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PubMed1979

Gap junctional vesicles in the neural tube of the splotch (Sp) mutant mouse.

The lumbosacral region of the neural tube was studied by means of transmission electron microscopy in retrospectively confirmed normal (+/+; Sp/+) and abnormal (Sp/Sp) embryos of the splotch mutant mouse early on the ninth day of gestation when the caudal neural groove is normally in the process of closing to form the neural tube. In abnormal embryos, a consistent feature is the presence of gap junctional vesicles, particularly in the region of the neural groove which subsequently fails to close, whereas these structures are rarely observed in similar areas of normal embryos. The possible significance of gap junctional vesicles is discussed in terms of cellular adhesion during early neurogenesis.

Animals↗

PubMed1989

A mouse model for neural tube defects: the curtailed (Tc) mutation produces spina bifida occulta in Tc/+ animals and spina bifida with meningomyelocele in Tc/t.

Curtailed (Tc), a dominant mutation on mouse chromosome 17, causes a tailless phenotype and occasional hindlimb paralysis in heterozygotes. Histologically, Tc/+ embryos show a variety of abnormalities including budding and ventral duplication of the developing spinal cord, duplication and intermittent absence of the notochord, and partial or complete absence of bony vertebrae, all posterior to midliver level. When Tc is heterozygous with t-haplotypes that contain the "tail interaction factor," tct, the phenotype is more severe, and a dorsal blood blister exists in the lumbosacral area. Our microscopic observations reveal that Tc/tw5 mice have a lumbosacral spina bifida with meningomyelocele. This results from the absence of bony vertebrae, extensive thinning of the dermis dorsally, and the rupturing of the previously closed neural tube, probably by increased cerebrospinal fluid (CSF) pressure on the necrotic, attenuated roof plate. Thinning of the roof plate, which facilitates the rupturing of the spinal cord, is not observed in Tc/+, which suggests that this phenomenon is associated with the interaction of Tc with the t-allele. Later in the development of Tc/tw5 embryos, adjacent blood vessels are ruptured, resulting in hemorrhage into the CSF space to give the external appearance of a blood blister. Tc/+ mice also show an absence of bony vertebrae dorsally in the lumbosacral region, but they lack the dorsal blood blister, and the dermal layer overlying the bony defect retains its normal thickness; these observations describe a spina bifida occulta.

Animals↗

PubMed1990

Expression of a new mutation (Axd) causing axial defects in mice correlates with maternal phenotype and age.

A new autosomal mutation, Axd (axial defects), is described. Axd segregates in a simple Mendelian fashion, and it is dominant with incomplete penetrance and variable expressivity. The phenotype of Axd heterozygotes ranges from a variety of tail anomalies to visibly normal tails. Approximately 12% of neonates from curly-tail (CT) F1 (Axd/+) x F1 (Axd/+) matings exhibit open neural tube defects (NTD) in the lumbosacral region and 16% have curly tails. Mean litter sizes and resorption rates comparable to wild type indicate that homozygosity for Axd is not obligately lethal. Genetic background plays a major role in Axd expression. Strains such as BALB/cByJ allow the highest penetrance of the mutation in single dose (46%), whereas, in CF-1 mice Axd is recessive. The tail phenotype of heterozygous Axd/+ dams, in part reflective of their genetic background, correlates with the incidence of NTD in F2 offspring: CT mothers produce significantly more neonates with frank NTD than normal tail mothers. At the one embryonic period examined for this study (D13/D14 post-coitus), an 85% higher incidence of total axial defects is observed than among the F2 at birth. Unchanging litter size and the relative increase in phenotypically normal offspring by birth suggest that Axd acts by delaying posterior neural tube closure. One of the most significant findings in this study is that maternal age influences the survival of Axd embryos in utero. Axd/+ dams older than 8 months yield fewer mean implants, higher resorption rates, and fewer viable embryos with axial defects than do Axd/+ dams younger than 8 months. Axd is not allelic to nor linked to the Sp (splotch) gene which also affects neurulation.

Animals↗

PubMed1992

Valproic acid-induced spina bifida: a mouse model.

Prenatal exposure to the antiepileptic drug valproic acid (VPA) has been associated with the formation of spina bifida aperta, meningocele, and meningomyelocele in the human. Until now, a direct relationship between VPA application and spina bifida has not been experimentally demonstrated. VPA was known only to induce exencephaly in mice, a defect of the anterior neural tube. Maximal sensitivity toward production of this defect was on day 8 of gestation (plug day = day 0). The closure of the posterior neuropore occurs later in the development of mice than the closure of the anterior neuropore. To investigate whether there is a direct relationship between VPA application during pregnancy and induction of spina bifida in mice, we administered various doses of the drug on day 9 of gestation, at three time intervals (at 0, 6, and 12 hr). This administration of VPA produced spina bifida aperta and spina bifida occulta in mice. High doses of VPA (3 x 450 and 3 x 500 mg/kg) induced a low rate of spina bifida aperta in the lumbosacral region. High incidences of spina bifida occulta, a less serious form of spina bifida, were induced with lower doses. This malformation was demonstrated in double-stained fetal skeletons by measurements of the distance between the cartilaginous ends of each vertebral arch. The occurrence of this defect and its localization was dose-dependent. The lumbar region was affected by all doses investigated (3 x 300, 3 x 350, 3 x 400, 3 x 450, and 3 x 500 mg/kg). The sacral/coccygeal region was affected additionally, but with higher doses (3 x 400, 3 x 450, and 3 x 500 mg/kg). A comparison of the results obtained with day 16 and 17 control fetuses showed that the pattern of gaps present in the lumbar and sacral region of the spinal cord in treated groups was drug-specific and not related to a developmental delay. Our results indicate that multiple administrations of VPA on day 9 of gestation in mice result in a low incidence of spina bifida aperta and a high incidence of spina bifida occulta, and provides a relevant model for the study of human spina bifida defects.

Abnormalities, Drug-Induced↗

PubMed1992

Neural tube defects without neural crest defects in splotch mice.

Homozygous Splotch mutant mice (Sp/Sp) die on day 14 of gestation with neural tube defects, curly tail, and malformations of neural crest derivatives. Sp1H mice, which have a radiation-induced allele of Splotch with a similar phenotype, were used for this study. The neural tube defects are always located in the lumbosacral region and in 50% of the cases also in the region of the hindbrain. In this report, rare cases of neural tube defects and tail defects among the offspring of crosses between Splotch (Sp1H) heterozygotes are presented, which are not associated with a neural crest defect. This suggests that the development of the neural tube and neural crest defects in this mutant is caused by independent mechanisms or is dependent on the dosage of the mutant gene, with different thresholds being pathogenetic in the neural tube and neural crest, respectively.

Abnormalities, Multiple↗

PubMed1977

Neuronal cytoplasmic inclusions in the dorsal horn and supraoptic nucleus of the squirrel monkey, Saimiri sciureus.

In the squirrel monkey (Saimiri sciureus) two types of cytoplasmic inclusion bodies have been observed sporadically in neurons of both the dorsal horn (Rexed's laminae I-III in the lumbosacral region) and the supraoptic nucleus. One of these, designated here the "vesicular body", is a round inclusion which measures up to 1.4 mu in diameter. It occurs only in perikarya and is composed of vesicular-like chambers 300-400 A in diameter. We have not found previous references to this structure in the literature, but its 50 A substructural particles are similar in size to those described in nematosomes. The other inclusion, a "filamentous whorl", is found in nerve cell bodies and dendrites and it is structurally similar to the Hirano body. The structure measures up to 2.2 mu in diameter and is composed of circularly arrayed filaments which vary in configuration and size depending on the plane of section. There are no indications that the vesicular body and the filamentous whorl are in any way related to each other; and usually both are not found in the same cell profiles.

Animals↗

PubMed1991

Spontaneous and NMDA evoked motor rhythms in the neonatal mouse spinal cord: an in vitro study with comparisons to in situ activity.

The current paper presents our initial efforts to establish an in vitro spinal preparation for investigating locomotor pattern generation in mice. We have characterized the step cycle timing from EMG activity in the gastrocnemius (G) and tibialis anterior (TA) muscles of freely moving intact adult as well as neonatal mice and then compared those data with rhythmic EMG activity in an isolated spinal cord-hindlimb preparation. The motor output during the first four days of life was evaluated in an effort to identify the optimal post-partum period for in vitro locomotor studies. The in vitro pattern generating capabilities of the lumbosacral region were tested in both nonhemisected and hemisected preparations. Spontaneous as well as NMDA evoked in vitro activity in the antagonist set of hindlimb muscles included sequences of: 1) synchronous bursting; 2) mixed synchrony and alternation; and/or 3) irregular alternations. The alternating bursting observed in vitro was more often an alternation of sequences rather than a cycle-to-cycle phasing between G and TA muscles. In summary, while there was evidence of reciprocal inhibition in neonates, the circuitry for cycle-to-cycle alternation between antagonists was found to be labile.

Animals↗

PubMed1989

Bone marrow investigation with technetium-99m microcolloid and magnetic resonance imaging in patients with malignant myelolympho-proliferative diseases.

In 63 patients with primary extramedullary malignant lymphoma or plasmacytoma, a study was performed in order to evaluate bone marrow involvement. All patients underwent a 99mTc microcolloid bone marrow whole body imaging (scintigraphy), using a gamma camera interfaced with a computer, followed by nuclear magnetic resonance bone marrow imaging (MRI), (1.5 Tesla). MR images were made of the lumbosacral region, the pelvic region, both femoral and other parts of the skeleton, according to focal lesions in the scintigraphy. A posterior iliac crest bone marrow biopsy was used as a standard reference. In the present study, both scintigraphy and MRI showed a dissiminated or focal involvement or a combination of both. In 53 of the 63 patients (84%) the results were in accordance. Pathological MR signals or pathological findings in scintigraphy did not always correspond to tumorous bone marrow involvement, and were shown to reflect reactive changes in the central part of the skeleton in combination with a periphery radionuclide extention interpreted as a periphery compensatory hematopoietic proliferation. The negative predictive value of scintigraphy and MRI was 92% and 100%, respectively. When combining the results of both examinations, the positive predictive value increased from 49% to 58%, if the bone marrow biopsy is accepted as gold standard. The results indicate that bone marrow investigation performed simultaneously using scintigraphy and MRI is superior both to the use of either of the methods alone and to the traditional iliac crest bone marrow biopsy.

Adolescent↗

PubMed1996

Tethered cord syndrome presenting as a nonhealing cutaneous ulcer.

The usual clinical presentations of tethered cord syndrome include pain in the lumbosacral region, gait difficulty, weakness, and bladder abnormalities. We describe an unusual presentation of tethered cord - a nonhealing gluteal ulcer in an anesthetic cutaneous territory supplied by the S2-4 segments. Unexplained cutaneous lesions may be the presenting sign of an underlying neurological condition.

Adolescent↗

PubMed1990

Spina bifida cystica in northern Nigeria.

At the Ahmadu Bello University Hospitals in northern Nigeria 152 boys and 160 girls with spina bifida cystica were registered from 1971 to 1985. Only 21% of the patients were registered at the hospital within 24 h of birth; 90% had been delivered at home and without antenatal care. The malformation occurred in the lumbar or lumbosacral region in 75% of cases. Meningomyeloceles comprised 81%. Surgical closure was performed by general surgeons in 112 (36%) of the patients mainly for nursing care and social reasons. Of the children, 56 died in the hospital, 33 moved and 166 were lost to follow-up at 1 month. Only 8 were seen up to 1 year but 4 have lived beyond 4 years. This series serves as a baseline for comparison with future experience in this part of the world.

Female↗

PubMed1989

Ultrastructural defects in the apical neural folds in mutant embryos with spina bifida.

Ultrastructural pathology in the apical neural folds was analyzed by means of tannic acid (TA) and ruthenium red (RR) cytochemistry in abnormal (vl/vl) mutant mouse embryos ranging in age from 17-35 somites. At lumbosacral levels of the spinal cord where closure fails to occur, as well as at more cranial levels where closure occurs but results in dorsal midline abnormalities, normal deposition of TA-positive and RR-positive material occurred in the space that develops between the overlying surface ectoderm (SE) and neuroepithelium (NE). However, in lumbosacral regions, pleomorphic excrescences projected abnormally from the apices of the transitional zone cells between SE and NE cells of the open neural folds. These abnormal projections consisted of enlarged cytoplasmic blebs, as well as entire cells. The cells were not necrotic nor did they show evidence of incipient degeneration. However, it is possible that they represent aberrant putative neural crest cells, as indicated by their location in the transitional zone and by the filopodia and lamellipodia projecting from their luminal surfaces.

Abnormalities, Multiple↗

PubMed1978

CT of the spine.

The level of CT section in the lumbosacral region may be correlated with routine AP views of the spine using a reference plane constructed according to the distance between the iliac crests. CT scans of the spine in 100 patients have been analyzed. The majority of these cases consisted of primary or secondary bone or soft-tissue tumors. CT examination was valuable to supplement plain films and/or myelograms in evaluation of the extent of pathology. It was also useful in the work-up of patients with malignant tumors whose other studies were equivocal.

Humans↗

PubMed1981

Early diagnosis and prompt treatment by surgery in Jorge Lobo's disease (keloidal blastomycosis).

In 1931 the Brazilian doctor Jorge Lobo examined a patient from the Amazon Basin who had nodular confluent skin lesions over the lumbosacral region and encountered a new fungus pathogenic for man Paracoccidioides loboi. This classification was based on the morphological aspect of the parasite which was very similar to Paracoccidioides brasiliensis the causative agent of a systemic mycosis Paracoccidioidomycosis or South American Blastomycosis. Other authors use the name Loboa loboi. The final determination of the name must await cultivation of the fungus.

Adult↗

PubMed1988

Intraspinal epidermoid and dermoid cysts. Surgical results of seven cases.

Seven cases of intraspinal inclusion cysts, surgically treated between 1970 and 1984, are reported in this paper. Four were epidermoid cysts and three dermoid. Two cysts were located in the thoracic spine (one dermoid and one epidermoid) and five in the lumbosacral region (three epidermoid and two dermoid). Associated spinal dysraphia was noted in five cases. Congenital dermal sinus was found in two cases, spina bifida cystica in one, spina bifida occulta in one, and diastematomyelia in one case. The average postoperative follow-up period was 5 years. No neurological symptoms were found in the five patients who received early surgical treatment, but for the two patients whose operations were late, there were some residual neurological deficits. Therefore, early and accurate diagnosis and radical surgical extirpation are emphasized.

Adult↗

PubMed1992

Motor evoked potentials to magnetic stimulation: technical considerations and normative data from 50 subjects.

Magnetic stimulation of the brain and cervical and lumbar spinal roots was performed on 50 healthy volunteers. Compound muscle action potentials (CMAPs) were recorded from biceps brachii, abductor digiti minimi (ADM), rectus femoris and tibialis anterior (TA). We assessed central conduction times by subtraction of peripheral from central latencies and compared results using either spinal root stimulation or the F-wave method. Side-to-side differences of total conduction time, peripheral conduction time and central conduction time (CCT) were measured and the effect of clockwise vs counterclockwise stimulations on latencies and sizes of CMAPs is emphasized. Amplitudes and areas of CMAPs were expressed as a percentage of the peripheral M response for ADM and TA. There was a positive correlation between CCT to the lumbosacral region and height, but not between the cervical region and height. No correlation was observed between genders and central conduction times, amplitudes or areas of CMAPs.

Action Potentials↗

PubMed1978

Morphogenesis of the Hirano body in neurons of the squirrel monkey dorsal horn.

Electron microscopic investigation of laminae I-III in the lumbosacral region of the squirrel monkey spinal cord has disclosed possible stages in the morphogenesis of the Hirano body. These bodies occur occasionally in nerve cell bodies and dendrites. They are round to oval in shape, measure up to 2.2 micrometer in diameter and are composed of circular layers of 10 nm filaments. In several instances in the present study, Hirano bodies were observed in close association with the Golgi apparatus. Here Golgi-related vesicles were attached to the external surface of the Hirano bodies. In one instance a cluster of developing Hirano bodies of various sizes was observed. The smaller bodies were located nearest the Golgi apparatus while the larger were further away. In this case several short filaments, which may be precursors of the longer filaments which make up the layers of the inclusion, were observed in the cytoplasm between the Golgi cisternae and the smaller Hirano bodies. These observations suggest that the Golgi apparatus plays a major role in the production of the Hirano body. The significance of the occurrence of these inclusions is discussed.

Animals↗

PubMed1982

Lumbar spondylolisthesis. Clinical syndrome and operative experience with Cloward's technique.

The paper gives a survey, based on literature reports and our own experiences in 59 cases. According to Kilian (1853) spondylolisthesis is defined as ventral slipping of a vertebral body together with the pedicles. In pseudospondylolisthesis (Junghanns) the whole vertebra slips ventrally. Elongation of the isthmus of the pedicle or a cleft in the interarticular portion are prerequisites for spondylolisthesis. A dysplastic origin during childhood and adolescence is assumed. The relation of males to females is 2 : 1. Evolution of spondylolisthesis occurs during childhood and adolescence. The slipping process is finished in adults. Most often the condition is encountered in the lumbar, in particular in the lumbosacral, region. A third to one half of patients with spondylolysis (5-7%) demonstrate spondylolisthesis. Spondylolisthesis is usually an accidental finding, although the condition may lead to low back pain and sciatica. The earlier symptoms arise the gloomier usually is the prognosis. Very rarely a herniated disc in the cause of symptoms. Sciatica is mostly due to irritation of a nerve root by compression on the vertebral edge. Low back pain is caused by arthrogenic, pseudoarthrotic, and spondylotic degenerative disease. Diagnosis is established by AP, lateral, and oblique X-rays, and functional investigations. Myelogram and ossovenogram demonstrate compression of caudal sac and nerve roots. Conservative treatment consists of drugs and physical therapy, and cures one fifth of the patients. The best operative results are found after decompression and stabilisation (Cloward).

Adolescent↗

PubMed1990

Lumbosacral dural anomalies in von Recklinghausen neurofibromatosis.

The lumbosacral dural abnormalities in two patients with von Recklinghausen neurofibromatosis (vRNF) are described. Analysis of 18 previously reported cases revealed considerable morphological variations of the lumbosacral dural lesions associated with vRNF, but three basic forms may be distinguished. The pathogenesis of these lesions is still controversial. The contrast studies in our patients, especially the computed tomographic myelography (CTM), suggest that the meningocoeles in vRNF are, in fact, abnormally dilated and elongated nerve root sleeves and should, therefore, be distinguished from other types of meningeal cysts occurring in the lumbosacral region. The clinical significance of these dural anomalies are discussed.

Adult↗