Cervical spinal cord delivery of a rabies G protein pseudotyped lentiviral vector in the SOD-1 transgenic mouse

2004 ◽  
Vol 1 (1) ◽  
pp. 128-136 ◽  
Author(s):  
Kiana Tanase ◽  
Qingshan Teng ◽  
Ajit A. Krishnaney ◽  
James K. Liu ◽  
Mary E. Garrity-Moses ◽  
...  

Object. Lentiviral vectors may constitute a vehicle for long-term therapeutic gene expression in the spinal cord. In amyotrophic lateral sclerosis, spinal cord sclerosis and altered axonal transport pose barriers to therapeutic gene distribution. In the present study the authors characterize gene expression distribution and the behavioral impact of the rabies G (RabG) protein pseudotyped lentiviral vector EIAV.LacZ through cervical spinal cord injection in control and Cu/Zn superoxide dismutase—1 (SOD-1) transgenic mice. Methods. Seven-week-old SOD-1 transgenic mice and their wild-type littermates underwent exposure of the cervicomedullary junction and microinjection of RabG.EIAV.LacZ or vehicle. The Basso-Beattie-Bresnahan locomotor score, grip strength meter, and Rotarod assays were used to assess the effects of disease progression, spinal cord microinjection, and lentiviral gene expression. Spinal cords were removed when the mice were in the terminal stage of the disease. The distribution of LacZ gene expression was histologically evaluated and quantified. Direct cervical spinal cord microinjection of RabG.EIAV.LacZ results in extensive central nervous system uptake in SOD-1 transgenic mice; these findings were statistically similar to those in wild-type mice (p > 0.05). Gene expression lasts for the duration of the animal's survival (132 days). The SOD-1 mutation does not prevent retrograde axonal transport of the vector. Three behavioral assays were used to demonstrate that long-term gene expression does not alter sensorimotor function. In comparison with normative data, vector injection and transgene expression do not accelerate disease progression. Conclusions. Direct spinal cord injection of RabG.EIAV vectors represents a feasible method for delivering therapeutic genes to upper cervical spinal cord and brainstem motor neurons. Distribution is not affected by the SOD-1 mutation or disease phenotype.

1997 ◽  
Vol 87 (6) ◽  
pp. 961-962 ◽  
Author(s):  
Elon Eisenberg ◽  
Hanan Waisbrod

✓ The authors present a case in which electrical injury to the central nervous system resulted from uncontrolled activation of a cervical spinal cord stimulation device by an antitheft device. The injury resulted in long-term neurological sequelae.


1973 ◽  
Vol 39 (4) ◽  
pp. 533-536 ◽  
Author(s):  
Cully Cobb ◽  
George Ehni

✓ The authors describe a case in which the cervical spinal cord became incarcerated in the mouth of an iatrogenic meningocele or “pseudocyst.”


1986 ◽  
Vol 65 (1) ◽  
pp. 108-110 ◽  
Author(s):  
Daniel Dumitru ◽  
James E. Lang

✓ A rare case of cruciate paralysis is reported in a 39-year-old man following a motor-vehicle accident. The differentiation of this syndrome from a central cervical spinal cord injury is delineated.


1996 ◽  
Vol 85 (4) ◽  
pp. 701-708 ◽  
Author(s):  
Emile A. M. Beuls ◽  
Marie-Anne M. Vandersteen ◽  
Linda M. Vanormelingen ◽  
Peter J. Adriaensens ◽  
Gerard Freling ◽  
...  

✓ The lower brainstem and cervical spinal cord from an ordinarily treated case of Chiari Type I hindbrain hernia associated with syringomyelia was examined using high-resolution magnetic resonance microscopy and standard neuropathological techniques. Magnetic resonance microscopy allows total screening and visualizes the disturbed internal and external microanatomy in the three orthogonal planes with the resolution of low-power optical microscopy. An additional advantage is the in situ visualization of the shunts. Afterwards the intact specimen is still available for microscopic examination. Part of the deformation of the medulla is caused by chronic tonsillar compression and molding inside the foramen magnum. Other anomalies, such as atrophy caused by demyelination, elongation, and unusual disturbances at the level of the trigeminal and solitary nuclear complexes contribute to the deformation. At the level of the syrinx-free upper part of the cervical cord, anomalies of the dorsal root and the dorsal horn are demonstrated.


1972 ◽  
Vol 37 (5) ◽  
pp. 538-542 ◽  
Author(s):  
George J. Dohrmann

✓ Adult dogs were rendered hydrocephalic by the injection of kaolin into the cisterna magna. One group of dogs was sacrificed 1 month after kaolin administration, and ventriculojugular shunts were performed on the other group. Hydrocephalic dogs with shunts were sacrificed 1 day or 1 week after the shunting procedure. All dogs were perfused with formalin at physiological pressure, and the brain stem and cervical spinal cord were examined by light microscopy. Subarachnoid granulomata encompassed the superior cervical spinal cord and dependent surface of the brain stem. Rarefaction of the posterior white columns and clefts or cavities involving the gray matter posterior to the central canal and/or posterior white columns were present in the spinal cords of both hydrocephalic and shunted hydrocephalic dogs. Predominantly in the dogs with shunts, hemorrhages were noted in the spinal cord in association with the clefts or cavities. A mechanism of ischemia followed by reflow of blood is postulated to explain the hemorrhages in the spinal cords of hydrocephalic dogs with shunts.


1982 ◽  
Vol 57 (2) ◽  
pp. 270-273 ◽  
Author(s):  
J. Bob Blacklock ◽  
Terry W. Hood ◽  
Robert E. Maxwell

✓ A case of spontaneous intramedullary cervical spinal cord abscess is presented. The clinical and laboratory findings in cases of spinal cord abscess vary. Prompt diagnosis and drainage are stressed as critical factors in effectively managing the disease.


1984 ◽  
Vol 61 (3) ◽  
pp. 523-530 ◽  
Author(s):  
Mahmoud G. Nagib ◽  
Robert E. Maxwell ◽  
Shelley N. Chou

✓ Patients with Klippel-Feil syndrome are often at high risk for neurological injury. The cervicomedullary junction and cervical spinal cord are especially vulnerable. Twenty-one patients examined and treated over a 20-year period are reviewed. The salient features of the syndrome are identified, and an approach to management is proposed.


1976 ◽  
Vol 45 (6) ◽  
pp. 677-682 ◽  
Author(s):  
Robert L. Mason ◽  
Richard F. Gunst

✓ A measure of mobility for patients with spinal cord injuries is introduced that is very useful in determining patient recovery. The index is used to obtain a prediction equation for motor skills 1 year after injury. Important predictor variables identified include the patient's sex, rectal status, total reflexes, two treatment combinations, motor and sensory neurological history since injury, neurological status, and initial mobility score. Interpretations are made to explain the meaning of the contributions of these variables and show the usefulness of the prediction equation.


1998 ◽  
Vol 88 (6) ◽  
pp. 958-961 ◽  
Author(s):  
Bermans J. Iskandar ◽  
Benjamin B. Fulmer ◽  
Mark N. Hadley ◽  
W. Jerry Oakes

Object. The management of tethered spinal cord syndrome with onset of symptomatology occurring in adulthood remains controversial, although the necessity of early surgery in the pediatric tethered cord syndrome population is well established. To ascertain the results of surgery in adult patients with this anomaly, the authors undertook a retrospective review of 34 cases. Methods. The authors studied the hospital records of 34 consecutive patients who presented in adulthood with tethered cord syndrome and conducted follow-up phone interviews with 28 of them. The population consisted of 12 men and 22 women, ranging in age from 18 to 70 years (mean 34 years). The most common presenting feature was pain, followed by weakness and incontinence. All patients underwent surgery. The most common operative findings were tight filum terminale, split cord malformation, and lipomyelomeningocele, paralleling those observed in pediatric studies. Long-term surgical results and patient outcome ratings were encouraging. After a mean clinical follow-up period of 4 years, significant improvement occurred in 22 of 27 patients presenting with pain, 13 of 27 patients with motor or sensory dysfunction, and 11 of 18 patients with bowel and bladder disturbance. In addition, telephone interviews were obtained after a period of 8.6 years. Twenty-two (79%) of 28 patients called the operation a long-term success; 21 (75%) of 28 patients believed that they had significant postoperative improvement (and not just stabilization) in pain and/or neurological function. Surgical complications were generally minor. Nineteen (86%) of 22 employed patients returned to work after surgery. Two (33%) of six patients who were not employed before surgery worked full time postoperatively. Only two of the 28 patients interviewed had received Workers' Compensation benefits; both of these had good outcomes and returned to work. Conclusions. Tethered spinal cord syndrome in adults is an uncommon entity that can become symptomatic. Although surgery in adults involves greater risk of neurological injury than in children, it is a low-risk procedure with encouraging results. Because neurological deficits are generally irreversible, early surgery is recommended.


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