ptosis. The disease was diagnosed on clinical features, nerve conduction velocity test (NCV), electromyogram (EMG) and cerebrospinal fluid (CSF) tests. After treatment with intravenous immunoglobulins and physical treatment the patient improved. She was able to walk by her own, mild semiptosis remained and she had no paresthesia. PMID:18669237

  13. Neuromyelitis Optica (NMO) with Abdominal Tuberculosis (TB).

    PubMed

    Bhatty, Shaheen A; Lal, Hari; Talib, Abu; Mahmood, Khalid; Naqvi, Iftekhar; Zaidi, Syeda Shaheera

    2015-10-01

    Neuromyelitis Optica (NMO), previously regarded as a form of multiple sclerosis, is defined by Gault and Devic, as a retrobulbar neuritis or papillitis accompanied by acute myelitis and occasionally other neurological symptom or signs not restricted to the spinal cord or optic nerves. With the diagnosis of specific antibodies, probable role of humoral immunity supports its pathogenesis. Only a few cases of NMO have been reported in association with pulmonary tuberculosis (TB). Here we report a case of young girl with acute onset paraplegia diagnosed to have NMO, who later on during hospital stay developed ascites which cultured positive for Mycobacterium tuberculosis. This association of abdominal TB with NMO is under-reported in literature. PMID:26522188

  14. Spina Bifida Cystica

    PubMed Central

    Lorber, John

    1972-01-01

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

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

    PubMed

    Vuillerme, N; Chenu, O; Pinsault, N; Moreau-Gaudry, A; Fleury, A; Demongeot, J; Payan, Y

    2007-01-01

    We introduce the innovative technologies, based on the concept of "sensory substitution", we are developing in the fields of biomedical engineering and human disability. Precisely, our goal is to design, develop and validate practical assistive biomedical and/or technical devices and/or rehabilitating procedures for persons with disabilities, using artificial tongue-placed tactile biofeedback systems. Proposed applications are dealing with: (1) pressure sores prevention in case of spinal cord injuries (persons with paraplegia, or tetraplegia); and (2) balance control improvement to prevent fall in older and/or disabled adults. This paper describes the architecture and the functioning principle of these biofeedback systems and presents preliminary results of two feasibility studies performed on young healthy adults. PMID:18003410

  16. 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

  17. [2 cases of vertebral hydatidosis treated by the association of surgery and mebendazole].

    PubMed

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

    1983-01-01

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

  18. 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

  19. [Long-term follow-up in patients with spinal cord injury - prevention and comprehensive care].

    PubMed

    Spreyermann, Regula; Michel, Franz

    2014-01-15

    Patients with spinal cord injuries suffer not only from sensory and motor deficits, but from failure of the autonomic nerve system which in consequence involves many organs and metabolic pathways. These deficits lead to a different approach to these patients and their medical, psychological and social problems. Three examples will illustrate the different approaches to typical medical problems of these patients. Regularly ambulatory long term follow up visits in specialized centres in close collaboration with general practitioners help to diminish complications and rehospitalisations. Facing the now ageing population with a spinal cord injury we need evidence based guidelines in follow up and preventive strategies for these patients. We updated these recommendations recently. The brochure is available on the webside oft he swiss society of paraplegia www.ssop.ch. PMID:24425548

  20. Cystic hydatidosis: a rare case of spine localization.

    PubMed

    Scarlata, Francesco; Giordano, Salvatore; Saporito, Laura; Marasa, Lorenzo; Li Pani, Giuseppe; Odierna, Antonio; Scaglione, Vincenzo; Di Carlo, Paola; Romano, Amelia

    2011-03-01

    Cystic hydatidosis is a zoonosis endemic both to Sicily and other Mediterranean areas. Generally, Echinococcus granulosus tapeworms develop in the liver, lung and less frequently in the peritoneum, spleen or kidney. We present a rare case of spinal hydatid disease. The patient was a 38-year-old housewife with a vertebral echinococcosis revealed by acute paraplegia of the legs. Medical treatment with albendazole and surgical intervention improved the clinical symptoms. This case is emblematic both for the unusual localization and for the need of a multidisciplinary approach for diagnosing and monitoring suspected hydatid lesions. Patients with suspected abdominal or lung echinococcosis should also be investigated for other localizations such as the brain, spine and heart. Furthermore, in endemic areas hydatidosis must be suspected in the presence of lesions occupying space in these districts. PMID:21471745

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

    PubMed Central

    Wong, Albert Sii Hieng; Yu, Denis Hee youg

    2015-01-01

    Full recovery from tetraplegia is uncommon in cervical spine injury. This has not being reported for cervical spine fracture in a patient with ankylosing spondylitis causing spinal epidural hematoma. We report on a case of cervical spine fracture in a patient with ankylosing spondylitis who came with tetraplegia. He underwent a two stage fixation and fusion. He had a complete recovery. Two hours after the operation he regained full strength in all the limbs while in the Intensive Care Unit. He went back to full employment. There are only two other reports in the literature where patients with ankylosing spondylitis and extradural hematoma who underwent treatment within 12 h and recovered completely from tetraparesis and paraplegia respectively. Patient with ankylosing spondylitis has a higher incidence of spinal fracture and extradural hematoma. Good outcome can be achieved by early diagnosis and treatment. This can ensure not only a stable spine, but also a rapid and complete recovery in a tetraplegic patient. PMID:25767586

  2. Indirect Neuromonitoring of the Spinal Cord by Near-Infrared Spectroscopy of the Paraspinous Thoracic and Lumbar Muscles in Aortic Surgery.

    PubMed

    Luehr, Maximilian; Mohr, Friedrich-Wilhelm; Etz, Christian D

    2016-06-01

    Paraplegia remains the most devastating complication of open and endovascular thoracic/thoracoabdominal aortic aneurysm (TAA/A) repair. However, the assessment of currently available neuromonitoring modalities remains challenging and difficult to interpret. Near-infrared spectroscopy (NIRS) has been introduced as a strategy for noninvasive, real-time monitoring of the paraspinous collateral network (CN) to detect potential spinal cord ischemia at our institution. Prior to TAA/A repair, a cerebrospinal fluid catheter is placed and four NIRS optodes are bilaterally positioned on the patient's back to transcutaneously monitor regional muscle oxygenation at the thoracic and lumbar levels. Indirect surveillance of the spinal cord by NIRS seems to be a tempting option with increasing evidence supporting the CN concept. PMID:26011674

  3. Human genetic disorders of sphingolipid biosynthesis.

    PubMed

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

    2015-01-01

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

  4. 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

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

    PubMed

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

    2008-09-01

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

  6. Severe obstructive calcifications affecting the descending and suprarenal abdominal aorta without coexisting peripheral atherosclerotic disease--coral reef aorta.

    PubMed

    Teebken, O E; Pichlmaier, M A; Kühn, C; Haverich, A

    2006-08-01

    The case of a 58-year-old woman with leg claudication due to a very rare form of atherosclerosis affecting the descending thoracic and abdominal aorta--known as coral reef aorta--without involvement of the femoro-distal vessels is reported. The patient was treated with a polyester bifurcation graft from the proximal descending aorta to both common iliac arteries via a left dorsal mini-thoracotomy and a second left retroperitoneal approach. This unusual approach was chosen instead of direct aortic replacement in order to prevent paraplegia. In case of future visceral or left renal malperfusion the diseased artery can be connected to the prosthesis directly or by the use of an additional bypass graft. This would not be the case with a conventional axillo-bifemoral graft. PMID:16941413

  7. [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

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

    PubMed

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

    2016-01-01

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

  9. 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

  10. 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

  11. 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

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

    PubMed

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

    2016-07-01

    Troyer syndrome is a complex hereditary spastic paraplegia (HSP) due to a mutation in SPG20 first reported in the Old Amish population. A genetic mutation in SPG20 is responsible for a loss of function of the protein spartin in this disease. Since its initial report, this syndrome has also been reported in Turkish and Omani families. Here we report the case of three patients of Filipino descent with Troyer syndrome. Whole exome sequencing (WES) identified a homozygous mutation c.364_365delAT which predicts p.Met122Valfs*2 in SPG20. This is the same mutation identified in affected patients from the Omani and Turkish families, and is the first report of this syndrome in the Filipino population. Although Troyer syndrome has characteristic phenotypic manifestations it is likely underdiagnosed due to its rarity and we expect that WES will lead to identifying this disease in other individuals. © 2016 Wiley Periodicals, Inc. PMID:27112432

  13. Radial Basis Function Neural Network-based PID model for functional electrical stimulation system control.

    PubMed

    Cheng, Longlong; Zhang, Guangju; Wan, Baikun; Hao, Linlin; Qi, Hongzhi; Ming, Dong

    2009-01-01

    Functional electrical stimulation (FES) has been widely used in the area of neural engineering. It utilizes electrical current to activate nerves innervating extremities affected by paralysis. An effective combination of a traditional PID controller and a neural network, being capable of nonlinear expression and adaptive learning property, supply a more reliable approach to construct FES controller that help the paraplegia complete the action they want. A FES system tuned by Radial Basis Function (RBF) Neural Network-based Proportional-Integral-Derivative (PID) model was designed to control the knee joint according to the desired trajectory through stimulation of lower limbs muscles in this paper. Experiment result shows that the FES system with RBF Neural Network-based PID model get a better performance when tracking the preset trajectory of knee angle comparing with the system adjusted by Ziegler- Nichols tuning PID model. PMID:19964991

  14. 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.

  15. 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

  16. 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

  17. 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.

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

    PubMed Central

    2016-01-01

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

  19. 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

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

    PubMed

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

    2016-09-01

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

  1. 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

  2. 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

  3. 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.

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

    PubMed Central

    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

  5. Palliative Surgical Approach to Rehabilitate Spinal Injury Patient in Indian Rural Setup

    PubMed Central

    Singh, Pradeep K; Sakale, Harshal; Shrivastva, Sandeep; Dulani, Rajesh

    2010-01-01

    Objective: To evaluate the usefulness of conventional spinal surgery as palliative procedure to rehabilitate dorsolumbar injuries in a rural setup. Materials and Methods: Twenty-three patients with dorsolumbar spine injury with complete paraplegia were assessed on the clinical and social rehabilitation parameters after surgical stabilization at Acharya Vinoba Bhave Rural Hospital Sawangi, Wardha, India. The study group comprised 21 male and 2 female patients. The dorsolumbar spine injury was fixed by conventional posterior instrumentation using short-segment pedicle screw system and Harrington rod system with or without fusion. Functional and neurologic outcome was recorded in the follow-up period by using Functional Independence Measure and Frankel grade, respectively. Correlation and analysis of results was established statistically. Results: Functional outcome showed statistically significant improvement. Social cognition was found intact in a significant number of patients. Conclusion: This study demonstrates the usefulness of conventional instrumentation as palliative surgical approach to stabilize and rehabilitate patients from deprived sector of rural India. PMID:21218006

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

    PubMed

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

    2012-10-01

    The purpose of this study was to determine preferences of people with spinal cord injury (SCI) and health care professionals (HCP) regarding the content and format of a SCI physical activity guide to support recently released SCI physical activity guidelines. Seventy-eight people with SCI and 80 HCP completed a survey questionnaire. Participants with SCI identified desired content items and their preferences for format. HCP rated the helpfulness of content items to prescribe physical activity. All content items were rated favorably by participants with SCI and useful by HCP. The risks and benefits of activity and inactivity, and strategies for becoming more active, were rated high by both samples. Photographs and separate information for those with paraplegia versus tetraplegia were strongly endorsed. These data were used to guide the development of an SCI physical activity guide to enhance the uptake of physical activity guidelines for people with SCI. The guide was publically released November 11, 2011. PMID:23027146

  7. Spinal cord schistosomiasis

    PubMed Central

    Adeel, Ahmed Awad

    2015-01-01

    Acute myelopathy is increasingly being recognized as a common neurological complication of schistosomiasis. Schistosome eggs reach the spinal cord either as egg emboli or as eggs produced by ectopic worms. This leads to inflammatory reaction and granuloma formation around the eggs. Patients with spinal schistosomiasis may not have clinical evidence of schistosomiasis. The typical clinical picture is that of lumbar pain preceded by other symptoms by hours or up to 3 weeks. Patients may present with paraparesis, urinary retention or paraplegia. Definitive diagnosis of spinal cord schistosomiasis is by detection of the eggs in a spinal cord biopsy or at autopsy. However, most cases are diagnosed based on a presumptive diagnosis that depends on a suggestive clinical picture, history or evidence of active schistosomiasis and exclusion of other conditions. Investigations include stools and urine examination for schistosome eggs, blood tests, magnetic resonance imaging (MRI) and examination of the cerebrospinal fluid. Treatment of cases is mainly by praziquantel, corticosteroids, surgical intervention and rehabilitation.

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

    PubMed Central

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

    2011-01-01

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

  9. Multifocal Epithelioid Hemangioendothelioma Derived from the Spine Region: Case Report and Literature Review

    PubMed Central

    Kerry, G.; Marx, O.; Kraus, D.; Vogel, M.; Kaiser, A.; Ruedinger, C.; Steiner, H.H.

    2012-01-01

    Background Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor with malignant biological behavior. It arises from endothelial cells, usually within soft tissues, and can occur in almost all locations. Case Report We report a unique case of a 25-year-old man who presented with sudden attacks of severe back pain followed by acute non-traumatic paraplegia. Emergency diagnostics revealed a pathologic fracture of the T7 vertebra with tumor tissue invasion of the spinal canal. Furthermore, multifocal metastases were found. Results To achieve en bloc resection, interdisciplinary surgical approaches were indicated. Despite multimodal therapy concepts, including radiotherapy and chemotherapy as well as endovascular embolization, the patient died within 8 weeks. Conclusion Prognosis of EHE is unpredictable and mainly determined by its location. The lesions are potentially aggressive; therefore, en bloc resection should be attempted whenever possible. However, as shown in the literature, only 15% of patients are suitable for total resection. PMID:22539920

  10. 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.

  11. Acute onset of postoperative syringohydromyelia.

    PubMed

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

    2015-01-01

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

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

    PubMed Central

    Curtis, Erik; Gonda, David; Ciacci, Joseph

    2015-01-01

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

  13. Nontraumatic Myelopathy Associated With Surfing

    PubMed Central

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

    2007-01-01

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

  14. 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

  15. Acute onset of postoperative syringohydromyelia

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

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

    2012-02-15

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

  17. Challenges to treatment of leukemia in HIV-positive children.

    PubMed

    Stefan, D Cristina; Dippenaar, Anel; De Bruin, Gerhard; Uys, Ronelle; van Toorn, Ronald

    2012-12-01

    We describe the challenges to treatment of leukemia in three cases of human immunodeficiency virus (HIV)-infected children with multiple infections and complications. Two of the three patients had acute myeloid leukemia and the other one acute lymphoblastic leukemia. Two of the patients were known with HIV infection; the third was diagnosed on admission. All patients received antiretroviral therapy with standard doses of lamivudine, stavudine and efavirenz or lopinavir/retonavir. All three were diagnosed with Mycobacterium tuberculosis on one or more occasions: pulmonary or miliary involvement or tuberculous meningitis. One patient developed spinal paraplegia and needed an urgent laminectomy. Later he recovered almost completely. The interaction between antiretroviral and antituberculosis treatments combined with chemotherapy, antibiotics and supportive care is not known. Despite the severity and the complexity of several associated diseases, the outcome of the patients was rewarding and encouraging. PMID:22421805

  18. 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

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

    PubMed

    Charoenwattanasatien, Ratana; Pengthaisong, Salila; Breen, Imogen; Mutoh, Risa; Sansenya, Sompong; Hua, Yanling; Tankrathok, Anupong; Wu, Liang; Songsiriritthigul, Chomphunuch; Tanaka, Hideaki; Williams, Spencer J; Davies, Gideon J; Kurisu, Genji; Cairns, James R Ketudat

    2016-07-15

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

  20. Idiopathic Thoracic Spontaneous Spinal Epidural Hematoma.

    PubMed

    Aycan, Abdurrahman; Ozdemir, Seymen; Arslan, Harun; 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

  1. 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

  2. Spinal cord protection in aortic endovascular surgery.

    PubMed

    Scott, D A; Denton, M J

    2016-09-01

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

  3. Delayed Visceral and Spinal Cord Malperfusion after Axillo-Bifemoral Bypass for Complicated Acute Type B Aortic Dissection

    PubMed Central

    Tomioka, Hideyuki; Katahira, Seiichiro; Hoshino, Takeshi; Hanzawa, Kazuhiko

    2014-01-01

    We describe a successfully treated case of acute type B aortic dissection complicated with lower extremity, visceral, and spinal cord malperfusion. To restore perfusion to both lower extremities, we performed an emergency right axillo-bifemoral bypass. Furthermore, we performed total arch replacement, including primary entry closure, because of delayed visceral organ ischemia. Unexpectedly, delayed paraplegia occurred after hospital discharge; however, the patient recovered without any neurologic sequelae after early introduction of hyperbaric oxygen therapy. Because another episode of organ malperfusion in the long term cannot be anticipated, and even though the previous organ malperfusion episode was treated successfully, close observation is mandatory for detecting clinical manifestations in combination with the availability of imaging modalities. PMID:25298840

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

    PubMed Central

    2014-01-01

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

  5. 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

  6. 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

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

    PubMed

    Yamamoto, Seizo

    2011-07-01

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

  8. 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

  9. Epidemiology of spinal cord injury.

    PubMed

    Kurtzke, J F

    1977-01-01

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

  10. 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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2014-05-01

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

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

    PubMed

    Frankel, H L

    2012-11-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-04-01

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

  16. 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

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

    PubMed Central

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

    2015-01-01

    Adaptor proteins (AP 1–5) are heterotetrameric complexes that facilitate specialized cargo sorting in vesicular-mediated trafficking. Mutations in AP5Z1, encoding a subunit of the AP-5 complex, have been reported to cause hereditary spastic paraplegia (HSP), although their impact at the cellular level has not been assessed. Here we characterize three independent fibroblast lines derived from skin biopsies of patients harbouring nonsense mutations in AP5Z1 and presenting with spastic paraplegia accompanied by neuropathy, parkinsonism and/or cognitive impairment. In all three patient-derived lines, we show that there is complete loss of AP-5 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

  18. Elephant trunk technique for hybrid aortic arch repair.

    PubMed

    Miyamoto, Yuji

    2014-03-01

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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. Combined open and endovascular treatment of thoracoabdominal aortic pathologies: a systematic review and meta-analysis

    PubMed Central

    Mylonas, Spyridon N.; Antonopoulos, Constantinos N.; Liapis, Christos D.

    2012-01-01

    Background A combined open-endovascular technique has emerged as an alternative treatment option for thoracoabdominal pathologies. However, reported experiences from various medical centers have been contradictory and heterogeneous. The aim of this study is to assess the mortality rate and various complication rates associated with this approach. Methods An electronic health database search was performed on all articles published up to March of 2012 describing combined open-endovascular repair of thoracoabdominal pathologies. Studies were included in the meta-analysis if they had ≥10 patients and reported the basic outcome criteria. End points of the meta-analysis were defined as primary technical success, endoprosthesis related complications, 30-day/in-hospital mortality, symptoms of spinal cord ischemia (SCI) and irreversible paraplegia, permanent renal function impairment, and other major complications. Results Fourteen studies were deemed eligible for this meta-analysis with a total of 528 patients (68.0% male, mean age 70.5 years). The mean follow-up period was 34.2 months. The pooled estimate for primary technical success and visceral graft patency was 95.4% and 96.5% respectively. An endoleak developed in 106 (21.1%) patients in whom both stages had been completed. The pooled rate for symptomatic SCI was 7.0% and for irreversible paraplegia 4.4%. The pooled proportion for permanent renal failure was 7.0% and for mesenteric ischemia 4.5%. Prolonged respiratory support and cardiac complications were observed in a pooled rate of 7.8% and 4.6% respectively. The meta-analysis for 30-day/in-hospital mortality revealed a pooled rate of 14.3%. Conclusions Although the hybrid technique for thoracoabdominal aortic pathology provides a less invasive approach, the technique is still associated with a considerable morbidity and mortality rates. High risk patients unfit to withstand open repair, are equally likely to suffer significant complications with the hybrid

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

    PubMed

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

    2016-10-01

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

  8. 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

  9. 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

  10. 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

  11. Genetic and clinical analysis of spinocerebellar ataxia type 36 in Mainland China.

    PubMed

    Zeng, S; Zeng, J; He, M; Zeng, X; Zhou, Y; Liu, Z; Xia, K; Pan, Q; Jiang, H; Shen, L; Yan, X; Tang, B; Wang, J

    2016-08-01

    Spinocerebellar ataxia type 36 (SCA36) is a new SCA subtype recently reported in Japanese and Spanish pedigrees. To assess the frequency and clinical characteristics of SCA36 in patients from Mainland China, we combined the repeat-primed polymerase chain reaction method and Southern blot analysis to detect the GGCCTG hexanucleotide repeats of NOP56 in 364 probands with SCA, 126 probands with hereditary spastic paraplegia and 99 probands with amyotrophic lateral sclerosis (ALS). Systematic and targeted clinical evaluations and investigations were conducted in the SCA36 patients. As a result, eight autosomal dominant spinocerebellar ataxia (ADCA) pedigrees (a total of 13 patients) and one sporadic SCA (S-SCA) patient were identified as SCA36 in the SCA cohort, accounting for approximately 1.60% of the cases in the ADCA group and 0.32% of those in the S-SCA group in Mainland China. The characteristics include late onset and slow progression accompanied by acoustic impairments and 'possible' ALS phenotype in patients from Mainland China. PMID:26661328

  12. The Seatbelt Syndrome-Do We Have a Chance?: A Report of 3 Cases With Review of Literature.

    PubMed

    Eberhardt, Christiane S; Zand, Tristan; Ceroni, Dimitri; Wildhaber, Barbara E; La Scala, Giorgio

    2016-05-01

    The seatbelt syndrome represents an injury pattern seen after motor vehicle accidents. It is secondary to either the misplacement of seatbelts over the abdomen or the misuse of the restraint systems. This syndrome is infrequent in the pediatric population and occurs mostly in school-aged children because recommended lap-shoulder belts and booster seats are often not used in this age group, so that the seatbelt lies over the abdomen. Sudden deceleration bends the child around the lap belt causing injuries to the viscera, head, and spine (Chance fracture), often associated with paraplegia. Because not all patients have an abdominal seatbelt sign, this syndrome can easily not be recognized with potentially life-threatening consequences.We report on 3 patients with the seatbelt syndrome and review the literature regarding prevalence, diagnosis, treatment, and prognosis of the different injuries and discuss the diagnostic challenges of intestinal lesions and their management.Following this accident pattern, in hemodynamically stable patients with a normal abdominal computed tomography scan, close surveillance is warranted to rule out intestinal lesions manifesting with progressive peritoneal irritation. In hemodynamically unstable patients, or if there is evidence of free air on the computed tomography scan, emergency abdominal exploration is required. PMID:26087444

  13. Magnetic resonance imaging characteristics of suspected vertebral instability associated with fracture or subluxation in eleven dogs.

    PubMed

    Johnson, Philippa; Beltran, Elsa; Dennis, Ruth; Taeymans, Olivier

    2012-01-01

    The purpose of this study was to describe the magnetic resonance imaging (MRI) characteristics of suspected instability in dogs with vertebral fractures or subluxations. Eleven dogs that had MRI examinations of the spine prior to surgical stabilization of vertebral fractures and/or subluxations were included in the study. Nine dogs also had survey radiographs. Four dogs had cervical fracture or fracture-subluxation and presented with tetraplegia with intact nociception (n = 2) or nonambulatory tetraparesis (n = 2). Seven dogs had thoracolumbar fracture-subluxation or subluxation and presented with paraplegia with intact nociception (n = 5) or nonambulatory paraparesis (n = 2). A three-compartment model was applied to the interpretation of both the radiographic and MRI studies. Radiography identified compartmental disruption consistent with spinal instability in seven out of the nine cases radiographed. In MRI studies, rupture of the supportive soft tissue structures and/or fracture in at least two compartments could be visualized. Nine cases had spinal cord changes on MRI including signal intensity changes, swelling, compression, and intramedullary hemorrhage. Paravertebral muscle intensity changes were also visible at each trauma site. Magnetic resonance imaging provided helpful information on the location and extent of damage to supportive soft tissue structures and enabled assessment of spinal cord injury in this group of dogs with surgically confirmed vertebral fractures and subluxations. PMID:22703283

  14. Spinal Cord Infarction Caused by Non-dissected and Unruptured Thoracoabdominal Aortic Aneurysm with Intraluminal Thrombus.

    PubMed

    Ki, Young Jin; Jeon, Byoung Hyun; Bang, Heui Je

    2012-04-01

    Spinal cord infarction, especially anterior spinal artery syndrome, is a relatively rare disease. We report a case of spinal cord infarction caused by thoracoabdominal aortic aneurysm with intraluminal thrombus. A 52-year-old man presented with sudden onset paraplegia. At first, he was diagnosed with cervical myelopathy due to a C6-7 herniated intervertebral disc, and had an operation for C6-7 discetomy and anterior interbody fusion. Approximately 1 month after the operation, he was transferred to the department of rehabilitation in our hospital. Thoracoabdominal aortic aneurysm with intraluminal thrombus was found incidentally on an enhanced computed tomography scan, and high signal intensities were detected at the anterior horns of gray matter from the T8 to cauda equina level on T2-weighted magnetic resonance imaging. There was no evidence of aortic rupture, dissection, or complete occlusion of the aorta. We diagnosed his case as a spinal cord infarction caused by thoracoabdominal aortic aneurysm with intraluminal thrombus. PMID:22639759

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

    PubMed Central

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

    2012-01-01

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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

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

    PubMed

    Costa, A

    1989-01-01

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

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

    PubMed

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

    2014-03-01

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

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

    PubMed

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

    1989-11-01

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

  4. 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

  5. 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

  6. Tyrosine hydroxylase deficiency with severe clinical course.

    PubMed

    Zafeiriou, D I; Willemsen, M A; Verbeek, M M; Vargiami, E; Ververi, A; Wevers, R

    2009-05-01

    Tyrosine hydroxylase (TH) deficiency is a rare autosomal recessive disorder mapped to chromosome 11p15.5. Its clinical expression varies with presentations as dopa-responsive dystonia (recessive Segawa's disease), dopa-responsive infantile parkinsonism, dopa-responsive spastic paraplegia, progressive infantile encephalopathy or dopa-non-responsive dystonia. We describe a 7-year-old boy with progressive infantile encephalopathy and non-responsiveness to dopamine. The patient demonstrated generalized hypotonia, pyramidal tract dysfunction and temperature instability after the second month of life. Dystonia, tremor and oculogyric crises complicated the clinical picture during the following months. Neurotransmitter analysis in CSF disclosed almost undetectable levels of HVA and MHPG, whereas serum prolactin was profoundly increased. Subsequent molecular analysis revealed homozygosity for a missense mutation (c.707T>C) in the TH gene. l-Dopa therapy in both high and low doses resulted in massive hyperkinesias, while substitution with selegiline exerted only a mild beneficial effect. Today, at the age of 7 years, the patient demonstrates severe developmental retardation with marked trunkal hypotonia, hypokinesia and occasionally dystonic and/or hyperkinetic crises. He is the third Greek patient with TH deficiency to be reported. Since all three patients carry the same pathogenetic mutation, a founder effect is suspected. PMID:19282209

  7. [Destructive spondylarthropathy in dialysis patients].

    PubMed

    Stein, G; Schneider, A; Marzoll, I; Sperschneider, H; Ritz, E

    1991-01-01

    Back pain and a cervicobrachial syndrome, as well as progressive sensory and motor deficits as far as symptoms of paraplegia, developed in two dialysis patients two and five years after the start of dialysis. One was a 60-year-old woman with pyelonephritis, the other a 55-year-old man with glomerulonephritis. There were typical radiological signs of destructive spondylarthropathy (narrowed intervertebral spaces and slippage of the vertebral bodies). The female patient required several operations (spondylothesis and orthothesis) and both patients received daily 10,000 IU vitamin D and 3-4 g calcium carbonate. In the woman the destructive process no longer progressed one year after onset of symptoms, but she still required many analgesics. She died three months later of circulatory failure. The man died four weeks after the onset of symptoms from purulent meningitis. At autopsy only renal fibrous ostitis was still demonstrable. Amyloidosis resulting from an increase in beta 2-microglobulin level were excluded by both histological and immunohistochemical examinations. PMID:1985800

  8. Experience of endovascular repair of thoracic aortic dissection after blunt trauma injury in a district general hospital

    PubMed Central

    Lee, Chih-Hsien; Huang, Jau-Kang

    2016-01-01

    Background Traumatic thoracic aortic dissection is uncommon in clinical practice; however, it is associated with high morbidity and mortality. Thoracic aortic dissection is usually caused by sudden deceleration resulting from a traffic accident or fall. Aortic injury after blunt trauma is a critical condition. This study reported the outcomes of endovascular repair of acute traumatic aortic dissection in patients at a district general hospital. Methods In this study, we retrospectively reviewed the clinical data of eight patients with acute traumatic aortic dissection after a blunt trauma who had undergone thoracic endovascular aortic repair (TEVAR) between January 2012 and December 2015 at a district general hospital in Taiwan. Results The median age of the patients was 49±22 years (range, 20–77 years), and 6 of the 8 (75%) patients were men. Five patients were involved in traffic accidents, and 3 patients had fallen from heights. The injury severity score (ISS) of the patients ranged from 17 to 66. In all patients, the aortic injury was located near the origin of the left subclavian artery (LSA). Four patients had seal ostium of subclavian artery, left. None of the patients developed paraplegia or lower extremity ischemia. Moreover, all patients had concomitant injuries, and no patients died postoperatively. Conclusions Endovascular repair is a rapid and minimally invasive therapy for patients with traumatic aortic injury and is associated with favorable technical results. PMID:27293831

  9. [Emergency Thoracic Endovascular Aortic Repair of Ruptured Kommerell's Diverticulum with an Acute Aortic Dissection].

    PubMed

    Seguchi, Ryuta; Ohtake, Hiroshi; Yoshimura, Takahiro; Shintani, Yoshiko; Nishida, Yuji; Kiuchi, Ryuta; Yamaguchi, Shojiro; Tomita, Shigeyuki; Sanada, Junichiro; Matsui, Osamu; Watanabe, Go

    2016-06-01

    This case report describes emergency thoracic endovascular aortic repair (TEVAR) of a ruptured Kommerell's diverticulum associated with a type B acute aortic dissection in a patient with a right aortic arch. A 64-year-old male was admitted with symptoms of sudden paraplegia and shock. The computed tomography imaging showed right aortic arch anomaly, with mirror image branching of the major arteries. The aorta was dissected from the origin of the right subclavian artery to the terminal aorta, with a thrombosed false lumen. Rupture was found in a 6.3 cm aneurysm located in the distal arch, which was diagnosed as Kommerell's diverticulum. We performed emergency TEVAR, and the aneurysm was successfully excluded using deployment of a Gore Tag stent-graft. At 3 months' follow-up, the patient was doing well and showed shrinkage of the aneurysm was confirmed. TEVAR is considered to be a suitable procedure for an emergency aortic catastrophe even in patients with aortic anomaly. PMID:27246128

  10. 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

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

    PubMed

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

    2014-05-01

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

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

    PubMed

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

    2016-09-01

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

  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. 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

  15. 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

  16. 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

  17. 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

  18. Assessing the socioeconomic impact of improved treatment of head and spinal cord injuries.

    PubMed

    Berkowitz, M

    1993-01-01

    Assessment of improved treatment of neurotrauma presents two basic challenges: 1) measurement of the medical effects of treatment, and 2) evaluation of these effects in socioeconomic terms. A nationwide survey was conducted in 1988 to estimate the prevalence of persons in the United States who suffered traumatic spinal cord injury and to calculate its economic consequences. Seven hundred fifty-eight persons weighted to be representative of the spinal cord injury population were interviewed. The prevalence rate was found to be 721 cases per million people. Conservative calculations for 1988 showed that the average direct costs per person were $103,000 for hospitalization and home modifications during the first 2 years postinjury and $14,000 per year thereafter for medical care. Losses in earnings and homemaker services averaged $12,726 per year. Total aggregate costs for 1 year were estimated at $5.6 billion. Lifetime costs for a representative person with complete paraplegia injured at age 33 were estimated to be $500,000. For a representative person with complete quadriplegia injured at age 27, these costs amounted to $1 million. These data can be used to estimate cost savings related to decreased disability resulting from improved treatment. PMID:8445206

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  1. 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

  2. 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.

  3. 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

  4. The articles of Babinski on his sign and the paper of 1898.

    PubMed

    Bruno, Estañol; Horacio, Sentíes-Madrid; Yolanda, Elías; Guillermo, García Ramos

    2007-01-01

    In 1896 Joseph François Felix Babinski described for the first time the phenomenon of the toes; nevertheless in this first paper he simply described extension of all toes with pricking of the sole of the foot. It was not until the second paper of 1898 that he specifically described the extension of the hallux with strong tactile stimulation (stroking) of the lateral border of the sole. Babinski probably discovered his sign by a combination of chance observation and careful re-observation and replication. He also had in mind practical applications of the sign, particularly in the differential diagnosis with hysteria and in medico-legal areas. Several of the observations and physiopathological mechanisms proposed by Babinski are still valid today, e.g, he realized since 1896 that the reflex was part of the flexor reflex synergy and observed that several patients during the first hours of an acute cerebral or spinal insult had absent extensor responses. He also found that most patients with the abnormal reflex had weakness of dorsiflexion of the toes and ankles and observed a lack of correlation between hyperactive myotatic reflexes and the presence of an upgoing hallux. He discovered that not all patients with hemiplegia or paraplegia had the sign but thought erroneously that some normal subjects could have an upgoing toe. Between 1896 and 1903 Babinski continued to think on the sign that bears his name and enrich its semiological and physiopathological value. PMID:18040103

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

    PubMed

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

    2015-12-15

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

  6. Hippocrates: the forefather of neurology.

    PubMed

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

    2014-09-01

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

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

    PubMed Central

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

    2016-01-01

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

  8. 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.

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

    PubMed

    Horvath, Emoke; Demian, Smaranda; Nagy, Elod

    2016-01-01

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

  10. 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

  11. 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

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

    PubMed

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

    1991-01-01

    We studied motor evoked potentials to transcranial magnetic stimulation in patients with unilateral upper limb amputations, complete T10-T12 spinal cord transection, and congenital mirror movements and in controls. Different muscles in the trunk and upper and lower extremities were evaluated at rest. In controls, muscles could be activated with stimulation of regions several centimeters wide. These areas overlapped extensively when muscles studied were from the same limb and shifted positions abruptly when muscles were from different limbs. Distal muscles were easier to activate than proximal muscles and normally evidenced exclusively a contralateral representation. Congenital defects in motor control in patients with mirror movements resulted in marked derangement of the map of outputs of distal hand muscles with enlarged and ipsilateral representations. Peripheral lesions, either acquired (amputations) or congenital (congenital absence of a limb), resulted in plastic reorganization of motor outputs targeting muscles immediately proximal to the stump. Central nervous system lesions (i.e., spinal cord injury producing paraplegia) also resulted in enlargement of the map of outputs targeting muscles proximal to the lesion. These results indicate that magnetic stimulation is a useful non-invasive tool for exploring plastic changes in human motor pathways following different types of injury. PMID:1773774

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

    PubMed

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

    2015-11-22

    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

  14. Microsurgical procedures in the peripheral nerves and the dorsal root entry zone for the treatment of spasticity.

    PubMed

    Sindou, M; Keravel, Y

    1988-01-01

    When spasticity becomes severe and harmful, in spite of physical and medical therapy, neurosurgery can give functional improvement. This paper deals with the long term results of Selective Peripheral Neurotomies of the Tibial Nerve and Selective Posterior Rhizotomies in the Dorsal Root Entry Zone, in 123 patients with spastic disorders localized to the limbs. The micro-techniques and intra-operative electro-stimulation for identification of the nervous structures responsible for the spastic components, can give a substantial reduction of the harmful spasticity, without suppressing the useful muscle tone and impairing the residual motor and sensory functions. The results were effective, with a 1 to 13 year follow-up (5 on average), in 89% of 47 Selective Peripheral Neurotomies of the tibial nerve for spastic foot, in 92% of 53 Selective Posterior Rhizotomies for paraplegia and in 87% of 23 Selective Posterior Rhizotomies for hemiplegia. In the most severe situations ("comfort" indications), correction of the abnormal postures and relief of pain facilitated nursing and physiotherapy. Sometimes there was reappearance of some useful voluntary movements. In the less affected patients ("functional" indications), the suppression of the harmful spastic components made the persistant capacities more effective. PMID:3165206

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

    PubMed Central

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

    2012-01-01

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

  16. Mutation analysis of genes within the dynactin complex in a cohort of hereditary peripheral neuropathies.

    PubMed

    Tey, S; Ahmad-Annuar, A; Drew, A P; Shahrizaila, N; Nicholson, G A; Kennerson, M L

    2016-08-01

    The cytoplasmic dynein-dynactin genes are attractive candidates for neurodegenerative disorders given their functional role in retrograde transport along neurons. The cytoplasmic dynein heavy chain (DYNC1H1) gene has been implicated in various neurodegenerative disorders, and dynactin 1 (DCTN1) genes have been implicated in a wide spectrum of disorders including motor neuron disease, Parkinson's disease, spinobulbar muscular atrophy and hereditary spastic paraplegia. However, the involvement of other dynactin genes with inherited peripheral neuropathies (IPN) namely, hereditary sensory neuropathy, hereditary motor neuropathy and Charcot-Marie-Tooth disease is under reported. We screened eight genes; DCTN1-6 and ACTR1A and ACTR1B in 136 IPN patients using whole-exome sequencing and high-resolution melt (HRM) analysis. Eight non-synonymous variants (including one novel variant) and three synonymous variants were identified. Four variants have been reported previously in other studies, however segregation analysis within family members excluded them from causing IPN in these families. No variants of disease significance were identified in this study suggesting the dynactin genes are unlikely to be a common cause of IPNs. However, with the ease of querying gene variants from exome data, these genes remain worthwhile candidates to assess unsolved IPN families for variants that may affect the function of the proteins. PMID:26662454

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

    Human PNPLA6 gene encodes Neuropathy Target Esterase protein (NTE). PNPLA6 gene mutations cause hereditary spastic paraplegia (SPG39 HSP), Gordon-Holmes syndrome, Boucher-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

  20. 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.

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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

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

    PubMed Central

    Fregly, Benjamin J.

    2011-01-01

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

  9. 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

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

    PubMed

    Dolinger, Cami; Strider, David V

    2010-12-01

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

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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

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

    SciTech Connect

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

    1995-11-01

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

  17. 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

  18. 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

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

    PubMed Central

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

    2014-01-01

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

  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. Extramedullary relapse after allogeneic bone marrow transplantation plus buffy-coat in two high risk patients.

    PubMed

    Salutari, P; Sica, S; Micciulli, G; Rutella, S; Di Mario, A; Leone, G

    1996-01-01

    In order to obtain an additional graft versus leukemia effect (GVL) and rapid engraftment, donor leukocyte infusion (DLI) was added to unseparated, sex-mismatched allogeneic bone marrow transplantation in two male patients (age 21, 26) affected by high risk hematological malignancies (refractory T-ALL, refractory B-LBL in leukemic phase). Graft versus host disease (GVHD) prophylaxis consisted of methotrexate (MTX) alone. DLI were obtained after G-CSF 16 ug/kg/day sc. A total of 2.36 and 5.8 x 10(6)/kg MNC, 5.4 and 11 x 10(6)/kg CD34+ cells, 1.3 and 1.3 x 10(6)/kg CD3+ lymphocytes, respectively, were infused. Hemopoietic recovery occurred promptly. Complete chimerism was detected by cytogenetic examination. One patient developed an extramedullary relapse that first involved the cranial nerves, and then the testes, soft tissue and skin; the other patient developed central nervous system disease and then bilateral paravertebral masses with progressive paraplegia. Despite complete medullary remission with normal female karyotype, both patients died from extramedullary progression of their disease. Our observation shows that, at least in high risk patients, no additional GVHD or GVL effect was evident after donor leukocyte infusion. Extramedullary relapse was not prevented despite good control of medullary disease. PMID:8641654

  2. [Thoracoabdominal aortic aneurysm].

    PubMed

    Kalder, J; Kotelis, D; Jacobs, M J

    2016-09-01

    Thoracoabdominal aortic aneurysms (TAAA) are rare events with an incidence of 5.9 cases per 100,000 persons per year. In Germany approximately 940 TAAA procedures are performed annually. The cause of TAAA is mostly degenerative but they can also occur on the basis of an aortic dissection or connective tissue disease (e. g. Marfan's syndrome). Patients often have severe comorbidities and suffer from hypertension, coronary heart disease or chronic obstructive pulmonary disease, mostly as a result of smoking. Operative treatment is indicated when the maximum aortic diameter has reached 6 cm (> 5 cm in patients with connective tissue disease) or the aortic diameter rapidly increases (> 5 mm/year). Treatment options are open surgical aortic repair with extracorporeal circulation, endovascular repair with branched/fenestrated endografts and parallel grafts (chimneys) or a combination of open and endovascular procedures (hybrid procedures). Mortality rates after both open and endovascular procedures are approximately 8 % depending on the extent of the repair. Furthermore, there are relevant risks of complications, such as paraplegia (up to 20 %) and the necessity for dialysis. In recent years several approaches to minimize these risks have been proposed. Besides cardiopulmonary risk evaluation, clinical assessment of patients by the physician with respect to the patient-specific anatomy influences the allocation of patients to one treatment option or another. Surgery of TAAA should ideally be performed in high-volume centers in order to achieve better results. PMID:27558261

  3. Hereditary and metabolic myelopathies.

    PubMed

    Hedera, Peter

    2016-01-01

    Hereditary and metabolic myelopathies are a heterogeneous group of neurologic disorders characterized by clinical signs suggesting spinal cord dysfunction. Spastic weakness, limb ataxia without additional cerebellar signs, impaired vibration, and positional sensation are hallmark phenotypic features of these disorders. Hereditary, and to some extent, metabolic myelopathies are now recognized as more widespread systemic processes with axonal loss and demyelination. However, the concept of predominantly spinal cord disorders remains clinically helpful to differentiate these disorders from other neurodegenerative conditions. Furthermore, metabolic myelopathies are potentially treatable and an earlier diagnosis increases the likelihood of a good clinical recovery. This chapter reviews major types of degenerative myelopathies, hereditary spastic paraplegia, motor neuron disorders, spastic ataxias, and metabolic disorders, including leukodystrophies and nutritionally induced myelopathies, such as vitamin B12, E, and copper deficiencies. Neuroimaging studies usually detect a nonspecific spinal cord atrophy or demyelination of the corticospinal tracts and dorsal columns. Brain imaging can be also helpful in myelopathies caused by generalized neurodegeneration. Given the nonspecific nature of neuroimaging findings, we also review metabolic or genetic assays needed for the specific diagnosis of hereditary and metabolic myelopathies. PMID:27430441

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

    PubMed

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

    2016-01-01

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

  5. 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

  6. 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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    SciTech Connect

    Alexander, T.S.

    1987-01-01

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

  10. [Is there a place for surgery in Pott's disease in adults? Our experience in Gabon].

    PubMed

    Loembe, P M; Chouteau, Y

    1994-01-01

    Tuberculous spondylitis treatment in developing nations remains controversial. We report our experience, working in a Center where appropriate medical and human structures are available. 22 of 78 adults treated at Jeanne-Ebori Hospital (Gabon), for tuberculous spondylitis, between August 1982 and June 1992, underwent surgery. The average age was 48 years (range, twenty-six to sixty-eight years). Eighteen patients had neurological complications: progressive spinal cord lesions: 15 cases (tetraplegia: 3, paraplegia: 11, tetraparesis: 1) and radicular syndromes (3 cases). The patients were seen in advanced stages of the disease with bone destruction, associated with collapse of vertebrae in ten cases. Indications for surgery were: neurologic in eleven cases, mechanical in one case, and mixed in ten cases (neurologic and mechanical: 5, etiologic and mechanical: 3, etiologic and neurologic: 2). Anterior approach were performed in 10 cases, posterior approach in 12 cases, generally, following an initial three weeks course of antituberculous therapy. The average length of time spent in hospital including rehabilitation had been 10.4 weeks. The average follow-up was 23.7 months (range: 8 months to 8 years). All patients obtained fusion, and stability was achieved after 3-5 months. The neurological recovery was complete in 9 cases, partial in 8 cases, unchanged in one case. All patients were considered medically cured. The analysis of material and socio economic difficulties obliges us to reduce the treatment length by favoring surgical intervention in relatively advanced lesions. Moreover, that allows to specify the diagnosis. PMID:7753296

  11. 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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Wijemanne, Subhashie; Jankovic, Joseph

    2015-07-01

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

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

    PubMed

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

    2016-07-01

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

  15. 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

  16. 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

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

    PubMed Central

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

    2012-01-01

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

  18. [A case of multiple sclerosis with alien hand (diagonistic dyspraxia)].

    PubMed

    Konagaya, Masaaki; Sakai, Motoko

    2007-05-01

    In this paper, we describe a case of mutiple sclerosis (MS) with diagonistic dyspraxia and the callosal lesions in MRI. The patient was a 54-year-old woman with 12 year-history of suffering from MS. Her clinical symptoms were left alien hand, mild euphoria, right blindness, left visual deficit (0.06), mild weakness of right upper limb, complete paraplegia of lower limbs, total sensory deficit below middle sternal level and neurogenic bladder. She was right-handed person and her alien hand was such a manner; when she intended to use spoon with right hand, her left hand aimlessly began to hold and release a cup or dish. Then, she was diagnosed as diagnostic dyspraxia. Neuropsychological examinations disclosed left hemispheric dysfunction including left hand agraphia and disconnection of the callosum. MRI showed patchy lesions in the callosum, right optic radiation, both side thalamus (left > right), left cerebral peduncle, and spinal cord of cervical to the thoracal portion. Although the functional disorders and the radiological atrophy of the callosum, the clinical manifestation of the callosal disconnection in MS cases has been scarcely reported, and this case seems to be a quite rare condition to be described. PMID:17533980

  19. 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

  20. 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

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

    PubMed Central

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

    2009-01-01

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

  3. 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

  4. Extensive thoracoabdominal aortic aneurysm repair using deep hypothermic bypass and circulatory arrest.

    PubMed

    Nishi, Hiroyuki; Miyamoto, Satoru; Minamimura, Hirokazu; Ishikawa, Takumi; Kato, Yasuyuki; Arimoto, Hideki; Ohue, Kensuke; Shimizu, Yoshihiro

    2004-03-01

    We sought to evaluate the safety and usefulness of deep hypothermic cardiopulmonary bypass with intervals of circulatory arrest for extensive thoracoabdominal aortic aneurysms. Between March 1994 and December 2002, 17 patients with Crawford type I and II were reviewed retrospectively. The patients were divided into two groups: group H (hypothermic circulatory arrest, n = 8) and group N (normothermic cardiopulmonary bypass, n = 9). In group H, in-hospital mortality was 12.5%, and that in group N was 11.1%. Operation times were similar between the two groups though the cardiopulmonary bypass time was significantly shorter in group N than in group H (p < 0.05). Postoperative paraplegia occurred in 1 patient of group N. Postoperative renal dysfunction occurred in none of group H except in 1 preoperative dialysis case, whilst it occurred in 6 patients of group N. Postoperative creatinine levels were significantly higher in group N than in group H. Three cases in group H required tracheostomy. Our experience with hypothermic cardiopulmonary bypass and circulatory arrest for diffuse type thoracoabdominal aortic aneurysm confirms the safety and efficacy of this technique. Although respiratory complications remain a problem, the technique is considered to be effective for renal protection. PMID:14977747

  5. 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

  6. 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

  7. Unique function of Kinesin Kif5A in localization of mitochondria in axons.

    PubMed

    Campbell, Philip D; Shen, Kimberle; Sapio, Matthew R; Glenn, Thomas D; Talbot, William S; Marlow, Florence L

    2014-10-29

    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

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

    PubMed Central

    Campbell, Philip D.; Marlow, Florence L.

    2013-01-01

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

  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. 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

  11. The relationship between electrical stimulus and joint torque: a dynamic model.

    PubMed

    Ferrarin, M; Pedotti, A

    2000-09-01

    The knowledge of the behavior of electrically activated muscles is an important requisite for the development of functional electrical stimulation (FES) systems to restore mobility to persons with paralysis. The aim of this work was to develop a model capable of relating electrical parameters to dynamic joint torque for FES applications. The knee extensor muscles, stimulated using surface electrodes, were used for the experimental preparation. Both healthy subjects and people with paraplegia were tested. The dynamics of the lower limb were represented by a nonlinear second order model, which took account of the gravitational and inertial characteristics of the anatomical segments as well as the damping and stiffness properties of the knee joint. The viscous-elastic parameters of the system were identified experimentally through free pendular movements of the leg. Leg movements induced by quadriceps stimulation were acquired too, using a motion analysis system. Results showed that, for the considered experimental conditions, a simple one-pole transfer function is able to model the relationship between stimulus pulsewidth (PW) and active muscle torque. The time constant of the pole was found to depend on the stimulus pattern (ramp or step) while gain was directly dependent on stimulation frequency. PMID:11001514

  12. High Frequency of Pathogenic Rearrangements in SPG11 and Extensive Contribution of Mutational Hotspots and Founder Alleles.

    PubMed

    Günther, Sven; Elert-Dobkowska, Ewelina; Soehn, Anne S; Hinreiner, Sophie; Yoon, Grace; Heller, Raoul; Hellenbroich, Yorck; Hübner, Christian A; Ray, Peter N; Hehr, Ute; Bauer, Peter; Sulek, Anna; Beetz, Christian

    2016-07-01

    Biallelic loss-of-function mutations in SPG11 cause a wide spectrum of recessively inherited, neurodegenerative disorders including hereditary spastic paraplegia (HSP), amyotrophic lateral sclerosis, and Charcot-Marie-Tooth disease. By comprehensive screening of three large cohorts of HSP index patients, we identified 83 alleles with "small" mutations and 13 alleles that carry large genomic rearrangements. Including relevant data from previous studies, we estimate that copy number variants (CNVs) account for ∼19% of pathogenic SPG11 alleles. The breakpoints for all novel and some previously reported CNVs were determined by long-range PCR and sequencing. This revealed several Alu-associated recombination hotspots. We also found evidence for additional mutational mechanisms, including for a two-step event in which an Alu retrotransposition preceded the actual rearrangement. Apparently independent samples with identical breakpoints were analyzed by microsatellite PCRs. The resulting haplotypes suggested the existence of two rearrangement founder alleles. Our findings widen the spectra of mutations and mutational mechanisms in SPG11, underscore the pivotal role played by Alus, and are of high diagnostic relevance for a wide spectrum of clinical phenotypes including the most frequent form of recessive HSP. PMID:27071356

  13. WES in a family trio suggests involvement of TECPR2 in a complex form of progressive motor neuron disease.

    PubMed

    Covone, A E; Fiorillo, C; Acquaviva, M; Trucco, F; Morana, G; Ravazzolo, R; Minetti, C

    2016-08-01

    We have performed whole-exome sequencing in a family trio with a 16-year-old girl suffering of progressive motor neuron disease. There was no family history of the disease and no parental consanguinity. Our exome analysis indicated the proband as a compound heterozygote for two missense variants in the TECPR2 gene according to a recessive mode of inheritance. The TECPR2 gene has been reported as a positive regulator of autophagy which is an essential mechanism for maintaining neuron homeostasis and survival and plays a key role in major adult and pediatric neurodegenerative diseases. Variants in this gene have been found responsible for a recently described form of hereditary spastic paraplegia called SPG49 in two previous reports. We propose that both variants causing amino acid substitution, p.Leu684Val and p.Thr903Met, inherited in trans-phase compound heterozygote form, can be responsible for the phenotype observed in our patient. We also consider the possible contribution of a heterozygous variant in the SPG7 gene. Sanger sequencing confirmed the segregation of variants within the family tree including the patient's unaffected brother. PMID:27406698

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

    PubMed

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

    2015-01-01

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

  15. Evaluation of a proposed therapeutic protocol in 12 dogs with tentative degenerative myelopathy.

    PubMed

    Polizopoulou, Zoe S; Koutinas, Alexander F; Patsikas, Michael N; Soubasis, Nektarios

    2008-09-01

    The objective of this work was to evaluate the long-term efficacy of a proposed therapeutic protocol in 12 dogs with a tentative diagnosis of degenerative myelopathy, followed-up for a 6-month period. Twelve dogs fulfilling the antemortem inclusion criteria (breed, age, adequate vaccination, history of progressive posterior ataxia and/or paraparesis, no radiographic and myelographic abnormalities in the spinal cord and vertebral column) were allocated. All these dogs presented signs of thoracolumbar syndrome (T3-L3), scored as grade I (mild to moderate ataxia and paraparesis) in 10 and grade II (severe ataxia and ambulatory paraparesis) in 2 cases. Treatment included the use of epsilon-aminocaproic acid and N-acetylcysteine, supplemented with vitamins B, C and E. Prednisolone was given for the first two weeks and upon worsening of neurological signs. Daily exercise, performed as walking or swimming, was strongly recommended. Clinicopathological evaluation was normal in all 12 dogs, and survey radiographs and myelograms did not show spinal cord compression. Magnetic resonance imaging (MRI), performed only in 4 dogs, did not disclose compressive disorders or intramedullary lesions. Neurological signs were progressively worsening in all 12 animals, eventually resulting in severe paraparesis (grade III) or paraplegia (grade IV). The applied medications do not appear to be an attractive alternative to conservative management (physiotherapy) or euthanasia in canine degenerative myelopathy, irrespective of its chronicity. PMID:18828481

  16. 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

  17. 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

  18. Percivall Pott: tuberculous spondylitis.

    PubMed

    Sternbach, G

    1996-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  20. 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