Wednesday, January 30, 2008

Neurosurgical management of myelomeningocele (spina bifida).

Dias, MS. Neurosurgical management of myelomeningocele (spina bifida). Pediatrics in Review. 2005 Feb;26(2):50-60; discussion 50-60.


PMID: 15687475

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Assessment of brainstem function in Chiari II malformation utilizing brainstem auditory evoked potentials (BAEP), blink reflex and masseter reflex.

Koehler J, Schwarz M, Boor R, Hölker C, Hopf HC, Voth D, Urban PP, Ermert A. Assessment of brainstem function in Chiari II malformation utilizing brainstem auditory evoked potentials (BAEP), blink reflex and masseter reflex. Brain Development. 2000 Oct;22(7):417-20.

Brainstem dysfunction was evaluated in 67 patients with myelomeningocele and Chiari II malformation using brainstem auditory evoked potentials (BAEP), blink reflex (BR) and masseter reflex (MR). Signs and symptoms related to Chiari II malformation were observed in 18 patients while 49 patients had normal brainstem findings. BAEP and BR showed a higher sensitivity of brainstem involvement than MR (BAEP=1.0, BR=0.83, MR=0.50). BR, and in particular, MR were of higher accuracy (BR=0.52, MR=0.72) than BAEP (0.39) in separating patients with brainstem signs and symptoms related to Chiari II malformation. We feel that this is due to anatomic and physiologic peculiarities of the brainstem structures mediating BR and MR. Our results suggest that brainstem reflexes can support the decision of further treatment.

PMID: 11102725

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Brain stem auditory-evoked potentials in meningomyelocele. Natural history of Chiari II malformations

Nishimura T, Mori K, Uchida Y, Ohira T, Tamura K. Brain stem auditory-evoked potentials in meningomyelocele. Natural history of Chiari II malformations. Child's Nervous System. 1991 Oct;7(6):316-26. Review.

Brain stem auditory-evoked potentials (BAEPs) were recorded in 30 patients with meningomyelocele and shunted hydrocephalus ranging in age from birth to 33 years. Twenty-two of them had Chiari II malformation, one of which was symptomatic. In 22 cases, including 15 with Chiari II malformation, BAEPs were recorded repeatedly after periods ranging from 18 months to 7 years. The results were as follows: (1) III-V interpeak latency (IPL) decreased progressively from prolonged to the normal range with growth until 25 years of age; (2) I-III IPL tended to prolong gradually from the normal range; (3) these findings may indicate that the natural history of Chiari II malformation is delayed maturation of the brain stem and intensification in the elongation and stretching of the hindbrain and lower cranial nerves.

PMID: 1764707

Electrophysiological studies on brainstem function in patients with myelomeningocele

Mori K, Nishimura T. Electrophysiological studies on brainstem function in patients with myelomeningocele. Pediatric Neurosurgery. 1995;22(3):120-31.

We investigated the brainstem auditory evoked potentials (BAEPs), somatosensory evoked potentials (SEPs), and electrically elicited blink reflexes (BRs) to evaluate the brainstem function in 31 patients with meyelomeningocele (MMC) including 22 with Chiari type-II malformation. The I-III interpeak latency (IPL) of the BAEPs and the N9-N13 IPL of the SEPs tended to become gradually prolonged from the normal range with increasing age. The III-V IPL of the BAEPs and the N13-N20 IPL of the SEPs were initially prolonged and decreased progressively to the normal range. These findings indicated a gradual latency shortening of the brainstem components and latency prolongation of the peripheral components. Thus, while primary brainstem dysfunction may improve with age, secondary dysfunction due to stretching and elongation of the lower cranial nerves and cervical nerve roots may intensify. The BRs showed an abnormal R2 in 90% of the cases, disclosing subclinical lesions in the medulla oblongata which were not detected by BAEPs alone. BAEPs, SEPs and BRs were combined to yield a functional evaluation of the brainstem and lower cranial nerves that could not be done by magnetic resonance imaging alone. No close relation was found between electrophysiological abnormalities and the degree of hindbrain anomaly by neuroimaging.

PMID: 7786804

Somatosensory evoked potentials to median nerve stimulation in meningomyelocele

Nishimura T, Mori K. Somatosensory evoked potentials to median nerve stimulation in meningomyelocele: what is occurring in the hindbrain and its connections during growth? Childs Nervous System. 1996 Jan;12(1):13-26. Review.

Twenty patients with meningomyelocele (MMC) and shunted hydrocephalus, ranging in age from 3 to 23 years old, underwent serial recording of short-latency somatosensory evoked potentials (SEPs) to median nerve stimulation, on the basis of which to assess the evolution of dysfunction in the brainstem and its connections (cervical spinal cord, cervical nerve roots, lower cranial nerves). Eighteen patients had Chiari type II malformations, none of which was symptomatic. In all 20 patients, serial SEP recordings were obtained repeatedly after periods ranging from 2 to 7 years. The results were as follows: (1) the ratio of EP-N13 interpeak latencies (IPLs) to body height (BH) tended to lengthen gradually after starting in the normal range with growth. (2) In contrast, the ratio N13-N20 IPLs/BH decreased continuously to the normal range with growth, after initial prolongation. These findings and our earlier studies of brainstem auditory evoked potentials suggest that compression and traction result in strangulation of the cervical spinal cord and kinked medulla as well as stretching of the cervical nerve roots and lower cranial nerves. However, primary intrinsic functional disorders of the brainstem appeared to improve gradually during growth. The natural history of Chiari type II malformations involves these opposing dynamic phenomena in the hindbrain and its connections.

PMID: 8869170

Anatomical progression of the Chiari II malformation.

Ruge JR, Masciopinto J, Storrs BB, McLone DG. Anatomical progression of the Chiari II malformation. Childs Nervous System. 1992 Mar;8(2):86-91.

To evaluate whether anatomic change of the relationship of the Chiari II malformation and the cranial base was occurring, 22 children with meningomyelocele had serial MRI scans reviewed. A ratio (B/A) was established between the distance from the foramen magnum to the caudalmost portion of herniated cerebellum (B) and the diameter of the foramen magnum (A) and this ratio was compared on serial MRI scans. Eighteen children had an increase in the B/A ratio, two children had a decrease, and two had no change. This indicates that continuous anatomic change of the Chiari II malformation and the skull base is occurring. Clinical deterioration in the older child may be explained by a combination of compressive and traction forces due to this change.


PMID: 1591752

Friday, January 18, 2008

Mouse mutants with neural tube closure defects and their role in understanding human neural tube defects

Harris MJ, Juriloff DM. Mouse mutants with neural tube closure defects and their role in understanding human neural tube defects. Birth Defects Research Part A: Clinical and Molecular Teratology. 2007 Mar;79(3):187-210. Review.

BACKGROUND: The number of mouse mutants and strains with neural tube closure defects (NTDs) now exceeds 190, including 155 involving known genes, 33 with unidentified genes, and eight "multifactorial" strains.

METHODS: The emerging patterns of mouse NTDs are considered in relation to the unknown genetics of the common human NTDs, anencephaly, and spina bifida aperta.

RESULTS: Of the 150 mouse mutants that survive past midgestation, 20% have risk of either exencephaly and spina bifida aperta or both, parallel to the majority of human NTDs, whereas 70% have only exencephaly, 5% have only spina bifida, and 5% have craniorachischisis. The primary defect in most mouse NTDs is failure of neural fold elevation. Most null mutations (>90%) produce syndromes of multiple affected structures with high penetrance in homozygotes, whereas the "multifactorial" strains and several null-mutant heterozygotes and mutants with partial gene function (hypomorphs) have low-penetrance nonsyndromic NTDs, like the majority of human NTDs. The normal functions of the mutated genes are diverse, with clusters in pathways of actin function, apoptosis, and chromatin methylation and structure. The female excess observed in human anencephaly is found in all mouse exencephaly mutants for which gender has been studied. Maternal agents, including folate, methionine, inositol, or alternative commercial diets, have specific preventative effects in eight mutants and strains.

CONCLUSIONS: If the human homologs of the mouse NTD mutants contribute to risk of common human NTDs, it seems likely to be in multifactorial combinations of hypomorphs and low-penetrance heterozygotes, as exemplified by mouse digenic mutants and the oligogenic SELH/Bc strain.

PMID: 17177317

Mini-review: toward understanding mechanisms of genetic neural tube defects in mice

Harris MJ, Juriloff DM. Mini-review: toward understanding mechanisms of genetic neural tube defects in mice. Teratology. 1999 Nov;60(5):292-305. Review.

We review the data from studies of mouse mutants that lend insight to the mechanisms that lead to neural tube defects (NTDs). Most of the 50 single-gene mutations that cause neural tube defects (NTDs) in mice also cause severe embryonic-lethal syndromes, in which exencephaly is a nonspecific feature. In a few mutants (e.g., Trp53, Macs, Mlp or Sp), other defects may be present, but affected fetuses can survive to birth. Multifactorial genetic causes, as are present in the curly tail stock (15-20% spina bifida), or the SELH/Bc strain (15-20% exencephaly), lead to nonsyndromic NTDs. The mutations indicate that "spina bifida occulta," a dorsal gap in the vertebral arches over an intact neural tube, is usually genetically and developmentally unrelated to exencephaly or "spina bifida" (aperta). Almost all exencephaly or spina bifida aperta of genetic origin is caused by failure of neural fold elevation. The developmental mechanisms in genetic NTDs are considered in terms of distinct rostro-caudal zones along the neural folds that likely differ in mechanism of elevation. Failure of elevation leads to: split face (zone A), exencephaly (zone B), rachischisis (all of zone D), or spina bifida (caudal zone D). The developmental mechanisms leading to these genetic NTDs are heterogeneous, even within one zone. At the tissue level, the mutants show that the mechanism of failure of elevation can involve, e.g., (1) slow growth of adjacent tethered tissue (curly tail), (2) defective forebrain mesenchyme (Cart1 or twist), (3) defective basal lamina in surface ectoderm (Lama5), (4) excessive breadth of floorplate and notochord (Lp), (5) abnormal neuroepithelium (Apob, Sp, Tcfap2a), (6) morphological deformation of neural folds (jmj), (7) abnormal neuroepithelial and neural crest cell gap-junction communication (Gja1), or (8) incomplete compensation for a defective step in the elevation sequence (SELH/Bc). At the biochemical level, mutants suggest involvement of: (1) faulty regulation of apoptosis (Trp53 or p300), (2) premature differentiation (Hes1), (3) disruption of actin function (Macs or Mlp), (4) abnormal telomerase complex (Terc), or (5) faulty pyrimidine synthesis (Sp). The NTD preventative effect of maternal dietary supplementation is also heterogeneous, as demonstrated by: (1) methionine (Axd), (2) folic acid or thymidine (Sp), or (3) inositol (curly tail). The heterogeneity of mechanism of mouse NTDs suggests that human NTDs, including the common nonsyndromic anencephaly or spina bifida, may also reflect a variety of genetically caused defects in developmental mechanisms normally responsible for elevation of the neural folds.

PMID: 10525207

Disruption of PDGFR{alpha}-initiated PI3K activation and migration of somite derivatives leads to spina bifida

Pickett EA, Olsen GS, Tallquist MD. Disruption of PDGFR{alpha}-initiated PI3K activation and migration of somite derivatives leads to spina bifida. Development. 2008 Feb;135(3):589-98.

Spina bifida, or failure of the vertebrae to close at the midline, is a common congenital malformation in humans that is often synonymous with neural tube defects (NTDs). However, it is likely that other etiologies exist. Genetic disruption of platelet-derived growth factor receptor (PDGFR) alpha results in spina bifida, but the underlying mechanism has not been identified. To elucidate the cause of this birth defect in PDGFRalpha mutant embryos, we examined the developmental processes involved in vertebrae formation. Exposure of chick embryos to the PDGFR inhibitor imatinib mesylate resulted in spina bifida in the absence of NTDs. We next examined embryos with a tissue-specific deletion of the receptor. We found that loss of the receptor from chondrocytes did not recapitulate the spina bifida phenotype. By contrast, loss of the receptor from all sclerotome and dermatome derivatives or disruption of PDGFRalpha-driven phosphatidyl-inositol 3' kinase (PI3K) activity resulted in spina bifida. Furthermore, we identified a migration defect in the sclerotome as the cause of the abnormal vertebral development. We found that primary cells from these mice exhibited defects in PAK1 activation and paxillin localization. Taken together, these results indicate that PDGFRalpha downstream effectors, especially PI3K, are essential for cell migration of a somite-derived dorsal mesenchyme and disruption of receptor signaling in these cells leads to spina bifida.

PMID: 18192285

Wednesday, January 2, 2008

Ventriculo-peritoneal shunt performance under hyperbaric conditions

Huang ET, Hardy KR, Stubbs JM, Lowe RA, Thom SR. Ventriculo-peritoneal shunt performance under hyperbaric conditions. Undersea & hyperbaric medicine. 2000 Winter;27(4):191-4.

A novice scuba diver with an implanted ventriculo-peritoneal (VP) shunt inquired about the performance characteristics of his shunt while diving. A literature search revealed no information regarding shunt performance under hyperbaric conditions. The manufacturer could not certify that the shunt would function under pressure. Therefore, four VP shunts were tested according to the manufacturer's testing protocol at 1 and 4 atm abs in a multiplace hyperbaric chamber. The pressure (in mm of H2O) required to establish flow through the shunts was recorded. Trials at 1 atm abs (n = 12) and 4 atm abs (n = 12) show that all shunts performed within the pressure range specified by the manufacturer.

PMID: 11419359