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1

Hereditary Spastic Paraplegia  

MedlinePLUS

... help maintain the function of axons in the spinal cord. Understanding how mutations of these genes cause HSP should lead to ways to prevent, treat, and cure HSP. NIH Patient Recruitment for Hereditary Spastic Paraplegia Clinical Trials At NIH Clinical Center Throughout the U.S. and ...

2

Genetics Home Reference: Spastic paraplegia type 11  

MedlinePLUS

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

3

Genetics Home Reference: Spastic paraplegia type 4  

MedlinePLUS

... OMIM Genetic disorder catalog Conditions > Spastic paraplegia type 4 On this page: Description Genetic changes Inheritance Diagnosis ... Reviewed January 2008 What is spastic paraplegia type 4? Spastic paraplegia type 4 is part of a ...

4

Paraplegia following oesophagectomy  

PubMed Central

We report a rare case of postoperative paraplegia in a patient with carcinoma of the oesophagus following oesophagectomy. Neurological deficit was characterised by loss of sensation from the spinal level T2 down to T6, together with flaccid paraparesis of both lower extremities. This was initially thought to be secondary to an epidural haematoma and a magnetic resonance scan was arranged. This suggested changes consistent with spinal cord infarction from D2 to D6 with no haematoma or abscess. This severe complication was most probably caused by embolisation from an atherosclerotic plaque of the thoracic aorta, as the nature of the surgery requires aortic manipulation. This may have consequently led to occlusion of a significant part of the spinal blood supply. Even though anterior spinal artery syndrome is a well known problem in the operative management of thoracic aortic aneurysms, this complication is extremely rare after oesophagectomy. PMID:22355297

Shahi, Navneel; Asante-Siaw, Julius; Marzouk, Joseph F K

2010-01-01

5

[Paraplegia episodes revealing tuberculous myelitis].  

PubMed

A 38 year-old woman, without previous medical history, presented, since 1993, several paraplegic fits carrying herself progressively through to a severe paraplegia. Diagnoses successively proposed were spinal cord compressions by slipped discs, spinal cord infarct and multiple sclerosis. In November 1998, the patient presented back pain and fever. Spinal cord magnetic resonance imaging (MRI) revealed a mildly enlarged dorsal cord with signal abnormalities. The lesions were isointense on T1-weighted images, hyperintense on T2-weighted images and showed a ringlike contrast enhancement. A lumbar puncture showed a trouble cerebrospinal fluid (CSF) with leucocytes 600/mm(3) (85 p.100 polynuclear), protein 6.7 g/l, glucose 0.26 g/l, chloride 109 mmol/l. The patient was first treated with parenteral unspecific antibiotherapy. Microbiological studies of blood and CSF were negative. CSF examination with polymerase chain reaction (PCR) was positive for Mycobacterium tuberculosis. Clinical (pain and fever) symptoms and CSF abnormalities decreased after antituberculous treatment. However, paraparesis remain severe. Spinal tuberculous localizations often lead to diagnostic and therapeutic errors. Improvement of spinal cord MRI sequences and using of PCR technics in CSF would contribute to reduce these difficulties. PMID:10891803

Douay, X; de Seze, J; Stojkovic, T; Gauvrit, J Y; Savage, C; Pruvo, J P; Vermersch, P

2000-07-01

6

Leptospirosis presenting as a flaccid paraplegia.  

PubMed Central

A fatal case of leptospirosis in a 64 year old farm worker is described. The dramatic neurological presentation with a rapidly evolving flaccid paraplegia associated with biochemical evidence of renal and hepatic dysfunction is discussed. Attention is drawn to the wide range of neurological symptoms reported in leptospirosis, and to the possibility that this infectious disease may present neurologically. PMID:2362889

Mumford, C.; Dudley, N.; Terry, H.

1990-01-01

7

Strümpell's familial spastic paraplegia: genetics and neuropathology  

PubMed Central

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

Behan, Wilhelmina M. H.; Maia, Maria

1974-01-01

8

Spondyloepiphyseal dysplasia tarda with progressive arthropathy complicated with paraplegia.  

PubMed

Spondyloepiphyseal dysplasia tarda with progressive arthropathy is characterized by short stature resulting from platyspondylia and progressive arthropathy. This disorder may cause a predisposition to disk herniations, which may rarely lead to spastic paraplegia. We report a 21-yr-old male patient with spondyloepiphyseal dysplasia tarda with progressive arthropathy who developed spastic paraplegia because of spinal stenosis caused by thoracic disk herniations. PMID:21273896

Yoleri, Ozlem; Oz, Bengi; Olmez, Ne?e; Memi, Asuman; Gelal, Fazl

2011-06-01

9

Paraplegia after intercostal neurolysis with phenol  

PubMed Central

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

Gollapalli, Lakshman; Muppuri, Rudramanaidu

2014-01-01

10

Paraplegia due to Acute Aortic Coarctation and Occlusion.  

PubMed

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

Park, Chang-Bum; Jo, Dae-Jean; Kim, Min-Ki; Kim, Sang-Hyun

2014-03-01

11

Spinal Arteriovenous Fistula with Progressive Paraplegia after Spinal Anaesthesia  

PubMed Central

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

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

2014-01-01

12

Factors influencing bone loss in paraplegia  

PubMed Central

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

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

2011-01-01

13

I. Social, sexual and personal implications of paraplegia  

Microsoft Academic Search

Paraplegia can lead to social stigmatisation, sexual difficulties, and emotional maladjustment. The specific nature of problems experienced in these areas were investigated in an interview study of 22 male and female paraplegics. These interviews were followed up by a postal questionnaire and both qualitative and quantitative data are presented in this report. Effective counselling can only be offered on the

Colette Ray; Julia West

1984-01-01

14

Primary Ewing's sarcoma of the spine presenting as acute paraplegia  

PubMed Central

Ewing's sarcoma is a primary bone malignancy with the highest incidence in the second decade of life. Although it mostly affects the metaphyseal region of long growing bones, involvement of spine is not very uncommon especially the sacrum. Nonsacral spinal Ewing's sarcoma is rarer and often mimics a benign condition before spreading extensively. They present with neurologic deficits due to spinal cord compression, but acute onset paraplegia has not been previously reported. A high index of clinical suspicion can clinch the diagnosis early in the course of the disease. A prompt intervention is required to keep neurological damage to a minimum, and a correct combination of surgery, chemotherapy, and radiotherapy is required for better long-term patient outcome. We report a 16-year-old female who presented with acute paraplegia and had an excellent postoperative outcome after radical excision of a D9 Ewing's sarcoma. PMID:22837785

Gopalakrishnan, C. V.; Shrivastava, Adesh; Easwer, H. V.; Nair, Suresh

2012-01-01

15

Spontaneous acute hemorrhage of intraspinal canal cellular schwannoma with paraplegia: A case report.  

PubMed

Cellular schwannoma, an unusual histological subtype of schwannoma, is a benign hypercellular variant of a peripheral nerve sheath tumor. We report a 48-year-old woman with sudden onset of paraplegia. The complete surgical resection was achieved. This is the first report about intraspinal canal cellular schwannoma following spontaneous acute hemorrhage and paraplegia. PMID:25488387

Zhang, Heng-Zhu; Li, Yuping; Han, Yang; Wang, Xiaodong; She, Lei; Yan, Zhengcun; Dong, Lun

2014-12-01

16

Interventions for reversing delayed-onset postoperative paraplegia after thoracic aortic reconstruction  

Microsoft Academic Search

Background. Delayed postoperative paraplegia is a recognized complication of thoracic (TAA) or thoracoabdominal aortic aneurysm (TAAA) repair. The purpose of this study was to evaluate the effectiveness of interventions to treat delayed-onset paraplegia.Methods. Between January 1, 2000 and August 31, 2001, 99 patients underwent surgical repair of TAA, Crawford type I, II, or III TAAA. Standard intraoperative management included distal

Albert T Cheung; Stuart J Weiss; Michael L McGarvey; Mark M Stecker; Michael S Hogan; Alison Escherich; Joseph E Bavaria

2002-01-01

17

Simulated paraplegia: an occasional problem for the neurosurgeon.  

PubMed Central

Fourteen cases of simulated paraplegia and tetraplegia encountered amongst 4,800 neurosurgical admissions are described. The classification of such cases is difficult. Use of the term "hysteria" depends on whether the behaviour is judged to be conscious or not, but this can rarely be decided. In most of the patients the paralysis was of relatively short duration and recovered rapidly with simple methods of treatment which permitted this to occur without loss of face, but such cases presenting as acute neurological emergencies represent only one relatively simple form of pretended or "hysterical" illness. Many of these patients are probably never seen by psychiatrists. PMID:4031935

Maurice-Williams, R S; Marsh, H

1985-01-01

18

Paraplegia after thoracotomy under combined general and epidural anesthesia in a child.  

PubMed

A 9-year-old boy underwent a thoracotomy for excision of his right third rib under combined general and epidural anesthesia for a Ewings sarcoma. Postoperatively, he was found to have a complete T2-3 paraplegia. Permanent paraplegia was described as a rare complication of thoracotomy in adults, and very rarely after epidural analgesia in adults and babies. This was the first report in a child. PMID:18445201

Allison, C E; Aronson, D C; Geukers, V G M; van den Berg, R; Schlack, W S; Hollmann, M W

2008-06-01

19

Phenotype of autosomal dominant spastic paraplegia linked to chromosome 2.  

PubMed

We report the clinical features of 12 families with autosomal dominant spastic paraplegia (ADSP) linked to the SPG4 locus on chromosome 2p, the major locus for this disorder that accounts for approximately 40% of the families. Among 93 gene carriers, 32 (34%) were unaware of symptoms but were clinically affected. Haplotype reconstruction showed that 90% of the asymptomatic gene carriers presented increased reflexes and/or extensor plantar responses independent of age at examination. The mean age at onset was 29 years, ranging from 1 to 63 years. Intra- as well as inter-familial variability of age at onset was important, but did not result from anticipation. Phenotype-genotype correlations and comparison with SPG3 and SPG5 families indicated that despite the variability of age at onset, SPG4 is a single genetic entity but no clinical features distinguish individual SPG4 patients from those with SPG3 or SPG5 mutations. PMID:8931574

Dürr, A; Davoine, C S; Paternotte, C; von Fellenberg, J; Cogilinicean, S; Coutinho, P; Lamy, C; Bourgeois, S; Prud'homme, J F; Penet, C; Mas, J L; Burgunder, J M; Hazan, J; Weissenbach, J; Brice, A; Fontaine, B

1996-10-01

20

Acute paraplegia and pulmonary edema after benzathine penicillin injection.  

PubMed

Accidental intra-arterial injection is a potentially devastating complication of the intragluteal injection of benzathine penicillin. A 35-year-old woman developed after intramuscular injection of benzathine penicillin G acute paraplegia and noncardiogenic pulmonary edema. Noninvasive positive pressure ventilation was initiated with furosemide and corticosteroids. A magnetic resonance imaging scan showed findings consistent with syringomyelia and spinal cord ischemia at T9 through T10. Vascular injury may be the result of microemboli of the injected crystals of the penicillin salts. The mechanism of noncardiogenic pulmonary edema is perhaps an immunogically mediated one. At 2-year follow-up, she had no improvement in neurologic status. The deficit is considered permanent. PMID:18272127

Mjahed, Khalid; Alaoui, Sd Youssef; Salam, Siham; Lhoucine, Barrou

2008-02-01

21

Spastic paraplegia proteins spastizin and spatacsin mediate autophagic lysosome reformation.  

PubMed

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

Chang, Jaerak; Lee, Seongju; Blackstone, Craig

2014-12-01

22

A Kinesin Heavy Chain (KIF5A) Mutation in Hereditary Spastic Paraplegia (SPG10)  

PubMed Central

We have identified a missense mutation in the motor domain of the neuronal kinesin heavy chain gene KIF5A, in a family with hereditary spastic paraplegia. The mutation occurs in the family in which the SPG10 locus was originally identified, at an invariant asparagine residue that, when mutated in orthologous kinesin heavy chain motor proteins, prevents stimulation of the motor ATPase by microtubule-binding. Mutation of kinesin orthologues in various species leads to phenotypes resembling hereditary spastic paraplegia. The conventional kinesin motor powers intracellular movement of membranous organelles and other macromolecular cargo from the neuronal cell body to the distal tip of the axon. This finding suggests that the underlying pathology of SPG10 and possibly of other forms of hereditary spastic paraplegia may involve perturbation of neuronal anterograde (or retrograde) axoplasmic flow, leading to axonal degeneration, especially in the longest axons of the central nervous system. PMID:12355402

Reid, Evan; Kloos, Mark; Ashley-Koch, Allison; Hughes, Lori; Bevan, Simon; Svenson, Ingrid K.; Graham, Felicia Lennon; Gaskell, Perry C.; Dearlove, Andrew; Pericak-Vance, Margaret A.; Rubinsztein, David C.; Marchuk, Douglas A.

2002-01-01

23

Coagulopathy associated with sac reperfusion for reversing paraplegia after endovascular repair of type II thoracoabdominal aneurysm.  

PubMed

Sac perfusion may be helpful in preventing or reversing spinal cord injury after endovascular repair of thoracoabdominal aneurysms and it has been used as an adjunct to the standard physiologic measures of sustained hypertension and cerebrospinal fluid drainage. Coagulopathy as a result of endoleak after endovascular aneurysm repair has been reported, and very rare cases of treatment after repair of these endoleaks have been described. We report a 73-year-old man who had endovascular repair of a type II thoracoabdominal aneurysm with a branched stent graft. Sac reperfusion was initiated to manage postoperative paraplegia. The paraplegia partially resolved but severe hemorrhagic complications developed that were attributed to sac perfusion-related hyperfibrinolysis. Discontinuation of sac perfusion resolved the coagulopathy but resulted in paraplegia. PMID:23988546

Lioupis, Christos; Katsanos, Konstantinos; Clough, Rachel; Matharu, Nick; Modarai, Bijan; Carrell, Tom; Taylor, Peter

2013-11-01

24

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

PubMed

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

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

2014-06-01

25

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

SciTech Connect

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.

Kobayashi, H.; Hoffman, E.P.; Matise, T.C. [and others

1994-09-01

26

MODIFIED CONCEPT 2 TM ROWING MACHINE WITH MANUAL FES CONTROLLER FOR TOTAL BODY EXERCISE IN PARAPLEGIA  

Microsoft Academic Search

Concept 2 indoor rowing machine (Concept 2 Inc., USA), an exercise and training machine for able-bodied population, was modified for total body exercise in paraplegia. A new seating system provides trunk stability and constrains the leg motion to the sagittal plane. A 4-channel electrical stimulator activates the quadriceps and hamstrings in drive and recovery phases of rowing cycle. Force sensing

Rahman Davoodi; Brian Andrews; Garry Wheeler

2001-01-01

27

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

Microsoft Academic Search

Concept 2 indoor rowing machine (Concept 2 Inc., USA) was modified for functional electrical stimulation (FES) rowing exercise in paraplegia. A new seating system provides trunk stability and constrains the leg motion to the sagittal plane. A 4-channel electrical stimulator activates the quadriceps and hamstrings in Drive and Recovery phases of the rowing cycle, respectively. Two force-sensing resistors (FSR) on

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

2002-01-01

28

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

ERIC Educational Resources Information Center

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"…

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

29

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

PubMed Central

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

2013-01-01

30

Acquired urethral diverticulum in a man with paraplegia presenting with a scrotal mass: a case report  

PubMed Central

Introduction Male urethral diverticula are rare. Patients with paraplegia may present with acquired diverticula as a result of prolonged catheterization. Diverticula may be asymptomatic or lead to lower urinary tract symptoms. Rarely, the diverticulum may initially present as a scrotal mass. Case presentation We report the case of a male 45-year-old Arab with paraplegia who presented with a mass in the peno-scrotal junction. He had in his medical history iterative prolonged urethral catheterizations associated with urine leakage through the urethral meatus upon applying compression. Diagnosis confirmation of urethral diverticula is obtained by retrograde urethrography. The patient underwent a diverticulectomy with urethroplasty. Conclusion Male acquired urethral diverticula can be found in patients who have a spinal cord injury because of prolonged urethral catheterization. Clinical presentations are different and sometimes can be misleading. Retrograde urethrography is the key to diagnosis and open surgery is the treatment of reference. PMID:23171575

2012-01-01

31

Diagnosis, investigation and management of hereditary spastic paraplegias in the era of next-generation sequencing  

E-print Network

Inherited OMIM Comment P/C* Clinical features of complex forms SPG44/GJC2 Gap junction gamma-2 protein AR #613206 C Cerebellar signs, seizures, cognitive impairment, scoliosis, leukodystrophy, thin corpus callosum. SPG45/ NT5C2 Cytosolic purine 5... and related disorders. Churchill Livingston, Edinburgh 4. Ruano L, Melo C, Silva MC, Coutinho P (2014) The global epi- demiology of hereditary ataxia and spastic paraplegia: a systematic review of prevalence studies. Neuroepidemiology 42:174–183 5. Harding AE...

Hensiek, Anke; Kirker, Stephen; Reid, Evan

2014-12-06

32

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

Microsoft Academic Search

Spinal epidural angiolipoma is a rare benign tumor containing vascular and mature adipose elements. A slow progressive clinical\\u000a course was mostly presented and rarely a fluctuating course during pregnancy. The authors report the original case of spontaneous\\u000a spinal epidural bleeding resulting from thoracic epidural angiolipoma who presented with hyperacute onset of paraplegia, simulating\\u000a an extradural hematoma. The patient was admitted

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

2008-01-01

33

Spastic Paraplegia and OXPHOS Impairment Caused by Mutations in Paraplegin, a Nuclear-Encoded Mitochondrial Metalloprotease  

Microsoft Academic Search

Hereditary spastic paraplegia (HSP) is characterized by progressive weakness and spasticity of the lower limbs due to degeneration of corticospinal axons. We found that patients from a chromosome 16q24.3–linked HSP family are homozygous for a 9.5 kb deletion involving a gene encoding a novel protein, named Paraplegin. Two additional Paraplegin mutations, both resulting in a frameshift, were found in a

Giorgio Casari; Maurizio De Fusco; Sonia Ciarmatori; Massimo Zeviani; Marina Mora; Patricio Fernandez; Giuseppe De Michele; Alessandro Filla; Sergio Cocozza; Roberto Marconi; Alexandre Dürr; Bertrand Fontaine; Andrea Ballabio

1998-01-01

34

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

PubMed Central

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

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

2014-01-01

35

Exclusion of the candidate locus FSP1 in six families with late-onset autosomal dominant spastic paraplegia.  

PubMed

Hereditary spastic paraplegias are neurological hereditary conditions of unknown aetiology. In pure spastic paraplegia, most of the pedigrees display an autosomal dominant mode of inheritance. A gene for pure autosomal dominant spastic paraplegia (ADSP), termed FSP1, was mapped to chromosome 14q in a large pedigree with early-onset disease. This locus was tested by linkage analysis in six large French kindreds of ADSP with late-onset disease, using four microsatellites spanning a 9 cM interval including FSP1. FSP1 could be excluded in five of the six families, while no evidence for linkage was found in the remaining family. These results suggest that FSP1 is not involved in late onset ADSP, at least in the six families studied. PMID:7719135

Fontaine, B; Rime, C S; Hazan, J; Dürr, A; Stevanin, G; Penet, C; Reboul, J; Agid, Y; Lyon-Caen, O; Baumann, N

1995-01-01

36

Spinocerebellar ataxia type 3/Machado-Joseph disease manifested as spastic paraplegia: A clinical and genetic study  

PubMed Central

The aim of the present study was to conduct a familial investigation and provide a genetic diagnosis to a family presenting with spastic paraplegia and clinically diagnosed with hereditary spastic paraplegia (HSP). Blood samples were obtained from the family, and mutations in the gene causing spinocerebellar ataxia type 3 (SCA3)/Machado-Joseph disease (MJD), known as MJD1, were analyzed using the polymerase chain reaction, 8% denaturing polyacrylamide gel electrophoresis, and T-vector ligation and sequencing. The trinucleotide repeat number of the mutant allele was 80, leading to a genetic diagnosis of SCA3/MJD. This suggests that patients with SCA3/MJD characteristically present with typical spastic paraplegia without evident manifestations of ataxia. For those families with HSP involving the nervous system and showing genetic anticipation, an MJD1 genetic diagnosis should be considered to assist in clinical diagnosis of HSP. PMID:25574208

SONG, YANMIN; LIU, YUNHAI; ZHANG, NING; LONG, LILI

2015-01-01

37

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

PubMed

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

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

2014-09-15

38

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

PubMed Central

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

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

39

Sudden paraplegia following epidural lipomatosis and thoracal compression fracture after long-term steroid therapy: a case report.  

PubMed

Sudden paraplegia secondary to the posterior spinal epidural compression and vertebral compression fracture as a complication in corticosteroid treatment is extremely rare. The authors presented a case 49-year-old man with chronic relapsing attack of Still's disease. After the identification of pathology, the surgical evacuation of lipid tissue and pedicle-based instrumentation showed therapeutic success. To the authors' knowledge, this is the first case showing both vertebral fracture and paraplegia that required urgent surgery in the follow-up Still's disease. PMID:20012627

Celik, Suat Erol; Erer, Sait B; Güleç, Ilker; Gökcan, Recai; Naderi, Sait

2011-09-01

40

Irreversible paraplegia following one time prophylactic intrathecal chemotherapy in an adult patient with acute lymphoblastic leukemia.  

PubMed

We present an adult female patient who developed irreversible paraplegia and areflexia four days post intrathecal chemotherapy with methotrexate, cytosine arabinoside and hydrocortisone. On magnetic resonance imaging (MRI) of the lumbar spine, diffuse gadolinium enhancement of the anterior spinal nerve roots (ventral roots) was detected. Methylprednisolone was intravenously administered at a daily dose of 30mg/kg for three days. Despite this treatment, flaccid weakness in the lower extremities and urinary retention persisted. Following consolidation chemotherapy, no improvement in neurologic status was noted. Six months later, a follow-up MRI revealed severe atrophy of the thoracic spinal cord. PMID:18306482

Lee, Hea Yong; Im, Sung-il; Kang, Myoung-Hee; Kim, Kwang Min; Kim, Seok Hyun; Kim, Hun-Gu; Kang, Jung Hun; Lee, Gyeong-Won

2008-02-29

41

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

PubMed

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

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

2013-10-01

42

REEPing the benefits of an animal model of hereditary spastic paraplegia  

PubMed Central

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

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

2013-01-01

43

Familial spastic paraplegia, bilateral sensorineural deafness, and intellectual retardation associated with a progressive nephropathy.  

PubMed Central

We present a family in which at least four persons have evidence of an inherited disorder comprising a variable spastic paraplegia, bilateral sensorineural deafness, intellectual retardation, and a progressive nephropathy. Focal segmental proliferative lesions with sclerosis suggestive of mesangial IgA nephropathy (Berger's disease) were found on renal renal biopsy in two affected persons. The glomerular basement membrane showed none of the changes characteristic of Alport's syndrome. Males and females are affected and the segregation of the disease is consistent with dominant transmission. Images PMID:3351903

Fitzsimmons, J S; Watson, A R; Mellor, D; Guilbert, P R

1988-01-01

44

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

PubMed

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 in the SPG21/ACP33 and SPG54/DDH2H genes. Our study confirms that the phenotype of patients with SPG11 and with SPG15 is homogeneous, whereas cases with SPG35 and with SPG48 cases present overlapping features, and a broader clinical spectrum. The large group of non-diagnosed subjects (51%) suggests further genetic heterogeneity. The observation of common clinical features in association with defects in different causative genes, suggest a general vulnerability of the corticospinal tract axons to a wide spectrum of cellular alterations. PMID:24833714

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

45

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

PubMed

Hereditary spastic paraplegias (HSP) are a genetically heterogeneous group of disorders characterized by a distal axonopathy of the corticospinal tract motor neurons leading to progressive lower limb spasticity and weakness. Intracellular membrane trafficking, mitochondrial dysfunction and myelin formation are key functions involved in HSP pathogenesis. Only recently defects in metabolism of complex lipids have been implicated in a number of HSP subtypes. Mutations in the 23 known autosomal recessive HSP genes explain less than half of autosomal recessive HSP cases. To identify novel autosomal recessive HSP disease genes, exome sequencing was performed in 79 index cases with autosomal recessive forms of HSP. Resulting variants were filtered and intersected between families to allow identification of new disease genes. We identified two deleterious mutations in the phospholipase DDHD2 gene in two families with complicated HSP. The phenotype is characterized by early onset of spastic paraplegia, mental retardation, short stature and dysgenesis of the corpus callosum. Phospholipase DDHD2 is involved in intracellular membrane trafficking at the golgi/ endoplasmic reticulum interface and has been shown to possess phospholipase A1 activity in vitro. Discovery of DDHD2 mutations in HSP might therefore provide a link between two key pathogenic themes in HSP: membrane trafficking and lipid metabolism. PMID:23486545

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

2013-11-01

46

Phlegmasia Cerulea Dolens: Rare Complication of Vena Cava Filter Placement in Man With Paraplegia  

PubMed Central

Objective: To describe a complication of placement of an inferior vena cava (IVC) filter in a man with paraplegia. Design: Case report. Participants/Methods: A 48-year-old man with T11 paraplegia secondary to an L1 burst fracture underwent thoracic spinal fusion. The postoperative course was complicated by deep vein thrombosis (DVT) of the right common femoral vein, which was treated with warfarin. Results: During rehabilitation, the hematocrit declined, and fluctuance was noted along the surgical site. Computed tomographic scan suggested a hematoma in the paraspinal and latissimus dorsi muscles. Warfarin was discontinued, and an IVC filter was placed. He subsequently developed severe leg pain, followed by hypotension, acute renal failure, and compartment syndrome in bilateral lower extremities requiring fasciotomies. Ultrasound and computed tomographic angiogram showed extensive bilateral lower extremity DVTs and pulmonary emboli. The diagnosis of cerulea dolens was made. Mechanical and pharmacological thrombectomy was aborted secondary to bleeding complications and hypotension. The patient died shortly after care was withdrawn at the family's request. The autopsy revealed multiple thrombi in IVC, bilateral pelvic and femoral veins, and left pulmonary artery embolus, consistent with phlegmasia cerulea dolens. Conclusions: Inferior vena cava filters may prevent pulmonary embolism but do not affect the underlying thrombotic process. An IVC filter should be recognized as a possible thrombogenic nidus in patients with spinal cord injury who have known DVT. PMID:18959358

Shem, Kazuko

2008-01-01

47

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

PubMed

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

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

2014-02-01

48

Paraplegia in a Patient With IgG4-Related Sclerosing Disease: A Case Report.  

PubMed

Immunoglobulin G4 (IgG4)-related sclerosing disease is a systemic disease, characterized by mass forming inflammatory lesions which respond well to steroid therapy. Pancreas is the most common site of involvement, and other organ involvements are also common. However, there are only a few reports about central nervous system involvement. We report a case of IgG4-related sclerosing disease which involves spinal cord causing paraplegia. A middle-aged female presented with sudden lower limb weakness. Magnetic resonance imaging showed a soft tissue mass which was diffusely compressing spinal cord along the C7 to T5 levels. Intravenous steroid pulse therapy and emergent operation was performed. The immunopathologic findings revealed IgG4-related sclerosing pachymeningitis postoperatively. There was no evidence of other organ involvement. Her neurologic deficit remained unchanged after two months of comprehensive rehabilitation therapy. PMID:25566488

Kim, Sung Heon; Kang, Yeon; Oh, Sung Han; Paik, Soya; Kim, Joo Sup

2014-12-01

49

Mutation Screening of Spastin, Atlastin, and REEP1 in Hereditary Spastic Paraplegia  

PubMed Central

Hereditary spastic paraplegia (HSP) comprises a group of clinically and genetically heterogeneous diseases that affect the upper motor neurons and their axonal projections. Over 40 chromosomal loci have been identified for autosomal dominant, recessive, and X-linked HSP. Mutations in the genes atlastin, spastin and REEP1 are estimated to account for up to 50% of autosomal dominant HSP and currently guide the molecular diagnosis of HSP. Here we report the mutation screening results of 120 HSP patients from North America for spastin, atlastin, and REEP1, with the latter one partially reported previously. We identified mutations in 36.7% of all tested HSP patients and describe 20 novel changes in spastin and atlastin. Our results add to a growing number of HSP disease associated variants and confirm the high prevalence of atlastin, spastin, and REEP1 mutations in the HSP patient population. PMID:20718791

McCorquodale, Donald S.; Ozomaro, Uzoezi; Huang, Jia; Montenegro, Gladys; Kushman, Arielle; Citrigno, Luigi; Price, Justin; Speziani, Fiorella; Pericak-Vance, Margaret A.; Züchner, Stephan

2010-01-01

50

Is the Transportation Highway the Right Road for Hereditary Spastic Paraplegia?  

PubMed Central

The term “hereditary spastic paraplegia” (HSP) refers to a genetically and clinically diverse group of disorders whose primary feature is progressive spasticity of the lower extremities. The condition arises because of degeneration of the longest motor and sensory axons on the spinal cord, which appear to be most sensitive to the underlying mutations. The marked genetic heterogeneity in HSP, with 20 loci chromosomally mapped and eight genes now identified, suggests that a number of defective cellular processes may be shown to result in the disease. Although previous studies have suggested a mitochondrial basis for at least one form of the disease, a mechanism common to a number of the other genes mutated in HSP has remained elusive until now. The identification of the most recent genes for the condition suggests that aberrant cellular-trafficking dynamics may be a common process responsible for the specific pattern of neurodegeneration seen in HSP. PMID:12355399

Crosby, Andrew H.; Proukakis, Christos

2002-01-01

51

Paraplegia in a Patient With IgG4-Related Sclerosing Disease: A Case Report  

PubMed Central

Immunoglobulin G4 (IgG4)-related sclerosing disease is a systemic disease, characterized by mass forming inflammatory lesions which respond well to steroid therapy. Pancreas is the most common site of involvement, and other organ involvements are also common. However, there are only a few reports about central nervous system involvement. We report a case of IgG4-related sclerosing disease which involves spinal cord causing paraplegia. A middle-aged female presented with sudden lower limb weakness. Magnetic resonance imaging showed a soft tissue mass which was diffusely compressing spinal cord along the C7 to T5 levels. Intravenous steroid pulse therapy and emergent operation was performed. The immunopathologic findings revealed IgG4-related sclerosing pachymeningitis postoperatively. There was no evidence of other organ involvement. Her neurologic deficit remained unchanged after two months of comprehensive rehabilitation therapy.

Kim, Sung Heon; Oh, Sung Han; Paik, Soya; Kim, Joo Sup

2014-01-01

52

Acute paraplegia secondary to thoracic disc herniation of the adjacent segment following thoracolumbar fusion and instrumentation.  

PubMed

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

Badra, Mohammad Ibrahim; Assaker, Richard; Musharrafieh, Ramzi Sharif

2013-03-01

53

Protrudin regulates endoplasmic reticulum morphology and function associated with the pathogenesis of hereditary spastic paraplegia.  

PubMed

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

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

2014-05-01

54

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

PubMed Central

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

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

2014-01-01

55

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

PubMed Central

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.

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

2014-01-01

56

Lysosomal abnormalities in hereditary spastic paraplegia types SPG15 and SPG11  

PubMed Central

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

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

2014-01-01

57

Disturbed Mental Imagery of Affected Body-Parts in Patients with Hysterical Conversion Paraplegia Correlates with Pathological Limbic Activity  

PubMed Central

Patients with conversion disorder generally suffer from a severe neurological deficit which cannot be attributed to a structural neurological damage. In two patients with acute conversion paraplegia, investigation with functional magnetic resonance imaging (fMRI) showed that the insular cortex, a limbic-related cortex involved in body-representation and subjective emotional experience, was activated not only during attempt to move the paralytic body-parts, but also during mental imagery of their movements. In addition, mental rotation of affected body-parts was found to be disturbed, as compared to unaffected body parts or external objects. fMRI during mental rotation of the paralytic body-part showed an activation of another limbic related region, the anterior cingulate cortex. These data suggest that conversion paraplegia is associated with pathological activity in limbic structures involved in body representation and a deficit in mental processing of the affected body-parts. PMID:24961768

Saj, Arnaud; Raz, Noa; Levin, Netta; Ben-Hur, Tamir; Arzy, Shahar

2014-01-01

58

Cardiovascular responses to an orthostatic challenge and electrical-stimulation-induced leg muscle contractions in individuals with paraplegia  

Microsoft Academic Search

The purpose of this study was to investigate the cardiovascular and haemodynamic responses that occur during moderate orthostatic\\u000a challenge in people with paraplegia, and the effect of electrical stimulation (ES)-induced leg muscle contractions on their\\u000a responses to orthostatic challenge. Eight males with complete spinal lesions between the 5th and 12th thoracic vertebrae (PARA)\\u000a and eight able-bodied individuals (AB) volunteered for

Jacqui Raymond; Glen M. Davis; Grace Bryant; Jill Clarke

1999-01-01

59

Differences in functioning of individuals with tetraplegia and paraplegia according to the International Classification of Functioning, Disability and Health (ICF)  

Microsoft Academic Search

Study design:Cross-sectional, multicenter study.Objectives:To identify and quantify the differences in functioning of individuals with tetraplegia versus paraplegia using the International Classification of Functioning, Disability and Health (ICF) as a frame of reference.Setting:International.Methods:Functional problems of 1048 participants with spinal cord injury in 16 study centers in 14 countries were recorded using ICF categories. The level of significance and odds ratios (OR)

K H Herrmann; I Kirchberger; F Biering-Sørensen; A Cieza

2011-01-01

60

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

PubMed

The saphenous nerve is the terminal branch of the femoral nerve and a pure sensory nerve that provide sensation to medial leg. Injury to saphanous nerve following trauma or surgery of the knee can result in formation of a painful neuroma along its distribution. We present a case of saphenous neuroma following use of an ankle-foot orthosis (AFO) in a patient with paraplegia. A 36-year-old patient with paraplegia who was capable of walking independently with his AFO presented to our department with a 3-month history of pain in his left calf. Examination revealed tenderness, paresthesias and positive Tinel sign over the anteromedial aspect of the calf. Ultrasonographic examination of the painful area showed a mass with heterogenous echogenity which was consistent with a saphenous neuroma at the site where fastener band of AFO compressed to skin. We performed a nerve block with steroid and local anesthetic injection under ultrasound guidance to the neuroma. The patient reported pain relief following injection. The use of the AFO may cause a painful saphenous neuroma which is an unusual cause of extremity pain in patients with paraplegia. Ultrasound may be a beneficial diagnostic tool and a guidance for the therapeutic interventions in this condition. PMID:24398411

Kesikburun, S; Köro?lu Omaç, Ö; Ya?ar, E; Yilmaz, B; Kenan Tan, A

2014-04-01

61

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

PubMed Central

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

Fink, John K.

2014-01-01

62

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

PubMed

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

Fink, John K

2013-09-01

63

Hereditary spastic paraplegia type 43 (SPG43) is caused by mutation in C19orf12  

PubMed Central

We report here the genetic basis for a form of progressive hereditary spastic paraplegia (SPG43) previously described in two Malian sisters. Exome sequencing revealed a homozygous missense variant (c.187G>C; p.Ala63Pro) in C19orf12, a gene recently implicated in neurodegeneration with brain iron accumulation (NBIA). The same mutation was subsequently also found in a Brazilian family with features of NBIA, and we identified another NBIA patient with a three-nucleotide deletion (c.197_199del; p.Gly66del). Haplotype analysis revealed that the p.Ala63Pro mutations have a common origin, but MRI scans showed no brain iron deposition in the Malian SPG43 subjects. Heterologous expression of these SPG43 and NBIA variants resulted in similar alterations in the subcellular distribution of C19orf12. The SPG43 and NBIA variants reported here as well as the most common C19orf12 missense mutation reported in NBIA patients are found within a highly-conserved, extended hydrophobic domain in C19orf12, underscoring the functional importance of this domain. PMID:23857908

Landouré, Guida; Zhu, Peng-Peng; Lourenço, Charles M.; Johnson, Janel O.; Toro, Camilo; Bricceno, Katherine V.; Rinaldi, Carlo; Meilleur, Katherine G.; Sangaré, Modibo; Diallo, Oumarou; Pierson, Tyler M.; Ishiura, Hiroyuki; Tsuji, Shoji; Hein, Nichole; Fink, John K.; Stoll, Marion; Nicholson, Garth; Gonzalez, Michael; Speziani, Fiorella; Dürr, Alexandra; Stevanin, Giovanni; Biesecker, Leslie G.; Accardi, John; Landis, Dennis M. D.; Gahl, William A.; Traynor, Bryan J.; Marques, Wilson; Züchner, Stephan; Blackstone, Craig; Fischbeck, Kenneth H.; Burnett, Barrington G.

2013-01-01

64

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

PubMed Central

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

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

65

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

PubMed Central

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

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

2006-01-01

66

Hereditary spastic paraplegia-causing mutations in atlastin-1 interfere with BMPRII trafficking.  

PubMed

Disruption of the bone morphogenic protein (BMP)-linked signaling pathway has been suggested as an important factor in the development of hereditary spastic paraplegia (HSP). HSP-causing proteins spastin, spartin and NIPA1 were reported to inhibit the BMP pathway. We have previously shown a strong interaction of NIPA1 and atlastin-1 proteins. Hence, we investigated the role of another HSP-associated protein atlastin-1 in this signaling cascade. Endogenous and expressed atlastin-1 showed a strong interaction with BMP receptors II (BMPRII) and analyzed missense, HSP-causing mutations R239C and R495W disrupted BMPRII trafficking to the cell surface. BMPRII does not require the presence of atlastin-1 because knockdown expression of atlastin-1 did not alter endogenous BMPRII cellular distribution. Expression of mutant forms of atlastin-1 also interfered with the signaling response to BMP4 stimulation and reduced phosphorylation of Smad 1/5 proteins. Our results suggest that HSP-causing atlastin-1 mutations exhibit a dominant-negative effect on trafficking of BMPRII, which disrupts the BMP pathway in neurons. This, together with previously demonstrated inhibition of atlastin-1 of BMP pathway, further supports the role of this signaling cascade in axonal maintenance and axonal degeneration, which is seen in various types of HSP. PMID:23079343

Zhao, Jiali; Hedera, Peter

2013-01-01

67

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

PubMed

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

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

2013-11-01

68

Alteration of fatty-acid-metabolizing enzymes affects mitochondrial form and function in hereditary spastic paraplegia.  

PubMed

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

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

2012-12-01

69

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

PubMed

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

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

2002-09-01

70

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

PubMed Central

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

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

71

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

PubMed

Hereditary spastic paraplegias (HSPs) are characterized by progressive spasticity and weakness in the lower extremities that result from length-dependent central to peripheral axonal degeneration. Mutations in the non-imprinted Prader-Willi/Angelman syndrome locus 1 (NIPA1) transmembrane protein cause an autosomal dominant form of HSP (SPG6). Here, we report that transgenic (Tg) rats expressing a human NIPA1/SPG6 mutation in neurons (Thy1.2-hNIPA1) show marked early onset behavioral and electrophysiologic abnormalities. Detailed morphologic analyses reveal unique histopathologic findings, including the accumulation of tubulovesicular organelles with endosomal features that start at axonal and dendritic terminals, followed by multifocal vacuolar degeneration in both the CNS and peripheral nerves. In addition, the NIPA1 mutation in the spinal cord from older Tg rats results in an increase in bone morphogenetic protein type II receptor expression, suggesting that its degradation is impaired. This Thy1.2-hNIPA1 Tg rat model may serve as a valuable tool for understanding endosomal trafficking in the pathogenesis of a subgroup of HSP with an abnormal interaction with bone morphogenetic protein type II receptor, as well as for developing potential therapeutic strategies for diseases with axonal degeneration and similar pathogenetic mechanisms. PMID:24128679

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

2013-11-01

72

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

PubMed Central

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

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

2013-01-01

73

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

PubMed Central

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

2013-01-01

74

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

PubMed

Autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC) is genetically heterogenous and approximately 35% of patients carry mutations in either of the SPG11 or SPG15 genes. Disease onset is during the first three decades of life with spastic paraplegia and mental impairment. Peripheral neuropathy and amyotrophy may occur. Kjellin syndrome is characterized by central retinal degeneration in addition to ARHSP-TCC and the disease is associated with mutations in the SPG15 gene. We identified five patients in four unrelated kindreds with spastic paraplegia and mental impairment. Magnetic resonance imaging revealed TCC, atrophy elsewhere in the brain and increased T2 signal intensity in the periventricular white matter. Probands from the four kindreds were screened for mutations in the SPG11 gene. All patients were found homozygous or compound heterozygous for truncating SPG11 mutations of which four are reported for the first time. Ophthalmological investigations revealed that the four index cases have central retinal degeneration consistent with Kjellin syndrome. PET examinations with N-[11C-methyl]-L-deuterodeprenyl (DED) and fluor-18 2-fluorodeoxyglucose (FDG) were performed in two patients with Kjellin syndrome. We observed a reduced glucose uptake in the thalami, anterior cingulum, and sensorimotor cortex indicating neuronal loss, and an increased DED binding in the thalami and pons which suggests astrogliosis. From our results we extend the SPG11 associated phenotype to comprise also Kjellin syndrome, previously found to be associated with mutations in the SPG15 gene. We anticipate that degeneration of the central retina is a common and previously unrecognized feature in SPG11 related disease. PMID:19194956

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

2009-10-01

75

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

PubMed Central

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

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

2011-01-01

76

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

PubMed

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

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

77

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

PubMed Central

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

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

2014-01-01

78

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

PubMed

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 ?-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 ?-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

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

2013-03-01

79

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

SciTech Connect

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.

Fink, J.K.; Wu, C.T.B.; Jones, S.M.

1994-09-01

80

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

PubMed Central

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

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

81

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

PubMed

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

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

2012-02-01

82

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

PubMed Central

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

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

2012-01-01

83

Paraplegia increased cardiac NGF content, sympathetic tonus, and the susceptibility to ischemia-induced ventricular tachycardia in conscious rats  

PubMed Central

Midthoracic spinal cord injury is associated with ventricular arrhythmias that are mediated, in part, by enhanced cardiac sympathetic activity. Furthermore, it is well known that sympathetic neurons have a lifelong requirement for nerve growth factor (NGF). NGF is a neurotrophin that supports the survival and differentiation of sympathetic neurons and enhances target innervation. Therefore, we tested the hypothesis that paraplegia is associated with an increased cardiac NGF content, sympathetic tonus, and susceptibility to ischemia-induced ventricular tachyarrhythmias. Intact and paraplegic (6–9 wk posttransection, T5 spinal cord transection) rats were instrumented with a radiotelemetry device for recording arterial pressure, temperature, and ECG, and a snare was placed around the left main coronary artery. Following recovery, the susceptibility to ventricular arrhythmias (coronary artery occlusion) was determined in intact and paraplegic rats. In additional groups of matched intact and paraplegic rats, cardiac nerve growth factor content (ELISA) and cardiac sympathetic tonus were determined. Paraplegia, compared with intact, increased cardiac nerve growth factor content (2,146 ± 286 vs. 180 ± 36 pg/ml, P < 0.05) and cardiac sympathetic tonus (154 ± 4 vs. 68 ± 4 beats/min, P < 0.05) and decreased the ventricular arrhythmia threshold (3.6 ± 0.2 vs. 4.9 ± 0.2 min, P < 0.05). Thus altered autonomic behavior increases the susceptibility to ventricular arrhythmias in paraplegic rats. PMID:19286942

Lujan, Heidi L.; Chen, Ying; DiCarlo, Stephen E.

2009-01-01

84

Autosomal dominant spastic paraplegia linked to chromosome 2p: clinical and genetic studies of a large Japanese pedigree.  

PubMed

Autosomal dominant spastic paraplegia (ADSP) is a genetically heterogenous disorder. To date, 3 loci of ADSP have been identified on chromosome 2p, 14q, and 15q, but specific gene mutations remain unknown. To determine the genetic background of ADSP in the Japanese, we studied a large 3-generation pedigree, clinically and genetically. Of the 36 individuals clinically examined, 15 were affected. The main feature in the affected individuals was a slowly progressive spastic paraplegia, associated with upper limb hyperreflexia (58%), reduction of vibration sense (27%) and bladder disturbance (13%). Age at onset ranged from 13 to 50 years with a mean of 30.3 +/- 14.2 (SD). There were 6 parent-child pairs with anticipation and at least 3 others with 'anti-anticipation'. Linkage with 14q and 15q ADSP loci was excluded, and a highly significant lod score was obtained only in the case of the 2p locus (Zmax = 3.53 for D2S400/D2S352, at theta = 0.00). Our study is the first to confirm the existence of 2p-linked ADSP in the Japanese. There is a significant variety in age at onset and disease severity in these 2p-linked families, but the implication for underlying ADSP mutation is not clear. PMID:9335012

Matsuura, T; Sasaki, H; Wakisaka, A; Hamada, T; Moriwaka, F; Tashiro, K

1997-10-01

85

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

PubMed

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

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

2014-11-16

86

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

PubMed

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

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

1999-11-01

87

Paraplegia and squamous cell carcinoma of the bladder in young women: findings from a case-control study.  

PubMed Central

A death certificate-based case-control study was conducted on 207 women aged 25-44 who died of bladder cancer in England and Wales in the period 1971-89 and 411 controls matched on sex, year of death and age at death. An odds ratio of 12.0 (95% CI 1.5-99.7) was found for women with a history of paraplegia. Four of the six paraplegic women were reported to have had squamous cell carcinoma of the bladder compared with only 19 of the 201 non-paraplegic women. These findings suggest that squamous cell carcinomas of the bladder, especially in paraplegics, may be the result of chronic urinary tract infection. PMID:8018530

Dolin, P. J.; Darby, S. C.; Beral, V.

1994-01-01

88

Interaction of two hereditary spastic paraplegia gene products, spastin and atlastin, suggests a common pathway for axonal maintenance  

PubMed Central

Hereditary spastic paraplegia (HSP) is a neurodegenerative disorder that is characterized by retrograde axonal degeneration that primarily affects long spinal neurons. The disease is clinically heterogeneous, and there are >20 genetic loci identified. Here, we show a physical interaction between spastin and atlastin, two autosomal dominant HSP gene products. Spastin encodes a microtubule (MT)-severing AAA ATPase (ATPase associated with various activities), and atlastin encodes a Golgi-localized integral membrane protein GTPase. Atlastin does not regulate the enzymatic activity of spastin. We also identified a clinical mutation in atlastin outside of the GTPase domain that prevents interaction with spastin in cells. Therefore, we hypothesize that failure of appropriate interaction between these two HSP gene products may be pathogenetically relevant. These data indicate that at least a subset of HSP genes may define a cellular biological pathway that is important in axonal maintenance. PMID:16815977

Evans, Katia; Keller, Christian; Pavur, Karen; Glasgow, Kristen; Conn, Bryan; Lauring, Brett

2006-01-01

89

Interaction of two hereditary spastic paraplegia gene products, spastin and atlastin, suggests a common pathway for axonal maintenance.  

PubMed

Hereditary spastic paraplegia (HSP) is a neurodegenerative disorder that is characterized by retrograde axonal degeneration that primarily affects long spinal neurons. The disease is clinically heterogeneous, and there are >20 genetic loci identified. Here, we show a physical interaction between spastin and atlastin, two autosomal dominant HSP gene products. Spastin encodes a microtubule (MT)-severing AAA ATPase (ATPase associated with various activities), and atlastin encodes a Golgi-localized integral membrane protein GTPase. Atlastin does not regulate the enzymatic activity of spastin. We also identified a clinical mutation in atlastin outside of the GTPase domain that prevents interaction with spastin in cells. Therefore, we hypothesize that failure of appropriate interaction between these two HSP gene products may be pathogenetically relevant. These data indicate that at least a subset of HSP genes may define a cellular biological pathway that is important in axonal maintenance. PMID:16815977

Evans, Katia; Keller, Christian; Pavur, Karen; Glasgow, Kristen; Conn, Bryan; Lauring, Brett

2006-07-11

90

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

PubMed Central

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

2014-01-01

91

Spastic paraplegia with thin corpus callosum: description of 20 new families, refinement of the SPG11 locus, candidate gene analysis and evidence of genetic heterogeneity  

Microsoft Academic Search

We studied 20 Mediterranean families (40 patients) with autosomal recessive hereditary spastic paraplegia and thin corpus callosum (ARHSP-TCC, MIM 604360) to characterize their clinical and genetic features. In six families (17 patients) of Algerian Italian, Moroccan, and Portuguese ancestry, we found data consistent with linkage to the SPG11 locus on chromosome 15q13–15, whereas, in four families (nine patients of Italian,

Giovanni Stevanin; Giorgia Montagna; Hamid Azzedine; Enza Maria Valente; Alexandra Durr; Valentina Scarano; Naima Bouslam; Denise Cassandrini; Paola S. Denora; Chiara Criscuolo; Soraya Belarbi; Antonio Orlacchio; Philippe Jonveaux; Gabriella Silvestri; Anne Marie Ouvrad Hernandez; Giuseppe De Michele; Meriem Tazir; Caterina Mariotti; Knut Brockmann; Alessandro Malandrini; Marjo S. van der Knapp; Marcella Neri; Hassan Tonekaboni; Mariarosa A. B. Melone; Alessandra Tessa; M. Teresa Dotti; Michela Tosetti; Flavia Pauri; Antonio Federico; Carlo Casali; Vitor T. Cruz; José L. Loureiro; Federico Zara; Sylvie Forlani; Enrico Bertini; Paula Coutinho; Alessandro Filla; Alexis Brice; Filippo M. Santorelli

2006-01-01

92

Genetic mapping of a susceptibility locus for disc herniation and spastic paraplegia on 6q23.3-q24.1  

PubMed Central

It has been suggested that a genetic factor(s) or a familial predisposition may contribute to the clinical manifestations of disc herniation; moreover, no genetic linkage between spinal disc herniation and spastic paraplegia has ever been described. A family with consanguineous parents and four of eight sibs affected by multiple disc herniations and spastic paraplegia was clinically and genetically analysed. Surgery caused partial improvement in all of them. After the exclusion of type II collagen and vitamin D receptor genes and the recessive loci for HSPs, a genome wide search was performed with about 500 fluorescent markers. Positive lod score values were obtained for chromosome 6q22.31-q24.1, with evidence of three homozygous intervals. The maximum multipoint lod score of 3.28 was obtained in only one interval, between markers D6S1699 and D6S314. On the whole, a susceptibility locus for disc herniation and autosomal recessive spastic paraplegia was found on chromosome 6q23.3-q24.1. This is the first time that disc herniation and the associated neurological syndrome has been linked to a human chromosomal region. PMID:12070243

Zortea, M; Vettori, A; Trevisan, C; Bellini, S; Vazza, G; Armani, M; Simonati, A; Mostacciuolo, M

2002-01-01

93

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

SciTech Connect

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

Schrander-Stumpel, C.; Hoeweler, C. [Univ. of Limburg (Netherlands); Jones, M. [Children`s Hospital, Sandiego, CA (United States)] [and others

1995-05-22

94

Transcriptional and Post-Transcriptional Regulation of SPAST, the Gene Most Frequently Mutated in Hereditary Spastic Paraplegia  

PubMed Central

Hereditary spastic paraplegias (HSPs) comprise a group of neurodegenerative disorders that are characterized by progressive spasticity of the lower extremities, due to axonal degeneration in the corticospinal motor tracts. HSPs are genetically heterogeneous and show autosomal dominant inheritance in ?70–80% of cases, with additional cases being recessive or X-linked. The most common type of HSP is SPG4 with mutations in the SPAST gene, encoding spastin, which occurs in 40% of dominantly inherited cases and in ?10% of sporadic cases. Both loss-of-function and dominant-negative mutation mechanisms have been described for SPG4, suggesting that precise or stoichiometric levels of spastin are necessary for biological function. Therefore, we hypothesized that regulatory mechanisms controlling expression of SPAST are important determinants of spastin biology, and if altered, could contribute to the development and progression of the disease. To examine the transcriptional and post-transcriptional regulation of SPAST, we used molecular phylogenetic methods to identify conserved sequences for putative transcription factor binding sites and miRNA targeting motifs in the SPAST promoter and 3?-UTR, respectively. By a variety of molecular methods, we demonstrate that SPAST transcription is positively regulated by NRF1 and SOX11. Furthermore, we show that miR-96 and miR-182 negatively regulate SPAST by effects on mRNA stability and protein level. These transcriptional and miRNA regulatory mechanisms provide new functional targets for mutation screening and therapeutic targeting in HSP. PMID:22574173

Henson, Brian J.; Zhu, Wan; Hardaway, Kelsey; Wetzel, Jaime L.; Stefan, Mihaela; Albers, Kathryn M.; Nicholls, Robert D.

2012-01-01

95

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

SciTech Connect

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.

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

2006-09-10

96

[Transient paraplegia of the legs after sigmoid resection--late complication after implantation of an aortic bifurcation prosthesis in arterial occlusive disease?].  

PubMed

Ischemic spinal lesions following graft replacement of an infrarenal aortic aneurysm are rare complications. Even more rare is the development of this complication in case of aortoiliac occlusive disease. We report one further case who developed transient paraplegia following sigma resection six years after implantation of an aortobifemoral bifurcation graft because of aortoiliac occlusive disease. The abdominal vessel and the collateral situation of this site of the caudal aorta is discussed and the possibility of late ischemic spinal lesions is pointed out. PMID:8036839

Graupe, F; Badke, A; Taleb, N; Mackrodt, H G; Stock, W

1994-01-01

97

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

PubMed Central

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

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

2010-01-01

98

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

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

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

2012-08-01

99

Age, outcome, and rehabilitation costs after paraplegia caused by traumatic injury of the thoracic spinal cord, conus medullaris, and cauda equina.  

PubMed

The object of this study was to investigate the relationships of age on neurologic and functional outcome, hospitalization length of stay (LOS), and hospital charges after spinal cord injury (SCI). At 20 medical centers, 2,169 consecutive adult patients with paraplegia SCI were assessed in acute care and inpatient rehabilitation. Outcome and treatment measures included the ASIA motor index score, functional independence measure, discharge to community ratio, LOS, and hospital charges. Age differences were examined by separating the sample into 11 age categories and conducting one-way analyses of variance on treatment, medical expense, and outcome measures that included the Functional Independence Measure (FIM) and ASIA motor index scores. Cramer's statistic was used to derive a chi-square value that indicated whether variables differed significantly in terms of age. Post-hoc Tukey tests were also performed. Age-related differences were found with multiple demographic variables. Significant differences between age categories were found with regard to the following treatment measures: ASIA motor index scores at acute-care admission and at discharge, rehabilitation LOS, inpatient rehabilitation hospitalization charges, total LOS, total hospitalization charges, FIM scores at inpatient rehabilitation admission and discharge, FIM change, and FIM efficiency. In conclusion, in patients with paraplegia, age appears to adversely affect functional outcome, rehabilitation LOS, and hospital costs. However, neurologic recovery as defined by the ASIA motor scores does not appear to be related to age. PMID:10521140

Cifu, D X; Huang, M E; Kolakowsky-Hayner, S A; Seel, R T

1999-09-01

100

A New Locus for Autosomal Recessive Spastic Paraplegia Associated with Mental Retardation and Distal Motor Neuropathy, SPG14, Maps to Chromosome 3q27-q28  

PubMed Central

Hereditary spastic paraplegias (HSPs), a group of neurodegenerative disorders that cause progressive spasticity of the lower limbs, are characterized by clinical and genetic heterogeneity. To date, three loci for autosomal recessive HSP have been mapped on chromosomes 8p, 16q, and 15q. After exclusion of linkage at these loci, we performed a genomewide search in a consanguineous Italian family with autosomal recessive HSP complicated by mild mental retardation and distal motor neuropathy. Using homozygosity mapping, we obtained positive LOD scores for markers on chromosome region 3q27-q28, with a maximum multipoint LOD score of 3.9 for marker D3S1601. Haplotype analysis allowed us to identify a homozygous region (4.5 cM), flanked by markers D3S1580 and D3S3669, that cosegregates with the disease. These data strongly support the presence, on chromosome 3q27-28, of a new locus for complicated recessive spastic paraplegia, which we have named “SPG14.” PMID:10877981

Vazza, G.; Zortea, M.; Boaretto, F.; Micaglio, G. F.; Sartori, V.; Mostacciuolo, M. L.

2000-01-01

101

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

PubMed

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

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

2014-06-01

102

Brain magnetic resonance imaging findings and auditory brainstem response in a child with spastic paraplegia 2 due to a PLP1 splice site mutation.  

PubMed

A boy with spastic paraplegia type 2 (SPG2) due to a novel splice site mutation of PLP1 presented with progressive spasticity of lower limbs, which was first observed during late infancy, when he gained the ability to walk with support. His speech was slow and he had dysarthria. The patient showed mildly delayed intellectual development. Subtotal dysmyelination in the central nervous system was revealed, which was especially prominent in structures known to be myelinated during earlier period, whereas structures that are myelinated later were better myelinated. These findings on the brain magnetic resonance imaging were unusual for subjects with PLP1 mutations. Peaks I and II of the auditory brainstem response (ABR) were normally provoked, but peaks III-V were not clearly demarcated, similarly to the findings in Pelizaeus-Merzbacher disease. These findings of brain MRI and ABR may be characteristic for a subtype of SPG2 patients. PMID:24685771

Kubota, Kazuo; Saito, Yoshiaki; Ohba, Chihiro; Saitsu, Hirotomo; Fukuyama, Tetsuhiro; Ishiyama, Akihiko; Saito, Takashi; Komaki, Hirofumi; Nakagawa, Eiji; Sugai, Kenji; Sasaki, Masayuki; Matsumoto, Naomichi

2015-01-01

103

Hypokalemic Paraplegia in Pregnancy  

PubMed Central

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

TV, Srividya; Gopal, N

2014-01-01

104

A new locus for autosomal dominant "pure" hereditary spastic paraplegia mapping to chromosome 12q13, and evidence for further genetic heterogeneity.  

PubMed Central

Autosomal dominant pure hereditary spastic paraplegia (ADPHSP) is clinically characterized by slowly progressive lower-limb spasticity. The condition is genetically heterogeneous, and loci have been mapped at chromosomes 2p, 8q, 14q, and 15q. We have performed a genomewide linkage screen on a large family with ADPHSP, in which linkage to all four previously known loci was excluded. Analysis of markers on chromosome 12q gave a peak pairwise LOD score of 3.61 at D12S1691, allowing us to assign a new locus for ADPHSP (a locus that we have designated "SPG10") to this region. Haplotype construction and analysis of recombination events narrowed the SPG10 locus to a 9.2-cM region between markers D12S368 and D12S83. In addition, our data strongly suggest that there are at least six ADPHSP loci, since we describe a further family in which linkage to all five known ADPHSP loci has been excluded. PMID:10441583

Reid, E; Dearlove, A M; Rhodes, M; Rubinsztein, D C

1999-01-01

105

A comparison of hip guidance with reciprocating gait orthoses in children with spinal paraplegia: results of a ten-year prospective study.  

PubMed

Twenty-two children with spinal paraplegia were entered into a prospective randomised study to assess the efficacy of two reciprocating orthoses and to identify any prognostic factors that might affect continuing use of the devices. Thirteen received a hip guidance orthosis (HGO) and nine a reciprocating gait orthosis (RGO). They were followed for a mean of ten years. At one year follow-up there were three statistically significant differences between the two groups at the 5% level: repairs were commoner in the RGO group, the RGO group improved in their ability to walk over difficult outdoor surfaces and the HGO group improved more in their ability to rise from a sitting to standing position. At one year follow-up there was a positive parental and child's view of the benefits of the orthoses, but by ten years only 24% of the patients were still using the orthoses. We were not able to show any definite advantage of one device over the other or any statistically significant prognostic factors for walking in the longer term with a reciprocating orthosis. We question whether or not the routine provision of these types of orthosis is justifiable when it appears that, in the longer term, the patients we studied preferred wheelchair mobility. PMID:10661784

Robb, J E; Gordon, L; Ferguson, D; Dunhill, Z; Elton, R A; Minns, R A

1999-12-01

106

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

PubMed Central

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

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

2012-01-01

107

Loss of spastin function results in disease-specific axonal defects in human pluripotent stem cell-based models of hereditary spastic paraplegia  

PubMed Central

Human neuronal models of hereditary spastic paraplegias (HSP) that recapitulate disease-specific axonal pathology hold the key to understanding why certain axons degenerate in patients and to developing therapies. SPG4, the most common form of HSP, is caused by autosomal dominant mutations in the SPAST gene, which encodes the microtubule-severing ATPase spastin. Here, we have generated a human neuronal model of SPG4 by establishing induced pluripotent stem cells (iPSCs) from an SPG4 patient and differentiating these cells into telencephalic glutamatergic neurons. The SPG4 neurons displayed a significant increase in axonal swellings, which stained strongly for mitochondria and tau, indicating the accumulation of axonal transport cargoes. In addition, mitochondrial transport was decreased in SPG4 neurons, revealing that these patient iPSC-derived neurons recapitulate disease-specific axonal phenotypes. Interestingly, spastin protein levels were significantly decreased in SPG4 neurons, supporting a haploinsufficiency mechanism. Furthermore, cortical neurons derived from spastin-knockdown human embryonic stem cells (hESCs) exhibited similar axonal swellings, confirming that the axonal defects can be caused by loss of spastin function. These spastin-knockdown hESCs serve as an additional model for studying HSP. Finally, levels of stabilized acetylated-tubulin were significantly increased in SPG4 neurons. Vinblastine, a microtubule-destabilizing drug, rescued this axonal swelling phenotype in neurons derived from both SPG4 iPSCs and spastin-knockdown hESCs. Thus, this study demonstrates the successful establishment of human pluripotent stem cell-based neuronal models of SPG4, which will be valuable for dissecting the pathogenic cellular mechanisms and screening compounds to rescue the axonal degeneration in HSP. PMID:24123785

Denton, Kyle R.; Lei, Ling; Grenier, Jeremy; Rodionov, Vladimir; Blackstone, Craig; Li, Xue-Jun

2013-01-01

108

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

PubMed Central

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

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

109

A new locus (SPG47) maps to 1p13.2-1p12 in an Arabic family with complicated autosomal recessive hereditary spastic paraplegia and thin corpus callosum.  

PubMed

The hereditary spastic paraplegias (HSP) are a heterogeneous group of genetic neurodegenerative disorders in which the main feature is progressive spasticity of the lower limbs due to pyramidal tract dysfunction. Clinically HSP are divided into two forms: a pure form that presents with progressive lower limb spasticity and weakness, sensory signs and bladder dysfunction, and a complicated form, associated with more extensive neurological and extra neurological signs as well as pathological findings on brain imaging. The clinical variability observed in HSP is supported by the large underlying genetic heterogeneity. Hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) is a frequent subtype of complicated HSP clinically characterized by a slowly progressive spastic paraparesis with cognitive impairment and thin corpus callosum (TCC). SPG11, the most frequent gene associated with HSP-TCC, encodes spatacsin, a protein of unknown function. We describe two siblings from an Arabic consanguineous family with slowly progressive spastic paraparesis, mental retardation, seizures, thin corpus callosum and periventricular white matter abnormalities. Homozygosity mapping identified a novel single candidate region of 7.3 Mb on chromosome 1p13.2-1p12. The finding of a new locus for AR-HSP-TCC further demonstrates the extensive genetic heterogeneity of this condition. PMID:21440262

Blumkin, Lubov; Lerman-Sagie, Tally; Lev, Dorit; Yosovich, Keren; Leshinsky-Silver, Esther

2011-06-15

110

Marked hydronephrosis and hydroureter after distigmine therapy in an adult male patient with paraplegia due to spinal cord injury: a case report  

PubMed Central

Introduction Distigmine, a long-acting anti-cholinesterase, is associated with side effects such as Parkinsonism, cholinergic crisis, and rhabdomyolysis. We report a spinal cord injury patient, who developed marked hydronephrosis and hydroureter after distigmine therapy, which led to a series of complications over subsequent years. Case presentation A 38-year-old male developed T-9 paraplegia in 1989. Intravenous urography, performed in 1989, showed normal kidneys, ureters and bladder. He was prescribed distigmine bromide orally and was allowed to pass urine spontaneously. In 1992, intravenous urography showed bilateral marked hydronephrosis and hydroureter. Distigmine was discontinued. He continued to pass urine spontaneously. In 2006, intravenous urography showed moderate dilatation of both pelvicalyceal systems and ureters down to the level of urinary bladder. This patient was performing self-catheterisation only once a day. He was advised to do catheterisations at least three times a day. In December 2008, this patient developed haematuriawhich lasted for nearly four months.. He received trimethoprim, then cephalexin, followed by Macrodantin, amoxicillin and ciprofloxacin. In February 2009, intravenous urography showed calculus at the lower pole of left kidney. Both kidneys were moderately hydronephrotic. Ureters were dilated down to the bladder. Dilute contrast was seen in the bladder due to residual urine. This patient was advised to perform six catheterisations a day, and take propiverine hydrochloride 15 mg, three times a day. Microbiology of urine showed Klebsiella oxytoca, Pseudomonas aeruginosa, and Enterococcus faecalis. Cystoscopy revealed papillary lesions in bladder neck and trigone. Transurethral resection was performed. Histology showed marked chronic cystitis including follicular cystitis and papillary/polypoid cystitis. There was no evidence of malignancy. Conclusion Distigmine therapy resulted in marked bilateral hydronephrosis and hydroureter. Persistence of hydronephrosis after omitting distigmine, and presence of residual urine in bladder over many years probably predisposed to formation of polypoid cystitis and follicular cystitis, and contributed to prolonged haematuria, which occurred after an episode of urine infection. This case illustrates the dangers of prescribing distigmine to promote spontaneous voiding in spinal cord injury patients. Instead of using distigmine, spinal cord injury patients should be advised to consider intermittent catheterisation together with oxybutynin or propiverine to achieve complete, low-pressure emptying of urinary bladder. PMID:19918519

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

2009-01-01

111

Genetics Home Reference: Spastic paraplegia type 15  

MedlinePLUS

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

112

Paraplegia due to thoracic disc herniation.  

PubMed

Disc herniation at the thoracic the spine level is more common than generally thought. Localisation of pain may be vague and may erroneously point to cardiopulmonary, gastrointestinal, genito-urinary or even psychiatric disease. Magnetic resonance imaging is the investigation of choice, especially if spinal cord compression is suspected. PMID:9338030

Pal, B; Johnson, A

1997-07-01

113

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 ...

114

Functional electrical stimulation: cardiorespiratory adaptations and applications for training in paraplegia.  

PubMed

Regular exercise can be broadly beneficial to health and quality of life in humans with spinal cord injury (SCI). However, exercises must meet certain criteria, such as the intensity and muscle mass involved, to induce significant benefits. SCI patients can have difficulty achieving these exercise requirements since the paralysed muscles cannot contribute to overall oxygen consumption. One solution is functional electrical stimulation (FES) and, more importantly, hybrid training that combines volitional arm and electrically controlled contractions of the lower limb muscles. However, it might be rather complicated for therapists to use FES because of the wide variety of protocols that can be employed, such as stimulation parameters or movements induced. Moreover, although the short-term physiological and psychological responses during different types of FES exercises have been extensively reported, there are fewer data regarding the long-term effects of FES. Therefore, the purpose of this brief review is to provide a critical appraisal and synthesis of the literature on the use of FES for exercise in paraplegic individuals. After a short introduction underlying the importance of exercise for SCI patients, the main applications and effects of FES are reviewed and discussed. Major findings reveal an increased physiological demand during FES hybrid exercises as compared with arms only exercises. In addition, when repeated within a training period, FES exercises showed beneficial effects on muscle characteristics, force output, exercise capacity, bone mineral density and cardiovascular parameters. In conclusion, there appears to be promising evidence of beneficial effects of FES training, and particularly FES hybrid training, for paraplegic individuals. PMID:25205000

Deley, Gaëlle; Denuziller, Jérémy; Babault, Nicolas

2015-01-01

115

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

ERIC Educational Resources Information Center

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…

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

2012-01-01

116

Genetics Home Reference: L1 syndrome  

MedlinePLUS

... complicated hereditary spastic paraplegia type 1 X-linked corpus callosum agenesis X-linked hydrocephalus syndrome X-linked hydrocephalus with ... What glossary definitions help with understanding L1 syndrome? agenesis ; cell ; chromosome ; ... hereditary ; hydrocephalus ; inheritance ; inherited ; mutation ; nervous ...

117

Genetics Home Reference: Fatty acid hydroxylase-associated neurodegeneration  

MedlinePLUS

... visual acuity), decreased field of vision, impaired color perception, eyes that do not look in the same ... neurological ; nystagmus ; optic nerve ; oxygen ; palsy ; paraparesis ; paraplegia ; perception ; pneumonia ; pyramidal tract ; recessive ; spasticity ; strabismus ; visual acuity ; ...

118

Accommodation Information by Disability  

MedlinePLUS

... Illness Multiple Sclerosis Muscular Dystrophy Myasthenia Gravis O Obesity One Hand Use P Paraplegia Parkinson's Disease Post-Polio Syndrome Post-Traumatic Stress Disorder Pregnancy Psychiatric Impairments (See Mental Health Impairments) Q Quadriplegia R Reflex Sympathetic Dystrophy ( ...

119

Genetics Home Reference: Allan-Herndon-Dudley syndrome  

MedlinePLUS

... MCT8 (SLC16A2)-specific thyroid hormone cell transporter deficiency mental retardation, X-linked, with hypotonia monocarboxylate transporter 8 (MCT8) ... hormone ; hypoplasia ; hypothyroidism ; hypotonia ; inheritance ; inherited ; involuntary ; ... metabolism ; muscle tone ; mutation ; nervous system ; paraplegia ; population ; ...

120

The effect of level of spinal cord injury on shoulder joint kinetics during manual wheelchair propulsion  

Microsoft Academic Search

Objective. The effects of spinal cord injury level on shoulder kinetics during manual wheelchair propulsion were studied.Design. Single session data collection in a laboratory environment.Methods. Male subjects were divided into four groups: low level paraplegia (n=17), high level paraplegia (n=19), C7 tetraplegia (C7, n=16) and C6 tetraplegia (C6, n=17). Measurements were recorded using a six-camera VICON motion analysis system, a

Kornelia Kulig; Craig J Newsam; Sara J Mulroy; Sreesha Rao; JoAnne K Gronley; Ernest L Bontrager; Jacquelin Perry

2001-01-01

121

Neurological Complications Following Endoluminal Repair of Thoracic Aortic Disease  

SciTech Connect

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.

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

2007-09-15

122

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

PubMed

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

Hedera, Peter

2013-12-15

123

Multimodal MRI-Based Study in Patients with SPG4 Mutations  

PubMed Central

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

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

124

Malignant Rhabdoid Tumor of the Kidney and Spine in an Infant  

PubMed Central

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

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

2014-01-01

125

Acute pneumococcal myelitis in an adult patient.  

PubMed

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

Viškovi?, Klaudija; Mustapi?, Matej; Kutleša, Marko; Lepur, Dragan

2014-04-01

126

Genetics of motor neuron disorders: new insights into pathogenic mechanisms  

Microsoft Academic Search

The past few years have seen the identification of dozens of genes with causal roles in motor neuron diseases (MNDs), particularly for amyotrophic lateral sclerosis and hereditary spastic paraplegia. Although many additional MND genes remain to be identified, the accumulated genetic evidence has already provided new insights into MND pathogenesis, which adds to the well-established involvement of superoxide dismutase 1

Patrick A. Dion; Hussein Daoud; Guy A. Rouleau

2009-01-01

127

Pathophysiology of Hydrocephalus  

Microsoft Academic Search

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

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

128

Swimming for the Handicapped Child and Adult: Occasional Papers No. 10.  

ERIC Educational Resources Information Center

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,…

Neishloss, Lou

129

Microtubule-targeting drugs rescue axonal swellings in cortical neurons from spastin knock-out mice  

E-print Network

Biologie du Développement et Reproduction, F- 78352 Jouy-en-Josas, France. * To whom correspondence should permits unrestricted non-commercial use, distribution and reproduction in any medium provided paraplegia; AAA, ATPase associated with diverse cellular activities; GFP, green fluorescent protein; CTb

Boyer, Edmond

130

Spinal Cord Demyelination Associated with Biotinidase Deficiency in 3 Chinese Patients  

Microsoft Academic Search

Biotinidase deficiency is a treatable cause of severe neurological disorders and skin problems. Spinal cord impairment is a rare complication of this disease and is commonly unrecognized. The authors encountered 3 Chinese patients with progressive spinal cord demyelination associated with biotinidase deficiency. Case 1 exhibited fatigue, proximal muscular weakness, and hypotonic paraplegia from the age of 7 years 4 months.

Yanling Yang; Chaoyang Li; Zhaoyue Qi; Jiangxi Xiao; Yao Zhang; Seiji Yamaguchi; Yuki Hasegawa; Yasuko Tagami; Yuwu Jiang; Hui Xiong; Yuehua Zhang; Jiong Qin; Xi-Ru Wu

2007-01-01

131

Disseminated tuberculomas in spinal cord and brain demonstrated by MRI with gadolinium-DTPA  

Microsoft Academic Search

Intramedullary tuberculoma is rare, and there has been no report of concurrent intramedullary and intracerebral tuberculomas. We report a 30-year-old man with miliary tuberculosis of the lung. He suffered sudden paraplegia due to tuberculomas in the thoracic spinal cord and MRI showed more tuberculomas in the cervical spinal cord, brain stem, and cerebral and cerebellar hemispheres. The tuberculomas were isointense

W.-C. Shen; T.-Y. Cheng; S.-K. Lee; Y.-J. Ho; K.-R. Lee

1993-01-01

132

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

ERIC Educational Resources Information Center

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

Bross, Michael H.; Spellicy, Martin J.

1994-01-01

133

Energetics in the pathogenesis of neurodegenerative diseases  

Microsoft Academic Search

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

M. Flint Beal

2000-01-01

134

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

PubMed

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

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

1975-01-01

135

A profile of psychosexual functioning in males following spinal cord injury  

Microsoft Academic Search

The psychosexual functioning of 47 men with spinal cord injury was studied using the Derogatis Sexual Functioning Inventory (DSFI). Subjects with paraplegia did not differ significantly from subjects with quadriplegia on any of the scales of the DSFI. Subject groups were then aggregated, and the means across DSFI scales were compared to the means of the non-disabled DSFI normative group.

Allen J. Romeo; Richard Wanlass; Silverio Arenas

1993-01-01

136

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

Microsoft Academic Search

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

Ruben J. Cauchi; Marcel van den Heuvel

2006-01-01

137

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

E-print Network

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

Brest, Université de

138

M3S system prototype - a comprehensive system with straightforward implementation  

Microsoft Academic Search

There is a growing demand for powered wheelchairs to provide mobility for people with upper-limb impairments, i.e., individuals suffering from cerebral palsy, paraplegia, or multiple sclerosis, and others who may depend on a human-friendly wheelchair to conduct their daily activities. The design of the multiple master multiple slave (\\

Chiun-fan Chen; Yi-chu Chang; Jer-junn Luh; Fok-ching Chong

2004-01-01

139

A generic input device for the multiple master multiple slave system  

Microsoft Academic Search

The growing demand for input devices designed for the severely handicapped led to development of modular features for the open architecture multiple master multiple slave (M3S) system. With its central safety monitor, M3S allows individuals suffering from cerebral palsy, paraplegia, or multiple sclerosis, and other physically debilitating illnesses greater autonomy by allowing them to access a wide range of input

Chiun-fan Chen; Yi-chu Chang; Heng-Yin Chen; Jin-shin Lai; Fok-ching Chong

2004-01-01

140

Neural arch tuberculosis: a morbid disease  

Microsoft Academic Search

We have reviewed the clinical features, together with the radiographs and computerised tomography, in 9 patients with tuberculosis of the vertebral body and neural arch. All presented with paraparesis or paraplegia. The morbidity associated with this disease is so serious that it is essential to have an accurate means of evaluating the lesion as early as possible. Routine radiographs can

A. Solomon; A. J. Sacks; R. P. Goldschmidt

1995-01-01

141

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

PubMed

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

Miskovic, A M; Dob, D P

2013-07-01

142

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

PubMed

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

Ebert, B; Badke, A

1995-03-01

143

Relationship between duration of spinal cord ischemia and postoperative neurologic deficits in animals.  

PubMed

Stagnara wake-up tests, blood flow measures, somatosensory evoked potentials (SEPs), and neurogenic-motor evoked potentials (NMEPs) were elicited from 20 hogs before and after spinal cord overdistraction at L3-L4. Overdistraction was maintained from 5 to 30 minutes after loss of NMEPs. Results suggest that the longer the duration of overdistraction the greater the likelihood of paraplegia. Blood flow measures indicated that reduced perfusion was greatest at the distraction site but extended proximally and distally. Finally, NMEPs were more sensitive to onset of overdistraction and a more valid indicator of paraplegia than SEPs. NMEPs should provide the surgeon with more time for initiation of intervention techniques than SEPs. Because NMEPs and SEPs provide information regarding different spinal cord tracts, the authors continue to use both methods for monitoring the functional integrity of the human spinal cord during corrective spine surgery. PMID:2259969

Owen, J H; Naito, M; Bridwell, K H; Oakley, D M

1990-09-01

144

[Cost and benefit of intensive care of seriously injured patients].  

PubMed

59 (82%) of 72 patients with multiple injuries but excluding severe brain trauma or paraplegia, studied 5 or 6 years after intensive care, were fully reintegrated, working normally, and not in receipt of insurance compensation. In patients with severe head injury studied 8 years after intensive care, 38 (55%) of 66 patients had the same final outcome. Disability due to head injury or paraplegia was the predominant factor in costs caused by trauma. Treatment during intensive care was found to be the most costly part of therapy. Considerations on costs and benefits demonstrate that the treatment of severely injured patients, who otherwise would die, results in a considerable social and economic saving (approximately 90 million Swiss francs for the 316 trauma patients analyzed). PMID:3132739

Glinz, W; Ruckert, R

1988-04-30

145

Spinal epidural hematoma following epidural catheter removal in a paraplegic patient  

Microsoft Academic Search

Spinal epidural hematoma is a rare and devastating complication of epidural catheter removal in an anticoagulated patient. The diagnosis could be quite challenging, especially in patients with preexisting neurological deficits. A 35-year-old patient with remote spinal cord injury and T4 level paraplegia developed a spinal epidural hematoma on the 7th postoperative day. The hematoma developed after epidural catheter removal with

Naveen Eipe; Carlos E. Restrepo-Garces; Richard I. Aviv; Imad T. Awad

2009-01-01

146

Complex regional pain syndrome in a patient with spinal cord injury: management with pulsed radiofrequency lumbar sympatholysis  

Microsoft Academic Search

Study design:Short communication.Objectives:To report a case with bilateral lower extremity complex regional pain syndrome (CRPS) in a patient with paraplegia occurring following spinal disc herniation surgery, who was treated successfully with pulse radiofrequency (PRF) lumbar sympatholysis.Setting:Departments of Physical Medicine and Rehabilitation, Algology Department of Anaesthesiology and Nuclear Medicine, Medical Faculty of Ege University, Izmir, Turkey.Methods:A 55-year-old woman had neuropathic pain

Y Akkoc; M Uyar; J Oncu; Z Ozcan; B Durmaz

2008-01-01

147

The neural cell adhesion molecule L1: genomic organisation and differential splicing is conserved between man and the pufferfish Fugu 1 O.C. and G.N. share first authorship. 1 2 EMBL Accession Nos. Z29373 and Z71926. 2  

Microsoft Academic Search

The human gene for the neural cell adhesion molecule L1 is located on Xq28 between the ALD and MeCP2 loci. Mutations in the L1 gene are associated with four related neurological disorders, X-linked hydrocephalus, spastic paraplegia (SPG1), MASA syndrome, and X-linked corpus callosum agenesis. The clinical relevance of L1 has led us to sequence the L1 gene in human and

Oliver Coutelle; Gerald Nyakatura; Stefan Taudien; Greg Elgar; Sydney Brenner; Matthias Platzer; Bernd Drescher; Monique Jouet; Sue Kenwrick; André Rosenthal

1998-01-01

148

Human-induced pluripotent stem cells pave the road for a better understanding of motor neuron disease.  

PubMed

While motor neuron diseases are currently incurable, induced pluripotent stem cell research has uncovered some disease-relevant phenotypes. We will discuss strategies to model different aspects of motor neuron disease and the specific neurons involved in the disease. We will then describe recent progress to investigate common forms of motor neuron disease: amyotrophic lateral sclerosis, hereditary spastic paraplegia and spinal muscular atrophy. PMID:24821704

Winner, Beate; Marchetto, Maria C; Winkler, Jürgen; Gage, Fred H

2014-09-15

149

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

PubMed

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

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

2010-07-01

150

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

PubMed Central

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

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

2010-01-01

151

Effects of motor imagery training after chronic, complete spinal cord injury  

Microsoft Academic Search

Abnormalities in brain motor system function are present following spinal cord injury (SCI) and could reduce effectiveness\\u000a of restorative interventions. Motor imagery training, which can improve motor behavior and modulate brain function, might\\u000a address this concern but has not been examined in subjects with SCI. Ten subjects with SCI and complete tetra-\\/paraplegia\\u000a plus ten healthy controls underwent assessment before and

Steven C. Cramer; Elizabeth L. R. Orr; Michael J. Cohen; Michael G. Lacourse

2007-01-01

152

Demineralization and pathological physiology of the skeleton in paraplegic rats  

Microsoft Academic Search

Summary  The mechanism of bone loss after a spinal cord section with paraplegia is still largely unknown. The purpose of this study\\u000a was to investigate in paraplegic rats the rate and distribution of bone loss, changes in bone calcium metabolism, and bone\\u000a blood flow. Female Sprague-Dawley rats aged 100–120 days were rendered paraplegic by sectioning the spinal cord at the 11th

M. Verhas; Y. Martinello; M. Mone; A. Heilporn; P. Bergmann; A. Tricot; A. Schoutens

1980-01-01

153

Os odontoideum with bipartite atlas and segmental instability: a case report  

Microsoft Academic Search

We report on the case of a 15-year-old adolescent who presented with a transient paraplegia and hyposensibility of the upper\\u000a extremities after sustaining a minor hyperflexion trauma to the cervical spine. Neuroimaging studies revealed atlantoaxial\\u000a dislocation and ventral compression of the rostral spinal cord with increased cord signal at C1\\/C2 levels caused by an os\\u000a odontoideum, as well as anterior

Michael Osti; Helmut Philipp; Berthold Meusburger; Karl-Peter Benedetto

2006-01-01

154

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

PubMed Central

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

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

2013-01-01

155

Three-dimensional kinematics of wheelchair propulsion  

Microsoft Academic Search

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

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

1996-01-01

156

Propulsion patterns and pushrim biomechanics in manual wheelchair propulsion  

Microsoft Academic Search

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

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

2002-01-01

157

Anterior approach to the second thoracic vertebral body for surgical treatment (vertebrectomy, bone grafting, and titanium alloy plate fixation)  

Microsoft Academic Search

The surgical approach to the second thoracic vertebral body is difficult from the anterior side. A 38-year-old woman suffering\\u000a from plasmacytoma in the second thoracic vertebra showed paraplegia for 2 weeks prior to surgery. X-ray, computed tomography\\u000a (CT), and magnetic resonance imaging (MRI) examinations indicated breakdown of the second thoracic vertebral body and arch,\\u000a associated with spinal cord compression. A

Z. Fang; X. Yi; M. Li; T. Zhu

2001-01-01

158

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

PubMed Central

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

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

159

Gastrointestinal transit after spinal cord injury: effect of cisapride.  

PubMed

Heartburn, bloating, and abdominal discomfort are common problems in patients with spinal cord injury but, despite its clinical significance, little is known about the gastrointestinal effects of spinal transections. To address the potential gastrointestinal pathophysiology of spinal cord injury, we measured mouth-to-cecum transit time (MCTT) in seven subjects with paraplegia and seven with quadriplegia. Gastric emptying was studied in six subjects with quadriplegia. MCTT was significantly prolonged in patients with quadriplegia, an abnormality corrected by the administration of cisapride. Patients with paraplegia, in contrast to those with quadriplegia, have normal mouth-to-cecum transit time. In addition, patients with quadriplegia had neither a prolonged gastric emptying time nor a change in gastric emptying time, with cisapride. Changes in gastrointestinal transit after spinal cord injury and the improvement of mouth-to-cecum transit time in subjects with quadriplegia, but not in those with paraplegia, may be explained by an imbalance between parasympathetic and sympathetic outflows to the gastrointestinal tract in this group of subjects. PMID:1442685

Rajendran, S K; Reiser, J R; Bauman, W; Zhang, R L; Gordon, S K; Korsten, M A

1992-11-01

160

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

PubMed Central

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

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

161

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

PubMed Central

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

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

2008-01-01

162

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

NASA Astrophysics Data System (ADS)

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

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

2006-10-01

163

Imaging of Vascular Remodeling Following Simulated Thoracoabdominal Aneurysm Repair  

PubMed Central

Objective A better understanding of the response of the spinal cord blood supply to segmental artery (SA) sacrifice should help minimize the risk of paraplegia following both open and endovascular repair of thoracoabdominal aortic aneurysms (TAAA). Methods 12 female juvenile Yorkshire pigs were randomized into three groups and perfused with a barium-latex solution. Pigs in group 1 (control) had infusion without previous intervention. Pigs in group 2 were infused 48 hours after ligation of all SAs (T4-L5), and those in group 3 at 120 hours after ligation. Post-mortem CT scanning of the entire pig enabled overall comparisons and measurement of vessel diameters in the spinal cord circulation. Results 14.5±0.8 SAs were ligated: all filled retrograde to the ligature. Paraplegia occurred in 38% of operated pigs. A significant increase in the mean diameter of the anterior spinal artery (ASA) was evident after SA sacrifice (p=<0.0001 for 48h and 120h). The internal thoracic and intercostal arteries also increased in diameter. Quantitative assessment showed an increase in vessel density 48h after ligation of SAs, reflected by an obvious increase in small collateral vessels seen on 3-D reconstructions of CT scans at 120h. Conclusions Remodeling of the spinal cord blood supply—including dilatation of the ASA and proliferation of small collateral vessels—is evident at 48 and 120 hours after extensive SA sacrifice. It is likely that exploitation of this process will prove valuable in the quest to eliminate paraplegia after TAAA repair. PMID:23010582

Geisbuesch, Sarah; Schray, Deborah; Bischoff, Moritz S; Lin, Hung-Mo; Griepp1, Randall B; Di Luozzo1, Gabriele

2012-01-01

164

Completely intracorporeal robotic-assisted laparoscopic ileovesicostomy.  

PubMed

We present a report of a completely intracorporeal robotic-assisted laparoscopic ileovesicostomy with long term follow-up. The patient was a 55-year-old man with paraplegia secondary to tropical spastic paresis resulting neurogenic bladder dysfunction. The procedure was performed using a da Vinci Surgical system (Intuitive Surgical, Sunnyvale, CA) and took 330 minutes with an estimated blood loss of 100?mL. The patient recovered without perioperative complications. He continues to have low pressure drainage without urethral incontinence over two years postoperatively. PMID:24600527

Dolat, Maryellen T; Wade, Greg; Grob, B Mayer; Hampton, Lance J; Klausner, Adam P

2014-01-01

165

Completely Intracorporeal Robotic-Assisted Laparoscopic Ileovesicostomy  

PubMed Central

We present a report of a completely intracorporeal robotic-assisted laparoscopic ileovesicostomy with long term follow-up. The patient was a 55-year-old man with paraplegia secondary to tropical spastic paresis resulting neurogenic bladder dysfunction. The procedure was performed using a da Vinci Surgical system (Intuitive Surgical, Sunnyvale, CA) and took 330 minutes with an estimated blood loss of 100?mL. The patient recovered without perioperative complications. He continues to have low pressure drainage without urethral incontinence over two years postoperatively. PMID:24600527

Dolat, MaryEllen T.; Wade, Greg; Grob, B. Mayer; Hampton, Lance J.; Klausner, Adam P.

2014-01-01

166

Spinal Cord Compression Revealing an Intraosseous Schwannoma  

PubMed Central

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

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

2013-01-01

167

Hereditary myelopathies.  

PubMed

Hereditary myelopathies comprise a diverse group of disorders whose signs and symptoms include progressive spasticity, limb ataxia without additional cerebellar signs, impaired vibration and positional sensation, and a variable degree of neurogenic weakness, all suggesting spinal cord impairment. Recent progress in the understanding of hereditary myelopathies has revealed that many are systemic processes with widespread axonal degeneration. However, the concept of hereditary myelopathies remains clinically helpful in differentiating hereditary myelopathies from other potentially treatable myelopathies. In this article, hereditary myelopathies are divided into four categories: hereditary spastic paraplegias, motor neuron disorders, spinocerebellar and spastic ataxias, and metabolic disorders, including leukodystrophies. PMID:22810932

Hedera, Peter

2011-08-01

168

[Spinal infarction in the anterior spinal territory with possible relation with bilharziasis].  

PubMed

We report a case of spinal cord infarction in the anterior spinal artery territory with selective involvement of the anterior horns. A 35-year-old Mauritanian woman was hospitalized because of an acute and severe flaccid paraplegia without any sphincter dysfunction or sensory disturbance. MRI abnormalities (hypersignal on T2-weighted sequences) were restricted to the anterior horns of the lower thoracic spinal cord and conus medullaris. Adamkiewicz's artery appeared abnormally thin at arteriography. The infarction was probably related to vasculitis of schistosomal origin. PMID:1962071

Liblau, R; Chiras, J; Orssaud, C; Dormont, D; Duclos, H; Gentilini, M

1991-01-01

169

Telangiectatic osteosarcoma of the spine: a case report  

PubMed Central

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.

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

2008-01-01

170

[MR imaging in the diagnosis of intradural extramedullary tuberculoma. Report of a case and review of the literature].  

PubMed

Intradural extramedullary tuberculoma without any bony involvement is exceptional. Nineteen cases were found in the literature. We report the case of 5-year-old boy who presented acute paraplegia 8 months after a tuberculous meningitis under antituberculous treatment. Dorsal gadolinium enhanced MRI revealed an intradural extramedullary bunch-shaped enhancing mass at T5-T6 level. The tuberculous nature was confirmed by histology after surgical removal of the lesion followed by a good recovery. To our knowledge, this is the first intradural extramedullary tuberculoma detected by MRI. We underline the role of MRI in the diagnosis of this particular localisation of tuberculosis. PMID:10970962

Akhaddar, A; El Hassani, M Y; Gazzaz-Rifi, M; Chakir, N; El Khamlichi, A; Jiddane, M

2000-06-01

171

Intradural extramedullary tuberculoma of the thoracic spine: paradoxical response to antituberculous therapy.  

PubMed

Intradural extramedullary tuberculoma of the spinal cord (IETSC) is a rare complication of tuberculosis, which can occur as a paradoxical response to antituberculous therapy. A 46-year-old woman with tuberculosis meningitis developed an acute sensory disturbance and paraplegia eight weeks after the antituberculous treatment was started. MRI revealed a cystic lesion at the Th 2 and 3 vertebrae levels, and continuous dural thickening. Laminectomy was performed; soft granulomas were unexpectedly observed inside the dura matter. After the operation, the patient experienced progressive improvement in motor strength. IETSC should be known as rare but possible complication of tuberculous meningitis. PMID:18421202

Takahashi, Hirokatsu; Ito, Shoichi; Kojima, Shigeyuki; Tanno, Takaaki; Hattori, Takamichi

2008-01-01

172

Intradural extramedullary tuberculoma mimicking en plaque meningioma.  

PubMed

A 24-year-old man with tuberculosis meningitis developed acute paraplegia and sensory disturbances 5 weeks after receiving conventional antituberculous therapy. Magnetic resonance imaging revealed an intradural extramedullary long segmental mass mimicking en plaque meningioma at the T2-T6 vertebrae levels. Prompt surgical decompression was performed. A histology examination of the mass revealed a tuberculoma. After surgery, the patient showed improved motor power and a normal bladder function. Intradural extramedullary tuberculoma of the spinal cord is rare complication of tuberculosis meningitis, which can occur as a response to conventional antituberculous therapy. PMID:21119945

Shim, Dae Moo; Oh, Sung Kyun; Kim, Tae Kyun; Chae, Soo Uk

2010-12-01

173

Intradural Extramedullary Tuberculoma Mimicking En Plaque Meningioma  

PubMed Central

A 24-year-old man with tuberculosis meningitis developed acute paraplegia and sensory disturbances 5 weeks after receiving conventional antituberculous therapy. Magnetic resonance imaging revealed an intradural extramedullary long segmental mass mimicking en plaque meningioma at the T2-T6 vertebrae levels. Prompt surgical decompression was performed. A histology examination of the mass revealed a tuberculoma. After surgery, the patient showed improved motor power and a normal bladder function. Intradural extramedullary tuberculoma of the spinal cord is rare complication of tuberculosis meningitis, which can occur as a response to conventional antituberculous therapy. PMID:21119945

Shim, Dae Moo; Kim, Tae Kyun; Chae, Soo Uk

2010-01-01

174

[Costovertebral echinococcosis: a case report and review of the literature].  

PubMed

The bone involvement is uncommon in hydatid disease and represents less than 2 % of cases. Vertebral hydatidosis is the most common bone localization (44 %). The severity of vertebral echinococcosis is related to the neurological complications and therapeutic problems especially in advanced stages. The treatment relies on the actual surgical removal of hydatidosis. In endemic countries, prevention and health education are the best measures. We report a 17-year-old male who presented with an incomplete paraplegia with thoracic deformation, revealing a costovertebral hydatidosis. PMID:19939523

Zaalouni, I; Ouertatani, M; Meherzi, M H; Ben Hamida, M K; Rbai, H; Haggui, A; Bekkay, M A; Nouri, H; Bouhdiba, S; Daghfous, S; Mestiri, M

2010-01-01

175

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

SciTech Connect

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.

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

1996-07-12

176

From new genetics to everyday knowledge: Ideas about how genetic diseases are transmitted in two large Brazilian families  

NASA Astrophysics Data System (ADS)

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.

Santos, Silvana; Bizzo, Nelio

2005-07-01

177

[The fate of critically injured patients].  

PubMed

The prognosis of patients with multiple injuries is very favourable once the critically injured have survived the acute life threatening period. Five to six years after the accident 82% of the surviving patients with injuries of three or more body areas who needed intensive care are fully capable of work and are not receiving any financial compensation. In severe head injuries or in paraplegia, lethality during hospitalization is higher and late prognosis worse: nevertheless, five to six years after the accident 55% of these patients are working full time and do not receive any compensation. PMID:6461986

Glinz, W; Ruckert, R; Affentranger, P

1982-02-01

178

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

PubMed Central

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

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

2014-01-01

179

Tropical myelopathies.  

PubMed

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

Román, Gustavo C

2014-01-01

180

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

PubMed

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

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

2015-02-01

181

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

PubMed

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

Chang, Jaerak; Lee, Seongju; Blackstone, Craig

2013-09-10

182

Replacement of the descending thoracic aorta with intraluminal ring graft.  

PubMed

Renal failure and paraplegia are major complications of operations on the descending thoracic aorta. To minimize cross-clamp time and reduce the incidence of such complications, we have used an intraluminal ring graft to reestablish aortic continuity in patients with descending thoracic aortic lesions. From March 1978 to December 1986, we used this technique alone in 28 patients. There were 4 patients with traumatic aortic disruptions, 4 with dissections, 4 with expanding aneurysms, 2 with ruptured aneurysms, 1 with Marfan's syndrome, and 13 with atherosclerotic aneurysms that were repaired electively. The cross-clamp times ranged from 4 to 28 minutes. There were three early postoperative deaths (within 30 days) and one late postoperative death in the follow-up period (mean, 28.2 months). Ring dislodgement occurred only once, in the first patient in this series. There were no instances of postoperative renal failure or paraplegia. We conclude that the use of an intraluminal ring graft greatly reduces the aortic cross-clamp time and is a safe and effective technique. PMID:2818061

Serra, A J; McNicholas, K W; Spagna, P M; Karmilowicz, N P; Lemole, G M

1989-11-01

183

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

PubMed Central

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

Chang, Jaerak; Lee, Seongju; Blackstone, Craig

2013-01-01

184

The Troyer syndrome (SPG20) protein spartin interacts with Eps15  

SciTech Connect

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.

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

2005-09-09

185

Motor Evoked Potentials in 43 High Risk Spine Deformities  

PubMed Central

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

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

2014-01-01

186

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

PubMed

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

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

2014-10-01

187

Spinal Hydatid Disease: A Case Series  

PubMed Central

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

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

2005-01-01

188

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

PubMed Central

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

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

2013-01-01

189

Artificial Tongue-Placed Tactile Biofeedback for perceptual supplementation: application to human disability and biomedical engineering  

E-print Network

The present paper aims at introducing the innovative technologies, based on the concept of "sensory substitution" or "perceptual supplementation", we are developing in the fields of human disability and biomedical engineering. Precisely, our goal is to design, develop and validate practical assistive biomedical and/technical devices and/or rehabilitating procedures for persons with disabilities, using artificial tongue-placed tactile biofeedback systems. Proposed applications are dealing with: (1) pressure sores prevention in case of spinal cord injuries (persons with paraplegia, or tetraplegia); (2) ankle proprioceptive acuity improvement for driving assistance in older and/or disabled adults; and (3) balance control improvement to prevent fall in older and/or disabled adults. This paper presents results of three feasibility studies performed on young healthy adults.

Vuillerme, Nicolas; Moreau-Gaudry, Alexandre; Demongeot, Jacques; Payan, Yohan

2007-01-01

190

Spina Bifida Cystica  

PubMed Central

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

Lorber, John

1972-01-01

191

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

PubMed

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

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

2014-11-14

192

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

PubMed Central

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

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

2014-01-01

193

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

PubMed

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

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

2014-01-01

194

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

PubMed Central

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

2011-01-01

195

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

PubMed

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

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

2015-01-01

196

CRASH syndrome: clinical spectrum of corpus callosum hypoplasia, retardation, adducted thumbs, spastic paraparesis and hydrocephalus due to mutations in one single gene, L1.  

PubMed

L1 is a neuronal cell adhesion molecule with important functions in the development of the nervous system. The gene encoding L1 is located near the telomere of the long arm of the X chromosome in Xq28. We review here the evidence that several X-linked mental retardation syndromes including X-linked hydrocephalus (HSAS), MASA syndrome, X-linked complicated spastic paraparesis (SP1) and X-linked corpus callosum agenesis (ACC) are all due to mutations in the L1 gene. The inter- and intrafamilial variability in families with an L1 mutation is very wide, and patients with HSAS, MASA, SP1 and ACC can be present within the same family. Therefore, we propose here to refer to this clinical syndrome with the acronym CRASH, for Corpus callosum hypoplasia, Retardation, Adducted thumbs, Spastic paraplegia and Hydrocephalus. PMID:8556302

Fransen, E; Lemmon, V; Van Camp, G; Vits, L; Coucke, P; Willems, P J

1995-01-01

197

Management of Acute Aortic Syndrome and Chronic Aortic Dissection  

SciTech Connect

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.

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

2011-10-15

198

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

PubMed

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

Yamamoto, Seizo

2011-07-01

199

Recovery from and clearance of rabies virus in a domestic ferret.  

PubMed

Here we document the case of a domestic ferret (Mustela putorius) that survived experimental inoculation with rabies virus of skunk origin. The ferret showed initial clinical signs of rabies (hindlimb paralysis) on day 81 after inoculation. The animal survived with paraplegia but otherwise was in an adequate nutritional state until the end of the observation period (PI day 181). At necropsy, no gross lesions were observed. Microscopic lesions were found in sections of cerebrum and spinal cord. In both tissues, the lesions were similar but were more severe with loss of neuronal parenchyma in the spinal cord. The lesions consisted of locally extensive areas with proliferation of astrocytes and moderate numbers of glial cells. Severely affected areas also contained clearly defined vacuoles in the neuropil. Multifocal areas of involvement showed mononuclear cuffing of blood vessels. In a few areas, the cuffing extended to the meninges. Rabies virus antigen was not detected by immunohistochemistry of tissue sections. PMID:21439220

Hamir, Amir N; Niezgoda, Michael; Rupprecht, Charles E

2011-03-01

200

Atypical presentation of sinus histiocytosis with massive lymphadenopathy as an epidural spinal cord tumor: a case presentation and literature review.  

PubMed

Sinus histiocytosis with massive lymphadenopathy is a benign lymphoproliferative disorder growing in frequency as awareness of the disease increases. Also known as Rosai-Dorfman disease, it typically presents as painless cervical lymphadenopathy with fever and malaise. A review of the literature reveals approximately 400 cases of extranodal involvement and approximately 44 cases of central nervous system involvement. Less than 10 of the reported central nervous system tumors have presented as an epidural spinal cord tumor. The authors describe the case of a 29-year-old woman with progressive paraplegia and leg pain. Magnetic resonance imaging of the thoracic spine revealed a tumor mass from T5 to T9. The tumor was resected, and the spinal column was stabilized with pedicle screw fixation and fusion. Postoperative treatment was initiated with radiation and physical rehabilitation. The following is a case report with literature review of the entity. PMID:15800441

Hargett, Christopher; Bassett, Timothy

2005-04-01

201

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

PubMed

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

Bross, M H; Spellicy, M J

1994-03-01

202

Open fenestration for complicated acute aortic B dissection.  

PubMed

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

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

2014-07-01

203

Open fenestration for complicated acute aortic B dissection  

PubMed Central

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

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

2014-01-01

204

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

PubMed

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

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

1990-01-01

205

Cerebellar vermis hypoplasia in a patient with Bardet-Biedl syndrome.  

PubMed

Laurence-Moon-Bardet-Biedl syndome is an autosomal recessive condition characterized by retinal dystrophy, obesity, mental retardation, distal limb anomaly, hypogonadism, and renal dysfunction. The symptoms vary among families and even among affected siblings. Certain clinical signs have been used to identify subgroups of patients with this complex condition. Laurence-Moon syndrome as a distinct entity is rare and features paraplegia in the absence of polydactyly or obesity. Bardet-Biedl syndrome is characterized by distal limb anomaly, obesity, and renal involvement, but neurologic symptoms are very unusual. We report a patient exhibiting characteristic features of Bardet-Biedl syndrome in addition to cerebellar vermis hypoplasia and mega cisterna magna. PMID:12150587

Baskin, Esra; Kayiran, Sinan Mahir; Oto, Sibel; Alehan, Füsun; Agildere, A Muhtesem; Saatçi, Umit

2002-05-01

206

Cryptococcal meningitis in a goat – a case report  

PubMed Central

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

2014-01-01

207

Valproate Treatment in an ALS Patient Carrying a c.194G>A Spastin Mutation and SMN2 Homozygous Deletion  

PubMed Central

Here we report the case of an ALS patient found to carry both a novel heterozygous change (c.194G>A) within the spastin gene and a homozygous deletion of the SMN2 gene. The patient was started on valproic acid (VPA, 600?mg/die per os) considering the capacity of this drug of increasing survival motor neuron through an epigenetic mechanism. Patient clinical course and molecular effects of VPA on skin fibroblasts obtained from the proband are described. This c.194G>A spastin mutation might expand the previously known borders of type 4 spastic paraplegia (SPG4) and we suggest the intriguing possibility that the absence of SMN2 might have acted as a contributory risk factor for starting lower motor neuron damage. Exploring the relationship genocopy-phenocopy in selected ALS patients might represent an interesting strategy for understanding its clinical variability. PMID:25143843

Rodriguez-Menendez, Virginia; Fogli, Antonella; Simi, Paolo; Penco, Silvana; Corbo, Massimo

2014-01-01

208

Tuberculosis of spine  

PubMed Central

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

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

2010-01-01

209

Cervical Symmetric Dumbbell Ganglioneuromas Causing Severe Paresis  

PubMed Central

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

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

2014-01-01

210

Adaptor protein complexes and intracellular transport  

PubMed Central

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

Park, Sang Yoon; Guo, Xiaoli

2014-01-01

211

Steroid-induced Spinal Epidural Lipomatosis after Suprasella Tumor Resection  

PubMed Central

Spinal epidural lipomatosis (SEL) is an abnormal localized accumulation of fat tissues in the epidural space. It is strongly related with steroid administration. The symptoms of SEL are various and range from back pain to paraplegia. In severe cases, decompressive laminectomy is the choice of treatment. A 32-year-old woman who had been under long-term steroid administration after suprasellar tumor resection was admitted for both leg radiating pain and weakness. She was diagnosed with SEL and had a decompressive laminectomy. During the operation, we found the nerve roots were compressed by epidural fat tissues and engorged vessels. After the operation, her radiating pain was relieved and motor weakness was improved. PMID:24757466

Kim, Si On; Park, Keuk Kyu; Kwon, Young Jun; Shin, Hyun Chul

2013-01-01

212

Steroid-induced Spinal Epidural Lipomatosis after Suprasella Tumor Resection.  

PubMed

Spinal epidural lipomatosis (SEL) is an abnormal localized accumulation of fat tissues in the epidural space. It is strongly related with steroid administration. The symptoms of SEL are various and range from back pain to paraplegia. In severe cases, decompressive laminectomy is the choice of treatment. A 32-year-old woman who had been under long-term steroid administration after suprasellar tumor resection was admitted for both leg radiating pain and weakness. She was diagnosed with SEL and had a decompressive laminectomy. During the operation, we found the nerve roots were compressed by epidural fat tissues and engorged vessels. After the operation, her radiating pain was relieved and motor weakness was improved. PMID:24757466

Kim, Si On; Park, Keuk Kyu; Kwon, Young Jun; Shin, Hyun Chul; Choi, Chun Sik

2013-06-01

213

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

SciTech Connect

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.

Jouet, M.; Kenwick, S. [Univ. of Cambridge (United Kingdom); Moncla, A. [Hopital d`Enfants de la Timone, Marseillas (United Kingdom)] [and others

1995-06-01

214

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

SciTech Connect

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.

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

1995-11-20

215

Horner's syndrome and brachial paresis as a complication of lumbar sympathetic block: a case report.  

PubMed

An unusual case of Horner's syndrome secondary to a sympathetic block in a patient with chronic adhesive arachnoiditis (CAA) is described. The patient, a 40-year-old white woman, presented with spastic paraplegia, hyperreflexia, bilateral Babinski sign, superficial and deep sensitive hypoaesthesia at the T4 level, in addition to bladder and rectal dysfunction since she was 32. At age of 38 she complained of excessive daily sweating below the T4 level, mostly at night. A 4mL 0.5% bupivacaine lumbar sympathetic block was performed. Within 15 min a right brachial paresis and an ipsilateral Horner's syndrome were noted. Speculatively, an abnormal cephalic spread of the anaesthesic due to a putative erratic space secondary to the CAA may justify the clinical picture even using a relatively small amount of anaesthesic (4 mL). PMID:8729783

Maranhão-Filho, P A; Martins, M A; Lopes, H F

1995-12-01

216

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

PubMed

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

LeRoy, S C; Pryor, J L

1994-02-01

217

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

PubMed

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

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

2015-04-01

218

[Traumatic damage to the lower cervical spine--a diagnostic problem?].  

PubMed

Even today fractures and dislocations of the lower cervical spine are usually not recognized, or the interpretation of the results of the diagnostic procedures is not correct. These diagnostic failures are often caused by an incomplete representation of the cervical spine in the conventional radiograms, particularly in the lateral projection. Beyond that, the interpretation of the results of the neurological examination of patients with motoric or sensoric deficits after spine injury can be incorrect. Ignorance of the distribution of the segmental innervation of the upper extremities could lead to the wrong diagnosis of paraplegia in a tetraplegic patient. Two patients with injuries of the lower cervical spine are reported, in whom these problems led to an incorrect diagnosis. With regard to these cases we propose a standard diagnostic procedure for the clinical and radiological emergency examination of patients with neurological deficits after spine injury. The technical possibilities of obtaining correct radiographs of the lower cervical spine are described in detail. PMID:8928015

Volkmann, R; Badke, A; Winter, E; Höntzsch, D

1996-07-01

219

Spinal cord compression as initial presentation of metastatic occult follicular thyroid carcinoma.  

PubMed

Metastatic tumors are the most common tumors of the spine, accounting for 98% of all spine lesions. But spinal cord compression as the initial presentation of metastatic occult follicular carcinoma without any thyroid enlargement is unusual and relatively rare. This report describes a 35-years-old female patient presenting with paraplegia and urinary incontinence for the last two months. She had no thyroid enlargement; no thyroid related symptoms and her biochemical thyroid profile was normal. Magnetic resonance imaging (MRI) of spine shows a huge mass compressing the spinal cord at D11-D12 involving both the spinal and paraspinal areas. The patient was treated by surgery and radioiodine ablation as the histopathology showed metastatic follicular thyroid carcinoma. This case was reported because of the rarity of the disease. Early diagnosis and initiation of the treatment should promise a good prognosis for a patient with metastatic spinal cord compression. PMID:24966555

Khan, Md Nuruzzaman; Sharfuzzaman, Amsm; Mostafa, Md Golam

2014-04-01

220

Total knee arthroplasty in a spinal cord-injured patient: a case report.  

PubMed

Patients with spinal cord injuries are prone to knee hydrarthrosis (also known as "water on the knee"), which can cause pain, functional impairment and the restriction of social activities. Total knee arthroplasty is a potentially appropriate treatment. Here, we report on a patient presenting partial T12 AIS grade C paraplegia who was able to walk with two forearm crutches, an ankle-foot orthosis on the right leg and a knee-ankle-foot orthosis on the left leg. Thirteen years after the spinal cord injury, the patient presented with septic arthritis of the right knee, complicated by recurrent hydrarthrosis during standing and walking. Arthroscopy revealed advanced osteoarthritis. Total knee arthroplasty was performed, with very good functional and social outcomes two and half years after surgery. PMID:19720574

Koubaa, S; Ksibi, I; Lebib, S; Tlili, L; Ben Salah, F Z; Dziri, C; Zehi, K; Zouari, M

2009-01-01

221

Potential involvement of the mitochondrial unfolded protein response in depressive-like symptoms in mice.  

PubMed

Many evidences strongly suggest that a mitochondrial deficit is implicated in major depression. A mitochondrial deficit leads to mitochondrial stress responses, including the mitochondrial unfolded protein response (UPRmt), which is associated with certain brain disorders such as spastic paraplegia and Parkinson's disease. However, there is no evidence regarding the relationship between depressive disorder and UPRmt. Mice treated with chronic restraint stress showed significant depressive-like behaviors in the tail suspension and forced swim tests, decreased oxygen consumption rate, and increased levels of molecules associated with UPRmt such as Hspa9, Hspd1, Ubl5, Abcb10, and ClpP. All of the UPRmt-related molecules were significantly correlated with depressive-like behavior in the forced swim test. Thus, the present study is to reveal a relationship between the UPRmt and depressive disorder, suggesting that the UPRmt is a potential drug target for depressive disorders. PMID:25576703

Kambe, Yuki; Miyata, Atsuro

2015-02-19

222

A new clinical variant of the post-malaria neurological syndrome.  

PubMed

Post-malaria neurological syndrome (PMNS) is an uncommon, monophasic illness that occurs within two months following recovery from Plasmodium falciparum (Pf) malaria. Clinical manifestations of PMNS are variable, but published cases uniformly feature neurological and/or psychiatric symptoms without long tract signs. We describe a case of severe brainstem and spinal cord inflammation with paraplegia and sphincter involvement in a 48 year old woman following recovery from a Pf malarial illness. We propose that this case represents a previously unreported form of PMNS, which has features that distinguish it from acute disseminated encephalomyelitis, and that the recognised clinical spectrum of PMNS should be extended to include brainstem and spinal cord inflammation. PMID:24029237

Pace, Adrian A; Edwards, Simon; Weatherby, Stuart

2013-11-15

223

BSCL2 S90L mutation in a Chinese family with Silver syndrome with a review of the literature.  

PubMed

Silver syndrome/spastic paraplegia 17 is an autosomal dominant, complicated hereditary spastic paraparesis in which spasticity of the legs is accompanied by amyotrophy of the hands and occasionally also the lower limbs. Heterozygous mutations of its causative gene, the Berardinelli-Seip congenital lipodystrophy gene, have a broader spectrum of phenotypes including Silver syndrome, distal hereditary motor neuropathy type V and Charcot-Marie-Tooth disease type 2. We report a Chinese family carrying the S90L mutation with Silver syndrome and discuss our literature review of the clinical phenotypes of S90L. Most reported patients (21 of 26) with this mutation showed a phenotype of Silver syndrome. The S90L mutation is predominantly associated with Silver syndrome. PMID:25487175

Cen, Zhidong; Lu, Xingjiao; Wang, Zhenzhen; Ouyang, Zhiyuan; Xie, Fei; Luo, Wei

2015-02-01

224

The genetics of motor neuron diseases.  

PubMed

Motor neuron diseases may be divided into three categories: those with lower motor neuron involvement--spinal muscular atrophy (SMA) and spinobulbar muscular atrophy (SBMA or Kennedy's disease); those with upper motor neuron involvement--primary lateral sclerosis (PLS) and the spastic paraplegias; and those with combined upper and lower motor neuron involvement--amyotrophic lateral sclerosis (ALS). Other familial motor neuron disorders include hereditary neuronopathies, GM2 gangliosidosis, and possibly the ALS/PD syndrome of Guam. The contribution of genetics to the etiopathogenesis of motor neuron considerably, accounting for a high percentage of spinal muscular atrophies, but only a small fraction of cases of ALS. The mode of inheritance also varies, with examples of autosomal dominant (AD), autosomal recessive (AR), or X-linked kindreds. (Tables 1 and 2). PMID:14753656

Figlewicz, Denise A; Orrell, Richard W

2003-12-01

225

Genetics of familial and sporadic amyotrophic lateral sclerosis.  

PubMed

Diseases affecting motor neurons, such as amyotrophic lateral sclerosis (Lou Gerhig's disease), hereditary spastic paraplegia and spinal bulbar muscular atrophy (Kennedy's disease) are a heterogeneous group of chronic progressive diseases and are among the most puzzling yet untreatable illnesses. Over the last decade, identification of mutations in genes predisposing to these disorders has provided the means to better understand their pathogenesis. The discovery 13 years ago of SOD1 mutations linked to ALS, which account for less than 2% of total cases, had a major impact in the field. However, despite intensive research effort, the pathways leading to the specific motor neurons degeneration in the presence of SOD1 mutations have not been fully identified. This review provides an overview of the genetics of both familial and sporadic forms of ALS. PMID:16503123

Gros-Louis, Francois; Gaspar, Claudia; Rouleau, Guy A

2006-01-01

226

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

PubMed

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

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

2010-02-01

227

Spinal Cord Injury Without Radiological Abnormality in Adult Thoracic Spinal Trauma  

PubMed Central

Introduction: Spinal cord injury without radiological abnormality (SCIWORA) is a rare entity and usually involves the cervical spine. Thoracic spine involvement is very rare due to the stability provided by the rib cage. The mechanisms of injury and pathophysiology are still debatable. Case Presentation: We present a case of an adult male who had road traffic accident and presented with paraplegia. The initial radiological investigations carried out in the emergency department were reported to be normal, however, subsequent magnetic resonance imaging revealed spinal cord contusion without vertebral column disruption. The patient recovered partially with conservative treatment measures including bed rest and methylprednisolone. Conclusions: Spinal trauma patients presenting with neurological deficit but no radiological abnormality should be treated as a case of SCIWORA. PMID:25599065

Khatri, Kavin; Farooque, Kamran; Gupta, Ankit; Sharma, Vijay

2014-01-01

228

Exome Sequencing Links Corticospinal Motor Neuron Disease to Common Neurodegenerative Disorders  

PubMed Central

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

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

2014-01-01

229

Recognition of C-terminal amino acids in tubulin by pore loops in Spastin is important for microtubule severing.  

PubMed

Spastin, an AAA ATPase mutated in the neurodegenerative disease hereditary spastic paraplegia, severs microtubules. Many other AAA proteins form ring-shaped hexamers and contain pore loops, which project into the ring's central cavity and act as ratchets that pull on target proteins, leading, in some cases, to conformational changes. We show that Spastin assembles into a hexamer and that loops within the central pore recognize C-terminal amino acids of tubulin. Key pore loop amino acids are required for severing, including one altered by a disease-associated mutation. We also show that Spastin contains a second microtubule binding domain that makes a distinct interaction with microtubules and is required for severing. Given that Spastin engages the MT in two places and that both interactions are required for severing, we propose that severing occurs by forces exerted on the C-terminal tail of tubulin, which results in a conformational change in tubulin, which releases it from the polymer. PMID:17389232

White, Susan Roehl; Evans, Katia J; Lary, Jeffrey; Cole, James L; Lauring, Brett

2007-03-26

230

Recognition of C-terminal amino acids in tubulin by pore loops in Spastin is important for microtubule severing  

PubMed Central

Spastin, an AAA ATPase mutated in the neurodegenerative disease hereditary spastic paraplegia, severs microtubules. Many other AAA proteins form ring-shaped hexamers and contain pore loops, which project into the ring's central cavity and act as ratchets that pull on target proteins, leading, in some cases, to conformational changes. We show that Spastin assembles into a hexamer and that loops within the central pore recognize C-terminal amino acids of tubulin. Key pore loop amino acids are required for severing, including one altered by a disease-associated mutation. We also show that Spastin contains a second microtubule binding domain that makes a distinct interaction with microtubules and is required for severing. Given that Spastin engages the MT in two places and that both interactions are required for severing, we propose that severing occurs by forces exerted on the C-terminal tail of tubulin, which results in a conformational change in tubulin, which releases it from the polymer. PMID:17389232

White, Susan Roehl; Evans, Katia J.; Lary, Jeffrey; Cole, James L.; Lauring, Brett

2007-01-01

231

Crystal structure of the human spastin AAA domain  

PubMed Central

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

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

2012-01-01

232

Crystal structure of the human spastin AAA domain.  

PubMed

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

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

2012-08-01

233

[Results of surgical management of scoliosis and kyphoscoliosis in adults (author's transl)].  

PubMed

Report about 60 operated scoliosis and kyphoscoliosis experienced at adults above 18 years. After separating the patients into male and female groups, age and localisation the most severe preoperative findings which make the operative treatment more difficult, will be described. Much impact will be put on pre-operative respiratoric and cardial impairment. The evaluation of scoliosis in adults will be proofed by examples. The operative technique, whose basis is the Harrington instrumentation in the modification by Stagnara, will be described also. 72 operative treatments have been necessary at 60 patients. In many cases rip-resections and dorsal osteotomies of the spine have been done. In oposition to the correction results of 46.2% on scoliosis and 56.5% on kyphoscoliosis there is one pulmonary embolism ending deadly and one irreversible paraplegia. PMID:1094759

Zielke, K; Pellin, B

1975-04-01

234

[Surgery of traumatic aortic rupture].  

PubMed

This report describes the clinical presentation, diagnosis, surgery and results of patients with acute traumatic rupture of the aorta in a series of 21 consecutive patients. Direct cross-clamping without additional methods of spinal cord protection was used in 18/21 patients (86%). Direct suture was possible in 12/21 patients (60%). In the remaining patients, the repair was carried out by interposition of a Dacron graft. Overall mortality was 7/21 patients (33%). However, in 3 patients with severe polytrauma irreversible brain damage was the cause of death whereas 2 patients died from septicemia and myocardial infarction, respectively. No paraplegia nor paraparesis occurred in the surviving patients which were operated by direct cross-clamping of the aorta and rapid reanastomosis without additional methods of spinal cord protection. PMID:2777620

von Segesser, L; Schneider, K; Siebenmann, R; Glinz, W; Turina, M

1989-06-01

235

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

PubMed Central

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

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

2012-01-01

236

Ophthalmic manifestations of inherited neurodegenerative disorders.  

PubMed

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

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

2014-06-01

237

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

SciTech Connect

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.

Han, Young-Min, E-mail: ymhan@chonbuk.ac.kr; Kwak, Ho-Sung; Jin, Gong-Young; Chung, Gyung-Ho [Chonbuk National University Medical School, Departments of Radiology (Korea, Republic of); Song, Kyung-Jin [Chonbuk National University Medical School, Departments of Orthopedic Surgery (Korea, Republic of)

2006-06-15

238

Physiological Responses to Exergaming After Spinal Cord Injury  

PubMed Central

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

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

2012-01-01

239

Application of rapid artificial cardiac pacing in thoracic endovascular aortic repair in aged patients  

PubMed Central

Objective To compare the safety, efficacy, and impact on stent graft positioning between rapid artificial cardiac pacing (RACP), induced hypotension and sodium nitroprusside (SNP) induced hypotension during thoracic endovascular aortic repair (TEVAR) for Stanford B aortic dissection. Methods One hundred and sixty-eight patients, who were diagnosed with Stanford B aortic dissection and who underwent selective TEVAR in Guangdong General Hospital and the People’s Hospital of Baoan District, Shenzhen, People’s Republic of China, were enrolled in this study. Patients were randomly divided into a RACP group (n=77) and a SNP group (n=91). During localization and deployment of the stent graft, hypotension was induced by RACP or intravenous SNP, according to randomization. Hemodynamics, landing precision (deviation from planned placement site), duration of procedure, renal function, neurocognitive function, and incidence of endoleaks and paraplegia/hemiplegia were compared. Except for methods of inducing hypotension, TEVAR was performed according to the same protocol in each group. Results RACP was successfully performed in all patients assigned to the RACP group. Compared with the SNP group, blood pressure was significantly lower (43±5 versus 81±6 mmHg, P=0.003) and the restoration time of blood pressure and the operation duration were significantly shorter (7±2 versus 451±87 seconds, P<0.001; 87±15 versus 106±18 minutes, P<0.001, respectively) in the RACP group. Stent graft localization/deployment was more precise in the RACP group (2±1 versus 5±2 mm, P<0.001). Compared to baseline, there was no significant change after TEVAR in either group in regard to renal function, neurocognitive function, and incidence of endoleaks and paraplegia/hemiplegia. Conclusion RACP can be safely applied to patients undergoing TEVAR for Stanford B dissection. RACP can shorten the operation duration and facilitate precise graft localization/deployment. PMID:24403824

Chen, Jun; Huang, Wenhui; Luo, Songyuan; Yang, Dahao; Xu, Zhengrong; Luo, Jianfang

2014-01-01

240

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

PubMed Central

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

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

2015-01-01

241

Aculaser therapy for the treatment of cerebral palsy  

NASA Astrophysics Data System (ADS)

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

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

2012-03-01

242

Treating cerebral palsy with aculaser therapy  

NASA Astrophysics Data System (ADS)

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

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

2008-03-01

243

A retrospective chart review of heart rate and blood pressure abnormalities in veterans with spinal cord injury  

PubMed Central

Objective Autonomic impairment may lead to increased prevalence of heart rate (HR) and blood pressure (BP) abnormalities in veterans with spinal cord injury (SCI). In addition, comorbid medical conditions and prescription medication use may influence these abnormalities, including bradycardia, and tachycardia, hypotension, hypertension as well as autonomic dysreflexia (AD), and orthostatic hypotension (OH). Design A retrospective review of clinical and administrative datasets in veterans with SCI and compared the prevalence rates between clinical values and ICD-9 diagnostic codes in individuals with tetraplegia (T: C1–C8), high paraplegia (HP: T1–T6), and low paraplegia (LP: T7 and below). Results The prevalence of clinical values indicative of a HR ? 80  beats per minute was higher in the HP compared to the LP and T groups. A systolic BP (SBP) ? 110 mmHg was more common in the T compared to the HP and LP groups, whereas the prevalence of a SBP ? 140 mmHg was increased in the LP compared to the HP and T groups. Diagnosis of hypertension was 39–60% whereas the diagnosis of hypotension was less than 1%. Diagnosis of AD and OH was highest in the T group, but remained below 10%, regardless of categorical lesion level. Antihypertensive medications were commonly prescribed (55%), and patients on these medications were less likely to have high BP. The odds ratio of higher SBP and DBP increased with age and body mass index (BMI). Conclusion In veterans with SCI, the prevalence of HR and BP abnormalities varied depending on level of lesion, age, BMI, and prescription medication use. PMID:23941794

Zhu, Carolyn; Galea, Marinella; Livote, Elayne; Signor, Dan; Wecht, Jill M.

2013-01-01

244

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

PubMed Central

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

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

245

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

PubMed

This article describes the application of a model for analyzing industrial tasks that was developed to identify jobs that could potentially be filled by people with disabilities (DP) and to serve as a guideline for a company hiring policy. In Brazil, Law No. 8213/91 makes it obligatory to hire DP based on quotas that are established according to the number of employees in a public and private company. Using a set of methods and techniques based on ergonomic work analysis and on occupational therapy, we sought to build a model to indicate the skills required to perform industrial tasks. The model was applied at 19 workstations at a Brazilian aircraft manufacturer in 2002. The task supervisor and the operator performing the task were interviewed, the work activity was filmed, a kinesiological analysis was done, the task was observed and a checklist was applied to help recognize and systematize the skills involved in performing the job task. The last step consisted of correlating the skills required to perform the task to the potential skills of the various types of disability. It was found that 100% of the jobs could be filled by workers with low-level paraplegia, 89% by workers with general paraplegia, 0% with low-level tetraplegia, 47% with auditory impairment, 42% with hemiplegia, 68% with upper limb amputees wearing adequate prostheses, and 89% handicapped wheelchair users. The company hired 14 DP based on the results of this model. The model proved adequate for analyzing industrial tasks with a view to the inclusion of DP, and it can be applied to other sectors of industrial production. PMID:18452126

Simonelli, Angela Paula; Camarotto, João Alberto

2008-01-01

246

Atlastin GTPases are required for Golgi apparatus and ER morphogenesis  

PubMed Central

The hereditary spastic paraplegias (SPG1-33) comprise a cluster of inherited neurological disorders characterized principally by lower extremity spasticity and weakness due to a length-dependent, retrograde axonopathy of corticospinal motor neurons. Mutations in the gene encoding the large oligomeric GTPase atlastin-1 are responsible for SPG3A, a common autosomal dominant hereditary spastic paraplegia. Here we describe a family of human GTPases, atlastin-2 and -3 that are closely related to atlastin-1. Interestingly, while atlastin-1 is predominantly localized to vesicular tubular complexes and cis-Golgi cisternae, mostly in brain, atlastin-2 and -3 are localized to the endoplasmic reticulum (ER) and are most enriched in other tissues. Knockdown of atlastin-2 and -3 levels in HeLa cells using siRNA (small interfering RNA) causes disruption of Golgi morphology, and these Golgi structures remain sensitive to brefeldin A treatment. Interestingly, expression of SPG3A mutant or dominant-negative atlastin proteins lacking GTPase activity causes prominent inhibition of ER reticularization, suggesting a role for atlastin GTPases in the formation of three-way junctions in the ER. However, secretory pathway trafficking as assessed using vesicular stomatitis virus G protein fused to green fluorescent protein (VSVG-GFP) as a reporter was essentially normal in both knockdown and dominant-negative overexpression conditions for all atlastins. Thus, the atlastin family of GTPases functions prominently in both ER and Golgi morphogenesis, but they do not appear to be required generally for anterograde ER-to-Golgi trafficking. Abnormal morphogenesis of the ER and Golgi resulting from mutations in atlastin-1 may ultimately underlie SPG3A by interfering with proper membrane distribution or polarity of the long corticospinal motor neurons. PMID:18270207

Rismanchi, Neggy; Soderblom, Cynthia; Stadler, Julia; Zhu, Peng-Peng; Blackstone, Craig

2008-01-01

247

Spinal Cord Blood Flow and Ischemic Injury after Experimental Sacrifice of Thoracic and Abdominal Segmental Arteries  

PubMed Central

OBJECTIVE Spinal cord blood flow (SCBF) after sacrifice of thoracoabdominal aortic segmental arteries (TAASA) during thoracoabdominal aortic aneurysm (TAAA) repair remains poorly understood. This study explored SCBF for 72h after sacrifice of all TAASA. METHODS Fourteen juvenile Yorkshire pigs underwent complete serial TAASA sacrifice (T4-L5). Six control pigs underwent anesthesia and cooling to 32C with no TAASA sacrifice. In the experimental animals, spinal cord function was continuously monitored using motor evoked potentials (MEP) until 1 hour (h) after clamping the last TAASA. Fluorescent microspheres enabled segmental measurement of SCBF along the entire spinal cord before, and 5 min, 1h, 5h, 24h and 72h after complete TAASA sacrifice. A modified Tarlov score was obtained for 3 days after surgery. RESULTS All the pigs with complete TAASA sacrifice retained normal cord function (MEP) until 1h after TAASA ligation. 7 pigs (50%) with complete TAASA sacrifice recovered after 72h; 7 pigs suffered paraparesis or paraplegia. Intraoperatively— and until 1h postoperatively— SCBF was similar among the three groups along the entire cord. Postoperatively, SCBF did not decrease in any group, but significant hyperemia occurred at 5 hours in controls and recovery animals, but did not occur in pigs that developed paraparesis or paraplegia in the T8-L2 segments (p=.0002) and L3-S segments (p=.0007). At 24h, SCBF remained marginally lower from T8 caudally; at 72h, SCBF was similar among all groups along the entire cord. SCBF in the segments T8-L2 at 5h predicted functional recovery (p=.003). CONCLUSIONS This study suggests that critical spinal cord ischemia after complete TAASA sacrifice does not occur immediately (intraoperatively), but is delayed 1–5 hours or longer after clamping, and represents failure to mount a hyperemic response to rewarming and awakening. The short duration of low SCBF associated with spinal cord injury suggests that hemodynamic and metabolic manipulation lasting only 24–72 hours may allow routine preservation of normal cord function despite sacrifice of all TAASA secondary to surgical or endovascular repair of large TAAA. PMID:18374592

Etz, Christian D.; Homann, Tobias M.; Luehr, Maximilian; Zhang, Ning; Weisz, Donald J; Kleinman, George; Plestis, Konstadinos A.; Griepp, Randall B.

2011-01-01

248

Brain-computer interface controlled robotic gait orthosis  

PubMed Central

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

2013-01-01

249

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

PubMed Central

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

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

2013-01-01

250

The effects of exercise on human articular cartilage  

PubMed Central

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

Eckstein, F; Hudelmaier, M; Putz, R

2006-01-01

251

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

PubMed

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

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

2015-01-01

252

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

PubMed

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

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

2014-01-01

253

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

PubMed Central

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

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

2014-01-01

254

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

PubMed

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

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

2013-12-01

255

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

PubMed Central

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

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

2013-01-01

256

Long-Term Results of Endovascular Repair for Distal Arch and Descending Thoracic Aortic Aneurysms Treated by Custom-Made Endografts: Usefulness of Fenestrated Endografts  

PubMed Central

Objective: We evaluated early and long-term results of atherosclerotic aneurysm repair with custom-made endografts. Materials and Methods: Eighty-one consecutive patients underwent thoracic endovascular aortic repair with custom-made endografts. Fenestrated grafts were used in 37 patients (45.7%) to maintain blood flow of the neck and a landing zone for as long as possible for distal arch or proximal descending aneurysms. The rates of perioperative mortality, stroke, paraplegia, and primary endoleaks were assessed to evaluate in-hospital safety. The rates of endoleak development, survival, and freedom from aortic-related death were assessed to evaluate long-term efficiency. Results: Twenty-four patients (29.6%) underwent urgent operations, and 38 (46.9%) underwent distal arch or proximal descending aortic aneurysm repair. There was one case (1.2%) of in-hospital mortality and no cases of stroke. Permanent spinal injury occurred in one patient (1.2%). Early and late endoleaks occurred in one and 16 patients, respectively. The actuarial survival rates were 88.9%, 64.9%, and 51.7% at 1, 5, and 10 years, respectively. The actuarial rates of freedom from endoleaks were 90.1%, 81.3%, and 68.6% at 1, 5, and 10 years, respectively. Conclusion: Early results of custom-made endografts were excellent, and fenestrated endografts were safe for distal arch and proximal descending aortic aneurysms. PMID:25593623

Nakamura, Kunihide; Nagahama, Hiroyuki; Nina, Katsuhiko; Endou, Jouji; Kojima, Kazushi; Nishimura, Masanori; Ishii, Hirohito; Yokota, Atsuko

2014-01-01

257

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

PubMed Central

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

2013-01-01

258

Characterization of the Drosophila atlastin interactome reveals VCP as a functionally related interactor.  

PubMed

At least 25 genes, many involved in trafficking, localisation or shaping of membrane organelles, have been identified as causative genes for the neurodegenerative disorder hereditary spastic paraplegia (HSP). One of the most commonly mutated HSP genes, atlastin-1, encodes a dynamin-like GTPase that mediates homotypic fusion of endoplasmic reticulum (ER) membranes. However, the molecular mechanisms of atlastin-1-related membrane fusion and axonopathy remain unclear. To better understand its mode of action, we used affinity purification coupled with mass spectrometry to identify protein interactors of atlastin in Drosophila. Analysis of 72 identified proteins revealed that the atlastin interactome contains many proteins involved in protein processing and transport, in addition to proteins with roles in mRNA binding, metabolism and mitochondrial proteins. The highest confidence interactor from mass spectrometry analysis, the ubiquitin-selective AAA-ATPase valosin-containing protein (VCP), was validated as an atlastin-interacting protein, and VCP and atlastin showed overlapping subcellular distributions. Furthermore, VCP acted as a genetic modifier of atlastin: loss of VCP partially suppressed an eye phenotype caused by atlastin overexpression, whereas overexpression of VCP enhanced this phenotype. These interactions between atlastin and VCP suggest a functional relationship between these two proteins, and point to potential shared mechanisms between HSP and other forms of neurodegeneration. PMID:23790629

O'Sullivan, Niamh C; Dräger, Nina; O'Kane, Cahir J

2013-06-20

259

High incidence of morbidity following resection of metastatic pheochromocytoma in the spine.  

PubMed

Pheochromocytomas of the spine are uncommon and require careful preoperative planning. The authors retrospectively reviewed the charts of 5 patients with metastatic spinal pheochromocytoma who had undergone surgical treatment over the past 10 years at their medical center. They reviewed patient age, history of pheochromocytoma resection, extent and location of metastases, history of alpha blockage, surgical level, surgical procedure, postoperative complications, tumor recurrence, and survival. Metastases involved the cervical (1 patient), thoracic (3 patients), and lumbar (2 patients) levels. Preoperative treatment included primary pheochromocytoma resection, chemotherapy, alpha blockade, embolization, and radiation. Three patients had tumor recurrence, and 2 underwent 2-stage reoperations for tumor extension. Hemodynamic complications were common: 2 patients developed pulseless electrical activity arrest within 4 months after surgery, 1 patient had profound postoperative tachycardia with fever and an elevated creatine kinase level, and 1 patient experienced transient postoperative hypotension and paraplegia. One patient died of complications related to disseminated cerebral and spinal disease. With careful preoperative and surgical management, patients with symptomatic metastatic spinal pheochromocytoma can benefit from aggressive surgical treatment. Postoperative cardiovascular complications are common even months after surgery, and patients should be closely monitored long term. PMID:24725182

Kaloostian, Paul E; Zadnik, Patricia L; Kim, Jennifer E; Groves, Mari L; Wolinsky, Jean-Paul; Gokaslan, Ziya L; Witham, Timothy F; Bydon, Ali; Sciubba, Daniel M

2014-06-01

260

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

PubMed

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

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

2015-02-17

261

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

SciTech Connect

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.

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

2006-10-15

262

Protrudin serves as an adaptor molecule that connects KIF5 and its cargoes in vesicular transport during process formation.  

PubMed

Neurons are highly polarized cells with long neurites. Vesicular transport is required for neurite extension. We recently identified protrudin as a key regulator of vesicular transport during neurite extension. Expression of protrudin in nonneuronal cells thus induces formation of neurite-like membrane protrusions. We adopted a proteomics approach to identify proteins that associate with protrudin. Among the protrudin-associated proteins, including many with a function related to intracellular trafficking, we focused on KIF5, a motor protein that mediates anterograde vesicular transport in neurons. A coimmunoprecipitation assay confirmed that endogenous protrudin and KIF5 interact in mouse brain. Overexpression of KIF5 induced the formation of membrane protrusions in HeLa cells, reminiscent of the effect of protrudin overexpression. Forced expression of both protrudin and KIF5 promoted protrusion extension in a synergistic manner, whereas depletion of either protein attenuated protrusion formation. Protrudin facilitated the interaction of KIF5 with Rab11, VAP-A and -B, Surf4, and RTN3, suggesting that protrudin serves as an adaptor protein and that the protrudin-KIF5 complex contributes to the transport of these proteins in neurons. Given that mutation of protrudin or KIF5 is a cause of human hereditary spastic paraplegia, the protrudin-KIF5 axis appears to be integral to neuronal function. PMID:21976701

Matsuzaki, Fumiko; Shirane, Michiko; Matsumoto, Masaki; Nakayama, Keiichi I

2011-12-01

263

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

PubMed

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

Hübner, Christian A; Kurth, Ingo

2014-12-01

264

The role of reticulons in neurodegenerative diseases.  

PubMed

Reticulons (RTNs) are a group of membrane-associated proteins mainly responsible for shaping the tubular endoplasmic reticulum network, membrane trafficking, inhibition of axonal growth, and apoptosis. These proteins share a common sequence feature, the reticulon homology domain, which consists of paired hydrophobic stretches that are believed to induce membrane curvature by acting as a wedge in bilayer membranes. RTNs are ubiquitously expressed in all tissues, but each RTN member exhibits a unique expression pattern that prefers certain tissues or even cell types. Recently, accumulated evidence has suggested additional and unexpected roles for RTNs, including those on DNA binding, autophagy, and several inflammatory-related functions. These manifold actions of RTNs account for their ever-growing recognition of their involvement in neurodegenerative diseases like Alzheimer's disease, amyotrophic lateral sclerosis, multiple sclerosis, as well as hereditary spastic paraplegia. This review summarizes the latest discoveries on RTNs in human pathophysiology, and the engagement of these in neurodegeneration, along with the implications of these findings for a better understanding of the molecular events triggered by RTNs and their potential exploitation as next-generation therapeutics. PMID:24218324

Chiurchiù, Valerio; Maccarrone, Mauro; Orlacchio, Antonio

2014-03-01

265

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

PubMed Central

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

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

2014-01-01

266

Hazards of mattresses, beds and bedding in deaths of infants.  

PubMed

Of 52 infants who had died suddenly and were referred to autopsy, nine had lain on adult water beds for the first time; five had died as a result of accidents; two had died on water beds; two were in beds with widely spaced slats; and one had died as a result of strangulation. Three deaths were due to overlying. Three other infants had been placed on sheepskin rugs for the first time and were found dead shortly thereafter. These infants ranged in age from 2 to 9 months, except for a severely mentally retarded nine-year-old with spastic paraplegia. We believe that a general warning should be issued concerning water beds and that soft bedding should not be used for infants. Infants should not be placed unattended or left to sleep on water beds; only beds recommended for infants should be used. Overlying of a young infant is most likely to occur on a water bed, or if the parent is obese or has consumed alcohol. PMID:2063814

Gilbert-Barness, E; Hegstrand, L; Chandra, S; Emery, J L; Barness, L A; Franciosi, R; Huntington, R

1991-03-01

267

Aortic Replacement with Sutureless Intraluminal Grafts  

PubMed Central

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

Lemole, Gerald M.

1990-01-01

268

Cytomegalovirus ischemic colitis and transverse myelitis in a renal transplant recipient.  

PubMed

We report a rare case of cytomegalovirus (CMV)-associated ischemic colitis and transverse myelitis (TM) occurring precociously after renal transplantation. A 57-year-old male was transplanted with a cadaveric kidney on 5 June 2009. The patient was CMV seropositive and the donor was seronegative. Transplantation was followed shortly by TM, which resulted in paraplegia. The results of magnetic resonance imaging of the spinal cord showed abnormalities. Twenty days after transplantation, he developed abdominal pain with melena and was diagnosed as having CMV-associated ischemic colitis confirmed by colonoscopy and biopsy. Serological data and identification of the viral genome by polymerase chain reaction were confirmatory for CMV. Treatment consisted of intravenous ganciclovir, followed by polyvalent immunoglobulin. The outcome was favorable. Symptomatic CMV infection is relatively common among the renal transplant population. Early colonoscopy is beneficial for making a quick diagnosis and therefore helps to institute a prompt management of CMV colitis. Myelitis is less common in transplant recipients and diagnosis, therefore, was more difficult. PMID:23538355

Gorsane, Imen; Aloui, Sabra; Letaif, Ahmed; Hadhri, Rim; Haouala, Faouzi; Frih, Ameur; Dhia, Naceur Ben; Elmay, Mezri; Skhiri, Habib

2013-03-01

269

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

PubMed

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

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

2014-12-01

270

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

PubMed

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

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

2014-08-13

271

Fishing for causes and cures of motor neuron disorders  

PubMed Central

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

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

2014-01-01

272

Real-time strap pressure sensor system for powered exoskeletons.  

PubMed

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

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

2015-01-01

273

Epidural steroid injections: update on efficacy, safety, and newer medications for injection.  

PubMed

The best evidence for epidural injection appears to be in the setting of radicular pain with epidural steroid and non--steroid injections more efficacious than non-epidural injections. Studies showed the efficacy of non-particulate steroid to approach the efficacy of particulate steroid and very limited comparisons demonstrated no significant difference between epidural steroid and epidural non--steroid (local anesthetic) injection. Preliminary studies evaluating epidural injection of disease modifying anti--rheumatic drugs such etanercept and tocilizumab showed conflicting results and had significant limitations. Randomized studies support better efficacy of transforaminal injection due to greater incidence of ventral epidural spread of injectate when compared to interlaminar injection. Thus, the transforaminal approach is recommended when unilateral radicular pain is limited to one nerve root. However, the transforaminal approach is associated with greater incidence of central nervous system injury, including paraplegia, attributed to embolization of the particulate steroid. Recent studies showed that non--particulate steroids potentially last as long as particulate steroids. Therefore non-particulate steroid should be used in initial transforaminal epidural injection. Future studies should look into the role of adjunct diagnostic aids, including digital subtraction angiography, in detecting intravascular injection and the ideal site of needle placement, whether it is the safe triangle or the triangle of Kambin. Finally, the role of epidural disease-modifying anti-rheumatic drugs in the management of back pain needs to be better elucidated. PMID:25311951

Kozlov, N; Benzon, H T; Malik, K

2014-10-14

274

Development and Treatments of Inflammatory Cells and Cytokines in Spinal Cord Ischemia-Reperfusion Injury  

PubMed Central

During aortic surgery, interruption of spinal cord blood flow might cause spinal cord ischemia-reperfusion injury (IRI). The incidence of spinal cord IRI after aortic surgery is up to 28%, and patients with spinal cord IRI might suffer from postoperative paraplegia or paraparesis. Spinal cord IRI includes two phases. The immediate spinal cord injury is related to acute ischemia. And the delayed spinal cord injury involves both ischemic cellular death and reperfusion injury. Inflammation is a subsequent event of spinal cord ischemia and possibly a major contributor to spinal cord IRI. However, the development of inflammatory mediators is incompletely demonstrated. And treatments available for inflammation in spinal cord IRI are insufficient. Improved understanding about spinal cord IRI and the development of inflammatory cells and cytokines in this process will provide novel therapeutic strategies for spinal cord IRI. Inflammatory cytokines (e.g., TNF-? and IL-1) may play an important role in spinal cord IRI. For treatment of several intractable autoimmune diseases (e.g., rheumatoid arthritis), where inflammatory cytokines are involved in disease progression, anti-inflammatory cytokine antagonist is now available. Hence, there is great potential of anti-inflammatory cytokine antagonist for therapeutic use of spinal cord IRI. We here review the mediators and several possibilities of treatment in spinal cord IRI. PMID:23956505

Zhu, Ping; Li, Jia-xin; Fujino, Masayuki; Zhuang, Jian; Li, Xiao-Kang

2013-01-01

275

Effect of Locomotor Training on Motor Recovery and Walking Ability in Patients with Incomplete Spinal Cord Injury: A Case Series  

PubMed Central

[Purpose] The aim of this study was to describe the effect of locomotor training on a treadmill for three individuals who have an incomplete spinal cord injury (SCI). [Subjects and Methods] Three indivduals (2 males, 1 female) with incomplete paraplegia participated in this prospective case series. All subjects participated in locomotor training for a maximum of 20 minutes on a motorized treadmill without elevation at a comfortable walking speed three days a week for four weeks as an adjunct to a conventional physiotherapy program. The lower extremity strength and walking capabilities were used as the outcome measures of this study. Lower extremity strength was measured by lower extremity motor score (LEMS). Walking capability was assessed using the Walking Index for Spinal Cord Injury (WISCI II). [Results] An increase in lower extremity motor score and walking capabilities at the end of training program was found. [Conclusion] Gait training on a treadmill can enhance motor recovery and walking capabilities in subjects with incomplete SCI. Further research is needed to generalize these findings and to identify which patients might benefit from locomotor training. PMID:25013303

Anwer, Shahnawaz; Equebal, Ameed; Palekar, Tushar J; Nezamuddin, M; Neyaz, Osama; Alghadir, Ahmad

2014-01-01

276

The clinical maze of mitochondrial neurology  

PubMed Central

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

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

2014-01-01

277

The Fifth Adaptor Protein Complex  

PubMed Central

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

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

2011-01-01

278

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

PubMed

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

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

2014-03-01

279

L1CAM whole gene deletion in a child with L1 syndrome.  

PubMed

L1 syndrome is a group of overlapping, X-linked disorders caused by mutations in L1CAM. Clinical phenotypes within L1 syndrome include X-linked hydrocephalus with stenosis of the aqueduct of sylvius (HSAS); mental retardation, adducted thumbs, shuffling gait, and aphasia (MASA) syndrome; spastic paraplegia type 1; and agenesis of the corpus callosum. Over 200 mutations in L1CAM have been reported; however, only a few large gene deletions have been observed. We report on a 4-month-old male with a de novo whole gene deletion of L1CAM presenting with congenital hydrocephalus, aqueductal stenosis, and adducted thumbs. Initial failure of L1CAM gene sequencing suggested the possibility of a whole gene deletion of L1CAM. Further investigation through chromosome microarray analysis showed a 62Kb deletion encompassing the first exon of the PDZD4 gene and the entire L1CAM gene. Investigations into genotype-phenotype correlations have suggested that mutations leading to truncated or absent L1 protein cause more severe forms of L1 syndrome. Based on the presentation of the proband and other reported patients with whole gene deletions, we provide further evidence that L1CAM whole gene deletions result in L1 syndrome with a severe phenotype, deletions of PDZD4 do not cause additional manifestations, and that X-linked nephrogenic diabetes insipidus reported in a subset of patients with large L1CAM deletions results from the loss of AVPR2. PMID:24668863

Chidsey, Brandalyn A; Baldwin, Erin E; Toydemir, Reha; Ahles, Lauren; Hanson, Heather; Stevenson, David A

2014-06-01

280

Novel mutational mechanism in man: Expansion of trinucleotide repeats  

SciTech Connect

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.

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

1995-11-01

281

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

PubMed

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

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

2014-12-01

282

Restoration of muscle volume and shape induced by electrical stimulation of denervated degenerated muscles: qualitative and quantitative measurement of changes in rectus femoris using computer tomography and image segmentation.  

PubMed

This study demonstrates in a novel way how volume and shape are restored to denervated degenerated muscles due to a special pattern of electrical stimulation. To this purpose, Spiral Computer Tomography (CT) and special image processing tools were used to develop a method to isolate the rectus femoris from other muscle bellies in the thigh and monitor growth and morphology changes very accurately. During 4 years of electrical stimulation, three-dimensional (3D) reconstructions of the rectus femoris muscles from patients with long-term flaccid paraplegia were made at different points in time. The growth of the muscle and its changes through the time period are seen in the 3D representation and are measured quantitatively. Furthermore, changes in shape are compared with respect to healthy muscles in order to estimate the degree of restoration. The results clearly show a slow but continuing muscle growth induced by electrical stimulation; the increase of volume is accompanied by the return of a quasi-normal muscle shape. This technique allows a unique way of monitoring which provides qualitative and quantitative information on the denervated degenerated muscle behavior otherwise hidden. PMID:18782130

Gargiulo, Paolo; Vatnsdal, Brynjar; Ingvarsson, Páll; Knútsdóttir, Sigrún; Gudmundsdóttir, Vilborg; Yngvason, Stefán; Helgason, Thórdur

2008-08-01

283

Characterization of maspardin, responsible for human Mast syndrome, in an insect species and analysis of its evolution in metazoans  

NASA Astrophysics Data System (ADS)

Mast syndrome is a complicated form of human hereditary spastic paraplegias, caused by a mutation in the gene acid cluster protein 33, which encodes a protein designated as "maspardin." Maspardin presents similarity to the ?/?-hydrolase superfamily, but might lack enzymatic activity and rather be involved in protein-protein interactions. Association with the vesicles of the endosomal network also suggested that maspardin may be involved in the sorting and/or trafficking of molecules in the endosomal pathway, a crucial process for maintenance of neuron health. Despite a high conservation in living organisms, studies of maspardin in other animal species than mammals were lacking. In the cotton armyworm Spodoptera littoralis, an insect pest model, analysis of an expressed sequence tag collection from antenna, the olfactory organ, has allowed identifying a maspardin homolog ( SlMasp). We have investigated SlMasp tissue distribution and temporal expression by PCR and in situ hybridization techniques. Noteworthy, we found that maspardin was highly expressed in antennae and associated with the structures specialized in odorant detection. We have, in addition, identified maspardin sequences in numerous "nonmammalian" species and described here their phylogenetic analysis in the context of metazoan diversity. We observed a strong conservation of maspardin in metazoans, with surprisingly two independent losses of this gene in two relatively distant ecdysozoan taxa that include major model organisms, i.e., dipterans and nematodes.

Chertemps, Thomas; Montagné, Nicolas; Bozzolan, Françoise; Maria, Annick; Durand, Nicolas; Maïbèche-Coisne, Martine

2012-07-01

284

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

SciTech Connect

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.

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

2007-04-15

285

Surgical Treatment of Aortobronchial and Aortoesophageal Fistulae due to Thoracic Aortic Aneurysm  

PubMed Central

We present a review of our single-institution experience, over 19 years, with aortobronchial and aortoesophageal fistulae due to descending thoracic aortic aneurysm. We conducted a retrospective chart review of 10 cases involving surgery for aortobronchial and aortoesophageal fistulae in our clinic from February 1985 through October 2004. Pathologic or predisposing conditions associated with aortobronchial fistula were descending thoracic aortic aneurysm (n = 8), previous aortic surgery (n = 1), and concomitant aortoesophageal fistula (n = 1). Three patients presented emergently with aortobronchial fistula (n = 2) and aortoesophageal fistula (n = 1). Ages of the 10 patients ranged from 42 to 74 years (median, 63 years). The median cross-clamp time was 34 minutes (range, 27–41 min). Repairs, in 9 patients, involved an inlay of prosthetic tube graft using the clamp-and-sew technique, and in 1 patient repair involved patch aortoplasty. The operative mortality rate was 20%: 1 patient had acute concomitant aortoesophageal and aortobronchial fistulae, and another had chronic aortobronchial fistula. There was no embolic stroke or paraplegia. During follow-up (median, 2.5 years), there were no deaths or postoperative morbidity. We conclude that repair of aortobronchial and aortoesophageal fistulae using the clamp-and-sew technique can be performed with acceptable operative mortality and long-term results. However, the mortality rate continues to be highly significant in patients with acute bleeding aortobronchial fistula or with aortoesophageal fistula, despite rapid surgical intervention. PMID:16429896

Eren, Ercan; Keles, Cuneyt; Toker, Mehmet Erdem; Ersahin, Suat; Erentug, Vedat; Guler, Mustafa; Ipek, Gokhan; Akinci, Esat; Balkanay, Mehmet; Yakut, Cevat

2005-01-01

286

Scrotal Swelling and Testicular Atrophy due to Schistosomiasis in a 9-Year-Old Boy: A Case Report  

PubMed Central

Schistosomiasis is a communicable disease which commonly involves urinary bladder causing hematuria, or large bowel causing bloody stool. The common species encountered in this lake region surrounding Lake Victoria in Tanzania are Schistosoma haematobium and Schistosoma mansoni. Complications can lead to portal hypertension due portal fibrosis in liver, and fibrosis in lung can lead to pulmonary hypertension; this commonly seen with S. mansoni. Major complications of S. maeametobium are chronic cystitis with squamous metaplasia with subsequent development of squamous cell carcinoma. Involvement of spinal cord causing paraplegia has been observed in S. haematobium. Other unusual pathology of schistosomiasis has been described, such as involvement of the appendix, ovary, prostate, and cervix. Here, we present a case of schistosomiasis in a 9-year-old boy who presented with left scrotal pain for one year which was accompanied by scrotal swelling; surgical exploration was done, and the finding was hydrocele and atrophic testes with nodules on the surface. Histological examination reveals atrophic testis and heavy active granulomatous inflammation with schistosoma eggs consistent with Schistosoma haematobium in the tunica vaginalis. PMID:22567478

Rambau, Peter F.; Chandika, Alphonce; Chalya, Philipo L.; Jackson, Kahima

2011-01-01

287

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

PubMed

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

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

2014-10-01

288

Souffle/Spastizin Controls Secretory Vesicle Maturation during Zebrafish Oogenesis  

PubMed Central

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

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

2014-01-01

289

Treatment of tuberculosis of the cervical spine: operative versus nonoperative.  

PubMed

We retrospectively reviewed 15 children (four with paralysis) and 39 adults (10 with paralysis) with tuberculosis of the cervical spine to assess the drug responses, disease arrest, and healing times. Ten children and 13 adults were treated nonoperatively, while anterior débridement was performed in five children (two with paralysis) and anterior radical surgery in 26 adults (10 with paralysis). Triple chemotherapy (isoniazid, rifampin, ethambutol [or pyrazinamide for children]) was given to all patients for 12 months. The tuberculosis began to arrest after 3 months of chemotherapy and healed within 12 months. Spontaneous fusion occurred in all adults but only two of the 10 children. Surgical fusion was achieved within 12 to 16 weeks in adults. In nonoperated patients, an initial kyphosis of 12 degrees progressed to 17 degrees at final followup in the children and an initial kyphosis of 9 degrees progressed to 13 degrees in 13 adults. In operated patients, the initial kyphosis of 13 degrees in adults became 2 degrees at the time of the fusion, while the initial kyphosis of 14 degrees in the five children progressed to 18 degrees. Patients with paraplegia recovered completely within 14 days on average (range, 1-42 days) after treatment. Recovery was gradual in the nonoperative group, while it occurred within 3 days in the operative group. PMID:17414165

Moon, Myung-Sang; Moon, Jeong-Lim; Kim, Sung-Sim; Moon, Young-Wan

2007-07-01

290

Grave's Disease with Severe Hepatic Dysfunction: A Diagnostic and Therapeutic Challenge  

PubMed Central

Hepatic dysfunction in a patient with thyrotoxicosis may result from hyperthyroidism per se, as a side effect of antithyroid drugs, and causes unrelated to hyperthyroidism which sometimes causes diagnostic and therapeutic difficulties. A young female patient was admitted to our hospital with symptoms of thyrotoxicosis, diffuse goiter and ophthalmopathy along with cholestatic pattern of jaundice, and proximal muscle weakness. She was treated with propylthiouracil with gradual recovery. She was continuing her antithyroid medication with regular follow-up. The patient was readmitted a few months later with worsening thyrotoxicosis, proximal muscle weakness, fever, and a hepatocellular pattern of jaundice with sepsis. Propylthiouracil was stopped and lithium along with steroid coverage was given to control her thyrotoxicosis which was later changed to methimazole. Broad spectrum antibiotic therapy was also started but without any response. During her hospital stay, the patient also developed a flaccid paraplegia resembling Guillain-Barre syndrome. IV steroid was started for the neuropathy but meanwhile the patient succumbed to her illness. So in centers where facility for radioiodine therapy is not readily available, some definite well-tested protocols should be formulated to address such common but complicated clinical situations. PMID:25317178

Sarma, Dipti; Kaimal Saikia, Uma; Choudhury, Bipul Kumar

2014-01-01

291

Surgical treatment of acute traumatic tear of the thoracic aorta.  

PubMed Central

Acute traumatic tear of the thoracic aorta is a severe injury with a high mortality rate. This condition requires expeditious evaluation and prompt surgical intervention in order to improve patient survival. The experience at the authors' institution from 1971 to 1987 includes 41 patients who sustained acute traumatic tear of the thoracic aorta and reached the hospital alive. The purpose of the study was to evaluate the surgical management of this injury with regards to mortality rate and the incidence of spinal cord injury. Five patients died from exsanguination before definitive repair could be undertaken. Thirty-six patients had repair of traumatic aortic tear in the area of the isthmus. Nine patients were operated upon with the clamp and sew technique, 20 patients had a heparin-bonded shunt placed, and seven patients were treated by repair with cardiopulmonary bypass. There were five operative deaths that were not related to the technique employed. Two patients without preoperative evidence of spinal cord injury developed paraparesis. No patient had postoperative paraplegia. Despite rapid transport, expeditious evaluation, and emergency thoracotomy, some patients die from exsanguination prior to definitive repair. Even with the provision of distal aortic perfusion during clamping, the risk of spinal cord injury is not eliminated. PMID:3389938

Merrill, W H; Lee, R B; Hammon, J W; Frist, W H; Stewart, J R; Bender, H W

1988-01-01

292

Intracranial Extension of Spinal Subarachnoid Hematoma Causing Severe Cerebral Vasospasm  

PubMed Central

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

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

2014-01-01

293

THORACOLUMBAR INTRADURAL DISC HERNIATION IN EIGHT DOGS: CLINICAL, LOW-FIELD MAGNETIC RESONANCE IMAGING, AND COMPUTED TOMOGRAPHIC MYELOGRAPHY FINDINGS.  

PubMed

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

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

2014-09-26

294

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

PubMed

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

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

2013-05-01

295

Spinal tuberculosis: A review  

PubMed Central

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

Garg, Ravindra Kumar; Somvanshi, Dilip Singh

2011-01-01

296

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

PubMed Central

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

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

2009-01-01

297

A refined physical and transcriptional map of the SPG9 locus on 10q23.3-q24.2.  

PubMed

Hereditary spastic paraplegia (HSP) is a genetically heterogeneous disorder characterised by progressive spasticity of the lower limbs. Beside 'pure' forms of HSP, 'complicated' forms are reported, where spasticity occurs associated with additional symptoms. We recently described an Italian family with a complicated dominant form of HSP (SPG9) and we mapped the gene responsible to 10q23.3-q24.2, in a 12cM interval between markers D10S564 and D10S603. The phenotypic manifestations in our family are reminiscent of those already described in a smaller British pedigree. We typed individuals from this British family using markers located in the SPG9 critical interval and haplotype reconstruction showed the disorder co-segregating with SPG9. To characterise the SPG9 region better, we constructed a contig of 22 YACs, assigned it to 18 polymorphic markers and positioned 54 ESTs. Furthermore, we searched for ESTs containing a trinucleotide repeat sequence, since anticipation of symptoms was reported in both families. Finally, analysis of a muscle biopsy specimen from one patient was normal, suggesting that, contrary to SPG7, mitochondrial disturbance could not be a primary feature of SPG9. PMID:11039578

Lo Nigro, C; Cusano, R; Scaranari, M; Cinti, R; Forabosco, P; Morra, V B; De Michele, G; Santoro, L; Davies, S; Hurst, J; Devoto, M; Ravazzolo, R; Seri, M

2000-10-01

298

Endovascular Management of Thoracic Aortic Aneurysms  

SciTech Connect

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.

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

2011-12-15

299

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

PubMed

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

Flattau, Anna; Blank, Arthur E

2014-02-01

300

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

PubMed Central

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

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

2014-01-01

301

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

PubMed Central

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

2011-01-01

302

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

PubMed

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

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

2015-02-01

303

Neuroprotective effect of atorvastatin in spinal cord ischemia-reperfusion injury  

PubMed Central

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

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

2015-01-01

304

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

PubMed

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

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

2015-01-01

305

Non-Parkinson movement disorders  

PubMed Central

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

2013-01-01

306

Rare causes of dystonia parkinsonism.  

PubMed

The list of genetic causes of syndromes of dystonia parkinsonism grows constantly. As a consequence, the diagnosis becomes more and more challenging for the clinician. Here, we summarize the important causes of dystonia parkinsonism including autosomal-dominant, recessive, and x-linked forms. We cover dopa-responsive dystonia, Wilson's disease, Parkin-, PINK1-, and DJ-1-associated parkinsonism (PARK2, 6, and 7), x-linked dystonia-parkinsonism/Lubag (DYT3), rapid-onset dystonia-parkinsonism (DYT12) and DYT16 dystonia, the syndromes of Neurodegeneration with Brain Iron Accumulation (NBIA) including pantothenate kinase (PANK2)- and PLA2G6 (PARK14)-associated neurodegeneration, neuroferritinopathy, Kufor-Rakeb disease (PARK9) and the recently described SENDA syndrome; FBXO7-associated neurodegeneration (PARK15), autosomal-recessive spastic paraplegia with a thin corpus callosum (SPG11), and dystonia parkinsonism due to mutations in the SLC6A3 gene encoding the dopamine transporter. They have in common that in all these syndromes there may be a combination of dystonic and parkinsonian features, which may be complicated by pyramidal tract involvement. The aim of this review is to familiarize the clinician with the phenotypes of these disorders. PMID:20694531

Schneider, Susanne A; Bhatia, Kailash P

2010-11-01

307

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

PubMed Central

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

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

2014-01-01

308

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

PubMed Central

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

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

2013-01-01

309

Chapter 3: neurology in ancient Egypt.  

PubMed

Neurology, in the modern sense, did not exist in ancient Egypt, where medicine was a compound of natural, magical and religious elements, with different practitioners for each form of healing. Nevertheless, Egyptian doctors made careful observations of illness and injury, some of which involved the nervous system. Modern scholars have three sources of information about Egyptian medicine: papyri, inscriptions, and mummified remains. These tell us that the Egyptians had words for the skull, brain, vertebrae, spinal fluid and meninges, though they do not say if they assigned any function to them. They described unconsciousness, quadriparesis, hemiparesis and dementia. We can recognize neurological injuries, such as traumatic hemiparesis and cervical dislocation with paraplegia, in the well known Edwin Smith surgical papyrus. Similarly recognizable in the Ebers papyrus is a description of migraine. An inscription from the tomb of the vizier Weshptah, dated c. 2455 BCE, seems to describe stroke, and Herodotus describes epilepsy in Hellenistic Egypt. We have very little understanding of how Egyptian physicians organized these observations, but we may learn something of Egyptian culture by examining them. At the same time, modern physicians feel some connection to Egyptian physicians and can plausibly claim to be filling a similar societal role. PMID:19892106

York, George K; Steinberg, David A

2010-01-01

310

[Development of the spine after traumatic spinal cord injury in children and adolescents].  

PubMed

In the 1970s, there was growing concern about the risk of secondary deformations of the spine as these seemed to endanger the otherwise improving prognosis for the life of paraplegic subjects, especially of paralyzed children and adolescents. According to the literature, the level and extent of the spinal cord injury and the age at the time of injury are determinants of the development of scoliosis, hyperlordosis or global kyphosis. Correction of the deformity by brace orthosis is not indicated except for children. The indications for surgical intervention in terms of the extent of the scoliosis and technical performance corresponds to the well known situation for idiopathic scoliosis except for the length of fusion. A special form of scoliosis, the so called "collapsing spine", allows good surgical correction because it is usually not rigid. Early, substantial degenerative processes such as segmental intervertebral instability at the level of the paraplegia, as well as distinct uncarthrosis proximally distant from the innervated zones with secondary radicular damage, are observed. By means of modern surgical procedures, the appearance of the patient's body, as well as the quality of life, can be favorably influenced. PMID:15666137

Kaps, H-P; Badke, A

2005-02-01

311

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

PubMed

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

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

2014-10-29

312

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

PubMed Central

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

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

313

Management of blunt thoracic aortic injury.  

PubMed

Blunt traumatic aortic transection (TAT) is an uncommon injury in clinical practice that is associated with a high morbidity and mortality. The approach to patients with such an injury is controversial with specific regard to the most effective diagnostic tools, timing of surgical intervention and mechanisms of spinal cord protection. Chest X-ray with widening of the mediastinum is unreliable as a diagnostic tool. Contrast enhanced helical CT Scan has replaced the traditional angiography as the screening diagnostic tool of choice Emergency thoracotomy and repair should be reserved for the few patients with isolated TAT without any major concomitant injuries. Delayed management approach with aggressive blood pressure control and serial radiological monitoring is a safe and recommended option for those with severe concomitant injuries or other medical co-morbidity that puts surgery at high risk. Active augmentation of the distal perfusion pressure during cross clamp offers the best protection against development of paraplegia during open surgical repair. Endovascular stenting offers a minimally invasive method of treatment but the long-term durability of the endovascular stent is still unknown. We feel that the greater feasibility of the endovascular repair in the acute phase of the thoracic injury is an advantage over the open surgery and should be the treatment of choice in patients with severe concomitant injuries. PMID:16226902

Nzewi, O; Slight, R D; Zamvar, V

2006-01-01

314

Microtubule-severing protein Katanin regulates neuromuscular junction development and dendritic elaboration in Drosophila.  

PubMed

Microtubules (MTs) are crucial for diverse biological processes including cell division, cell growth and motility, intracellular transport and the maintenance of cell shape. MT abnormalities are associated with neurodevelopmental and neurodegenerative diseases such as hereditary spastic paraplegia. Among many MT regulators, katanin was the first identified MT-severing protein, but its neuronal functions have not yet been examined in a multicellular organism. Katanin consists of two subunits; the catalytic subunit katanin 60 contains an AAA (ATPases associated with a variety of cellular activities) domain and breaks MT fibers while hydrolyzing ATP, whereas katanin 80 is a targeting and regulatory subunit. To dissect the in vivo functions of Katanin, we generated mutations in Drosophila Katanin 60 and manipulated its expression in a tissue-specific manner. Null mutants of Katanin 60 are pupal lethal, demonstrating that it is essential for viability. Loss-of-function mutants of Katanin 60 showed excess satellite boutons, reduced neurotransmission efficacy, and more enlarged cisternae at neuromuscular junctions. In peripheral sensory neurons, loss of Katanin 60 led to increased elaboration of dendrites, whereas overexpression of Katanin 60 resulted in the opposite. Genetic interaction analyses indicated that increased levels of MT acetylation increase its susceptibility to Katanin-mediated severing in neuronal and non-neuronal systems. Taken together, our results demonstrate for the first time that Katanin 60 is required for the normal development of neuromuscular synapses and dendrites. PMID:24550114

Mao, Chuan-Xi; Xiong, Ying; Xiong, Zhaohuan; Wang, Qifu; Zhang, Yong Q; Jin, Shan

2014-03-01

315

Hippocrates: the forefather of neurology.  

PubMed

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

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

2014-09-01

316

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

PubMed Central

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

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

2013-01-01

317

Mutations in the PLP1 gene residue p. Gly198 as the molecular basis of Pelizeaus-Merzbacher phenotype.  

PubMed

Pelizaeus-Merzbacher disease (PMD) and spastic paraplegia type 2 (SPG2) are rare X-linked allelic disorders caused by mutations in the PLP1 gene, encoding the main component of myelin, proteolipid protein 1 (PLP1). Various types of mutations, acting through different molecular mechanism, cause the diseases. Duplications of variable size at Xq22.2, containing the entire PLP1, are responsible for more than 50% of PMD cases. Other causes of PMD include point mutations, gene deletions and triplications. There is a spectrum of PLP1-related disorders with some correlation between the type of mutation and phenotype. Generally the missense mutations cause the more severe forms of the disease, the most common PLP1 duplications, result in the classical PMD whereas deletions and null mutations in mild form of PMD and SPG2. We present a patient with c.593G>A substitution in the exon 4 of the PLP1 gene causing a novel missense mutation p.Gly198Asp, finally diagnosed as PMD but showing an atypical MRI picture. PMID:23245814

Hoffman-Zacharska, Dorota; Kmie?, Tomasz; Pozna?ski, Jaros?aw; Jurek, Marta; Bal, Jerzy

2013-10-01

318

Development of AMPA receptor and GABA B receptor-sensitive spinal hyper-reflexia after spinal air embolism in rat: a systematic neurological, electrophysiological and qualitative histopathological study  

PubMed Central

Decompression sickness results from formation of bubbles in the arterial and venous system, resulting in spinal disseminated neurodegenerative changes and may clinically be presented by motor dysfunction, spinal segmental stretch hyper-reflexia (i.e., spasticity) and muscle rigidity. In our current study, we describe a rat model of spinal air embolism characterized by the development of similar spinal disseminated neurodegenerative changes and functional deficit. In addition, the anti-spastic potency of systemic AMPA receptor antagonist (NGX424) or GABA B receptor agonist (baclofen) treatment was studied. To induce spinal air embolism, animals received an intra-aortic injection of air (50–200 ?l/kg). After embolism, the development of spasticity was measured using computer-controlled ankle rotation. Animals receiving 150 or 200 ?l of intra-aortic air injections displayed motor dysfunction with developed spastic (50–60% of animals) or flaccid (25–35% of animals) paraplegia at 5–7 days. MRI and spinal histopathological analysis showed disseminated spinal cord infarcts in the lower thoracic to sacral spinal segments. Treatment with NGX424 or baclofen provided a potent anti-spasticity effect (i.e., stretch hyper-reflexia inhibition). This model appears to provide a valuable experimental tool to study the pathophysiology of air embolism-induced spinal injury and permits the assessment of new treatment efficacy targeted to modulate neurological symptoms resulting from spinal air embolism. PMID:22721766

Kakinohana, Osamu; Scadeng, Miriam; Corleto, Jose A.; Sevc, Juraj; Lukacova, Nadezda; Marsala, Martin

2012-01-01

319

Factors That Influence Employment After Spinal Cord Injury in South Korea  

PubMed Central

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

Kang, Eun-Na; Shin, Hyung-Ik

2014-01-01

320

Linking axonal degeneration to microtubule remodeling by Spastin-mediated microtubule severing.  

PubMed

Mutations in the AAA adenosine triphosphatase (ATPase) Spastin (SPG4) cause an autosomal dominant form of hereditary spastic paraplegia, which is a retrograde axonopathy primarily characterized pathologically by the degeneration of long spinal neurons in the corticospinal tracts and the dorsal columns. Using recombinant Spastin, we find that six mutant forms of Spastin, including three disease-associated forms, are severely impaired in ATPase activity. In contrast to a mutation designed to prevent adenosine triphosphate (ATP) binding, an ATP hydrolysis-deficient Spastin mutant predicted to remain kinetically trapped on target proteins decorates microtubules in transfected cells. Analysis of disease-associated missense mutations shows that some more closely resemble the canonical hydrolysis mutant, whereas others resemble the ATP-binding mutant. Using real-time imaging, we show that Spastin severs microtubules when added to permeabilized, cytosol-depleted cells stably expressing GFP-tubulin. Using purified components, we also show that Spastin interacts directly with microtubules and is sufficient for severing. These studies suggest that defects in microtubule severing are a cause of axonal degeneration in human disease. PMID:15716377

Evans, Katia J; Gomes, Edgar R; Reisenweber, Steven M; Gundersen, Gregg G; Lauring, Brett P

2005-02-14

321

Linking axonal degeneration to microtubule remodeling by Spastin-mediated microtubule severing  

PubMed Central

Mutations in the AAA adenosine triphosphatase (ATPase) Spastin (SPG4) cause an autosomal dominant form of hereditary spastic paraplegia, which is a retrograde axonopathy primarily characterized pathologically by the degeneration of long spinal neurons in the corticospinal tracts and the dorsal columns. Using recombinant Spastin, we find that six mutant forms of Spastin, including three disease-associated forms, are severely impaired in ATPase activity. In contrast to a mutation designed to prevent adenosine triphosphate (ATP) binding, an ATP hydrolysis–deficient Spastin mutant predicted to remain kinetically trapped on target proteins decorates microtubules in transfected cells. Analysis of disease-associated missense mutations shows that some more closely resemble the canonical hydrolysis mutant, whereas others resemble the ATP-binding mutant. Using real-time imaging, we show that Spastin severs microtubules when added to permeabilized, cytosol-depleted cells stably expressing GFP-tubulin. Using purified components, we also show that Spastin interacts directly with microtubules and is sufficient for severing. These studies suggest that defects in microtubule severing are a cause of axonal degeneration in human disease. PMID:15716377

Evans, Katia J.; Gomes, Edgar R.; Reisenweber, Steven M.; Gundersen, Gregg G.; Lauring, Brett P.

2005-01-01

322

Targeted disruption of the mouse Npal3 gene leads to deficits in behavior, increased IgE levels, and impaired lung function.  

PubMed

The non-imprinted in Prader-Willi/Angelman syndrome (NIPA) proteins are highly conserved receptors or transporters. Translocation of NIPA genes were found in patients with Prader-Willi syndrome, and loss-of-function of the NIPA1 gene was identified in hereditary spastic paraplegia. The family of NIPA-like domain containing (NPAL) proteins is closely related to the NIPA proteins, but to date nothing is known about their function. Here, we could demonstrate that both human NPAL3 and mouse NPAL3 are ubiquitously expressed and encode highly conserved proteins. To further elucidate the function of the Npal3 gene, knockout (Npal3(-/-)) mice were generated. Intensive phenotypic analyses revealed that disruption of the Npal3 gene results in a pleiotropic phenotype. The function of the nervous system was impaired in both mutant males and females which could be demonstrated in behavioral tests. In addition, in NPAL3 mutants the number of NK cells was decreased and changes in IgM, IgG(2), and IgA were observed, indicating that the immune system is also affected. Interestingly, increased IgE levels as well as impaired lung functions were observed in mutant males but not in mutant females. It should be noted that the human Npal3 gene is located at 1p36.12-->p35.1, and atopic diseases were previously linked to this genomic region. Thus, the Npal3(-/-) mice could serve as a valuable model system for studying atopic diseases. PMID:19738379

Grzmil, P; Konietzko, J; Boehm, D; Hölter, S M; Hoelter, S M; Aguilar-Pimentel, A; Aguilar, A; Javaheri, A; Kalaydjiev, S; Adler, T; Bolle, I; Adham, I; Dixkens, C; Wolf, S; Fuchs, H; Gailus-Durner, V; Gailus-Durne, V; Wurst, W; Ollert, M; Busch, D H; Busch, D; Schulz, H; de Angelis, M Hrabe; Burfeind, P

2009-01-01

323

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

PubMed Central

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

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

2014-01-01

324

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

PubMed

The purpose of this study was to evaluate the ability of individuals with spinal cord injury (SCI) to reach a training threshold during on-court sport activity. Monitors collected heart rate (HR) data every 5 s for 11 wheelchair tennis players (WCT) with low paraplegia and 11 able-bodied controls matched on experience and skill level (ABT). Average HR was determined for time spent in practice (e.g, drills) and game (i.e., a competitive set), and the ability to surpass 50% peak HR (HRpeak) and 64% HRpeak in each condition was evaluated. Average exercise intensity (%HRpeak) was not significantly different between the groups during practice (M WCT = 68.18, SD = 7.53%, M ABT = 68.78, SD = 5.44%; t = .22, p = .83) or game (M WCT = 68.17, SD = .17%, M ABT = 71.55, SD = 4.75%; t = 1.12, p =.28). Allparticipants averaged an intensity > or = 50% HR-peak during practice and game, and the difference between group participants averaging an intensity > or = 64% HRpeak was not significant during practice (chi2 = .92, p = .34) or game (chi2 = 3.85, p = .05). In terms of reaching a health and fitness training threshold during tennis, individuals with low-level SCI are similar to matched controls. PMID:19408469

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

2009-03-01

325

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

PubMed

A bucket-type transpelvic socket was fabricated for a man with paraplegia from spinal cord injury, who underwent right partial pelvic amputation and left hip disarticulation. His main problem was inability to sit due to asymmetrical pelvic shape. We prescribed a transpelvic prosthetic socket to enable him to sit again. The socket consisted of a dual structure: a hard frame and soft liner. The main features of the socket were redistribution of pressure to prevent recurrence of pressure ulcer, and a slightly backward tilt to maintain a comfortable sitting position. In addition, the socket had small air holes for ventilation; a big window in the abdominal area for management of stoma and cystostomy; and two straps for donning it independently. In addition, we confirmed the internal pressure distribution in the socket by a pressure mapping system to prevent reoccurrence of skin trouble. Finally, the patient regained independence in activities of daily living, including driving a car, after two months of rehabilitative training. PMID:22768424

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

2012-06-01

326

Characteristics of traumatic spinal cord injuries in south-eastern Anatolia, Turkey: a comparative approach to 10 years' experience.  

PubMed

The purpose of this study was to determine the demographic and epidemiological characteristics of traumatic spinal cord-injured patients. The hospital records of 539 patients (416 men, 123 women) with spinal cord injuries (SCIs) admitted to four hospitals that were major referral centers for trauma in the south-eastern region of Turkey from 1990 to 1999 were reviewed retrospectively. The patients with SCI were investigated for two periods; the first period covered patients admitted between 1990 and 1994 during which time an influx of people from rural to urban areas occurred and firearm injuries were common. In the second period (1995-1999) the influx of people declined and firearm injuries were reduced. The most common causes of injuries were road traffic accidents (200, 37.12%), followed by falls (172, 31.90%) and bullet wounds (115, 21.34%). In the first period, incomplete paraplegia was encountered more often than in the second period (P<0.001). In conclusion, in our series, while the leading cause of SCI for the two time periods was road traffic accidents, firearm injuries for the first period and falls for the second period were second-most frequent causes of SCI. In addition, the present study suggests that demographic and epidemiological factors may affect the characteristics of SCI in a region-based population even in a 10-year period of time. PMID:15729098

Gur, Ali; Kemaloglu, M Serdar; Cevik, Remzi; Sarac, A Jale; Nas, Kemal; Kapukaya, Ahmet; Sahin, Hasan; Guloglu, Cahfer; Bakir, Abdurrahman

2005-03-01

327

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

PubMed Central

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

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

2010-01-01

328

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

PubMed

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

Fregly, Benjamin J

2009-07-01

329

Dermatological problems following spinal cord injury in Korean patients.  

PubMed

Objective To identify dermatological conditions following spinal cord injury (SCI) and analyze these conditions in relation to various characteristics of SCI. Design Retrospective chart review. Setting National Health Insurance Corporation Ilsan Hospital of Korea, Rehabilitation Center, Spinal Cord Unit. Participants Patients treated for SCI who were referred to dermatology for dermatological problems, 2000-2012. Results Of the 1408 SCI patients treated at the spinal cord unit, 253 patients with SCI were identified to have been referred to dermatology for skin problems and a total of 335 dermatological conditions were diagnosed. The most common dermatological finding was infectious (n = 123, 36.7%) followed by eczematous lesions (n = 109, 32.5%). Among the infectious lesions, fungal infection (n = 76, 61.8%) was the most common, followed by bacterial (n = 27, 21.9%) lesions. Seborrheic dermatitis (n = 59, 64.1%) was the most frequent eczematous lesion. Ingrown toenail occurred more frequently in tetraplegics whereas vascular skin lesions occurred more commonly in patients with paraplegia (P < 0.05). Xerotic dermatitis showed a higher occurrence within 12 months of injury rather than thereafter (P < 0.05). Of these, 72.4% of the infectious and 94.7% of the fungal skin lesions manifested below the neurological level of injury (NLI; P < 0.001) and 61.5% of the eczematous lesions and 94.9% of seborrheic dermatitis cases occurred above the NLI (P < 0.001). There was no significant difference in dermatological diagnoses between patients with neurologically complete and incomplete SCI. Conclusion The most common dermatological condition in patients with SCI among those referred to dermatology was fungal infection, followed by seborrheic dermatitis. Although dermatological problems after SCI are not critical in SCI outcome, they negatively affect the quality of life. Patients and caregivers should be educated about appropriate skin care and routine dermatological examinations. PMID:24090454

Han, Zee-A; Choi, Ja Young; Ko, Young Jin

2013-10-24

330

[Epidural abscess due to a Mycobacterium tuberculosis strain with primary resistance to isoniazid and ethambutol].  

PubMed

Tuberculosis is primarily characterized by pulmonary involvement, however, one third of the cases exhibit extrapulmonary tuberculosis. In this report, a case of epidural abscess due to Mycobacterium tuberculosis with primary resistance to isoniazid and ethambutol was presented. A 57-year-old male patient was admitted to emergency service with ten days history of weakness in legs, disability of walking and fever. Neurological examination revealed paraplegia of lower extremities, numbness distal to T2 disc level and hyperactivity of deep tendon reflexes indicating transverse myelitis. Laboratory findings were as follows; ESR: 74 mm/hour, CRP: 22 g/L, ALT: 42 IU/L, AST: 45 IU/L and white blood cell count 23.000/mm3 (45% polymorphonuclear leukocyte, 45% lymphocyte, 10% monocyte). Spinal magnetic resonance imaging showed a fusiform abscess localized at anterior epidural space and extending along levels of C5-6 and C6-7. The longitudinal dimension of the abscess was 3 cm. The lesion was hypointense on T1 and hyperintense on T2 weighted MRI images with prominent rim shaped contrast enhancement on contrast-enhanced T1-weighted images. At fourth day of hospitalization the patient underwent neurosurgical management. M.tuberculosis was isolated from the cultures of operation material by Mycobacteria Growth Incubator Tube system (MGIT, BBL; BD, USA) on the 12th day. The isolate was found susceptible to streptomycin and rifampisin, but resistant to isoniazid and ethambutol. The treatment was initiated with rifampicin 600 mg/day, pyrazinamid 2 g/day, ethambutol 1.5 g/day and levofloxacin 500 mg/day. At the end of second month levofloxacin 500 mg/day and rifampisin 600 mg/day combination was sustained and total treatment period was planned as nine months. As far as the national literature was considered, this was the first case of extrapulmonary tuberculosis with primary resistance to isoniazid and ethambutol. PMID:23188583

Sener, Alper; Akçal?, Alper; Karata?, Ozan; Ko?ar, Sule; De?irmenci, Y?ld?z; Akman, Tar?k

2012-10-01

331

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

PubMed Central

Objective Developments in assistive technology such as handcycling provide attractive possibilities to pursue a healthy lifestyle for patients with spinal cord injury. The objective of the study is to evaluate physical stress and strain of handcycling against training guidelines as defined by the American College of Sports Medicine (ACSM). Design Seven able-bodied males conducted an incremental peak exercise handcycling test on a treadmill. In addition, two indoor treadmill (1.3 m/second with an inclination of 0.7% and 1.0 m/second with an inclination of 4.8%) and three outdoor over ground exercise bouts were performed (1.7, 3.3, and 5.0 m/second). One individual handcycled a representative 8-km-distance outdoors. Outcome measures Physical stress and strain were described in terms of absolute and relative power output, oxygen uptake (VO2), gross efficiency (GE), and heart rate (HR). Also, local perceived discomfort (LPD) was determined. Results Relative handcycling exercise intensities varied between 23.3 ± 4.2 (below the ACSM lower limit of 46%VO2peak) and 72.5 ± 15.1%VO2peak (well above the ACSM lower limit), with GE ranging from 6.0 ± 1.5% at the lower to 13.0 ± 2.6% at the higher exercise intensities. Exercise intensities were performed at 49.8 ± 4.2 to 80.1 ± 10.5%HRpeak. LPD scores were low to moderate (<27 ± 7). Conclusion Handcycling is relatively efficient and exercise intensities > 46%VO2peak were elicited. However, exercise load seems to be underestimated using %HRpeak. LPD was not perceived as limiting. Physiological stress and strain in able-bodied individuals appear to be comparable to individuals with a paraplegia. To understand individualize and optimize upper-body training, different training programs must be evaluated. PMID:23820153

Hettinga, Florentina J.; de Groot, Sonja; van Dijk, Frank; Kerkhof, Faes; Woldring, Ferry; van der Woude, Luc

2013-01-01

332

Untangling the web: mechanisms underlying ER network formation.  

PubMed

The ER is a continuous membrane system consisting of the nuclear envelope, flat sheets often studded with ribosomes, and a polygonal network of highly-curved tubules extending throughout the cell. Although protein and lipid biosynthesis, protein modification, vesicular transport, Ca(2+)dynamics, and protein quality control have been investigated in great detail, mechanisms that generate the distinctive architecture of the ER have been uncovered only recently. Several protein families including the reticulons and REEPs/DP1/Yop1p harbor hydrophobic hairpin domains that shape high-curvature ER tubules and mediate intramembrane protein interactions. Members of the atlastin/RHD3/Sey1p family of dynamin-related GTPases interact with the ER-shaping proteins and mediate the formation of three-way junctions responsible for the polygonal structure of the tubular ER network, with Lunapark proteins acting antagonistically. Additional classes of tubular ER proteins including some REEPs and the M1 spastin ATPase interact with the microtubule cytoskeleton. Flat ER sheets possess a different complement of proteins such as p180, CLIMP-63 and kinectin implicated in shaping, cisternal stacking and cytoskeletal interactions. The ER is also in constant motion, and numerous signaling pathways as well as interactions among cytoskeletal elements, the plasma membrane, and organelles cooperate to position and shape the ER dynamically. Finally, many proteins involved in shaping the ER network are mutated in the most common forms of hereditary spastic paraplegia, indicating a particular importance for proper ER morphology and distribution in large, highly-polarized cells such as neurons. This article is part of a Special Issue entitled: Functional and structural diversity of endoplasmic reticulum. PMID:23602970

Goyal, Uma; Blackstone, Craig

2013-11-01

333

The human gephyrin (GPHN) gene: structure, chromosome localization and expression in non-neuronal cells.  

PubMed

Gephyrin was first described as a peripheral membrane protein of 93 kDa anchoring the glycine receptor (GlyR) to subsynaptic microtubules and cytoskeleton. Analysis of knock-out mice demonstrated that gephyrin has additional functions in GABA(A) receptor localization at the synapse and in the biosynthetic pathway of the molybdenum cofactor (Moco). Here we describe a human non-neuronal gephyrin cDNA and the exon/intron organization of the human gephyrin gene. We found the coding region to consist of 27 exons and to span approximately 800 kb on the long arm of chromosome 14. This structure is almost identical to that of the mouse gephyrin gene except that sequences corresponding to three exons described in rat and mouse could not be identified in human. Mutations of the GlyR subunits and of gephyrin lead to severe neuromotor phenotypes in human and mouse. Hyperekplexia involves most frequently a mutation in the GlyR alpha1 subunit in humans. However, inactivation of the Moco biosynthesis pathway results in very similar symptomatology. The recent characterization of a deletion of two exons of the gephyrin gene in a patient with symptoms typical of Moco deficiency confirmed that the involvement of gephyrin in these pathologies cannot be excluded. The precise localization of the gephyrin gene allowed us to exclude it from being a candidate for the autosomal dominant spastic paraplegia, the locus of which maps to 14q between markers D14S259 and D14S1018. A description of its structure and exon boundaries should lay the groundwork for further analysis of its expression in humans. PMID:11418245

David-Watine, B

2001-06-27

334

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

PubMed

We identified an identical and recurrent 9.4-Mbp deletion at chromosome bands 2p11.2-2p12, which occurred de novo in two unrelated patients. It is flanked at the distal and proximal breakpoints by two homologous segmental duplications consisting of low copy repeat (LCR) blocks in direct orientation, which have >99% sequence identity. Despite the fact that the deletion was almost 10?Mbp in size, the patients showed a relatively mild clinical phenotype, that is, mild-to-moderate intellectual disability, a happy disposition, speech delay and delayed motor development. Their phenotype matches with that of previously described patients. The 2p11.2-2p12 deletion includes the REEP1 gene that is associated with spastic paraplegia and phenotypic features related to this are apparent in most 2p11.2-2p12 deletion patients, but not in all. Other hemizygous genes that may contribute to the clinical phenotype include LRRTM1 and CTNNA2. We propose a recurrent but rare 2p11.2-2p12 deletion syndrome based on (1) the identical, non-random localisation of the de novo deletion breakpoints in two unrelated patients and a patient from literature, (2) the patients' phenotypic similarity and their phenotypic overlap with other 2p deletions and (3) the presence of highly identical LCR blocks flanking both breakpoints, consistent with a non-allelic homologous recombination (NAHR)-mediated rearrangement.European Journal of Human Genetics advance online publication, 2 July 2014; doi:10.1038/ejhg.2014.124. PMID:24986827

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

2014-07-01

335

The natural history of pressure sores in a community hospital environment.  

PubMed

A retrospective review of the medical records of a community hospital during a recent 2-year period identified 100 patients with a pressure sore at admission or who developed one thereafter. The mean age of the group was 82.5 years, with three fourths being women. Although 40% of patients were admitted from home, only 20% were discharged home. A minority (27%) of patients in the cohort were independently ambulatory. Likewise, a minority (40%) were alert and orientated at admission and able to feed themselves (46%). Associated conditions that impeded mobility, such as arthritis, joint contractures, hemiplegia, and paraplegia, were noted in 65% of the cohort. A total of 173 pressure sores were noted in 100 patients. The majority (89%) was located caudal to the apex of the iliac crests. No statistically significant variation in wound location or type was found between surviving or expiring patients or between patients whose wounds improved as compared to those whose wounds deteriorated. Seventy-four percent of pressure ulcers were grade II, that is, involving the subdermal layers, or worse. Again, no significant difference in pressure sore grade was noted between patients who lived and patients who died. Topical treatment of pressure sores was universal, though no logical approach was seen. No statistical advantage was achieved by any particular agent or combination of agents. Most patients (79%) were managed on pressure-release surfaces (sheepskin, eggcrate, gel cushion) or air flotation systems (Clinitron, Flexicare). Interestingly, no significant benefit was noted in wound healing or survival rate as related to bed type.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8585677

Isenberg, J S; Ozuner, G; Restifo, R J

1995-10-01

336

Evacuation preparedness in full-time wheelchair users with spinal cord injury  

PubMed Central

Objective To analyze and evaluate the efficacy of evacuation plans described by individuals with spinal cord injury (SCI). Design Descriptive study from a convenience sample. Setting Outpatient population center in Pittsburgh, PA, USA. Methods Twenty-one individuals with SCI who previously indicated that they had a plan of evacuation from either their homes, places of work, or towns/cities were contacted via telephone and asked to describe their evacuation plans. The number of critical elements (scale of 0–10 with 10 indicating a more thorough plan) and assistive technology (AT) devices were recorded. Outcome measures The number of critical elements (scale of 0–10 with 10 indicating a more thorough plan) and AT devices were recorded. Results Median home and town/city evacuation scores were both 3.00 (ranges: 1.0–4.0 and 0.0–8.0, respectively). Median evacuation scores of individuals with paraplegia were higher in home (P = 0.05, r = 0.44) and town/city (P = 0.045, r = 0.63) than individuals with tetraplegia. Median evacuation scores of subjects who were employed were higher in home (P = 0.036, r = 0.47) and town/city (P = 0.064, r = 0.59) than unemployed. Conclusion Low scores indicate that individuals with SCI who believe that they have plans are not adequately prepared for an emergency evacuation. Interventions are needed to improve evacuation readiness and lack of preparedness in a catastrophe should be considered by emergency personnel when responding. PMID:23820144

Hogaboom, Nathan S.; Oyster, Michelle L.; Riggins, Melissa S.; Boninger, Michael L.

2013-01-01

337

Protective and risk factors in amateur equestrians and description of injury patterns: A retrospective data analysis and a case - control survey  

PubMed Central

Background In Switzerland there are about 150,000 equestrians. Horse related injuries, including head and spinal injuries, are frequently treated at our level I trauma centre. Objectives To analyse injury patterns, protective factors, and risk factors related to horse riding, and to define groups of safer riders and those at greater risk Methods We present a retrospective and a case-control survey at conducted a tertiary trauma centre in Bern, Switzerland. Injured equestrians from July 2000 - June 2006 were retrospectively classified by injury pattern and neurological symptoms. Injured equestrians from July-December 2008 were prospectively collected using a questionnaire with 17 variables. The same questionnaire was applied in non-injured controls. Multiple logistic regression was performed, and combined risk factors were calculated using inference trees. Results Retrospective survey A total of 528 injuries occured in 365 patients. The injury pattern revealed as follows: extremities (32%: upper 17%, lower 15%), head (24%), spine (14%), thorax (9%), face (9%), pelvis (7%) and abdomen (2%). Two injuries were fatal. One case resulted in quadriplegia, one in paraplegia. Case-control survey 61 patients and 102 controls (patients: 72% female, 28% male; controls: 63% female, 37% male) were included. Falls were most frequent (65%), followed by horse kicks (19%) and horse bites (2%). Variables statistically significant for the controls were: Older age (p = 0.015), male gender (p = 0.04) and holding a diploma in horse riding (p = 0.004). Inference trees revealed typical groups less and more likely to suffer injury. Conclusions Experience with riding and having passed a diploma in horse riding seem to be protective factors. Educational levels and injury risk should be graded within an educational level-injury risk index. PMID:21294862

2011-01-01

338

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

PubMed Central

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

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

2014-01-01

339

[Brain MRI of reversible, recurrent white matter lesions in a patient with a 35-year history of neuro-Behçet disease].  

PubMed

Neuro-Behçet disease (NBD) can be categorized clinically as the acute type--characterized by meningoencephalitis--and the chronic progressive type- characterized by slowly progressive dementia, ataxia, and dysarthria. We describe a 35-year clinical course of NBD that was characterized by slowly progressive ataxia and dysarthria despite continued corticosteroid treatment. Because of difficulties in swallowing, which interrupted oral corticosteroid therapy, this case was characterized by recurrent manifestations of neurological symptoms and abnormal MRI findings. Resumption of corticosteroid therapy was effective. The patient was a 77-year-old woman who had presented with oral ulceration and dysarthria at the age of 42. She suffered from Entero-Behçet disease at the age of 52 and was treated with corticosteroids for 7 years. Oral corticosteroid therapy was resumed at the age of 64, but her neurological deficit slowly progressed and she developed paraplegia with dysphagia and dysarthria. Corticosteroids treatment was interrupted when she was 76; one year later, she was hospitalized in a state of somnolence. Brain MRI scans revealed new lesions with gadolinium enhancement. We diagnosed acute exacerbation of NBD attacks on the basis of positive findings for HLA-B51, protein elevation, and IL-6 in the cerebrospinal fluid. Corticosteroid treatment was effective. She became alert, and her MRI findings were no longer abnormal. Corticosteroids administration was continued via percutaneous endoscopic gastrostomy. Our case suggested that even if neurological exacertion is not obvious during the clinical course, immunosuppressive therapies should be continued for patients with chronic NBD to prevent acute aggravation. PMID:19526839

Fukuda, Kazuhiro; Ishida, Shimon; Sakane, Sadaki; Furukawa, Keizo; Sugino, Masakazu

2009-06-01

340

Clinical manifestations of AIDS in tropical countries.  

PubMed

Diagnosis of clinical AIDS can be difficult for clinicians in Africa, where there is only limited access to the sophisticated bacteriological diagnostic facilities needed for diagnoses based on the criteria laid down by the Center for Disease Control in the US. The most common presentation of AIDS in Africa is as an enteropathic condition known as 'Slim.' Based on this and other common presentations of the disease in Africa, a group of clinicians in Bangui, Central African Republic, drew up a list of criteria for the diagnosis of AIDS in Africa which are based on patient history and examination and the exclusion of other conditions rather than on serological confirmation of HIV infection. The major criteria are 1) unexplained fever for longer than 1 month; 2) unexplained diarrhea for longer than 1 month; and 3) weight loss greater than 10% of previous weight. Minor symptoms are presence of a maculopapular rash, oral candidiasis or thrush, herpes zoster or shingles, aggressive or uncontrollable herpes simplex, unexplained cough for longer than 1 month, or enlarged lymph nodes in more than 1 extrainguinal site. The finding of 2 major symptoms and at least 1 minor one is enough for diagnosis. These criteria have been found to be useful. However, they do not cover all the presentations which have been associated with AIDS. Unusual presentations of HIV infected persons which have been seen in Africa include serially developing abscesses in pyomyositis, gall bladder diseases, pericarditis or myocarditis, diseases of the Central Nervous System (cryptococcal meningitis, toxoplasmosis, non-specific leuko-encephalitis, atraumatic paraplegia, acute psychosis or chronic deterioration in mental capacity, lymphoma of the brain), prodromal illnesses, swollen lymph nodes, herpes zoster or shingles in young adults, or tumours of the lymphatic system. Differential diagnosis is extremely important. PMID:3194942

Carswell, J W

1988-10-01

341

REEPs Are Membrane Shaping Adapter Proteins That Modulate Specific G Protein-Coupled Receptor Trafficking by Affecting ER Cargo Capacity  

PubMed Central

Receptor expression enhancing proteins (REEPs) were identified by their ability to enhance cell surface expression of a subset of G protein-coupled receptors (GPCRs), specifically GPCRs that have proven difficult to express in heterologous cell systems. Further analysis revealed that they belong to the Yip (Ypt-interacting protein) family and that some REEP subtypes affect ER structure. Yip family comparisons have established other potential roles for REEPs, including regulation of ER-Golgi transport and processing/neuronal localization of cargo proteins. However, these other potential REEP functions and the mechanism by which they selectively enhance GPCR cell surface expression have not been clarified. By utilizing several REEP family members (REEP1, REEP2, and REEP6) and model GPCRs (?2A and ?2C adrenergic receptors), we examined REEP regulation of GPCR plasma membrane expression, intracellular processing, and trafficking. Using a combination of immunolocalization and biochemical methods, we demonstrated that this REEP subset is localized primarily to ER, but not plasma membranes. Single cell analysis demonstrated that these REEPs do not specifically enhance surface expression of all GPCRs, but affect ER cargo capacity of specific GPCRs and thus their surface expression. REEP co-expression with ?2 adrenergic receptors (ARs) revealed that this REEP subset interacts with and alter glycosidic processing of ?2C, but not ?2A ARs, demonstrating selective interaction with cargo proteins. Specifically, these REEPs enhanced expression of and interacted with minimally/non-glycosylated forms of ?2C ARs. Most importantly, expression of a mutant REEP1 allele (hereditary spastic paraplegia SPG31) lacking the carboxyl terminus led to loss of this interaction. Thus specific REEP isoforms have additional intracellular functions besides altering ER structure, such as enhancing ER cargo capacity, regulating ER-Golgi processing, and interacting with select cargo proteins. Therefore, some REEPs can be further described as ER membrane shaping adapter proteins. PMID:24098485

Ho, Vincent K.; Angelotti, Timothy

2013-01-01

342

Mice with a deletion of the major central myelin protein exhibit hypersensitivity to noxious thermal stimuli: involvement of central sensitization.  

PubMed

Null mutations in the gene encoding the major myelin protein of the central nervous system, proteolipid protein 1 (PLP1), cause an X-linked form of spastic paraplegia (SPG2) associated with axonal degeneration. While motor symptoms are the best known manifestations of this condition, its somatosensory disturbances have been described but poorly characterized. We carried out a longitudinal study in an animal model of SPG2 - mice carrying a deletion of the Plp1 gene (Plp-null mice). Plp-null mice exhibited severe early-onset thermal hyperalgesia, in the absence of thermal allodynia. We first performed an electrophysiological testing which showed an early decrease in peripheral and spinal conduction velocities in Plp null mice. Such as the abnormal sensitive behaviors, this slowing of nerve conduction was observed before the development of myelin abnormalities at the spinal level, from 3months of age, and without major morphological defects in the sciatic nerve. To understand the link between a decrease in nerve velocity and an increased response to thermal stimuli before the appearance of myelin abnormalities, we focused our attention on the dorsal horn of the spinal cord, the site of integration of somatosensory information. Immunohistochemical studies revealed an early-onset activation of astrocytes and microglia that worsened with age, associated later in age with perturbation of the expression of the sensory neuropeptides calcitonin-gene-related peptide and galanin. Taken together, these results represent complementary data supporting the hypothesis that Plp-null mice suffer from ganglionopathy associated with late onset central demyelination but with few peripheral nerve alterations, induced by the glial-cell-mediated sensitization of the spinal cord. The mechanism suggested here could underlie pain experiments in other leukodystrophies as well as in other non-genetic demyelinating diseases such as multiple sclerosis. PMID:24423646

Petit, Bérengère; Giraudet, Fabrice; Béchon, Céline; Bardin, Laurent; Avan, Paul; Boespflug-Tanguy, Odile; Bégou, Mélina

2014-05-01

343

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

PubMed Central

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

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

2013-01-01

344

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

PubMed Central

Glycosphingolipids are ubiquitous constituents of eukaryotic plasma membranes, and their sialylated derivatives, gangliosides, are the major class of glycoconjugates expressed by neurons. Deficiencies in their catabolic pathways give rise to a large and well-studied group of inherited disorders, the lysosomal storage diseases. Although many glycosphingolipid catabolic defects have been defined, only one proven inherited disease arising from a defect in ganglioside biosynthesis is known. This disease, because of defects in the first step of ganglioside biosynthesis (GM3 synthase), results in a severe epileptic disorder found at high frequency amongst the Old Order Amish. Here we investigated an unusual neurodegenerative phenotype, most commonly classified as a complex form of hereditary spastic paraplegia, present in families from Kuwait, Italy and the Old Order Amish. Our genetic studies identified mutations in B4GALNT1 (GM2 synthase), encoding the enzyme that catalyzes the second step in complex ganglioside biosynthesis, as the cause of this neurodegenerative phenotype. Biochemical profiling of glycosphingolipid biosynthesis confirmed a lack of GM2 in affected subjects in association with a predictable increase in levels of its precursor, GM3, a finding that will greatly facilitate diagnosis of this condition. With the description of two neurological human diseases involving defects in two sequentially acting enzymes in ganglioside biosynthesis, there is the real possibility that a previously unidentified family of ganglioside deficiency diseases exist. The study of patients and animal models of these disorders will pave the way for a greater understanding of the role gangliosides play in neuronal structure and function and provide insights into the development of effective treatment therapies. PMID:24103911

Lehman, Anna; Chioza, Barry; Baple, Emma L.; Maroofian, Reza; Cross, Harold; Sreekantan-Nair, Ajith; Priestman, David A.; Al-Turki, Saeed; McEntagart, Meriel E.; Proukakis, Christos; Royle, Louise; Kozak, Radoslaw P.; Bastaki, Laila; Patton, Michael; Wagner, Karin; Coblentz, Roselyn; Price, Joy; Mezei, Michelle; Schlade-Bartusiak, Kamilla; Hurles, Matthew E.

2013-01-01

345

Bronchial hyperresponsiveness testing in athletes of the Swiss Paralympic team  

PubMed Central

Background The aim of this study was to assess airway hyperresponsiveness to eucapnic voluntary hyperventilation and dry powder mannitol challenge in athletes aiming to participate at the Paralympic Games 2008 in Beijing, especially in athletes with spinal cord injury. Methods Forty-four athletes with a disability (27 with paraplegia (group 1), 3 with tetraplegia (group 2) and 14 with other disabilities such as blindness or single limb amputations (group 3) performed spirometry, skin prick testing, measurement of exhaled nitric oxide, eucapnic voluntary hyperventilation challenge test (EVH) and mannitol challenge test (MCT). A fall in FEV1 of ?10% in either challenge test was deemed positive for exercise-induced bronchoconstriction. Results Fourteen (32%) athletes were atopic and 7 (16%) had a history of physician-diagnosed asthma. Absolute lung function values were significantly lower in patients of group 1 and 2 compared to group 3. Nine (20%) athletes were positive to EVH (8 paraplegics, 1 tetraplegic), and 8 (18%) athletes were positive to MCT (7 paraplegics, 1 tetraplegic). Fourteen (22.7%) subjects were positive to at least one challenge; only three athletes were positive to both tests. None of the athletes in group 3 had a positive test. Both challenge tests showed a significant association with physician-diagnosed asthma status (p?=?0.0001). The positive and negative predictive value to diagnose physician-diagnosed asthma was 89% and 91% for EHV, and 75% and 86% for MCT, respectively. Conclusion EVH and MCT can be used to identify, but especially exclude asthma in Paralympic athletes. PMID:23845126

2013-01-01

346

Endovascular Stent-Graft Placement for Vascular Failure of the Thoracic Aorta  

PubMed Central

It still remains undetermined whether endovascular stent-graft placement (ESGP) is the optimal initial treatment for elective cases of thoracic aortic disease because of unknown long-term results. However, it is also recognized that ESGP contributes to better outcome as an initial treatment for aortic emergency, such as rupture, aortic injury, and complicated acute type B aortic dissection. Despite the fact that most patients are elderly, early mortality rates of ESGP are reportedly around 10% in cases of ruptured degenerative thoracic aortic aneurysm. Postoperative morbidity is also superior in ESGP compared with conventional open repair. Postoperative paraplegia has rarely occurred with ESGP. In cases of blunt aortic injury (BAI), other complications may also be present because of other serious injuries. ESGP has changed the surgical strategy for BAI and partially resolved some of the clinical dilemmas. Early mortality rate is almost zero when a stent graft can be placed before re-rupture. While BAI is a very good indication for ESGP, young patients need careful management and attention because of the unknown long-term outcome. In cases of complicated acute type B aortic dissection, the two main determinants of death, shock from rupture and visceral ischemia, could be managed by ESGP with or without conventional endovascular interventions. Recent reports disclosed less than 10% early mortality with ESGP for complicated acute aortic dissection. Even if the possibility of endotension remains, ESPG seems to be beneficial for these critical patients as the preferable initial treatment. The importance of close follow-up should be stressed to avoid some devastating late complications following ESGP. PMID:17319454

Kurimoto, Yoshihiko; Morishita, Kiyofumi; Asai, Yasufumi

2006-01-01

347

Untangling the web: Mechanisms underlying ER network formation  

PubMed Central

The ER is a continuous membrane system consisting of the nuclear envelope, flat sheets often studded with ribosomes, and a polygonal network of highly-curved tubules extending throughout the cell. Although protein and lipid biosynthesis, protein modification, vesicular transport, Ca2+dynamics, and protein quality control have been investigated in great detail, mechanisms that generate the distinctive architecture of the ER have been uncovered only recently. Several protein families including the reticulons and REEPs/DP1/Yop1p harbor hydrophobic hairpin domains that shape high-curvature ER tubules and mediate intramembrane protein interactions. Members of the atlastin/RHD3/Sey1p family of dynamin-related GTPases interact with the ER-shaping proteins and mediate the formation of three-way junctions responsible for the polygonal structure of the tubular ER network, with Lunapark proteins acting antagonistically. Additional classes of tubular ER proteins including some REEPs and the M1 spastin ATPase interact with the microtubule cytoskeleton. Flat ER sheets possess a different complement of proteins such as p180, CLIMP-63 and kinectin implicated in shaping, cisternal stacking and cytoskeletal interactions. The ER is also in constant motion, and numerous signaling pathways as well as interactions among cytoskeletal elements, the plasma membrane, and organelles cooperate to position and shape the ER dynamically. Finally, many proteins involved in shaping the ER network are mutated in the most common forms of hereditary spastic paraplegia, indicating a particular importance for proper ER morphology and distribution in large, highly-polarized cells such as neurons. PMID:23602970

Goyal, Uma; Blackstone, Craig

2013-01-01

348

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

PubMed

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

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

2014-05-01

349

Complications in Patients With Spinal Cord Injuries Sustained in an Earthquake in Northern Pakistan  

PubMed Central

Background: Spinal cord injury (SCI) is a devastating trauma suffered by many of the victims of an earthquake that struck Northern Pakistan on October 8, 2005. It rendered approximately 600 patients paraplegic, which is the highest number ever reported in any disaster. This study was conducted to evaluate the risk of complications. Methods: The cross-sectional retrospective study covering a 2-month period was conducted on 194 patients admitted to the surgical/neurosurgical wards of Rawalpindi Medical College and allied hospitals (Holy Family Hospital, Rawalpindi General Hospital, and District Headquarter Hospital) and Melody Relief and Rehabilitation Center, Islamabad. Results: The male-to-female ratio was approximately 1:3 (n = 50 [26%] and n = 144 [74%], respectively). The majority (78% [n = 151]) were 16 to 39 years of age; 62% (n = 120) had lumbar-level injuries, 25% (n = 48) had thoracic-level injuries, 9% (n = 18) had thoracolumbar-level injuries, and a few had cervical- or sacral-level injuries. Forty-six percent (n = 90) had American Spinal Injury Association type A injuries; 4% (n = 8) were graded B, 11% (n = 21) were graded C, 9% (n = 18) were graded D, and 14% (n = 27) were graded E. Twenty percent (n =39) developed pressure ulcers, of which 38% (n = 15) had grade 1, 36% (n = 14) had grade 2, 23% (n = 9) had grade 3, and 3% (n = 1) had grade 4. All patients developed urinary tract infections; 15% (n = 30) had bowel complaints; 2% (n = 3) developed deep-vein thrombosis (1 died of pulmonary embolism); and 0.05% (n = 1) developed wound infection. Conclusion: Awareness of potential complications in patients with paraplegia is essential to care planning in the disaster setting. The priorities include skin, bowel, and bladder care and provision of prophylactic heparin. SCI post-disaster care requires comprehensive long-term planning. PMID:17853661

Tauqir, Syeda Fizza; Mirza, Shirin; Gul, Shahzad; Ghaffar, Hirra; Zafar, Asif

2007-01-01

350

Early Results of Endovascular Treatment of the Thoracic Aorta Using the Valiant Endograft  

SciTech Connect

Endovascular repair of the thoracic aorta has been adopted as the first-line therapy for much pathology. Initial results from the early-generation endografts have highlighted the potential of this technique. Newer-generation endografts have now been introduced into clinical practice and careful assessment of their performance should be mandatory. This study describes the initial experience with the Valiant endograft and makes comparisons with similar series documenting previous-generation endografts. Data were retrospectively collected on 180 patients treated with the Valiant endograft at seven European centers between March 2005 and October 2006. The patient cohort consisted of 66 patients with thoracic aneurysms, 22 with thoracoabdominal aneurysms, 19 with an acute aortic syndrome, 52 with aneurysmal degeneration of a chronic dissection, and 21 patients with traumatic aortic transection. The overall 30-day mortality for the series was 7.2%, with a stroke rate of 3.8% and a paraplegia rate of 3.3%. Subgroup analysis demonstrated that mortality differed significantly between different indications; thoracic aneurysms (6.1%), thoracoabdominal aneurysms (27.3%), acute aortic syndrome (10.5%), chronic dissections (1.9%), and acute transections (0%). Adjunctive surgical procedures were required in 63 patients, and 51% of patients had grafts deployed proximal to the left subclavian artery. Comparison with a series of earlier-generation grafts demonstrated a significant increase in complexity of procedure as assessed by graft implantation site, number of grafts and patient comorbidity. The data demonstrate acceptable results for a new-generation endograft in series of patients with diverse thoracic aortic pathology. Comparison of clinical outcomes between different endografts poses considerable challenges due to differing case complexity.

Thompson, Matt, E-mail: matt.thompson@stgeorges.nhs.uk; Ivaz, Stella [4th Floor St James Wing, St George's Hospital NHS Trust, St George's Vascular Institute (United Kingdom); Cheshire, Nicholas [St Mary's Regional Vascular Unit (United Kingdom); Fattori, Rosella [University Hospital, Department of Cardiovascular Radiology (Italy); Rousseau, Herve [Centre Hospitalier Universitaire, Department of Radiology (France); Heijmen, Robin [St Antonius Hospital, Department of Cardiothoracic Surgery (Netherlands); Beregi, Jean-Paul [Hopital Cardiologique, Department of Vascular Radiology (France); Thony, Frederic [Hospitalier Universitaire de Grenoble, Service de Radiologie Centre (France); Horne, Gillian; Morgan, Robert; Loftus, Ian [4th Floor St James Wing, St George's Hospital NHS Trust, St George's Vascular Institute (United Kingdom)

2007-11-15

351

Gene dosage-dependent rescue of HSP neurite defects in SPG4 patients’ neurons  

PubMed Central

The hereditary spastic paraplegias (HSPs) are a heterogeneous group of motorneuron diseases characterized by progressive spasticity and paresis of the lower limbs. Mutations in Spastic Gait 4 (SPG4), encoding spastin, are the most frequent cause of HSP. To understand how mutations in SPG4 affect human neurons, we generated human induced pluripotent stem cells (hiPSCs) from fibroblasts of two patients carrying a c.1684C>T nonsense mutation and from two controls. These SPG4 and control hiPSCs were able to differentiate into neurons and glia at comparable efficiency. All known spastin isoforms were reduced in SPG4 neuronal cells. The complexity of SPG4 neurites was decreased, which was paralleled by an imbalance of axonal transport with less retrograde movement. Prominent neurite swellings with disrupted microtubules were present in SPG4 neurons at an ultrastructural level. While some of these swellings contain acetylated and detyrosinated tubulin, these tubulin modifications were unchanged in total cell lysates of SPG4 neurons. Upregulation of another microtubule-severing protein, p60 katanin, may partially compensate for microtubuli dynamics in SPG4 neurons. Overexpression of the M1 or M87 spastin isoforms restored neurite length, branching, numbers of primary neurites and reduced swellings in SPG4 neuronal cells. We conclude that neurite complexity and maintenance in HSP patient-derived neurons are critically sensitive to spastin gene dosage. Our data show that elevation of single spastin isoform levels is sufficient to restore neurite complexity and reduce neurite swellings in patient cells. Furthermore, our human model offers an ideal platform for pharmacological screenings with the goal to restore physiological spastin levels in SPG4 patients. PMID:24381312

Havlicek, Steven; Kohl, Zacharias; Mishra, Himanshu K.; Prots, Iryna; Eberhardt, Esther; Denguir, Naime; Wend, Holger; Plötz, Sonja; Boyer, Leah; Marchetto, Maria C.N.; Aigner, Stefan; Sticht, Heinrich; Groemer, Teja W.; Hehr, Ute; Lampert, Angelika; Schlötzer-Schrehardt, Ursula; Winkler, Jürgen; Gage, Fred H.; Winner, Beate

2014-01-01

352

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

PubMed Central

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

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

2010-01-01

353

The clinical spectrum of inherited diseases involved in the synthesis and remodeling of complex lipids. A tentative overview.  

PubMed

Over one hundred diseases related to inherited defects of complex lipids synthesis and remodeling are now reported. Most of them were described within the last 5 years. New descriptions and phenotypes are expanding rapidly. While the associated clinical phenotype is currently difficult to outline, with only a few patients identified, it appears that all organs and systems may be affected. The main clinical presentations can be divided into (1) Diseases affecting the central and peripheral nervous system. Complex lipid synthesis disorders produce prominent motor manifestations due to upper and/or lower motoneuron degeneration. Motor signs are often complex, associated with other neurological and extra-neurological signs. Three neurological phenotypes, spastic paraparesis, neurodegeneration with brain iron accumulation and peripheral neuropathies, deserve special attention. Many apparently well clinically defined syndromes are not distinct entities, but rather clusters on a continuous spectrum, like for the PNPLA6-associated diseases, extending from Boucher-Neuhauser syndrome via Gordon Holmes syndrome to spastic ataxia and pure hereditary spastic paraplegia; (2) Muscular/cardiac presentations; (3) Skin symptoms mostly represented by syndromic (neurocutaneous) and non syndromic ichthyosis; (4) Retinal dystrophies with syndromic and non syndromic retinitis pigmentosa, Leber congenital amaurosis, cone rod dystrophy, Stargardt disease; (5) Congenital bone dysplasia and segmental overgrowth disorders with congenital lipomatosis; (6) Liver presentations characterized mainly by transient neonatal cholestatic jaundice and non alcoholic liver steatosis with hypertriglyceridemia; and (7) Renal and immune presentations. Lipidomics and molecular functional studies could help to elucidate the mechanism(s) of dominant versus recessive inheritance observed for the same gene in a growing number of these disorders. PMID:25413954

Garcia-Cazorla, Àngels; Mochel, Fanny; Lamari, Foudil; Saudubray, Jean-Marie

2015-01-01

354

Liver transplantation for acute intermittent porphyria is complicated by a high rate of hepatic artery thrombosis.  

PubMed

Acute intermittent porphyria (AIP) is an autosomal-dominant condition resulting from a partial deficiency of the ubiquitously expressed enzyme porphobilinogen deaminase. Although its clinical expression is highly variable, a minority of patients suffer recurrent life-threatening neurovisceral attacks despite optimal medical therapy. Because the liver is the major source of excess precursor production, liver transplantation (LT) represents a potentially effective treatment for severely affected patients. Using data from the U.K. Transplant Registry, we analyzed all transplants performed for AIP in the United Kingdom and Ireland. Between 2002 and 2010, 10 patients underwent LT for AIP. In all cases, the indication for transplantation was recurrent, biochemically proven, medically nonresponsive acute attacks of porphyria resulting in significantly impaired quality of life. Five patients had developed significant neurological morbidities such as paraplegia before transplantation. The median follow-up time was 23.4 months, and there were 2 deaths from multiorgan failure at 98 days and 26 months. Eight recipients were alive for 3.2 to 109 months after transplantation. Complete biochemical and symptomatic resolution was observed in all patients after transplantation. However, there was a high rate of hepatic artery thrombosis (HAT; 4/10), with 1 patient requiring regrafting. The effects of previous neuronal damage such as joint contractures were not improved by transplantation. Thus, impaired quality of life in the surviving patients was usually a result of preoperative complications. Refractory AIP is an excellent indication for LT, and long-term outcomes for carefully selected patients are good. There is, however, an increased incidence of HAT in these patients, and we recommend routine antiplatelet therapy after transplantation. PMID:21618697

Dowman, Joanna K; Gunson, Bridget K; Mirza, Darius F; Bramhall, Simon R; Badminton, Mike N; Newsome, Philip N

2012-02-01

355

Depletion of Molecular Chaperones from the Endoplasmic Reticulum and Fragmentation of the Golgi Apparatus Associated with Pathogenesis in Pelizaeus-Merzbacher Disease*  

PubMed Central

Missense mutations in the proteolipid protein 1 (PLP1) gene cause a wide spectrum of hypomyelinating disorders, from mild spastic paraplegia type 2 to severe Pelizaeus-Merzbacher disease (PMD). Mutant PLP1 accumulates in the endoplasmic reticulum (ER) and induces ER stress. However, the link between the clinical severity of PMD and the cellular response induced by mutant PLP1 remains largely unknown. Accumulation of misfolded proteins in the ER generally leads to up-regulation of ER chaperones to alleviate ER stress. Here, we found that expression of the PLP1-A243V mutant, which causes severe disease, depletes some ER chaperones with a KDEL (Lys-Asp-Glu-Leu) motif, in HeLa cells, MO3.13 oligodendrocytic cells, and primary oligodendrocytes. The same PLP1 mutant also induces fragmentation of the Golgi apparatus (GA). These organelle changes are less prominent in cells with milder disease-associated PLP1 mutants. Similar changes are also observed in cells expressing another disease-causing gene that triggers ER stress, as well as in cells treated with brefeldin A, which induces ER stress and GA fragmentation by inhibiting GA to ER trafficking. We also found that mutant PLP1 disturbs localization of the KDEL receptor, which transports the chaperones with the KDEL motif from the GA to the ER. These data show that PLP1 mutants inhibit GA to ER trafficking, which reduces the supply of ER chaperones and induces GA fragmentation. We propose that depletion of ER chaperones and GA fragmentation induced by mutant misfolded proteins contribute to the pathogenesis of inherited ER stress-related diseases and affect the disease severity. PMID:23344956

Numata, Yurika; Morimura, Toshifumi; Nakamura, Shoko; Hirano, Eriko; Kure, Shigeo; Goto, Yu-ich; Inoue, Ken

2013-01-01

356

MRI as a tool to study brain structure from mouse models for mental retardation  

NASA Astrophysics Data System (ADS)

Nowadays, transgenic mice are a common tool to study brain abnormalities in neurological disorders. These studies usually rely on neuropathological examinations, which have a number of drawbacks, including the risk of artefacts introduced by fixation and dehydration procedures. Here we present 3D Fast Spin Echo Magnetic Resonance Imaging (MRI) in combination with 2D and 3D segmentation techniques as a powerful tool to study brain anatomy. We set up MRI of the brain in mouse models for the fragile X syndrome (FMR1 knockout) and Corpus callosum hypoplasia, mental Retardation, Adducted thumbs, Spastic paraplegia and Hydrocephalus (CRASH) syndrome (L1CAM knockout). Our major goal was to determine qualitative and quantitative differences in specific brain structures. MRI of the brain of fragile X and CRASH patients has revealed alterations in the size of specific brain structures, including the cerebellar vermis and the ventricular system. In the present MRI study of the brain from fragile X knockout mice, we have measured the size of the brain, cerebellum and 4th ventricle, which were reported as abnormal in human fragile X patients, but found no evidence for altered brain regions in the mouse model. In CRASH syndrome, the most specific brain abnormalities are vermis hypoplasia and abnormalities of the ventricular system with some degree of hydrocephalus. With the MRI study of L1CAM knockout mice we found vermis hypoplasia, abnormalities of the ventricular system including dilatation of the lateral and the 4th ventricles. These subtle abnormalities were not detected upon standard neuropathological examination. Here we proved that this sensitive MRI technique allows to measure small differences which can not always be detected by means of pathology.

Verhoye, Marleen; Sijbers, Jan; Kooy, R. F.; Reyniers, E.; Fransen, E.; Oostra, B. A.; Willems, Peter; Van der Linden, Anne-Marie

1998-07-01

357

Liver disease in infancy caused by oxysterol 7 ?-hydroxylase deficiency: successful treatment with chenodeoxycholic acid.  

PubMed

A child of consanguineous parents of Pakistani origin developed jaundice at 5 weeks and then, at 3 months, irritability, a prolonged prothrombin time, a low albumin, and episodes of hypoglycaemia. Investigation showed an elevated alanine aminotransferase with a normal ?-glutamyl-transpeptidase. Analysis of urine by electrospray ionisation tandem mass spectrometry (ESI-MS/MS) showed that the major peaks were m/z 480 (taurine-conjugated 3?-hydroxy-5-cholenoic acid) and m/z 453 (sulphated 3?-hydroxy-5-cholenoic acid). Analysis of plasma by gas chromatography-mass spectrometry (GC-MS) showed increased concentrations of 3?-hydroxy-5-cholenoic acid, 3?-hydroxy-5-cholestenoic acid and 27-hydroxycholesterol, indicating oxysterol 7 ?-hydroxylase deficiency. The patient was homozygous for a mutation (c.1249C>T) in CYP7B1 that alters a highly conserved residue in oxysterol 7 ?-hydroxylase (p.R417C) - previously reported in a family with hereditary spastic paraplegia type 5. On treatment with ursodeoxycholic acid (UDCA), his condition was worsening, but on chenodeoxycholic acid (CDCA), 15 mg/kg/d, he improved rapidly. A biopsy (after 2 weeks on CDCA), showed a giant cell hepatitis, an evolving micronodular cirrhosis, and steatosis. The improvement in liver function on CDCA was associated with a drop in the plasma concentrations and urinary excretions of the 3?-hydroxy-?5 bile acids which are considered hepatotoxic. At age 5 years (on CDCA, 6 mg/kg/d), he was thriving with normal liver function. Neurological development was normal apart from a tendency to trip. Examination revealed pes cavus but no upper motor neuron signs. The findings in this case suggest that CDCA can reduce the activity of cholesterol 27-hydroxylase - the first step in the acidic pathway for bile acid synthesis. PMID:24658845

Dai, Dongling; Mills, Philippa B; Footitt, Emma; Gissen, Paul; McClean, Patricia; Stahlschmidt, Jens; Coupry, Isabelle; Lavie, Julie; Mochel, Fanny; Goizet, Cyril; Mizuochi, Tatsuki; Kimura, Akihiko; Nittono, Hiroshi; Schwarz, Karin; Crick, Peter J; Wang, Yuqin; Griffiths, William J; Clayton, Peter T

2014-09-01

358

Traumatic spinal cord injury in Botswana: characteristics, aetiology and mortality.  

PubMed

Study design:Descriptive study with a cross-sectional design.Objectives:To describe the epidemiology of traumatic spinal cord injuries (TSCIs) in Botswana, with a specific focus on road traffic crashes (RTC).Setting:Main public referral hospital, Gaborone, Botswana.Method:Two samples were included. Sample one described the epidemiology and included patients admitted during a 2-year period with acute TSCI. Sample two included only patients with TSCI due to RTC.Results:Annual incidence was 13 per million population. Epidemiology of TSCI: 49 patients were included, 71% male, age ranging from 4 to 81 years, 80% ?45 years. Tetraplegia was more common than paraplegia (59/41%), and 39% had C1-C4 level of injury. The main cause of TSCI was RTC (68%), followed by assault (16%) and falls (10%). Mortality was 20%, where all, but one, had tetraplegia (18%). Median time from injury to spinal surgery was 12 days, with longer time for women, 16 days compared with 8 for men. Burst tire was the primary cause of RTC resulting in a TSCI, followed by hitting animals on the road. The majority had been passengers and 72% were involved in single crashes.Conclusion:The most common cause for TSCI was RTC, followed by assault. In-hospital mortality was high and the waiting period from the time of accident to spinal surgery was long, especially for women. The aetiology and high mortality of TSCI in Botswana indicate that improvements in roadway safety and medical care may decrease the TSCI incidence and mortality.Spinal Cord advance online publication, 25 November 2014; doi:10.1038/sc.2014.203. PMID:25420494

Löfvenmark, I; Norrbrink, C; Nilsson-Wikmar, L; Hultling, C; Chakandinakira, S; Hasselberg, M

2014-11-25

359

Multitasking a telemedicine training unit in earthquake disaster response: paraplegic rehabilitation assessment.  

PubMed

The objective of this work was to provide computer and telecommunications skill training for paraplegics using a telemedicine training center in a curriculum that would support connectivity and offer new skills for career applications in the rehabilitation phase and beyond. This was a hospital-based, cross-sectional study. The study was conducted from October 10, 2005 to May 10, 2006 in the hospitals of Rawalpindi Medical College and the Melody Rehabilitation Center, Rawalpindi, Pakistan. These centers provided care for casualties of the October 2005 earthquake in Pakistan. One hundred and ninety four (194) paraplegics were admitted to Rawalpindi Medical College allied hospitals after injuries in the rural mountains near the epicenter. Surveys assessed the education level of the patients, and a sample of 12 patients was enrolled in computer training classes. Of the 194 patients, 144 were female and 50 were male. The majority, 78% (151) were 16-39 years of age. Although only 60% were literate, the overall literacy rate of Pakistan is just 48.7%. Telephone service at home was available after discharge for 40% of patients. Only 8% of patients had basic computer skills. All patients participated in the survey and sought to take the course. All the enrolled patients demonstrated full competency in the skills taught. The social disruption of disaster plus the new challenge of a neurological deficit in paraplegia did not deter a remarkable number of patients from a rural area from engaging in computer and telemedicine training. This study demonstrated the feasibility of educating rural paraplegics in computer skills for telemedicine. The telemedicine training center was used for this task without special equipment or personnel, thereby increasing the utilization of the facility. PMID:18570553

Gul, Shahzad; Ghaffar, Hirra; Mirza, Shirin; Fizza Tauqir, Syeda; Murad, Faisal; Ali, Qasim; Zafar Malik, Asif; Merrell, Ronald C

2008-04-01

360

Clinical Investigations on the Spinal Osteoblastic Metastasis Treated by Combination of Percutaneous Vertebroplasty and 125I Seeds Implantation Versus Radiotherapy  

PubMed Central

Abstract To investigate the clinical efficacy of combining digital subtraction angiography-guided percutaneous vertebroplasty (PVP) and 125I seeds implantation for the treatment of spinal osteoplastic metastasis. A combination of PVP and 125I implantation was conducted for 50 patients with spinal osteoplastic metastasis, while the other 50 patients who received regular radiation therapy were used as a comparison. Visual analogue pain scale (VAS) and score of life quality (EORTCQLQ-30) were determined for all the patients. Surgery was successful in 89 spinal segments of vertebral body in 50 patients. Each segment of vertebral body was injected with 1–5?mL (2.8?mL for thoracic and 3.1?mL for lumbar vertebral body on average) of bone cement. Postoperative X-ray and CT examination showed that all the patients in the PVP group achieved spinal stability. During the follow-up examination from 6 months to 5 years, 49 patients (98.0%) had significantly relieved back pain, and only 1 case (2.0%) had no obvious improvement. Postoperative VAS score and Karnofsky performance score (KPS) were significantly different from the preoperative scores (p<0.05); and compared to the regular treatment group, PVP combined 125I seeds showed much better clinical efficacy (p<0.05). PVP is a minimally invasive treatment with easy operation and less complications. PVP can effectively relieve the pain, stabilize the spine, improve the life quality, and reduce the occurrence of paraplegia in patients with spinal osteoplastic metastasis. Utilization of 125I seeds with PVP can enhance the clinical efficacy. PMID:23009581

Tan, Jing; Zhao, Ruilian; Wang, Jiaping; Sun, Hongpu; Wang, Xiaoxue; Xu, Lei; Jiang, Hua; Zhang, Jinlei

2013-01-01

361

Hybrid Repair of Complex Thoracic Aortic Arch Pathology: Long-Term Outcomes of Extra-anatomic Bypass Grafting of the Supra-aortic Trunk  

SciTech Connect

Hybrid repair constitutes supra-aortic debranching before thoracic endovascular aortic repair (TEVAR). It offers improved short-term outcome compared with open surgery; however, longer-term studies are required to assess patient outcomes and patency of the extra-anatomic bypass grafts. A prospectively maintained database of 380 elective and urgent patients who had undergone TEVAR (1997-2011) was analyzed retrospectively. Fifty-one patients (34 males; 17 females) underwent hybrid repair. Median age was 71 (range, 18-90) years with mean follow-up of 15 (range, 0-61) months. Perioperative complications included death: 10 % (5/51), stroke: 12 % (6/51), paraplegia: 6 % (3/51), endoleak: 16 % (8/51), rupture: 4 % (2/51), upper-limb ischemia: 2 % (1/51), bypass graft occlusion: 4 % (2/51), and cardiopulmonary complications in 14 % (7/51). Three patients (6 %) required emergency intervention for retrograde dissection: (2 aortic root repairs; 2 innominate stents). Early reintervention was performed for type 1 endoleak in two patients (2 proximal cuff extensions). One patient underwent innominate stenting and revision of their bypass for symptomatic restenosis. At 48 months, survival was 73 %. Endoleak was detected in three (6 %) patients (type 1 = 2; type 2 = 1) requiring debranching with proximal stent graft (n = 2) and proximal extension cuff (n = 1). One patient had a fatal rupture of a mycotic aneurysm and two arch aneurysms expanded. No bypass graft occluded after the perioperative period. Hybrid operations to treat aortic arch disease can be performed with results comparable to open surgery. The longer-term outcomes demonstrate low rates of reintervention and high rates of graft patency.

Lotfi, S., E-mail: shamim.lotfi@kcl.ac.uk; Clough, R. E.; Ali, T. [Guy's and St. Thomas' NHS Trust, Vascular Surgery (United Kingdom)] [Guy's and St. Thomas' NHS Trust, Vascular Surgery (United Kingdom); Salter, R. [Guy's and St. Thomas' NHS Trust, Interventional Radiology (United Kingdom)] [Guy's and St. Thomas' NHS Trust, Interventional Radiology (United Kingdom); Young, C. P. [Guy's and St. Thomas' NHS Trust, Cardiac Surgery (United Kingdom)] [Guy's and St. Thomas' NHS Trust, Cardiac Surgery (United Kingdom); Bell, R.; Modarai, B.; Taylor, P., E-mail: peter.taylor@gstt.nhs.uk [Guy's and St. Thomas' NHS Trust, Vascular Surgery (United Kingdom)

2013-02-15

362

Posterior short segment pedicle screw fixation and TLIF for the treatment of unstable thoracolumbar/lumbar fracture  

PubMed Central

Background Currently, Posterior Short Segment Pedicle Screw Fixation is a popular procedure for treating unstable thoracolumbar/lumbar burst fracture. But progressive kyphosis and a high rate of hardware failure because of lack of the anterior column support remains a concern. The efficacy of different methods remains debatable and each technique has its advantages and disadvantages. Methods A consecutive series of 20 patients with isolated thoracolumbar/lumbar burst fractures were treated by posterior short segment pedicle screw fixation and transforaminal thoracolumbar/lumbar interbody fusion (TLIF) between January 2005 and December 2007. All patients were followed up for a minimum of 2 years. Demographic data, neurologic status, anterior vertebral body heights, segmental Cobb angle and treatment-related complications were evaluated. Results The mean operative time was 167 minutes (range, 150–220). Blood loss was 450 ~ 1200 ml, an average of 820 ml. All patients recovered with solid fusion of the intervertebral bone graft, without main complications like misplacement of the pedicle screw, nerve or vessel lesion or hard ware failure. The post-operative radiographs demonstrated a good fracture reduction and it was well maintained until the bone graft fusion. Neurological recovery of one to three Frankel grade was seen in 14 patients with partial neurological deficit, three grades of improvement was seen in one patient, two grades of improvement was observed in 6 patients and one grade of improvement was found in 6 patients. All the 6 patients with no paraplegia on admission remained neurological intact, and in one patient with Frankel D on admission no improvement was observed. Conclusion Posterior short-segment pedicle fixation in conjunction with TLIF seems to be a feasible option in the management of selected thoracolumbar/lumbar burst fractures, thereby addressing all the three columns through a single approach with less trauma and good results. PMID:24517217

2014-01-01

363

Obstacles to community participation among youth with spinal cord injury  

PubMed Central

Objective Examine caregiver-report of obstacles to community participation for youth with spinal cord injury (SCI), and explore relationships between obstacles and child, caregiver, and community characteristics. Design Two hundred and one primary caregivers of youth with SCI ages 7–17 years were interviewed at three pediatric SCI centers within a single-hospital system. Caregivers answered an open-ended question assessing obstacles to youth participation. A mixed-methods approach was incorporated, where qualitative methods analyzed caregiver-reported obstacles, and exploratory multivariate analyses examined relationships between obstacles and demographic variables. Results Caregivers were primarily mothers (74%), married (69%), employed (54%), had college experience (67%), and lived in small towns (55%). Youths' mean age was 12.60 years at interview and 7.19 years at injury, 70% had paraplegia, and 55% had complete injuries. Analyses revealed that youth participation was limited by obstacles across six domains: community, disability-related, practical concerns, child-internal, social, and other. Child, caregiver, and community characteristics were related to overall report of obstacles, and report of community obstacles, disability-related obstacles, and practical concerns. Caregiver college experience and small town living predicted overall report of obstacles. Having a child injured at a younger age, caregiver college experience, and small town living predicted community obstacles. Having a child with an incomplete injury and recent medical complication predicted disability-related obstacles. Caregiver employment predicted practical concerns. Conclusion Youth from small towns, those injured younger, those with incomplete injuries, and those experiencing recent medical complications may need additional supports and resources to maximize participation. Clinicians should work with caregivers to identify and problem-solve obstacles to youth participation. PMID:22330113

Gorzkowski, Julie; Kelly, Erin H.; Klaas, Sara J.; Vogel, Lawrence C.

2011-01-01

364

Access to health and support services: perspectives of people living with a long-term traumatic spinal cord injury in rural and urban areas.  

PubMed

Abstract Purpose: To examine the perspectives of persons living with traumatic spinal cord injuries (tSCI) on their access to health and support services. The specific aims were to identify the perceived gaps in access, classify the nature of the perceived gaps and compare differences in perceptions of access between urban and rural participants. Method: Using a descriptive, qualitative approach, semi-structured interviews were conducted with 23 adults living with tSCI, 13 of whom had paraplegia. Ten participants resided in rural areas and 16 were male. Thematic analysis allowed for the identification of patterns, which were then categorized according to the dimensions of access. Results: Opportunities to engage in health-promoting activities through a broad range of health and support services were at times limited, particularly by issues of affordability. In addition to core healthcare services, participants reported the need for complementary therapies, sports and leisure, peer support, equipment and mobility related services. Availability and accessibility of services was limited in some cases for rural participants, although rural residence conferred other valued benefits. Narratives of "not being heard" by providers were common. Conclusions: Maintaining health and well-being in people with tSCI demands access to both conventional health care and support services. Implications for Rehabilitation Access to both health and support services are important to maintaining the health and wellness of people with spinal cord injury. People with spinal cord injuries take an active role in coordinating their health, at times assuming various roles to compensate for perceived shortcomings of health care providers. Negotiating balances of power with gatekeepers in the health and insurance sectors was a key function of the coordinating role assumed by people with spinal cord injury. In order to effectively address the needs of this population, a coordinated interdisciplinary out-reach service, which includes peer support, must cross boundaries to engage sectors beyond traditional health care services, such as insurers and wellness providers. PMID:25332089

Goodridge, Donna; Rogers, Marla; Klassen, Laura; Jeffery, Bonnie; Knox, Katherine; Rohatinsky, Noelle; Linassi, Gary

2014-10-21

365

The short- and long-term risk of venous thromboembolism in patients with acute spinal cord injury: a prospective cohort study.  

PubMed

Venous thromboembolism (VTE) is a frequent complication in the acute setting after spinal cord injury (SCI). Less is known about the long-term risk of VTE in these patients. It was the aim of this study to prospectively evaluate the short- and long-term risk of VTE in a cohort of patients after acute SCI and during rehabilitation and post-rehabilitation follow-up period. From January 2003 to November 2007 all consecutive adult patients admitted to a Spinal Rehabilitation Unit (RU) after surgical treatment in three Neurosurgical Units for SCI, were enrolled. After an accurate evaluation of their neurosurgical medical records the patients were prospectively evaluated for VTE occurrence. Ninety-four patients (80 males; mean age 40.3 years, SD 15.9) were recruited. All the patients received thromboprophylaxis with low-molecular-weight heparin combined with compressive stockings during hospitalization (median duration 7 months, IQR 4.5-8.8). Over a median follow-up period of 36.3 months (IQR 4.4-48) after SCI, VTE was diagnosed in 22 patients (23.4%) The majority of VTE events were recorded during the first three months of follow-up (34.4 VTE events/100 patient-years in the first 3 months and 0.3 VTE events/100 patient-years thereafter); age over 45 years (HR 8.4, 95% CI 3-23.5), previous VTE (HR 6.0, 95% CI 1.6-23.3) and paraplegia (HR 4.7, 95% CI 1.6-13.7) were independently associated with the occurrence of VTE. In conclusion, the risk of VTE in patients suffering from SCI is high despite the use of thromboprophylaxis, in particular in some patients categories. However, this risk appears to be limited to the first 3 months after the index event. PMID:23223906

Giorgi Pierfranceschi, M; Donadini, Marco P; Dentali, Francesco; Ageno, Walter; Marazzi, Marina; Bocchi, Romeo; Imberti, Davide

2013-01-01

366

[Neurologic principles of edema in inactivity].  

PubMed

The complete immobilisation of a limb alone can lead to the formation of oedema. Whereas the oedema secondary to inactivity induced by immobilisation is completely reversible, and will only lead to tissue damage in the longterm, neglect of oedema secondary to inactivity in the presence of central and peripheral paresis (apoplectic insult, paraplegia, damage to the plexus brachialis) may entail serious consequences due to the danger of tissue fibrosis. With paresis of an extremity, the lymphovenous return is impaired by two decisive factors: increased hydrostatic pressure in the distal limb segment, and absence of the muscle pump. In flaccid paresis, where there is low muscle tone and no muscle pump action, there is also a low venous tone and the resultant hydrostatic pressure is especially high. Venous stasis in the sub- and prefascial veins leads to increased protein loss from the venous limb of the capillaries and the venules. Compensation initially occurs in the prefascial lymph outflow region (latent oedema) which becomes decompensated if overloaded (visible oedema). Fibrosis of the subcutis and trophic skin changes are the result. In spastic paresis the regional subfascial lymphatic system responds with lymphangiospasm. Where the sympathetic innervation is interrupted (e.g. brachial plexus paralysis) there is passive hyperaemia of the terminal vessels with vascular dilatation and lymphangioparalysis. Insufficiency of the vascular walls results in an accumulation of protein in the tissues, which ultimately ends in fibrosis with ankylosis and shortening of the tendons and muscles. The early administration of complex physical decongestion therapy with manual lymphatic drainage can prevent this state. PMID:1288027

Trettin, H

1992-12-01

367

[What is the role of the genetic survey in amyotrophic lateral sclerosis?].  

PubMed

The genetic inquiry in the diagnostic process of amyotrophic lateral sclerosis (ALS) need to be precise and systematic. Several hereditary neurologic disorders may initially mimic ALS, such as dominant spino-cerebellar ataxia or spastic paraplegia. Other hereditary motor neuron disorders are clinically more difficult to distinct from ALS such as Kennedy's disease, adult-onset spinal muscular atrophies or juvenile ALS. When a final diagnostic of ALS is established, the genetic inquiry aims at identifying a familial ALS (FALS) case. Almost 10 to 20 percent of ALS cases are familial. It is now admitted that 10 to 20 percent of those cases are due to SOD1 gene mutations. Such mutations may have a dominant or recessive inheritance. They are mainly found in multigenerational families. In 80 percent of the FALS cases, only two ALS cases are found in the pedigree. One cannot know whether this represent dominant cases with low penetrance, recessive inheritance or a multigenic, hereditary complex, disorder. More other, not all the SOD1 mutations have been demonstrated as causal. These elements are strong enough to suggest to precisely study, in the presence of a given SOD1 mutation, both the clinical phenotype, the data from the literature and, as often as possible, the segregation of the mutation into the family, before ascertaining that the mutation is responsible for a hereditary case of ALS. In every case, the genetic inquiry together with its conclusions should be done with caution, taking into account both the patient's need of a clear information and his anxiety regarding his descent. PMID:17128094

Camu, W

2006-06-01

368

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

PubMed Central

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

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

2014-01-01

369

Liver Transplantation for Acute Intermittent Porphyria is Complicated by a High Rate of Hepatic Artery Thrombosis  

PubMed Central

Acute intermittent porphyria (AIP) is an autosomal-dominant condition resulting from a partial deficiency of the ubiquitously expressed enzyme porphobilinogen deaminase. Although its clinical expression is highly variable, a minority of patients suffer recurrent life-threatening neurovisceral attacks despite optimal medical therapy. Because the liver is the major source of excess precursor production, liver transplantation (LT) represents a potentially effective treatment for severely affected patients. Using data from the UK Transplant Registry, we analyzed all transplants performed for AIP in the United Kingdom and Ireland. Between 2002 and 2010, 10 patients underwent LT for AIP. In all cases, the indication for transplantation was recurrent, biochemically proven, medically nonresponsive acute attacks of porphyria resulting in significantly impaired quality of life. Five patients had developed significant neurological morbidities such as paraplegia before transplantation. The median follow-up time was 23.4 months, and there were 2 deaths from multiorgan failure at 98 days and 26 months. Eight recipients were alive for 3.2 to 109 months after transplantation. Complete biochemical and symptomatic resolution was observed in all patients after transplantation. However, there was a high rate of hepatic artery thrombosis (HAT; 4/10), with 1 patient requiring regrafting. The effects of previous neuronal damage such as joint contractures were not improved by transplantation. Thus, impaired quality of life in the surviving patients was usually a result of preoperative complications. Refractory AIP is an excellent indication for LT, and long-term outcomes for carefully selected patients are good. There is, however, an increased incidence of HAT in these patients, and we recommend routine antiplatelet therapy after transplantation. Liver Transpl 18:195–200, 2012. © 2011 AASLD. PMID:21618697

Dowman, Joanna K; Gunson, Bridget K; Mirza, Darius F; Bramhall, Simon R; Badminton, Mike N; Newsome, Philip N

2012-01-01

370

N-methyl-D-aspartate receptor antagonist MK-801 prevents apoptosis in rats that have undergone fetal spinal cord transplantation following spinal hemisection  

PubMed Central

Spinal cord injury is the main cause of paraplegia, but effective therapies for it are lacking. Embryonic spinal cord transplantation is able to repair spinal cord injury, albeit with a large amount of neuronal apoptosis remaining in the spinal cord. MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, is able to reduce cell death by decreasing the concentration of excitatory amino acids and preventing extracellular calcium ion influx. In this study, the effect of MK-801 on the apoptosis of spinal cord neurons in rats that have received a fetal spinal cord (FSC) transplant following spinal hemisection was investigated. Wistar rats were divided into three groups: Spinal cord hemisection injury with a combination of FSC transplantation and MK-801 treatment (group A); spinal cord hemisection injury with FSC transplantation (group B); and spinal cord injury with insertion of a Gelfoam pledget (group C). The rats were sacrificed 1, 3, 7 and 14 days after the surgery. Apoptosis in spinal slices from the injured spinal cord was examined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling reaction, and the expression of B-cell lymphoma-2 (Bcl-2) was measured by immunohistochemistry. The positive cells were quantitatively analyzed using a computer image analysis system. The rate of apoptosis and the positive expression of Bcl-2 protein in the spinal cord neurons in the three groups decreased in the following order: C>B>A (P<0.05) and A>B>C (P<0.05), respectively. This indicates that treatment with the NMDA receptor antagonist MK-801 prevents apoptosis in the spinal cord neurons of rats that have undergone FSC transplantation following spinal hemisection. PMID:25371724

ZHANG, QIANG; SHAO, YANG; ZHAO, CHANGSONG; CAI, JUAN; SUN, SHENG

2014-01-01

371

Physiotherapy Secretion Removal Techniques in People With Spinal Cord Injury: A Systematic Review  

PubMed Central

Objective: To address whether secretion removal techniques increase airway clearance in people with chronic spinal cord injury (SCI). Data Sources and Study Selection: MEDLINE/PubMed, CINAHL, EMBASE, and PsycINFO were searched from inception to May 2009 for population keywords (spinal cord injury, paraplegia, tetraplegia, quadriplegia) paired with secretion removal–related interventions and outcomes. Inclusion criteria for articles were a research study, irrespective of design, that examined secretion removal in people with chronic SCI published in English. Review Methods: Two reviewers determined whether articles met the inclusion criteria, abstracted information, and performed a quality assessment using PEDro or Downs and Black criteria. Studies were then given a level of evidence based on a modified Sackett scale. Results: Of 2,416 abstracts and titles retrieved, 24 met the inclusion criteria. Subjects were young (mean, 31 years) and 84% were male. Most evidence was level 4 or 5 and only 2 studies were randomized controlled trials. Three reports described outcomes for secretion removal techniques in addition to cough, whereas most articles examined the immediate effects of various components of cough. Studies examining insufflation combined with manual assisted cough provided the most consistent, high-level evidence. Compelling recent evidence supports the use of respiratory muscle training or electrical stimulation of the expiratory muscles to facilitate airway clearance in people with SCI. Conclusion: Evidence supporting the use of secretion removal techniques in SCI, while positive, is limited and mostly of low level. Treatments that increase respiratory muscle force show promise as effective airway clearance techniques. PMID:21061895

Reid, W. Darlene; Brown, Jennifer A; Konnyu, Kristin J; Rurak, Jennifer M.E; Sakakibara, Brodie M

2010-01-01

372

Cholecalciferol (Vitamin D3) Improves Myelination and Recovery after Nerve Injury  

PubMed Central

Previously, we demonstrated i) that ergocalciferol (vitamin D2) increases axon diameter and potentiates nerve regeneration in a rat model of transected peripheral nerve and ii) that cholecalciferol (vitamin D3) improves breathing and hyper-reflexia in a rat model of paraplegia. However, before bringing this molecule to the clinic, it was of prime importance i) to assess which form – ergocalciferol versus cholecalciferol – and which dose were the most efficient and ii) to identify the molecular pathways activated by this pleiotropic molecule. The rat left peroneal nerve was cut out on a length of 10 mm and autografted in an inverted position. Animals were treated with either cholecalciferol or ergocalciferol, at the dose of 100 or 500 IU/kg/day, or excipient (Vehicle), and compared to unlesioned rats (Control). Functional recovery of hindlimb was measured weekly, during 12 weeks, using the peroneal functional index. Ventilatory, motor and sensitive responses of the regenerated axons were recorded and histological analysis was performed. In parallel, to identify the genes regulated by vitamin D in dorsal root ganglia and/or Schwann cells, we performed an in vitro transcriptome study. We observed that cholecalciferol is more efficient than ergocalciferol and, when delivered at a high dose (500 IU/kg/day), cholecalciferol induces a significant locomotor and electrophysiological recovery. We also demonstrated that cholecalciferol increases i) the number of preserved or newly formed axons in the proximal end, ii) the mean axon diameter in the distal end, and iii) neurite myelination in both distal and proximal ends. Finally, we found a modified expression of several genes involved in axogenesis and myelination, after 24 hours of vitamin supplementation. Our study is the first to demonstrate that vitamin D acts on myelination via the activation of several myelin-associated genes. It paves the way for future randomised controlled clinical trials for peripheral nerve or spinal cord repair. PMID:23741446

Chabas, Jean-Francois; Stephan, Delphine; Marqueste, Tanguy; Garcia, Stephane; Lavaut, Marie-Noelle; Nguyen, Catherine; Legre, Regis; Khrestchatisky, Michel

2013-01-01

373

Proton magnetic resonance spectroscopy and cognition in patients with spastin mutations.  

PubMed

The hereditary spastic paraplegias (HSP) are heterogeneous neurodegenerative disorders characterized by progressive spasticity and weakness in the lower limbs. Axonal loss in the long corticospinal tracts has been shown. Supraspinal symptoms and findings in the most common dominant HSP type, SPG4, support the theory that the disease also causes cerebral neuronal damage in specific parts of the brain. To investigate whether SPG4-HSP is associated with neuronal biochemical changes detectable on MR spectroscopy (MRS), single-voxel proton MRS of the brain was performed in eight subjects from four families with genetically confirmed SPG4-type HSP and eight healthy age-matched controls. Volumes of interest (VOI) were located in the frontal white matter and motor cortex. N-acetyl-aspartate-to-creatine ratio (NAA/Cr), N-acetyl-aspartate-to-choline (NAA/Cho), cholin to creatin (Cho/Cr) and myo-inositol-to-creatine (Ins/Cr) ratios were calculated for both locations. Neuropsychological tests were performed to support the neuroradiological findings. The Cho/Cr ratio in motor cortex (MC) of SPG4-HSP subjects was significantly lower than in controls. This reduction of the Cho/Cr ratio in SPG4 subjects was significantly associated with age-related verbal learning- and memory (CVLT) reduction. Our findings support involvement of motor cortex in SPG4-HSP. Proton MRS could be a useful tool for detecting metabolite abnormalities in areas of brain that appear normal on MRI. Cho/Cr ratio may be a marker of neurodegenerative process in SPG4-HSP. PMID:19084842

Erichsen, A K; Server, A; Landrø, N I; Sandvik, L; Tallaksen, C M E

2009-02-15

374

Inflammation-mediating cytokine response to acute handcycling exercise with/without functional electrical stimulation-evoked lower-limb cycling.  

PubMed

This feasibility study compared the plasma inflammation-mediating cytokine response to an acute bout of handcycling (HC) with and without the addition of functional electrical stimulation (FES)-evoked lower-limb cycling. On two separate occasions, five recreationally active, community-based participants with motor complete paraplegia (thoracic 5- 7) performed 30 min HC and hybrid exercise (HYB) at a fixed power output. Venous blood samples were collected at rest, immediately postexercise, 1 h postexercise (post+1) and 2 h postexercise (post+2). Plasma interleukin (IL)-6, IL-10, IL-1 receptor antagonist (IL-1ra), adrenaline, and cortisol concentrations were determined via enzyme-linked immunoassay. Plasma IL-6 concentrations were significantly (p < 0.04) elevated (~2.5-fold) at post+1 and post+2 in HYB only. A small (0.5-fold), nonsignificant (p > 0.05) increase in IL-6 was observed at post+1 in HC, with concentrations significantly higher in HYB at post+2 (p < 0.02). Plasma IL-1ra was unaffected in both trials. Although not reaching statistical significance (p = 0.15), a ~1-fold increase in IL-10 concentration was seen in HYB at post+2. In contrast, increases in adrenaline (p < 0.04) and cortisol (p = 0.08) were observed immediately postexercise in HC and HYB. Initial findings suggest paralyzed skeletal muscle releases IL-6 in response to FES-evoked contractions. HYB may provide a greater anti-inflammatory potential in individuals with a thoracic spinal cord injury compared with HC alone. PMID:25144177

Paulson, Thomas A W; Bishop, Nicolette C; Smith, Brett M; Goosey-Tolfrey, Victoria L

2014-01-01

375

[A case of intracranial multiple fibrous histiocytoma. Case report and review of literature].  

PubMed

A case of intracranial multiple fibrous histiocytom is arising from the dura mater and both lateral ventricles is presented. To the authors' knowledge, this is the ninth case of intracranial fibrous histiocytomas reported in the literature. A 10-year-old girl was admitted with a 6 month history of cerebellar ataxia. Radiological examination including CT scan revealed a large mass in occipito-suboccipital region. On November 1, 1978, subtotal resection of the tumor was performed. Yellowish hard tumor, weighing 195 g had wide attachment to the dura mater, but did not invade the brain tissue. Postoperative CT scan, three months later revealed the other tumors in the left lateral ventricle and in the suprasellar region in addition to the lesion that had been operated on. In the course of hospitalization, the suprasellar tumor enlarged rapidly despite of 60Co radiation therapy, then led her to hypothalamic dysfunction. In January, 1981, she had paraplegia and paresis of the right upper extremity. Spinal lesion at the level of C-5 was presumed, but further examination was not performed because of her poor condition. On February 19, 1981, she expired. Autopsy of the head revealed four independent lesions in both lateral ventricles, the suprasellar region and the residual lesion which had been resected subtotally at the operation, respectively. Entire falx cerebri was invaded continuously by the tumor in occipito-suboccipital area. Microscopically, all tumors were identical in histology and were composed of spindle shaped cells with storiform pattern, foam cells and rare giant cells. Any mitotic figures were not detected. Clinical behavior was aggressive but histological figures suggested fibrous histiocytoma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:6087179

Funakoshi, T; Yamada, H; Miwa, Y; Takada, M; Okuma, A; Shimokawa, K; Ikeda, T; Ushimaru, Y

1984-04-01

376

Central nervous system dysfunction in a mouse model of FA2H deficiency  

PubMed Central

Fatty acid 2-hydroxylase (FA2H) is responsible for the synthesis of myelin galactolipids containing hydroxy fatty acid (hFA) as the N-acyl chain. Mutations in the FA2H gene cause leukodystrophy, spastic paraplegia, and neurodegeneration with brain iron accumulation. Using the Cre-lox system, we developed two types of mouse mutants, Fa2h?/? mice (Fa2h deleted in all cells by germline deletion) and Fa2hflox/flox Cnp1-Cre mice (Fa2h deleted only in oligodendrocytes and Schwann cells). We found significant demyelination, profound axonal loss, and abnormally enlarged axons in the CNS of Fa2h?/? mice at 12 months of age, while structure and function of peripheral nerves were largely unaffected. Fa2h?/? mice also exhibited histological and functional disruption in the cerebellum at 12 months of age. In a time course study, significant deterioration of cerebellar function was first detected at 7 months of age. Further behavioral assessments in water T-maze and Morris water maze tasks revealed significant deficits in spatial learning and memory at 4 months of age. These data suggest that various regions of the CNS are functionally compromised in young adult Fa2h?/? mice. The cerebellar deficits in 12-month-old Fa2hflox/flox Cnp1-Cre mice were indistinguishable from Fa2h?/?mice, indicating that these phenotypes likely stem from the lack of myelin hFA-galactolipids. In contrast, Fa2hflox/flox Cnp1-Cre mice did not show reduced performance in water maze tasks, indicating that oligodendrocytes are not involved in the learning and memory deficits found in Fa2h?/? mice. These findings provide the first evidence that FA2H has an important function outside of oligodendrocytes in the CNS. PMID:21491498

Potter, Kathleen A.; Kern, Michael J.; Fullbright, George; Bielawski, Jacek; Scherer, Steven S.; Yum, Sabrina W.; Li, Jian J.; Cheng, Hua; Han, Xianlin; Venkata, Jagadish Kummetha; Khan, P. Akbar Ali; Rohrer, Bärbel; Hama, Hiroko

2011-01-01

377

Bridging defects in chronic spinal cord injury using peripheral nerve grafts combined with a chitosan-laminin scaffold and enhancing regeneration through them by co-transplantation with bone-marrow-derived mesenchymal stem cells: Case series of 14 patients  

PubMed Central

Objective To investigate the effect of bridging defects in chronic spinal cord injury using peripheral nerve grafts combined with a chitosan-laminin scaffold and enhancing regeneration through them by co-transplantation with bone-marrow-derived mesenchymal stem cells. Methods In 14 patients with chronic paraplegia caused by spinal cord injury, cord defects were grafted and stem cells injected into the whole construct and contained using a chitosan-laminin paste. Patients were evaluated using the International Standards for Classification of Spinal Cord Injuries. Results Chitosan disintegration leading to post-operative seroma formation was a complication. Motor level improved four levels in 2 cases and two levels in 12 cases. Sensory-level improved six levels in two cases, five levels in five cases, four levels in three cases, and three levels in four cases. A four-level neurological improvement was recorded in 2 cases and a two-level neurological improvement occurred in 12 cases. The American Spinal Impairment Association (ASIA) impairment scale improved from A to C in 12 cases and from A to B in 2 cases. Although motor power improvement was recorded in the abdominal muscles (2 grades), hip flexors (3 grades), hip adductors (3 grades), knee extensors (2–3 grades), ankle dorsiflexors (1–2 grades), long toe extensors (1–2 grades), and plantar flexors (0–2 grades), this improvement was too low to enable them to stand erect and hold their knees extended while walking unaided. Conclusion Mesenchymal stem cell-derived neural stem cell-like cell transplantation enhances recovery in chronic spinal cord injuries with defects bridged by sural nerve grafts combined with a chitosan-laminin scaffold. PMID:24090088

Amr, Sherif M.; Gouda, Ashraf; Koptan, Wael T.; Galal, Ahmad A.; Abdel-Fattah, Dina Sabry; Rashed, Laila A.; Atta, Hazem M.; Abdel-Aziz, Mohammad T.

2014-01-01

378

Examining health-care utilization in the first year following spinal cord injury.  

PubMed

Objective To identify factors associated with health-care utilization during the first year after inpatient rehabilitation (IR) in individuals with traumatic spinal cord injury (SCI). Design Prospective cohort. Methods One hundred and sixty-eight patients were prospectively enrolled and followed over 1 year after discharge from an SCI Model System IR program. Telephone follow-up occurred at 3, 6, 9, and 12 months. Participants were grouped into four impairment levels (C1-4 American Spinal Injury Association (ASIA) Impairment Scale (AIS) A-C, C5-C8 AIS A-C, paraplegia AIS A-C, and all AIS D). Three domains of health-care utilization were examined: hospital care, outpatient provider visits, and home services. Results Health-care utilization in the first year following IR was high with 45% of subjects reporting re-hospitalization. Twenty percent of patients were initially discharged to a skilled nursing facility (SNF), and an additional 10% required SNF care during this first year. Overall, those with C1-4 AIS A-C used the most services. Participants discharged home used less health care compared to those discharged elsewhere. SCI due to falls (vs. vehicular crashes) was associated with fewer in-home service visits. Age, sex, race, and education were unrelated to higher use. Conclusion Those with greater neurological impairment or not discharged home after IR had higher health-care utilization, while age was not associated with utilization. Targeted efforts to reduce genitourinary and respiratory complications may reduce the need for hospital care in the first year after IR. PMID:25299152

Skelton, Felicia; Hoffman, Jeanne M; Reyes, Maria; Burns, Stephen P

2014-10-01

379

Early- and medium-term results after aortic arch replacement with frozen elephant trunk techniques—a single center study  

PubMed Central

Background The treatment of patients with extensive thoracic aortic disease involving the arch and descending thoracic/thoracoabdominal aorta is often performed using the frozen elephant trunk technique (FET). We retrospectively analyzed our results of the FET operation. Methods A total of 51 consecutive patients underwent total aortic arch surgery with the FET technique between January 2006 and August 2013. For all patients, the E-vita hybrid open stent-graft (Jotec, Hechingen, Germany) was used. The patients had a mean age of 64±13 years, with 51.1% being female. Degenerative or atherosclerotic aneurysm was the indication for surgery in 62.7% of patients. Another 15.7% and 13.7% suffered from acute Type A, and Type B aortic dissection, respectively. Results The in-hospital and 30-day mortality was 7.8%. Stroke occurred in 11.8% (n=6), and new-onset paraplegia in 19.6% (n=10) of patients. The core body temperature ?28 °C during circulatory arrest, in combination with a prolonged circulatory arrest time of more than 45 minutes, was an independent predictor of permanent spinal cord injury [odds ratios (OR), 4.8; 95% confidence intervals (CI), 1.1-21; P=0.04]. The estimated 1- and 5-year survival was (80.2±5.5)% and (59.7±10.2)%, respectively, with a mean survival time of 3.4±0.4 years. The estimated mean freedom from endovascular intervention was 4.2±0.4 years. The unadjusted 1- and 5-year freedom from thoracic endovascular aortic repair (TEVAR) was (84.9±5.9)% and (69.2±11.2)%, respectively. Conclusions The FET procedure for extensive thoracic aortic disease is associated with an acceptable early and medium term mortality rate. This procedure is associated with a high incidence of perioperative spinal cord injury. In order to prevent the above complication, deep hypothermia is strongly recommended in patients with expected prolonged circulatory arrest time. PMID:24109568

Misfeld, Martin; Daviewala, Piroze; Borger, Michael A.; Etz, Christian D.; Belaev, Sergey; Seeburger, Joerg; Holzhey, David; Bakhtiary, Farhard; Mohr, Friedrich W.

2013-01-01

380

Phenotypic and molecular insights into spinal muscular atrophy due to mutations in BICD2.  

PubMed

Spinal muscular atrophy is a disorder of lower motor neurons, most commonly caused by recessive mutations in SMN1 on chromosome 5q. Cases without SMN1 mutations are subclassified according to phenotype. Spinal muscular atrophy, lower extremity-predominant, is characterized by lower limb muscle weakness and wasting, associated with reduced numbers of lumbar motor neurons and is caused by mutations in DYNC1H1, which encodes a microtubule motor protein in the dynein-dynactin complex and one of its cargo adaptors, BICD2. We have now identified 32 patients with BICD2 mutations from nine different families, providing detailed insights into the clinical phenotype and natural history of BICD2 disease. BICD2 spinal muscular atrophy, lower extremity predominant most commonly presents with delayed motor milestones and ankle contractures. Additional features at presentation include arthrogryposis and congenital dislocation of the hips. In all affected individuals, weakness and wasting is lower-limb predominant, and typically involves both proximal and distal muscle groups. There is no evidence of sensory nerve involvement. Upper motor neuron signs are a prominent feature in a subset of individuals, including one family with exclusively adult-onset upper motor neuron features, consistent with a diagnosis of hereditary spastic paraplegia. In all cohort members, lower motor neuron features were static or only slowly progressive, and the majority remained ambulant throughout life. Muscle MRI in six individuals showed a common pattern of muscle involvement with fat deposition in most thigh muscles, but sparing of the adductors and semitendinosus. Muscle pathology findings were highly variable and included pseudomyopathic features, neuropathic features, and minimal change. The six causative mutations, including one not previously reported, result in amino acid changes within all three coiled-coil domains of the BICD2 protein, and include a possible 'hot spot' mutation, p.Ser107Leu present in four families. We used the recently solved crystal structure of a highly conserved region of the Drosophila orthologue of BICD2 to further-explore how the p.Glu774Gly substitution inhibits the binding of BICD2 to Rab6. Overall, the features of BICD2 spinal muscular atrophy, lower extremity predominant are consistent with a pathological process that preferentially affects lumbar lower motor neurons, with or without additional upper motor neuron involvement. Defining the phenotypic features in this, the largest BICD2 disease cohort reported to date, will facilitate focused genetic testing and filtering of next generation sequencing-derived variants in cases with similar features. PMID:25497877

Rossor, Alexander M; Oates, Emily C; Salter, Hannah K; Liu, Yang; Murphy, Sinead M; Schule, Rebecca; Gonzalez, Michael A; Scoto, Mariacristina; Phadke, Rahul; Sewry, Caroline A; Houlden, Henry; Jordanova, Albena; Tournev, Iyailo; Chamova, Teodora; Litvinenko, Ivan; Zuchner, Stephan; Herrmann, David N; Blake, Julian; Sowden, Janet E; Acsadi, Gyuda; Rodriguez, Michael L; Menezes, Manoj P; Clarke, Nigel F; Auer Grumbach, Michaela; Bullock, Simon L; Muntoni, Francesco; Reilly, Mary M; North, Kathryn N

2015-02-01

381

The first ALS2 missense mutation associated with JPLS reveals new aspects of alsin biological function.  

PubMed

Primary lateral sclerosis (PLS) is a rare progressive paralytic disorder that results from dysfunction of the upper motoneurons. Although PLS is a sporadic disorder of adult middle age, it has also been described in children as juvenile PLS or JPLS. The causative gene for JPLS was found to be ALS2, which is also responsible for a recessive form of amyotrophic lateral sclerosis, for infantile onset ascending hereditary spastic paralysis (IAHSP) and for a form of complicated hereditary spastic paraplegia (cHSP). ALS2 gene encodes a protein termed alsin, containing multiple guanine nucleotide exchange factor domains, specifically binding to small GTPase Rab5 and acting as a GEF for Rab5. In vitrostudies performed with full-length and truncating forms of alsin protein support its role in endosomal dynamics and trafficking of mitochondria. All ALS2 mutations so far reported generate alsin protein truncation. Here, we describe the first homozygous missense mutation in ALS2, p.G540E. The mutation, which falls within the RCC1 domain, was identified in a 34-year-old patient with typical signs of JPLS such as ascending generalized and severe spasticity involving the limbs and the bulbar region, dysphagia, limb atrophy, preserved cognition and sensation. The father and two proband's sisters were found to be heterozygous carriers of the mutation with no signs of the disease. Studies in the neuronal cell line SK-N-BE indicated that the known subcellular localization of wild-type alsin with the early endosome antigen 1, in enlarged endosomal structures, and transferrin receptor is completely lost by the mutant protein, thus indicating that this mutation leads to protein delocalization. Mutant alsin induced neuronal death itself and also significantly enhanced the apoptogenic effect of NMDA and staurosporine. This effect was associated with decreased Bcl-xL : Bax ratio. In contrast, wild-type alsin was neuroprotective and increased Bcl-xL : Bax ratio. Our results provide the first demonstration that a missense mutation in alsin is cytotoxic. In addition, the identification of Bcl-xL/Bax as target of protection by alsin and of cytotoxicity by the mutant form provides a new signalling event regulated by alsin protein that may be important to define its role in neuronal physiology and neurodegeneration. Finally, the phenotype-genotype correlation in our patient, in view of all other ALS2 mutant cases reported previously, suggests a functional interplay of long and short forms of alsin in relation to disease onset and progression. PMID:16670179

Panzeri, Chris; De Palma, Clara; Martinuzzi, Andrea; Daga, Andrea; De Polo, Gianni; Bresolin, Nereo; Miller, Christopher C; Tudor, Elizabeth L; Clementi, Emilio; Bassi, Maria T

2006-07-01

382

Beneficial effect of the oxygen free radical scavenger amifostine (WR-2721) on spinal cord ischemia/reperfusion injury in rabbits  

PubMed Central

Background Paraplegia is the most devastating complication of thoracic or thoraco-abdominal aortic surgery. During these operations, an ischemia-reperfusion process is inevitable and the produced radical oxygen species cause severe oxidative stress for the spinal cord. In this study we examined the influence of Amifostine, a triphosphate free oxygen scavenger, on oxidative stress of spinal cord ischemia-reperfusion in rabbits. Methods Eighteen male, New Zealand white rabbits were anesthetized and spinal cord ischemia was induced by temporary occlusion of the descending thoracic aorta by a coronary artery balloon catheter, advanced through the femoral artery. The animals were randomly divided in 3 groups. Group I functioned as control. In group II the descending aorta was occluded for 30 minutes and then reperfused for 75 min. In group III, 500 mg Amifostine was infused into the distal aorta during the second half-time of ischemia period. At the end of reperfusion all animals were sacrificed and spinal cord specimens were examined for superoxide radicals by an ultra sensitive fluorescent assay. Results Superoxide radical levels ranged, in group I between 1.52 and 1.76 (1.64 ± 0.10), in group II between 1.96 and 2.50 (2.10 ± 0.23), and in group III (amifostine) between 1.21 and 1.60 (1.40 ± 0.19) (p = 0.00), showing a decrease of 43% in the Group of Amifostine. A lipid peroxidation marker measurement ranged, in group I between 0.278 and 0.305 (0.296 ± 0.013), in group II between 0.427 and 0.497 (0.463 ± 0.025), and in group III (amifostine) between 0.343 and 0.357 (0.350 ± 0.007) (p < 0.00), showing a decrease of 38% after Amifostine administration. Conclusion By direct and indirect methods of measuring the oxidative stress of spinal cord after ischemia/reperfusion, it is suggested that intra-aortic Amifostine infusion during spinal cord ischemia phase, significantly attenuated the spinal cord oxidative injury in rabbits. PMID:19758462

Chronidou, Fany; Apostolakis, Efstratios; Papapostolou, Ioannis; Grintzalis, Konstantinos; Georgiou, Christos D; Koletsis, Efstratios N; Karanikolas, Menelaos; Papathanasopoulos, Panagiotis; Dougenis, Dimitrios

2009-01-01

383

Cooling athletes with a spinal cord injury.  

PubMed

Cooling strategies that help prevent a reduction in exercise capacity whilst exercising in the heat have received considerable research interest over the past 3 decades, especially in the lead up to a relatively hot Olympic and Paralympic Games. Progressing into the next Olympic/Paralympic cycle, the host, Rio de Janeiro, could again present an environmental challenge for competing athletes. Despite the interest and vast array of research into cooling strategies for the able-bodied athlete, less is known regarding the application of these cooling strategies in the thermoregulatory impaired spinal cord injured (SCI) athletic population. Individuals with a spinal cord injury (SCI) have a reduced afferent input to the thermoregulatory centre and a loss of both sweating capacity and vasomotor control below the level of the spinal cord lesion. The magnitude of this thermoregulatory impairment is proportional to the level of the lesion. For instance, individuals with high-level lesions (tetraplegia) are at a greater risk of heat illness than individuals with lower-level lesions (paraplegia) at a given exercise intensity. Therefore, cooling strategies may be highly beneficial in this population group, even in moderate ambient conditions (~21 °C). This review was undertaken to examine the scientific literature that addresses the application of cooling strategies in individuals with an SCI. Each method is discussed in regards to the practical issues associated with the method and the potential underlying mechanism. For instance, site-specific cooling would be more suitable for an athlete with an SCI than whole body water immersion, due to the practical difficulties of administering this method in this population group. From the studies reviewed, wearing an ice vest during intermittent sprint exercise has been shown to decrease thermal strain and improve performance. These garments have also been shown to be effective during exercise in the able-bodied. Drawing on additional findings from the able-bodied literature, the combination of methods used prior to and during exercise and/or during rest periods/half-time may increase the effectiveness of a strategy. However, due to the paucity of research involving athletes with an SCI, it is difficult to establish an optimal cooling strategy. Future studies are needed to ensure that research outcomes can be translated into meaningful performance enhancements by investigating cooling strategies under the constraints of actual competition. Cooling strategies that meet the demands of intermittent wheelchair sports need to be identified, with particular attention to the logistics of the sport. PMID:25119157

Griggs, Katy E; Price, Michael J; Goosey-Tolfrey, Victoria L

2015-01-01

384

Ten-Year Follow-Up of Endovascular Aneurysm Treatment with Talent Stent-Grafts  

SciTech Connect

The purpose of this study was to evaluate the clinical results, complications, and secondary interventions during long-term follow-up after endovascular aneurysm repair (EVAR) and to investigate the impact of endoleak sizes on aneurysm shrinkage. From 1997 to March 2007, 127 patients (12 female, 115 male; age, 73.0 {+-} 7.2 years) with abdominal aortic aneurysms were treated with Talent stent-grafts. Follow-up included clinical visits, contrast-enhanced MDCT, and radiographs at 3, 6, and 12 months and then annually. Results were analyzed with respect to clinical outcome, secondary interventions, endoleak rate and management, and change in aneurysm size. There was no need for primary conversion surgery. Thirty-day mortality was 1.6% (two myocardial infarctions). Procedure-related morbidity was 2.4% (paraplegia, partial infarction of one kidney, and inguinal bleeding requiring surgery). Mean follow-up was 47.7 {+-} 34.2 months (range, 0-123 months). Thirty-nine patients died during follow-up; three of the deaths were related to aneurysm (aneurysm rupture due to endoleak, n = 1; secondary surgical reintervention n = 2). During follow-up, a total of 29 secondary procedures were performed in 19 patients, including 14 percutaneous procedures (10 patients) and 15 surgical procedures (12 patients), including 4 cases with late conversion to open aortic repair (stent-graft infection, n = 1; migration, endoleak, or endotension, n = 3). Overall mean survival was 84.5 {+-} 4.7 months. Mean survival and freedom from any event was 66.7 {+-} 4.5 months. MRI depicted significantly more endoleaks compared to MDCT (23.5% vs. 14.3%; P < 0.01). Patients in whom all aneurysm side branches were occluded prior to stent-grafting showed a significantly reduced incidence of large endoleaks. Endoleaks >10% of the aneurysm area were associated with reduced aneurysm shrinkage compared to no endoleaks or <10% endoleaks ({Delta} at 3 years, -1.8% vs. -12.0%; P < 0.05). In conclusion, endovascular aneurysm treatment with Talent stent-grafts demonstrated encouraging long-term results with moderate secondary intervention rates. Primary occlusion of all aortic side branches reduced the incidence of large endoleaks. Large endoleaks significantly impaired aneurysm shrinkage, whereas small endoleaks did not.

Pitton, Michael B., E-mail: pitton@radiologie.klinik.uni-mainz.de; Scheschkowski, Tobias; Ring, Markus; Herber, Sascha; Oberholzer, Katja; Leicher-Dueber, Annegret [University Hospital of Mainz, Johannes Gutenberg University of Mainz, Department of Diagnostic and Interventional Radiology (Germany); Neufang, Achim; Schmiedt, Walther [University Hospital of Mainz, Johannes Gutenberg University of Mainz, Department of Cardiovascular and Thoracic Surgery (Germany); Dueber, Christoph [University Hospital of Mainz, Johannes Gutenberg University of Mainz, Department of Diagnostic and Interventional Radiology (Germany)

2009-09-15

385

Chapter 15 Juvenile amyotrophic lateral sclerosis.  

PubMed

Several forms of genetically defined juvenile amy-otrophic lateral sclerosis (ALS) have now been charac-terized and discussion of these conditions will form the basis for this chapter. ALS2 is an autosomal recessive form of ALS with a juvenile onset and very slow progression that mapped to chromosome 2q33. Nine different mutations have been identified in the ALS2 gene that result in premature stop codons, suggesting a loss of function in the gene product, alsin. The alsin protein is thought to function as a guanine-nucleotide exchange factor for GTPases and may play a role in vesicle transport or membrane trafficking processes. ALS4 is an autosomal dominant form of juvenile onset ALS associated with slow progression, severe muscle weakness and pyramidal signs, in the absence of bulbar and sensory abnormalities. Mutations in the SETX gene cause ALS4, and the SETX gene product senataxin may have DNA and RNA helicase activity and play a role in the regulation of RNA and/or DNA in the cell. A third form of juvenile-onset ALS (ALS5) is associated with slowly progressing lower motor neuron signs (weak-ness and atrophy) initially of the hands and feet, with eventual bulbar involvement. Progressive upper motor neuron disease becomes more obvious with time. ALS5 has been linked to a 6 cM region of chromosome 15q15.1-q21.1, but the causative gene mutation for ALS5 has yet to be identified. The high degree of clin-ical and genetic heterogeneity in the various forms of juvenile ALS can make differential diagnosis difficult, other genetic disorders that must be considered include: spinal muscular atrophy, hereditary spastic paraplegia, SBMA, GM2 gangliosidosis and the hereditary motor neuronopathies/motor forms of Charcot-Marie-Tooth disease. Acquired disorders that must also be consid-ered include heavy metal intoxications (especially lead), multifocal motor neuropathy, paraneoplastic syndromes, vitamin deficiencies (B12) and infections (HTLV-II, HIV and poliomyelitis). PMID:18808900

Orban, Paul; Devon, Rebecca S; Hayden, Michael R; Leavitt, Blair R

2007-01-01

386

Human Disease-Drug Network Based on Genomic Expression Profiles  

PubMed Central

Background Drug repositioning offers the possibility of faster development times and reduced risks in drug discovery. With the rapid development of high-throughput technologies and ever-increasing accumulation of whole genome-level datasets, an increasing number of diseases and drugs can be comprehensively characterized by the changes they induce in gene expression, protein, metabolites and phenotypes. Methodology/Principal Findings We performed a systematic, large-scale analysis of genomic expression profiles of human diseases and drugs to create a disease-drug network. A network of 170,027 significant interactions was extracted from the ?24.5 million comparisons between ?7,000 publicly available transcriptomic profiles. The network includes 645 disease-disease, 5,008 disease-drug, and 164,374 drug-drug relationships. At least 60% of the disease-disease pairs were in the same disease area as determined by the Medical Subject Headings (MeSH) disease classification tree. The remaining can drive a molecular level nosology by discovering relationships between seemingly unrelated diseases, such as a connection between bipolar disorder and hereditary spastic paraplegia, and a connection between actinic keratosis and cancer. Among the 5,008 disease-drug links, connections with negative scores suggest new indications for existing drugs, such as the use of some antimalaria drugs for Crohn's disease, and a variety of existing drugs for Huntington's disease; while the positive scoring connections can aid in drug side effect identification, such as tamoxifen's undesired carcinogenic property. From the ?37K drug-drug relationships, we discover relationships that aid in target and pathway deconvolution, such as 1) KCNMA1 as a potential molecular target of lobeline, and 2) both apoptotic DNA fragmentation and G2/M DNA damage checkpoint regulation as potential pathway targets of daunorubicin. Conclusions/Significance We have automatically generated thousands of disease and drug expression profiles using GEO datasets, and constructed a large scale disease-drug network for effective and efficient drug repositioning as well as drug target/pathway identification. PMID:19657382

Hu, Guanghui; Agarwal, Pankaj

2009-01-01

387

Polymeric biomaterials for nerve regeneration applications: From promoting cellular organization to the delivery of bioactive molecules  

NASA Astrophysics Data System (ADS)

Thousands of new cases of injury to the central nervous system (CNS) occur each year in the USA and all over the world. However, despite recent advances, at present there is no cure for the resulting paraplegia or quadriplegia. This research is directed towards engineering biomaterial platforms to promote cellular organization at the surface of polymer scaffolds that will be conducive to proper regeneration of injured CNS. In addition, the formulation of a delivery system for neuroactive molecules using polymer-based materials will be evaluated to establish its potential to treat CNS disorders. Initial studies involved the chemical modification of an electrospun nonwoven matrix of nanofibers with fibroblast growth factor 2 (FGF-2). Nanofibers alone up-regulated FGF-2, albeit to a lesser extent than nanofibers covalently modified with FGF-2. These results underscore the importance of both surface topography and growth factor presentation on cellular function. Moreover, that FGF-2 modified nanofibrillar scaffolds may demonstrate utility in tissue engineering applications for replacement and regeneration of damaged tissue following CNS injury or disease. Subsequent research efforts focused on a novel micropatterning technique called microscale plasma-initiated patterning (microPIP). This patterning method uses a polydimethylsiloxane (PDMS) stamp to selectively protect regions of an underlying substrate from oxygen plasma treatment resulting in hydrophobic and hydrophilic regions. FGF-2 and laminin-1 were applied to an electrospun polyamide nanofibrillar matrix following plasma treatment. In this work it, was possible to demonstrate that textured surfaces, such as nanofibrillar scaffolds, can be micropatterned to provide external chemical cues for cellular organization. Finally, a microsphere system capable of encapsulating proteins while minimizing the mechanisms of protein degradation and providing a controlled release was investigated. Microspheres were comprised of a salicylic-acid based poly(anhydride-ester) (PAE), a biodegradable polymer that incorporates salicylic acid into the polymer backbone (PolyAspirin). The use of microspheres formulated from PolyAspirin as a delivery vehicle can be advantageous due its ability of performing a dual delivery; biomolecule (protein) and drug. By combining these two properties, it will be possible to release neurotrophic factors to induce a biological response while mitigating inflammatory pathways due to the localized delivery of salicylic acid.

Delgado-Rivera, Roberto L.

388

The spinal cord injury quality-of-life-23 questionnaire, Iranian validation study  

PubMed Central

Background: The spinal cord injury quality-of-life questionnaire (SCIQL-23) is an instrument that has been developed for clinical follow-up as well health related quality-of-life (QOL) measurement in people with spinal cord injury (SCI). The purpose of this study was to assess the validity and reliability of the Persian version of SCIQL-23 in individuals with chronic SCI. Materials and Methods: Medical outcomes study 36 item short-form health survey (SF-36) as well as the Persian version of the SCIQL-23 questionnaires applied to be used in 52 veterans with spinal cord injuries in the Orthopedic Research Center, Mashhad University of Medical Sciences from January 2011 to August 2011. Cronbach's alpha co-efficient computed to test the reliability of the survey. In order to assess the convergent validity the correlation of each item of the SCIQL-23 done with each dimension of the SF-36 by applying the Pearson correlation co-efficient. Independent samples t-test used to test power of discrimination. Results: All of veterans were male and married. The mean age of individuals at the time of interview was 49.3 years (standard deviation = 7.9); in a range between 38 and 80 years. Most of them (88.5%) had incomplete paraplegia. Cronbach's alpha test revealed strong reliability in questions of SCI QOL (Total Cronbach's alpha = 0.764). A negative significant correlation occurred between physical function and functioning (FUNC) (r = ?0.412**), bodily pain and problems related to injury (PROB) (r = ?0.313*), vitality (VT) and mood state (MOOD) (r = ?0.327*), social function and PROB (r = ?0.309*), mental health (MH) and MOOD (r = ?0.406**). Furthermore, the Mental component summary (MCS) of SF-36 had a negative significant correlation with MOOD (r = ?0.312*). Similar to MCS, physical component summery (PCS) had a negative significant correlation with MOOD (r = ?0.276*) in addition to FUNC (r = ?0.324*) and PROB (r = ?0.318*). Instead, GH (r = 0.455**), VT (r = 0.322*), MH (r = 0.276*) and PCS illustrated a positive significant correlation with global quality of life. Conclusion: The Persian version of the SCQL-23 discovered to be competent in terms of its valuable psychometric properties in assessing the QOL of SCI people by showing excellent internal consistency and no floor or ceiling effect. PMID:25097608

Ebrahimzadeh, Mohammad Hosein; Makhmalbaf, Hadi; Soltani-Moghaddas, Seyed Hosein; Mazloumi, Seyed Mahdi

2014-01-01

389

Hybrid FES-robot cooperative control of ambulatory gait rehabilitation exoskeleton.  

PubMed

Robotic and functional electrical stimulation (FES) approaches are used for rehabilitation of walking impairment of spinal cord injured individuals. Although devices are commercially available, there are still issues that remain to be solved. Control of hybrid exoskeletons aims at blending robotic exoskeletons and electrical stimulation to overcome the drawbacks of each approach while preserving their advantages. Hybrid actuation and control have a considerable potential for walking rehabilitation but there is a need of novel control strategies of hybrid systems that adequately manage the balance between FES and robotic controllers. Combination of FES and robotic control is a challenging issue, due to the non-linear behavior of muscle under stimulation and the lack of developments in the field of hybrid control. In this article, a cooperative control strategy of a hybrid exoskeleton is presented. This strategy is designed to overcome the main disadvantages of muscular stimulation: electromechanical delay and change in muscle performance over time, and to balance muscular and robotic actuation during walking.Experimental results in healthy subjects show the ability of the hybrid FES-robot cooperative control to balance power contribution between exoskeleton and muscle stimulation. The robotic exoskeleton decreases assistance while adequate knee kinematics are guaranteed. A new technique to monitor muscle performance is employed, which allows to estimate muscle fatigue and implement muscle fatigue management strategies. Kinesis is therefore the first ambulatory hybrid exoskeleton that can effectively balance robotic and FES actuation during walking. This represents a new opportunity to implement new rehabilitation interventions to induce locomotor activity in patients with paraplegia.Acronym list: 10 mWT: ten meters walking test; 6 MWT: six minutes walking test; FSM: finite-state machine; t-FSM: time-domain FSM; c-FSM: cycle-domain FSM; FES: functional electrical stimulation; HKAFO: hip-knee-ankle-foot orthosis; ILC: iterative error-based learning control; MFE: muscle fatigue estimator; NILC: Normalized stimulation output from ILC controller; PID: Proportional-Integral-derivative Control; PW: Stimulation pulse width; QUEST: Quebec User Evaluation of Satisfaction with assistive Technology; SCI: Spinal cord injury; TTI: torque-time integral; VAS: Visual Analog Scale. PMID:24594302

del-Ama, Antonio J; Gil-Agudo, Angel; Pons, José L; Moreno, Juan C

2014-01-01

390

Hybrid FES-robot cooperative control of ambulatory gait rehabilitation exoskeleton  

PubMed Central

Robotic and functional electrical stimulation (FES) approaches are used for rehabilitation of walking impairment of spinal cord injured individuals. Although devices are commercially available, there are still issues that remain to be solved. Control of hybrid exoskeletons aims at blending robotic exoskeletons and electrical stimulation to overcome the drawbacks of each approach while preserving their advantages. Hybrid actuation and control have a considerable potential for walking rehabilitation but there is a need of novel control strategies of hybrid systems that adequately manage the balance between FES and robotic controllers. Combination of FES and robotic control is a challenging issue, due to the non-linear behavior of muscle under stimulation and the lack of developments in the field of hybrid control. In this article, a cooperative control strategy of a hybrid exoskeleton is presented. This strategy is designed to overcome the main disadvantages of muscular stimulation: electromechanical delay and change in muscle performance over time, and to balance muscular and robotic actuation during walking. Experimental results in healthy subjects show the ability of the hybrid FES-robot cooperative control to balance power contribution between exoskeleton and muscle stimulation. The robotic exoskeleton decreases assistance while adequate knee kinematics are guaranteed. A new technique to monitor muscle performance is employed, which allows to estimate muscle fatigue and implement muscle fatigue management strategies. Kinesis is therefore the first ambulatory hybrid exoskeleton that can effectively balance robotic and FES actuation during walking. This represents a new opportunity to implement new rehabilitation interventions to induce locomotor activity in patients with paraplegia. Acronym list: 10mWT: ten meters walking test; 6MWT: six minutes walking test; FSM: finite-state machine; t-FSM: time-domain FSM; c-FSM: cycle-domain FSM; FES: functional electrical stimulation; HKAFO: hip-knee-ankle-foot orthosis; ILC: iterative error-based learning control; MFE: muscle fatigue estimator; NILC: Normalized stimulation output from ILC controller; PID: Proportional-Integral-derivative Control; PW: Stimulation pulse width; QUEST: Quebec User Evaluation of Satisfaction with assistive Technology; SCI: Spinal cord injury; TTI: torque-time integral; VAS: Visual Analog Scale. PMID:24594302

2014-01-01

391

Further evidence for genetic heterogeneity of distal HMN type V, CMT2 with predominant hand involvement and Silver syndrome  

PubMed Central

Objective Distal hereditary motor neuropathy type V (dHMN-V) and Charcot–Marie–Tooth syndrome (CMT) type 2 presenting with predominant hand involvement, also known as CMT2D and Silver syndrome (SS) are rare phenotypically overlapping diseases which can be caused by mutations in the Berardinelli–Seip Congenital Lipodystrophy 2 (BSCL2) and in the glycyl-tRNA synthetase encoding (GARS) genes. Mutations in the heat-shock proteins HSPB1 and HSPB8 can cause related distal hereditary motor neuropathies (dHMN) and are considered candidates for dHMN-V, CMT2, and SS. Design To define the frequency and distribution of mutations in the GARS, BSCL2, HSPB1 and HSPB8 genes we screened 33 unrelated sporadic and familial patients diagnosed as either dHMN-V, CMT2D or SS. Exon 3 of the BSCL2 gene was screened in further 69 individuals with an unclassified dHMN phenotype or diagnosed as hereditary spastic paraplegia (HSP) complicated by pure motor neuropathy. Results Four patients diagnosed with dHMN-Vor SS carried known heterozygous BSCL2 mutations (N88S and S90L). In one dHMN-V patient we detected a putative GARS mutation (A57V). No mutations were detected in HSPB1 and HSPB8. The diagnostic yield gained in the series of 33 probands was 12% for BSCL2 mutations and 3% for GARS mutations. In the series of unclassified dHMN and complicated HSP cases no mutations were found. Conclusions Our data confirm that most likely only two mutations (N88S, S90L) in exon 3 of BSCL2 may lead to dHMN-V or SS phenotypes. Mutations in GARS, HSPB1 and HSPB8. are not a common cause of dHMN-V, SS and CMT2D. We would therefore suggest that a genetic testing of dHMN-V and SS patients should begin with screening of exon 3 of the BSCL2 gene. Screening of the GARS gene is useful in patients with CMT2 with predominant hand involvement and dHMN-V. The rather low frequencies of BSCL2, GARS, HSPB1 and HSPB8 mutations in dHMN-V, CMT2D and SS patients strongly point to further genetic heterogeneity of these related disorders. PMID:17663003

Rohkamm, Barbara; Reilly, Mary M.; Lochmüller, Hanns; Schlotter-Weigel, Beate; Barisic, Nina; Schöls, Ludger; Nicholson, Garth; Pareyson, Davide; Laurà, Matilde; Janecke, Andreas R.; Miltenberger-Miltenyi, Gabriel; John, Elisabeth; Fischer, Carina; Grill, Franz; Wakeling, William; Davis, Mary; Pieber, Thomas R.; Auer-Grumbach, Michaela

2011-01-01

392

Composite cerebellar functional severity score: validation of a quantitative score of cerebellar impairment.  

PubMed

Reliable and easy to perform functional scales are a prerequisite for future therapeutic trials in cerebellar ataxias. In order to assess the specificity of quantitative functional tests of cerebellar dysfunction, we investigated 123 controls, 141 patients with an autosomal dominant cerebellar ataxia (ADCA) and 53 patients with autosomal dominant spastic paraplegia (ADSP). We evaluated four different functional tests (nine-hole pegboard, click, tapping and writing tests), in correlation with the scale for the assessment and rating of cerebellar ataxia (SARA), the scale of functional disability on daily activities (part IV of the Huntington disease rating scale), depression (the Public Health Questionnaire PHQ-9) and the EQ-5D visual analogue scale for self-evaluation of health status. There was a significant correlation between each functional test and a lower limb score. The performance of controls on the functional tests was significantly correlated with age. Subsequent analyses were therefore adjusted for this factor. The performances of ADCA patients on the different tests were significantly worse than that of controls and ADSP patients; there was no difference between ADSP patients and controls. Linear regression analysis showed that only two independent tests, the nine-hole pegboard and the click test on the dominant side (P < 0.0001), accounted for the severity of the cerebellar syndrome as reflected by the SARA scores, and could be represented by a composite cerebellar functional severity (CCFS) score calculated as follows: [Formula: see text]. The CCFS score was significantly higher in ADCA patients compared to controls (1.12 +/- 0.18 versus 0.85 +/- 0.05, P(c) < 0.0001) and ADSP patients (1.12 +/- 0.18 versus 0.90 +/- 0.08, P(c) < 0.0001) and was correlated with disease duration (P < 0.0001) but independent of self-evaluated depressive mood in ADCA. Among genetically homogeneous subgroups of ADCA patients (Spinocerebellar ataxia 1, 2, 3), SCA3 patients had significantly lower (better) CCFS scores than SCA2 (P(c) < 0.04) and the same tendency was observed in SCA1. Their CCFS scores remained significantly worse than those of ADSP patients with identified SPG4 mutations (P < 0.0001). The pegboard and click tests are easy to perform and accurately reflect the severity of the disease. The CCFS is a simple and validated method for assessing cerebellar ataxia over a wide range of severity, and will be particularly useful for discriminating paucisymptomatic carriers from affected patients and for evaluating disease progression in future therapeutic trials. PMID:18378516

du Montcel, Sophie Tezenas; Charles, Perrine; Ribai, Pascale; Goizet, Cyril; Le Bayon, Alice; Labauge, Pierre; Guyant-Maréchal, Lucie; Forlani, Sylvie; Jauffret, Celine; Vandenberghe, Nadia; N'guyen, Karine; Le Ber, Isabelle; Devos, David; Vincitorio, Carlo-Maria; Manto, Mario-Ubaldo; Tison, François; Hannequin, Didier; Ruberg, Merle; Brice, Alexis; Durr, Alexandra

2008-05-01

393

Neurology and the kidney  

PubMed Central

Renal failure is relatively common, but except in association with spina bifida or paraplegia it is unlikely to occur as a result of disease of the CNS. Renal failure, however, commonly affects the nervous system. The effects of kidney failure on the nervous system are more pronounced when failure is acute. In addition to the important problems related to renal failure there are both acquired and genetically determined diseases which may affect the kidney and the brain. Those acquired diseases include the vasculitides, the paraproteinaemias, and various granulomatous conditions (considered in other chapters of Neurology and Medicine). In two of the most commonly encountered genetically determined diseases, Von Hippel-Lindau disease and polycystic kidney disease, location of pathogenic mutations will provide improved screening programmes and, possibly, allow therapeutic intervention. Uraemia may affect both the central and peripheral nervous systems. Whereas the clinical features of uraemia are well documented, the pathophysiology is less well understood and probably multifactorial. Uraemic encephalopathy, which classically fluctuates, is associated with problems in cognition and memory and may progress to delirium, convulsions, and coma. The encephalopathy may initially worsen with periods of dialysis and almost certainly relates to altered metabolic states in association with ionic changes and possibly impaired synaptic function. Renal failure may affect the peripheral nervous system, resulting in a neuropathy which shows a predilection for large diameter axons. This may be reversed by dialysis and transplantation. The myopathy seen in renal failure, often associated with bone pain and tenderness, is similar to that encountered in primary hyperparathyroidism and osteomalacia.? Dialysis itself is associated with neurological syndromes including the dysequilibrium syndrome, subdural haematoma, and Wernicke's encephalopathy. Dialysis dementia, which was prevalent during the 1970s, has reduced in frequency with the use of aluminium free dialysate. With the introduction of transplantation and the concomitant use of powerful immunosuppressive drugs, the pattern of neurological problems encountered in renal replacement therapy has shifted. Five per cent of patients develop nerve injuries during renal transplantation, and up to 40% of patients experience neurological side effects from cyclosporine. Furthermore, CNS infections, often fungal in type, have been reported in up to 45% of transplant patients coming to postmortem. The nature of the involvement of neurologists with their nephrology colleagues is therefore evolving.?? PMID:9854955

Burn, D; Bates, D

1998-01-01

394

Pattern of neurological admissions in the tropics: Experience at Kano, Northwestern Nigeria  

PubMed Central

Background: Kano is the most populated state in Nigeria with a population totaling 9,383,682. The pattern of neurologic diseases in this area is not known. Objective: To determine the of pattern of neurologic diseases warranting admission in a tertiary hospital in Kano and compare it with those elsewhere in the country with the view to using the data generated as a baseline for planning purposes and for future studies. Materials and Methods: The medical records of all cases admitted with neurologic diseases in the Aminu Kano Teaching Hospital, Kano between January 2005 and September 2008, were retrospectively reviewed and the frequency of neurologic diseases, sex, age, and outcome of these diseases analyzed. Result: Stroke, predominantly ischemic, accounted for 77.6% of the neurological cases for the period of study. Central nervous system infections, comprising mainly of meningitis and tetanus, accounted for 6.6% (64) and 3% (29) of cases, respectively. The myelopathies were the cause of neurologic admissions in 5.4% (53) with paraplegia and quadriplegia resulting from myelopathies accounting for 5% (49) and 0.4% (4) of the cases. Hypertensive encephalopathy and status epilepticus as the causes of admissions accounted for 1.6% each. Gullain Barre syndrome, Parkinson’s disease, and cerebral malaria were relatively rare causes of neurologic admissions in this study. The average duration of hospitalization was 25 days, and regarding outcome, 219 (22.4%) of these cases died. Conclusions: Stroke appeared to be the most common neurologic admission and the most common cause of neurologic and medical death in Kano as observed in other regions of the country and a little over one-fifths of stroke patients die. Central nervous system infections mainly meningitis and tetanus are the next common cause of admission. In view of these findings, the provision of a regional stroke unit, the improvement of the sanitary conditions of the home and environment; the widespread use of immunizations against meningitis, tetanus cannot be over-emphasized. These interventions will go a long way to reduce morbidity and mortality of stroke and neurologic infections. PMID:21085525

Owolabi, L. F.; Shehu, M. Y.; Shehu, M. N.; Fadare, J.

2010-01-01

395

Effects of electrical stimulation and upper body training after spinal cord injury.  

PubMed

The purpose of this study was to measure the cardiorespiratory improvements during the initial weeks of training in individuals with spinal cord injury (SCI). Eight adult volunteers (ages 23-41) with paraplegia (T4-L1, N = 7) and low levels of quadriplegia (C7, N = 1) participated in a 12-wk training program consisting of 6 wk of computerized functional electrical stimulation leg ergometry (CFES LE) followed by 6 wk of combined arm ergometry and CFES LE (hybrid ergometry; HE). Measures of peak oxygen consumption (pV02) and immediate post-exercise blood lactate (La-) were collected during an intermittent CFES LE graded exercise test (3-min stages; 1/8-kp increments) prior to training (0T), following 6 wk of CFES LE training (6T) and following 6 wk of HE training (12T). Voluntary arm ergometry (AE) graded exercise tests were also completed at each of 0T, 6T, and 12T, and an intermittent graded HE test was also given at 6T and 12T. Following the 6 wk of CFES LE, AE pVO2 increased from 1.14 +/- 0.09 l.min-1 to 1.39 +/- 0.172 l.min-1 (P < 0.05), and CFES LE pVO2 increased from 0.51 +/- 0.05 l.min-1 to 0.83 +/- 0.06 l.min-1 (P < 0.05). Following the 6 wk of HE, HE pVO2 increased from 1.31 +/- 0.15 l.min-1 to 1.49 +/- 0.14 l.min-1 (P < 0.05). HE pVO2 was 58%-60% higher than CFES LE pVO2 at the mid- and post-testing periods. HE pVO2 was 14% higher than AE pVO2 at the post-testing period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8231775

Krauss, J C; Robergs, R A; Depaepe, J L; Kopriva, L M; Aisenbury, J A; Anderson, M A; Lange, E K

1993-09-01

396

Clinically relevant intronic splicing enhancer mutation in myelin proteolipid protein leads to progressive microglia and astrocyte activation in white and gray matter regions of the brain  

PubMed Central

Introduction Mutations in proteolipid protein (PLP), the most abundant myelin protein in the CNS, cause the X-linked dysmyelinating leukodystrophies, Pelizaeus-Merzbacher disease (PMD) and spastic paraplegia type 2 (SPG2). Point mutations, deletion, and duplication of the PLP1 gene cause PMD/SPG2 with varying clinical presentation. Deletion of an intronic splicing enhancer (ISEdel) within intron 3 of the PLP1 gene is associated with a mild form of PMD. Clinical and preclinical studies have indicated that mutations in myelin proteins, including PLP, can induce neuroinflammation, but the temporal and spatial onset of the reactive glia response in a clinically relevant mild form of PMD has not been defined. Methods A PLP-ISEdel knockin mouse was used to examine the behavioral and neuroinflammatory consequences of a deletion within intron 3 of the PLP gene, at two time points (two and four months old) early in the pathological progression. Mice were characterized functionally using the open field task, elevated plus maze, and nesting behavior. Quantitative neuropathological analysis was for markers of astrocytes (GFAP), microglia (IBA1, CD68, MHCII) and axons (APP). The Aperio ScanScope was used to generate a digital, high magnification photomicrograph of entire brain sections. These digital slides were used to quantify the immunohistochemical staining in ten different brain regions to assess the regional heterogeneity in the reactive astrocyte and microglial response. Results The PLP-ISEdel mice exhibited behavioral deficits in the open field and nesting behavior at two months, which did not worsen by four months of age. A marker of axonal injury (APP) increased from two months to four months of age. Striking was the robust reactive astrocyte and microglia response which was also progressive. In the two-month-old mice, the astrocyte and microglia reactivity was most apparent in white matter rich regions of the brain. By four months of age the gliosis had become widespread and included both white as well as gray matter regions of the brain. Conclusions Our results indicate, along with other preclinical models of PMD, that an early reactive glia response occurs following mutations in the PLP gene, which may represent a potentially clinically relevant, oligodendrocyte-independent therapeutic target for PMD. PMID:24314267

2013-01-01

397

Altered behavioral performance and live imaging of circuit-specific neural deficiencies in a zebrafish model for psychomotor retardation.  

PubMed

The mechanisms and treatment of psychomotor retardation, which includes motor and cognitive impairment, are indefinite. The Allan-Herndon-Dudley syndrome (AHDS) is an X-linked psychomotor retardation characterized by delayed development, severe intellectual disability, muscle hypotonia, and spastic paraplegia, in combination with disturbed thyroid hormone (TH) parameters. AHDS has been associated with mutations in the monocarboxylate transporter 8 (mct8/slc16a2) gene, which is a TH transporter. In order to determine the pathophysiological mechanisms of AHDS, MCT8 knockout mice were intensively studied. Although these mice faithfully replicated the abnormal serum TH levels, they failed to exhibit the neurological and behavioral symptoms of AHDS patients. Here, we generated an mct8 mutant (mct8-/-) zebrafish using zinc-finger nuclease (ZFN)-mediated targeted gene editing system. The elimination of MCT8 decreased the expression levels of TH receptors; however, it did not affect the expression of other TH-related genes. Similar to human patients, mct8-/- larvae exhibited neurological and behavioral deficiencies. High-throughput behavioral assays demonstrated that mct8-/- larvae exhibited reduced locomotor activity, altered response to external light and dark transitions and an increase in sleep time. These deficiencies in behavioral performance were associated with altered expression of myelin-related genes and neuron-specific deficiencies in circuit formation. Time-lapse imaging of single-axon arbors and synapses in live mct8-/- larvae revealed a reduction in filopodia dynamics and axon branching in sensory neurons and decreased synaptic density in motor neurons. These phenotypes enable assessment of the therapeutic potential of three TH analogs that can enter the cells in the absence of MCT8. The TH analogs restored the myelin and axon outgrowth deficiencies in mct8-/- larvae. These findings suggest a mechanism by which MCT8 regulates neural circuit assembly, ultimately mediating sensory and motor control of behavioral performance. We also propose that the administration of TH analogs early during embryo development can specifically reduce neurological damage in AHDS patients. PMID:25255244

Zada, David; Tovin, Adi; Lerer-Goldshtein, Tali; Vatine, Gad David; Appelbaum, Lior

2014-09-01

398

Systematic review of outcomes of combined proximal stent-grafting with distal bare stenting for management of aortic dissection  

PubMed Central

Objective Available data on outcomes of combined proximal stent-grafting with distal bare stenting for management of aortic dissection are limited. The objective of this study was to provide a systematic review of outcomes of this approach. Methods Studies involving combined proximal stent-grafting with distal bare stenting for management of aortic dissection were systematically searched and reviewed through MEDLINE databases. Results A total of four studies were included: 108 patients treated for management of acute (n=54) and chronic (n=54) aortic dissection. The technical success rate was 95.3% (range, 84-100%). The 30-day mortality rate was 2.7% (range from 0% to 5%). The morbidity rate occurring within 30 days was 51.8% (range from 0% to 65%) and included stroke (2.7%), paraplegia (2.7%), retrograde dissection (1.8%), renal failure (14.8%), severe cardiopulmonary complications (5.5%) and bowel ischemia (0.9%). The incidence of type I endoleak was 9.2% (10/108). During follow-up, 5 (4.6%) deaths were related to aortic rupture or aortic repair. Mean re-intervention rate was 12.9%. Two cases (1.9%) of delayed retrograde type A dissection and one case of aortobronchial fistula (0.9%) were reported. The most common delayed complication was thoracic stent-graft migration (4.7%). The rate of device failure was 9.2%. Favorable aortic remodeling was observed: studies reporting midterm follow-up of the true lumen demonstrated a high rate of both false lumen regression and true lumen expansion. At 12 months, complete false lumen thrombosis was observed at the thoracic level in 70.4% and at the abdominal level in 13.5% of patients. Conclusions Combined proximal stent-grafting with distal bare stenting appears to be a feasible approach for the management of Type B aortic dissection. Although this approach clearly improved true lumen perfusion and diameter, it failed to completely suppress false lumen patency. However, it should be acknowledged that contemporary data on this approach is limited to small studies with variable results. PMID:24967161

Faure, Elsa Madeleine; Ozdemir, Baris Ata; Alric, Pierre; Thompson, Matt

2014-01-01

399

Type I and Type II hybrid aortic arch replacement: postoperative and mid-term outcome analysis  

PubMed Central

Background Hybrid aortic arch replacement has emerged as a safe treatment modality for arch aneurysms, especially in patients of old age and with greater comorbid burden. We assessed our institutional outcomes in patients undergoing Types I and II hybrid aortic arch replacement. Methods From 2005 to 2012, 685 patients underwent thoracic endovascular repair (TEVAR), of whom 104 had hybrid arch repair (open + endovascular approach). 47 of these patients had treatment for aortic arch aneurysm ± proximal ascending aortic aneurysm. The hybrid repair entailed aortic arch vessel debranching and concomitant/delayed antegrade ± retrograde TEVAR stent grafting of the arch. Type III patients were excluded from the analysis. Data was prospectively maintained. Results 28 patients had Type I repair, 8 had Type II repair, and 11 had Type III repair. Mean age was 71±8 years. Primary aortic pathology was aneurysm (81%), followed by chronic arch dissection (11%). 14% of patients required reoperative cardiac surgery. Stent graft deployment rate was 100% after arch vessel debranching. Postoperative endoleak rate was zero. Average cardiopulmonary bypass time was 215±64 minutes, with crossclamp time of 70±55 minutes, and circulatory arrest time of 50±17 minutes. Paraplegia rate was 5.5% (n=2), with stroke rate of 8% (n=3) and renal failure rate of 3% (n=1) requiring hemodialysis. In-hospital mortality was 8% (n=3). Mean length of stay was 17.2±14 days. Median follow-up was 30±21 months. Freedom from all-cause mortality was 71%, 60%, and 48% at 1, 3, and 5 years respectively. Aortic reoperation rate was 2.7% (n=1). No patient had Type I or III endoleak at follow-up. Freedom from mortality was improved in cases performed more recently (July 2008 to 2012) than during our early experience (2005 to June 2008) (81% versus 44% at 3 years, P=0.05). Conclusions Hybrid aortic arch replacement can be performed with good postoperative and midterm results in a cohort of old patients with significant comorbidity. With greater experience, early and midterm outcomes continue to improve. The hybrid arch technique may represent a technical advancement in the field of aortic arch surgery. PMID:23977595

Vallabhajosyula, Prashanth; Szeto, Wilson; Desai, Nimesh

2013-01-01

400

Myelomeningocele (open spina bifida) - surgical management.  

PubMed

Myelomeningocele has been recognized since ancient times although written descriptions began not before the 17th century. Among all serious congenital malformations, myelomeningocele is unique that is has a steady and considerable prevalence while being compatible with life. It has a dismal prognosis when left untreated where virtually all die within the first year while aggressive treatment have a profound effect on survival and quality of life. Effective surgical treatment became possible parallel to the treatment of hydrocephalus in the late 1950s. Advent of the shunt systems undoubtedly changed the morbidity and mortality rates due to associated hydrocephalus. Aggressive and effective treatment improved survival rates but also those suffering physical and mental disabilities have increased as well. Ethical and socioeconomic concerns have led to proposal for selective treatment criteria which have raised arguments on medical and ethico-legal rounds. After the swing of the pendulum between early treatment in all affected children and selective treatment of those who fulfilled the criteria for good prognosis, early myelomeningocele repair is practiced widely unless the infant is critically ill.Incidence of myelomeningocele has been decreasing especially in the Western world, partly due to prenatal diagnosis and elective terminations, dietary folate supplementation. Still, it is the most common central nervous system malformation and one of the leading causes of paraplegia, worldwide. Unfortunately, gains in the management of myelomeningocele have been mainly on antenatal diagnosis and prevention while efforts on understanding its cause, mechanisms involved are still tentative. Concerning the surgical management, no revolutionary modification improving outcome has been introduced unlike other fields of neurosurgery.Medical management of a child with myelomeningocele requires a lifelong effort of several disciplines including urology, orthopedics physical and social therapy besides neurosurgery. The initial and probably the most crucial step begin with proper repair of the lesion. The aim of surgery, with its simplest definition should be towards maintaining the medical condition of the newborn. In other words, consequences of an open spinal cord segment with associated malformations have to be avoided with appropriate measures. Comparable to the surgical treatment of any congenital malformation, myelomeningocele repair consist of reversing the failed steps of normal neural tube closure. This requires a thorough understanding of the normal and abnormal embryological sequence of events in formation of the spinal cord. Although the purpose of this chapter is to describe the basic concepts and technique of myelomeningocele repair, contemporary information and progress on epidemiology, and etiology and embryology is presented with discussion of controversial issues regarding the selection process, optimal time for surgery and technical modifications. PMID:21997743

Akalan, N

2011-01-01