Spastic Paraplegias Due to Non-Traumatic Spinal Cord Disorders

Spinal cord disorders are induced by diseases of various categories: infectious, inflammatory, degenerative, genetic, traumatic, and so on. These diseases involve spastic paraplegia or tetraplegia, abnormal sensation, bladder and anal dysfunction, etc. This chapter describes the medical etiologies and treatments for spastic paraplegias. I will mention diagnostic and therapeutic aspects of spastic paraplegias due to non-traumatic spinal cord disorders. I will describe my cases who suffered from amyotrophic lateral sclerosis (ALS), hereditary spastic paraplegia (HSP), HTLV-1 associated myelopathy (HAM), and multiple sclerosis (MS). I also investigate the recent therapeutic strategies for spastic paraplegias. Spastic paraplegia is an intractable condition accompanied by many spinal cord disorders. Some therapeutic methods (intrathecal baclofen and botulinum toxin injection) have symptomatic effects. Rehabilitation and some devices are also effective for spasticity

Lysosomal Dysfunctions in Hereditary Spastic Paraplegias

Hereditary spastic paraplegias (HSPs) comprise a heterogeneous group of inherited neurodegenerative diseases with the cardinal feature of a length-dependent degeneration of corticospinal motor axons. They are classified by their mapped genetic loci, SPG1–SPG78. Recently, lysosomal dysfunction is one of the pathomechanism for some autosomal-recessive HSPs. SPG11 is caused by loss-of-function mutations in the SPG11 gene. Its gene product is called spatacsin, which is needed for the recycling of lysosomes from autolysosomes. SPG15 is caused by loss-of-function mutation in the ZFYVE26 gene. The ZFYVE26 gene encodes spastizin. Mutations in spastizin impair autophagosome maturation and lead to an accumulation of immature autophagosomes. SPG48/KIAA0415 encodes AP5Z1, known to be a spatacsin and spastizin interactor. Its mutations lead to loss of protein or mutated forms of protein with defective autophagy. The TECPR2 is a human ATG8-binding protein and positive regulator of autophagy, which plays a key role in major adult and pediatric neurodegenerative diseases. Mutations in the lysosomal trafficking regulator (LYST) gene have been reported to cause hereditary spastic paraplegia. The LYST protein is involved in control of the exocytosis of secretory lysosomes. Recently, Drosophila with a gene mutation of an LYST homolog was revealed to exhibit impaired autophagy

Adult-onset Alexander disease with typical "tadpole" brainstem atrophy and unusual bilateral basal ganglia involvement: a case report and review of the literature

<p>Abstract</p> <p>Background</p> <p>Alexander disease (ALX) is a rare neurological disorder characterized by white matter degeneration and cytoplasmic inclusions in astrocytes called Rosenthal fibers, labeled by antibodies against glial fibrillary acidic protein (GFAP). Three subtypes are distinguished according to age at onset: infantile (under age 2), juvenile (age 2 to 12) and adult (over age 12). Following the identification of heterozygous mutations in <it>GFAP </it>that cause this disease, cases of adult-onset ALX have been increasingly reported.</p> <p>Case Presentation</p> <p>We present a 60-year-old Japanese man with an unremarkable past and no family history of ALX. After head trauma in a traffic accident at the age of 46, his character changed, and dementia and dysarthria developed, but he remained independent. Spastic paresis and dysphagia were observed at age 57 and 59, respectively, and worsened progressively. Neurological examination at the age of 60 revealed dementia, pseudobulbar palsy, left-side predominant spastic tetraparesis, axial rigidity, bradykinesia and gaze-evoked nystagmus. Brain MRI showed tadpole-like atrophy of the brainstem, caused by marked atrophy of the medulla oblongata, cervical spinal cord and midbrain tegmentum, with an intact pontine base. Analysis of the <it>GFAP </it>gene revealed a heterozygous missense mutation, c.827G>T, p.R276L, which was already shown to be pathogenic in a case of pathologically proven hereditary adult-onset ALX.</p> <p>Conclusion</p> <p>The typical tadpole-like appearance of the brainstem is strongly suggestive of adult-onset ALX, and should lead to a genetic investigation of the <it>GFAP </it>gene. The unusual feature of this patient is the symmetrical involvement of the basal ganglia, which is rarely observed in the adult form of the disease. More patients must be examined to confirm, clinically and neuroradiologically, extrapyramidal involvement of the basal ganglia in adult-onset ALX.</p

Distribution of glucocorticoid receptors and 11 beta-hydroxysteroid dehydrogenase isoforms in the rat inner ear.

11β-hydroxysteroid dehydrogenase (11β-HSD) is an enzyme complex responsible for the conversion of hormonally active cortisol to inactive cortisone, and two isoforms of the enzyme (11β-HSD1 and 11β-HSD2) have been cloned and characterized. An immunohistochemical study was performed to determine the precise distribution of glucocorticoid receptors (GRs) and the isoforms of 11β-HSD in the rat (postnatal day 1, 4, 10, and adult). Immunoreactivity of GRs was detected in the stria vascularis (SV), the outer hair cells (OHCs), the inner hair cells (IHCs), the spiral ligament (SLig), the spiral limbus (SLib), the spiral ganglion cells (SGCs), Reissner\u27s membrane (RM), the cochlear nerve (CN), the vestibular hair cells (VHCs), the dark cells (DCs), and the vestibular nerve (VN) in the rats. Immunostaining of 11β-HSD1 was observed in almost all the tissues in the cochlea and the vestibule except SLig, SLib, SGCs, CN, VHCs, and VN during all developmental stages, whereas, immunoreactivity of 11β-HSD2 was not detected in any of the inner ear tissues. A polymerase chain reaction (PCR) study was also performed on GRs, 11β-HSD1, and 11β-HSD2 in the OC, SV and vestibule of the postnatal rats, and revealed that mRNAs were detected in all those and tissues in all the developmental days of postnatal days 1, 4, and 10. This data indicates that expression of GRs and 11β-HSD isoforms in the inner ear is tissue and age-specific, and that different local steroid regulation by GRs and the isoforms of 11β-HSD is present in each part of the inner ear

インドメサシンのプロラクチン放出抑制効果

インドメサシン100 mgの直腸内投与で男子血中プロラクチン濃度は有意に低下した.血中LHレベルは軽度低下したが, 有意差はなかった.血中FSHは変化しなかったIndomethacin administered intrarectally at a dose of 100 mg elicited a statistically significant decrease of serum prolactin level in men. Serum LH level was depressed slightly but the decrease was not statistically significant. There was no effect on serum FSH concentration