Wednesday, March 18, 2009

First experiences with an adjustable gravitational valve in childhood hydrocephalus

Rohde V, Haberl EJ, Ludwig H, Thomale UW. First experiences with an adjustable gravitational valve in childhood hydrocephalus. Journal of Neurosurgery: Pediatrics. 2009 Feb;3(2):90-3.

Department of Neurosurgery, Georg-August University, Goettingen; and.

Object The goal of this report was to describe the authors' initial experiences with an adjustable gravity-assisted valve (GAV) called the ProGAV in treating childhood hydrocephalus. Methods The ProGAV was implanted in 53 children (29 boys and 24 girls, median age 7.3 years) with hydrocephalus of various origins. The ProGAV consists of a differential-pressure unit with adjustable opening pressures and a gravitational unit with a fixed opening pressure. Results The mean follow-up period was 15.2 months (range 6-44 months). The authors did not observe any valve-related complications. Four infections (7.5%) occurred, warranting the removal of the shunt. In 19 children, the opening pressure was changed at least once during the follow-up period, for underdrainage in 10, overdrainage in 8, and shunt weaning in 1, with substantial clinical improvement in 18 children. Overall, good clinical results were obtained in 47 (88.7%) of the 53 valve placements. Conclusions With an overall success rate of 88.7%, the first experiences with the ProGAV in childhood hydrocephalus are promising and justify its further use in the pediatric population.

PMID: 19278305

Addressing a Folate Imbalance in Fetal Cerebrospinal Fluid Can Decrease the Incidence of Congenital Hydrocephalus

Cains S, Shepherd A, Nabiuni M, Owen-Lynch PJ, Miyan J. Addressing a Folate Imbalance in Fetal Cerebrospinal Fluid Can Decrease the Incidence of Congenital Hydrocephalus. Journal of Neuropathology and Experimental Neurology. 2009 Mar 12.

From the Faculty of Life Sciences, The University of Manchester, Manchester (SC, AS, MN, JM); and Division of Biomedical and Life Sciences, School of Health and Medicine, Lancaster University, Lancaster (PJOL), United Kingdom; and Department of Biology, Faculty of Basic Sciences, Tarbiat Moallem University (Kharazmi), Tehran, Iran (MN).

Fetal-onset hydrocephalus (HC), which affects between 1:500 and 1:5000 live human births, results from unequal production and drainage of cerebrospinal fluid (CSF) and is associated with abnormal development of the cerebral cortex leading to severe neurological deficits. We previously found that in the hydrocephalic Texas rat, the CSF of affected fetuses induced a cell cycle arrest in neural progenitor cells. Here, we show that alterations in folate metabolism in the CSF of the developing cerebrum are likely responsible for this effect. We identified 3 folate enzymes in the CSF and demonstrate that low levels of one of these, 10-formyltetrahydrofolate dehydrogenase, are associated with HC in the hydrocephalic Texas rat. Therefore, we tested whether supplementation with specific folate species would improve developmental outcome. After daily administration of a combination of tetrahydrofolic and 5-formyltetrahydrofolic acids to pregnant dams, there was a significant reduction in the incidence of HC and improved brain development. By contrast, supplementation with folic acid increased the incidence of congenital HC in this model. These results indicate the complexities of folate metabolism in the developing brain and suggest that folate imbalance leading to HC in the hydrocephalic Texas rat fetuses can be treated with maternal folate supplementation using specific folate metabolites and combinations thereof.

PMID: 19287311

Monday, March 16, 2009

A possible new reflex pathway for micturition after spinal cord injury

Xiao CG, Godec CJ. (1994) A possible new reflex pathway for micturition after spinal cord injury. Paraplegia. 1994 May;32(5):300-7.


In order to restore bladder function after spinal cord injury, a controllable new reflex pathway has been established in rats. It involves a somatic reflex arc with an artificially modified efferent branch which passes the somatic motor impulses to the bladder. This is achieved by intradural microanastomosis of the left L4 ventral root to L6 ventral root, while leaving the L4 dorsal root intact as a starter of micturition. The 'skin-CNS-bladder' reflex pathway is designed to initiate voiding by scratching the skin. After axonal regeneration, 15 of the 24 rats with the new pathway underwent electrophysiological study. Single stimuli (0.3-3 mA, 0.02-0.2 ms duration) to the left L4 nerve resulted in evoked potentials (0.5-1 mV) recorded from the left L6 nerve distal to the anastomosis. The bladder detrusor contraction was very quickly initiated by trains of the stimuli and bladder pressures increased rapidly to levels similar to controls. Neural tracing study with horseradish peroxidase (HRP) on six rats with the pathway demonstrated that the somatic motor axons regenerated successfully into the pelvic nerve, and the bladder was reinnervated by the L4 somatic motor neurons. The bladder contraction can also be initiated by electrostimulation of left sciatic nerve as well as scratching the L4 related skin. A new concept may be derived from the skin-CNS-bladder reflex pathway: the impulses delivered from the efferent neurons of a somatic reflex arc can be transferred to initiate responses of an autonomic effector.


PMID: 8058346

"Skin-CNS-bladder" reflex pathway for micturition after spinal cord injury and its underlying mechanisms.

Xiao CG, de Groat WC, Godec CJ, Dai C, Xiao Q. (1999) "Skin-CNS-bladder" reflex pathway for micturition after spinal cord injury and its underlying mechanisms.
Journal of Urology. 1999 Sep;162(3 Pt 1):936-42.


PURPOSE: A "skin-CNS-bladder" reflex pathway for inducing micturition after spinal cord injury has been established in cat. This reflex pathway which is basically a somatic reflex arc with a modified efferent limb that passes somatic motor impulses to the bladder, has been designed to allow spinal cord injured patients to initiate voiding by scratching the skin.

MATERIALS AND METHODS: The skin-CNS-bladder reflex was established in the cat by intradural microanastomosis of the left L7 ventral root (VR) to the S1 VR while leaving the L7 dorsal root (DR) intact to conduct cutaneous afferent signals that can trigger the new micturition reflex arc. After allowing 11 weeks for axonal regeneration, urodynamic, pharmacological and electrophysiological studies were conducted in pentobarbital or chloralose anesthetized animals.

RESULTS: A detrusor contraction was initiated at short latency by scratching the skin or by percutaneous electrical stimulation in the L7 dermatome. Maximal bladder pressures during this stimulation were similar to those activated by bladder distension in control animals. Electrophysiological recording revealed that single stimuli (0.3 to 3 mA, 0.02 to 0.2 msec duration) to the left L7 spinal nerve in which the efferent axons had degenerated evoked action potentials (0.5 to 1 mV) in the left S1 spinal nerve distal to the anastomosis. In addition, increases in bladder pressure were elicited by trains of the stimuli (5 to 20 Hz, 5 seconds) applied to the L7 spinal nerve. Urodynamic studies including external sphincter EMG recording demonstrated that the new reflex pathway could initiate voiding without detrusor-external urethral sphincter dyssynergia. Atropine (0.05 mg./kg., i.v.) or trimethaphan (5 mg./kg., i.v.), a ganglionic blocking agent, depressed the bladder contractions elicited by skin stimulation. The skin-CNS-bladder reflex could also be elicited after transecting the spinal cord at the L2-L3 or L7-S1 levels.

CONCLUSION: The cross-wired somato-autonomic bladder reflex is effective in initiating bladder contractions and coordinated voiding in cats with an intact neuraxis and can also induce bladder contractions after acute transection of the lumbar spinal cord. The new pathway is mediated by cholinergic transmission involving both nicotinic and muscarinic receptors. It is concluded that somatic motor axons can innervate bladder parasympathetic ganglion cells and thereby transfer somatic reflex activity to the bladder smooth muscle.

PMID: 10458412

Electrophysiological monitoring and identification of neural roots during somatic-autonomic reflex pathway procedure for neurogenic bladder.

Dai CF, Xiao CG. (2005) Electrophysiological monitoring and identification of neural roots during somatic-autonomic reflex pathway procedure for neurogenic bladder. Chinese journal of traumatology. 2005 Apr;8(2):74-6.

OBJECTIVE: To identify and separate the ventral root from dorsal root, which is the key for success of the artificial somatic-autonomic reflex pathway procedure for neurogenic bladder after spinal cord injury (SCI). Here we report the results of intra-operating room monitoring with 10 paralyzed patients.

METHODS: Ten male volunteers with complete suprasacral SCI underwent the artificial somatic-autonomic procedure under general anesthesia. Vastus medialis, tibialis anticus and gastrocnemius medialis of the left lower limb were monitored for electromyogram (EMG) activities resulted from L4, L5, and S1 stimulation respectively to differentiate the ventral root from dorsal root. A Laborie Urodynamics system was connected with a three channel urodynamic catheter inserted into the bladder. The L2 and L3 roots were stimulated separately while the intravesical pressure was monitored to evaluate the function of each root.

RESULTS: The thresholds of stimulation on ventral root were 0.02 ms duration, 0.2-0.4 mA, (mean 0.3 mA+/-0.07 mA), compared with 0.2-0.4 ms duration, 1.5-3 mA (mean 2.3 mA+/-0.5 mA) for dorsal root (P<0.01) to cause revoked potentials and EMG. Electrical stimulation on L4 roots resulted in the EMG being recorded mainly on vastus medialis, while stimulation on L5 or S1 roots caused electrical activities of tibialis anticus or gastrocnemius medialis respectively. The continuous stimulation for about 3-5 seconds on S2 or S3 ventral root (0.02 ms, 20 Hz, and 0.4 mA) could resulted in bladder detrusor contraction, but the strongest bladder contraction over 50 cm H2O was usually caused by stimulation on S3 ventral root in 7 of the 10 patients.

CONCLUSIONS: Intra-operating room electrophysiological monitoring is of great help to identify and separate ventral root from dorsal root, and to select the appropriate sacral ventral root for best bladder reinnervation. Different parameters and thresholds on different roots are the most important factors to keep in mind to avoid damaging the roots and to assure the best results.

PMID: 15769303

An artificial somatic-autonomic reflex pathway procedure for bladder control in children with spina bifida

Xiao CG, Du MX, Li B, Liu Z, Chen M, Chen ZH, Cheng P, Xue XN, Shapiro E, Lepor H. (2005) An artificial somatic-autonomic reflex pathway procedure for bladder control in children with spina bifida. Journal of Urology. 2005 Jun;173(6):2112-6.

PURPOSE: Neurogenic bladder is a major problem for children with spina bifida. Despite rigorous pharmacological and surgical treatment, incontinence, urinary tract infections and upper tract deterioration remain problematic. We have previously demonstrated the ability to establish surgically a skin-central nervous system-bladder reflex pathway in patients with spinal cord injury with restoration of bladder storage and emptying. We report our experience with this procedure in 20 children with spina bifida.

MATERIALS AND METHODS: All children with spina bifida and neurogenic bladder underwent limited laminectomy and a lumbar ventral root (VR) to S3 VR microanastomosis. The L5 dorsal root was left intact as the afferent branch of the somatic-autonomic reflex pathway after axonal regeneration. All patients underwent urodynamic evaluation before and after surgery.

RESULTS: Preoperative urodynamic studies revealed 2 types of bladder dysfunction- areflexic bladder (14 patients) and hyperreflexic bladder with detrusor external sphincter dyssynergia (6). All children were incontinent. Of the 20 patients 17 gained satisfactory bladder control and continence within 8 to 12 months after VR microanastomosis. Of the 14 patients with areflexic bladder 12 (86%) showed improvement. In these cases bladder capacity increased from 117.28 to 208.71 ml, and mean maximum detrusor pressure increased from 18.35 to 32.57 cm H2O. Five of the 6 patients with hyperreflexic bladder demonstrated improvement, with resolution of incontinence. Urodynamic studies in these cases revealed a change from detrusor hyperreflexia with detrusor external sphincter dyssynergia and high detrusor pressure to nearly normal storage and synergic voiding. In these cases mean bladder capacity increased from 94.33 to 177.83 ml, and post-void residual urine decreased from 70.17 to 23.67 ml. Overall, 3 patients failed to exhibit any improvement.

CONCLUSIONS: The artificial somatic-autonomic reflex arc procedure is an effective and safe treatment to restore bladder continence and reverse bladder dysfunction for patients with spina bifida.

PMID: 15879861

Reinnervation for neurogenic bladder: historic review and introduction of a somatic-autonomic reflex pathway procedure for patients with spinal cord i

Xiao CG. (2006) Reinnervation for neurogenic bladder: historic review and introduction of a somatic-autonomic reflex pathway procedure for patients with spinal cord injury or spina bifida. European urology. 2006 Jan;49(1):22-8; discussion 28-9. Review.

Neurogenic bladder caused by SCI or spina bifida is a major problem. Research in restoring functional micturition has mainly focused on electrical stimulation for many decades with good progress, but it is still not the definitive solution for majority of the SCI patients. An alternative approach has been to investigate restoring innervation to the lower urinary tract after spinal SCI. Different animal and clinical studies were reviewed historically in this article, focused on mainly cross over nerve surgery for reinnervation of the bladder. An artificial somatic-autonomic reflex pathway procedure and its mechanisms were introduced. Clinical application and the satisfactory results of the new procedure were reviewed in details in restoring voluntary bladder control in patients with SCI or spina bifida.

PMID: 16314037

Morphological changes of cholinergic nerve fibers in the urinary bladder after establishment of artificial somatic-autonomic reflex arc in rats

Wang HZ, Li SR, Wen C, Xiao CG, Su BY. (2007) Morphological changes of cholinergic nerve fibers in the urinary bladder after establishment of artificial somatic-autonomic reflex arc in rats. Neuroscience Bulletin. 2007 Sep;23(5):277-81.

OBJECTIVE: To establish an artificial somatic-autonomic reflex arc in rats and observe the following distributive changes of neural fibers in the bladder. METHODS: Adult Sprague-Dawley rats were randomly divided into three groups: control group, spinal cord injury (SCI) group, and reinnervation group. DiI retrograde tracing was used to verify establishment of the model and to investigate the transport function of the regenerated efferent axons in the new reflex arc. Choline acetyltransferase (ChAT) in the DiI-labeled neurons was detected by immunohistochemistry. Distribution of neural fibers in the bladder was observed by acetylcholine esterase staining. RESULTS: DiI-labeled neurons distributed mainly in the left ventral horn from L3 to L5, and some of them were also ChAT-positive. The neural fibers in the bladder detrusor reduced remarkably in the SCI group compared with the control (P < 0.05). After establishment of the somatic-autonomic reflex arc in the reinnervation group, the number of ipsilateral fibers in the bladder increased markedly compared with the SCI group (P < 0.05), though still much less than that in the control (P < 0.05). CONCLUSION: The efferent branches of the somatic nerves may grow and replace the parasympathetic preganglionic axons through axonal regeneration. Acetylcholine is still the major neurotransmitter of the new reflex arc. The controllability of detrusor may be promoted when it is reinnervated by the pelvic ganglia efferent somatic motor fibers from the postganglionic axons.

PMID: 17952136

The Chiari malformations: A constellation of anomalies

Robert M. Shuman RM. (1995) The Chiari malformations: A constellation of anomalies. Seminars in Pediatric Neurology. 1995 Sep;2(3):220-6. Review.


The Chiari malformations form a group of abnormalities that are pathogenetically interrelated. The most important member of the group is the Chiari type II malformation, known as the Arnold-Chiari malformation. Its cardinal features are the myelomeningocele in the thoraco-lumbar spine, the venting of the intracranial cerebrospinal fluid through the central canal, the hypoplasia of the posterior fossa, the herniation of hindbrain into the cervical spinal canal, and the compressive damage to cranial nerves. Some of the abnormalities are progressive, and thus treatable. Limitation of progression may improve outcomes. The challenges to our treatment programs involve early diagnosis, delivery by Caesarean section, emergent closure of the neural plaque and prophylaxis of hydrocephalus, anticipatory prevention of the neurological compression syndromes, multidisciplinary teams, and age-appropriate interventions.

Natural History of Spina Bifida Cystica and Cranium Bifidum Cysticum Major Central Nervous System Malformations in South Wales, Part IV

K. M. Laurence and B. J. Tew. (1971) Natural History of Spina Bifida Cystica and Cranium Bifidum Cysticum Major Central Nervous System Malformations in South Wales, Part IV. Archives of Disease in Childhood. 1971 April; 46(246): 127–138.

The 425 cases of spina bifida cystica and cranium bifidum cysticum born in a population of 850,000 between 1956 and 1962 (with an incidence of 4·12 per 1000 births) were followed. Most did not receive the modern treatment for the condition. Follow-up in 1968 showed that 25% were stillborn, 13% died during the first week of perinatal causes, a further 47% died mostly of the complications of the condition, and 15% are still alive. Life table survival figures suggest for the liveborns a 12·8% life expectancy to the 11th birthday. The series included 18 cases of meningocele (4·2% of the total), diagnosed largely by exclusion; all are surviving and are largely free from physical and mental handicap. 26 cases of encephalocele include 8 survivors who are all retarded but not much crippled. Of the 381 myeloceles, 37 survive who though not much affected mentally are severely handicapped physically with limb paralysis and incontinence, the pattern of which was largely determined by the level of the lesion. There is a close relation between degree of hydrocephalus and severity of mental retardation. Boys surviving show better performance than girls. The incontinent, whether treated or untreated, show no more emotional disturbance than the continent.

This series provides a `baseline' allowing modern and surgical treatment to be evaluated. 60% of the total (or 85% of those liveborn) should be regarded as potentially salvageable. Nearly all cases should probably have the `open' lesion closed as a surgical emergency, but thereafter no further procedure should be undertaken on those with severe hydrocephalus, established renal damage, persistent intracranial infection, or severe kyphosis, or if other severe malformations are present.

The Natural History of Spina Bifida Cystica: Detailed Analysis of 407 Cases

K. M. Laurence The Natural History of Spina Bifida Cystica: Detailed Analysis of 407 Cases Archives of Disease in Childhood. 1964 February; 39(203): 41–57.