Obvious Neurological Abnormalities Research Articles

Longus capitis and rectus capitis ventralis minor rupture in a horse following general anaesthesia for a laryngeal tie-forward procedure

The authors present a case of a racehorse with acute respiratory distress, bilateral epistaxis and laryngeal swelling following a laryngeal tie-forward procedure. An emergency tracheostomy was performed following brief endoscopic...

DEHP triggers cerebral mitochondrial dysfunction and oxidative stress in quail (Coturnix japonica) via modulating mitochondrial dynamics and biogenesis and activating Nrf2-mediated defense response

Di-(2-ethylhexyl) phthalate (DEHP) in the environment and food chain may impact cerebrum development and neurobehavioral in humans and wildlife. However, it is unclear that DEHP exposure caused cerebral toxicity. This experiment used gavage to expose female quail to 0, 250, 500, and 1000 mg/kg BW/day for 45 days to assess the potential neurotoxicity of DEHP to the cerebrum. It can be observed that there will be obvious neurological abnormalities in the experiment. Cerebrum histological lesions can be observed with HE-staining. Detecting oxidative stress indices, Nrf2 pathway, and mitochondrial dynamics factor, by analyzing the results, these results were observed that DEHP exposure can cause damage to the cerebrum by causing oxidative stress and affecting the balance of mitochondrial dynamics. Nrf2-mediated defense is not activated by exposure to 250 mg/kg DEHP. Nrf2-mediated defense is activated but is not resistant to exposure to medium and high doses of DEHP (500 mg/kg; 1000 mg/kg). DEHP triggers cerebral mitochondrial dysfunction via modulating mitochondrial dynamics.

Myocilin Mediates Myelination in the Peripheral Nervous System through ErbB2/3 Signaling

The glaucoma-associated gene, myocilin, is expressed in ocular and non-ocular tissues including the peripheral nervous system, but its functions in these tissues remain poorly understood. We demonstrate that in sciatic nerve, myocilin is expressed in Schwann cells with high concentrations at the nodes of Ranvier. There, myocilin interacts with gliomedin, neurofascin, and NrCAM, which are essential for node formation and function. Treatment of isolated dorsal root ganglion cultures with myocilin stimulates clustering of the nodal proteins neurofascin and sodium channel Nav1.2. Sciatic nerves of myocilin null mice express reduced levels of several myelin-associated and basal membrane proteins compared with those of wild-type littermates. They also demonstrate reduced myelin sheath thickness and partial disorganization of the nodes. Myocilin signaling through ErbB2/3 receptors may contribute to these observed effects. Myocilin binds to ErbB2/ErbB3, activates these receptors, and affects the downstream PI3K-AKT signaling pathway. These data implicate a role for myocilin in the development and/or maintenance of myelination and nodes of Ranvier in sciatic nerve.

Epileptic seizures induced by dexmedetomidine in a neonate

Background: Dexmedetomidine hydrochloride, a highly selective 2-adrenoceptoragonist, is used in combination with local anesthetics for sedation and analgesia. It is known to be efficacious in adult patients and is enthusiastically expected to be successful for sedation in neonates. Patient: The present case report details a term infant who was sedated by dexmedetomidine during artificial ventilation. He underwent electroencephalograms that confirmed epileptic seizures and non-epileptic abnormal movements. Twelve hours after the discontinuation of dexmedetomidine, both symptoms gradually disappeared without the use of any antiepileptic medication. After then, he had achieved normal development, with no obvious neurological abnormalities. Conclusion: Dexmedetomidine acts throughout the central nervous system and leads to a reduction in the anticonvulsant activity of the locus coeruleus. This case suggests potential adverse effects of dexmedetomidine in terms of inducing both epileptic seizures and non-epileptic movements in neonates.

Minireview: Thyroid Hormone Transporters: The Knowns and the Unknowns

The effects of thyroid hormone (TH) on development and metabolism are exerted at the cellular level. Metabolism and action of TH take place intracellularly, which require transport of the hormone across the plasma membrane. This process is mediated by TH transporter proteins. Many TH transporters have been identified at the molecular level, although a few are classified as specific TH transporters, including monocarboxylate transporter (MCT)8, MCT10, and organic anion-transporting polypeptide 1C1. The importance of TH transporters for physiology has been illustrated dramatically by the causative role of MCT8 mutations in males with psychomotor retardation and abnormal serum TH concentrations. Although Mct8 knockout animals have provided insight in the mechanisms underlying parts of the endocrine phenotype, they lack obvious neurological abnormalities. Thus, the pathogenesis of the neurological abnormalities in males with MCT8 mutations is not fully understood. The prospects of identifying other transporters and transporter-based syndromes promise an exciting future in the TH transporter field.

Minireview: Thyroid Hormone Transporters: The Knowns and the Unknowns

Androgen signaling through the androgen receptor (AR), a ligand-dependent transcription factor within the steroid receptor superfamily, plays an important role in the development and maintenance of many tissues. In muscle, androgens act as anabolic agents that increase both muscle mass and strength; however, a key unanswered question is the mechanism through which AR-mediated gene expression leads to these effects. To gain further insight into the mechanism of AR action in muscle, we identified AR-binding sites in primary human muscle cells using chromatin immunoprecipitation followed by tiling microarray detection. Through this analysis, we identified 32,518 potential AR-binding sites throughout the genome that were enriched upon androgen treatment. Sequence analysis of these regions indicated that approximately 90% possess a consensus androgen response element or half-site. Among the identified AR-binding sites are genes known to be directly regulated by AR, confirming the validity of our methodology. Additionally, we identified a number of novel AR targets, including genes and micro-RNAs implicated in muscle differentiation and function, suggesting a direct role for AR-mediated transcription in muscle development. Intriguingly, binding sequences for the Mef2 family of transcription factors were enriched in the AR-bound regions, and we show that several Mef2c-dependent genes are direct targets of AR, suggesting a functional interaction between Mef2c and AR in skeletal muscle. Our results provide new insights into the mechanisms by which androgens promote muscle growth and validate AR as a potential therapeutic target for sarcopenia, muscle wasting, and other androgen-related muscle disorders. Minireview: Thyroid Hormone Transporters: The Knowns and the Unknowns W. Edward Visser, Edith C.H. Friesema, and Theo J. Visser (Mol Endocrinol, 10.1210/me.2010-0095) ABSTRACT The effects of thyroid hormone (TH) on development and metabolism are exerted at the cellular level. Metabolism and action of TH take place intracellularly, which require transport of the hormone across the plasma membrane. This process is mediated by TH transporter proteins. Many TH transporters have been identified at the molecular level, although a few are classified as specific TH transporters, including monocarboxylate transporter (MCT)8, MCT10, and organic anion-transporting polypeptide 1C1. The importance of TH transporters for physiology has been illustrated dramatically by the causative role of MCT8 mutations in males with psychomotor retardation and abnormal serum TH concentrations. Although Mct8 knockout animals have provided insight in the mechanisms underlying parts of the endocrine phenotype, they lack obvious neurological abnormalities. Thus, the pathogenesis of the neurological abnormalities in males with MCT8 mutations is not fully understood. The prospects of identifying other transporters and transporter-based syndromes promise an exciting future in the TH transporter field. T R A N S L A T I O N A L H I G H L I G H T S F R O M M O L E C U L A R E N D O C R I N O L O G YThe effects of thyroid hormone (TH) on development and metabolism are exerted at the cellular level. Metabolism and action of TH take place intracellularly, which require transport of the hormone across the plasma membrane. This process is mediated by TH transporter proteins. Many TH transporters have been identified at the molecular level, although a few are classified as specific TH transporters, including monocarboxylate transporter (MCT)8, MCT10, and organic anion-transporting polypeptide 1C1. The importance of TH transporters for physiology has been illustrated dramatically by the causative role of MCT8 mutations in males with psychomotor retardation and abnormal serum TH concentrations. Although Mct8 knockout animals have provided insight in the mechanisms underlying parts of the endocrine phenotype, they lack obvious neurological abnormalities. Thus, the pathogenesis of the neurological abnormalities in males with MCT8 mutations is not fully understood. The prospects of identifying other transporters and transporter-based syndromes promise an exciting future in the TH transporter field. T R A N S L A T I O N A L H I G H L I G H T S F R O M M O L E C U L A R E N D O C R I N O L O G Y

Minireview: Thyroid Hormone Transporters: The Knowns and the Unknowns

The effects of thyroid hormone (TH) on development and metabolism are exerted at the cellular level. Metabolism and action of TH take place intracellularly, which require transport of the hormone across the plasma membrane. This process is mediated by TH transporter proteins. Many TH transporters have been identified at the molecular level, although a few are classified as specific TH transporters, including monocarboxylate transporter (MCT)8, MCT10, and organic anion-transporting polypeptide 1C1. The importance of TH transporters for physiology has been illustrated dramatically by the causative role of MCT8 mutations in males with psychomotor retardation and abnormal serum TH concentrations. Although Mct8 knockout animals have provided insight in the mechanisms underlying parts of the endocrine phenotype, they lack obvious neurological abnormalities. Thus, the pathogenesis of the neurological abnormalities in males with MCT8 mutations is not fully understood. The prospects of identifying other transporters and transporter-based syndromes promise an exciting future in the TH transporter field.

Central nervous system involvement in severe congenital neutropenia: neurological and neuropsychological abnormalities associated with specific HAX1 mutations

Homozygous mutations in the HAX1 gene were recently identified in severe congenital neutropenia patients belonging to the original Kostmann family in northern Sweden. Our observations suggested that these patients also develop neurological and neuropsychological symptoms. Detailed clinical studies and mutation analyses were performed in the surviving patients belonging to the Kostmann kindred and in two patients not related to this family, along with studies of HAX1 splice variant expression in normal human tissues. Five of six Kostmann family patients and one other patient from northern Sweden harboured homozygous HAX1 mutations (568C-->T, Q190X) and one carried a heterozygous ELA2 gene mutation. One Swedish patient of Kurdish extraction carried alternative homozygous HAX1 mutations (131G-->A, W44X). All the three patients with Q190X mutations who were alive and available for evaluation developed neurological disease with decreased cognitive function, and three of four patients who reached 10 years developed epilepsy. In contrast, the patients with the ELA2 and W44X HAX1 mutations, respectively, showed no obvious neurological abnormalities. Moreover, two alternative HAX1 splice variants were identified in normal human tissues, including the brain. Both transcripts contained exon 5, harbouring the Q190X mutation, whereas the 5' end of exon 2 containing the W44X mutation was spliced out from the second transcript. We describe neurological and neuropsychological abnormalities for the first time in Kostmann disease patients. These central nervous system symptoms appear to be associated with specific HAX1 mutations.

MATERNAL MERCURY LEVELS ARE RELATED TO NEURO-COGNITIVE DEVELOPMENT AT AGE 6 MONTHS

ISEE-79 Introduction: Coal-burning in Poland is a major source of environmental mercury exposure, via air pollution or bio- accumulation in the food chain. Aim: The purpose of the study was to assess the neuro-cognitive status of 6-month-old infants whose mothers were exposed to low but varying amounts of mercury during pregnancy. Methods: Mercury levels in maternal blood at delivery were used to assess environmental exposure to mercury; and the Fagan Test of Infant Intelligence (FTII) assessed visual recognition memory (VRM). The cohort consisted of 233 infants of mothers who gave birth to babies at 33–42 weeks of gestation, between January 2001 and March 2003. None of the children manifested obvious neurological abnormalities at the development check-up. Results: VRM in 6-month-olds, as measured by novelty scores from the FTII, was inversely related to maternal blood mercury levels. The estimated risk of scoring in the suspected or at risk groups for developmental delay (FTII risk group classifications 2+3) due to higher mercury blood levels (above 0.50 μg/L) was threefold greater (OR = 3.21, CI = 1,12 to 9.20), than for lower mercury blood levels (≤ 0.5 μg/dL), after adjusting for potential confounders such as gestational age, gender of the child, maternal education, exposure to environmental tobacco smoke and lead. Conlcusion: The results of the study suggest that the Fagan Test may be a sensitive end-point for low level mercury exposure and that the group of infants at risk of delayed neuro-cognitive development may be defined by a maternal blood mercury level exceeding 0.5 μg/L at delivery. As the risk of reduced VRM attributable to this exposure level is 63%, a large portion of developmental delay could be prevented by reducing maternal blood mercury level below 0.5 μg/L.

Meningitis–retention syndrome

A combination of acute urinary retention and aseptic meningitis has not been well known. This combination can be referred to as meningitis-retention syndrome (MRS), when accompanied by no other abnormalities. To describe the results of a uro-neurological assessment in our patients with MRS. In three patients (two men, one woman; age, 34-68 years), we performed urodynamic studies and relevant imaging and neurophysiological tests, in addition to cerebrospinal fluid (CSF) examination. All three patients developed acute urinary retention along with headache, fever and stiff neck. None had obvious neurological abnormalities, other than a slightly brisk reflex in the lower extremities. One had previously experienced generalized erythematous eruptions, but none had pain, hypalgesia or skin eruptions in the sacral dermatomes suggestive of Elsberg syndrome (infectious sacral polyradiculitis; mostly genital herpes). Brain/spinal/lumbar plexus MRI scans and nerve conduction studies were normal. CSF examination showed mild mononuclear pleocytosis, increased protein content, and normal to mildly decreased glucose content in all patients; increased myelin basic protein suggestive of central nervous system demyelination in one; and increased viral titers in none. Urodynamic study revealed, during the voiding phase, an underactive detrusor in all patients and an unrelaxing sphincter in one. These clinical manifestations were ameliorated within 3 weeks. We reported three cases of MRS, a peculiar syndrome that could be regarded as a mild variant of acute disseminated encephalomyelitis (ADEM). Urinary retention might reflect acute shock phase of this disorder. Although MRS has a benign and self-remitting course, management of the acute urinary retention is necessary.

Is lumbar spondylosis a cause of urinary retention in elderly women?

Lumbar spondylosis (LS) is a common spinal degenerative disorder which causes various types of lower urinary tract dysfunction (LUTD). However, it is not certain whether LS may cause urinary retention in elderly women. In a period covering the past 3 years, we retrospectively reviewed: a) urodynamic case records of women with urinary retention (post-void residuals, PVR > 100 ml), b) the records of women with LUTD due to LS (cauda equina syndrome and spinal canal narrowing by MRI), and c) uro-neurological features of women who belonged to both a) and b). a) One-hundred women with a mean age of 58 years had urinary retention. The most common underlying disease was multiple system atrophy [19], followed by multiple sclerosis [13] and cervical/thoracic tumours [8]. LS was the fourth most common [5], with the highest age (71 years) of all diseases. b) Nineteen women with LUTD had LS (12, canal narrowing of 50-70%; 7 > 70 %), with a mean PVR volume of 60 ml. A fourth [5] of them had urinary retention, with severe spinal canal narrowing (all 5 > 70%). c) Thus, 5 women belonged to both a) and b). In 4 of these women, LUTD followed or occurred together with typical cauda equina syndrome symptoms such as sciatica and saddle anesthesia. However, one elderly woman presented with painless urinary retention, and absent ankle reflexes were the sole neurological abnormality. The urodynamic abnormalities underlying urinary retention included an underactive detrusor in all 5, bladder sensory impairment in 3, an unrelaxing sphincter in 2, a low compliance detrusor in one, neurogenic sphincter motor unit potentials in 2 of 4 studied, and cholinergic supersensitivity of the detrusor in one of 3 studied. Surgical decompression ameliorated urinary retention in 1 of 2 women who had surgery. In our series, only 5 percent of the women with urinary retention had LS, but LS poses a potential risk for retention, particularly in elderly women with severe spinal canal narrowing. Preganglionic somato-autonomic dysfunctions underlie this condition. It may appear as the sole initial complaint in cases in which no other obvious neurological abnormalities are found.

Nocturnal enuresis in children with adenotonsillar hypertrophy

The relationship between upper airway obstruction and nocturnal enuresis (NE) was studied in 25 children with adenotonsillar hypertrophy. There were 11 males and 14 females. Their ages ranged from 4 to 10 years. Most of them received medical therapy for NE with unsatisfactory response. They were classified according to the presence or absence of diurnal voiding into two groups: monosymptomatic NE (16 children) and polysymptomatic NE (9 children). Obvious neurological abnormalities were excluded. All patients had been subjected to adenotonsillectomy and reevaluated 3–6 months later for their clinical response. Our results revealed (1) no significant differences between the two groups as far as age, sex, and manifestations of upper airway obstruction were concerned; (2) body mass index was significantly higher in group 2 (polysymptomatic) compared to group 1 (p<0.001); (3) detrusor instability was significantly higher in group 2 compared to group 1 (p<0.0001); (4) the preoperative apnea/hypopnea index (AHI) and percent oxygen saturation (SaO2%) showed no significant differences between the two groups; however, the postoperative values revealed significant improvement of both AHI and SaO2% in group 1 (monosymptomatic) when compared to group 2 (p=0.004 and p<0.001, respectively). The postoperative follow-up showed a complete response of NE among children of group 1 and inadequate or no response among children of group 2. We concluded that removal of the upper airway obstruction by adenotonsillectomy led to a complete cure of NE in all children with monosymptomatic category. The polysymptomatic category may get more benefit with bladder physiotherapy and/or reduction of body weight.

Uroneurological assessment of spina bifida cystica and occulta.

Spina bifida is a rare but well-documented congenital spinal anomaly comprising a cystic form, which appears in infancy, and an occult form, which appears in late childhood and in adulthood. Herein, we report the results of uroneurological assessment in patients with spina bifida cystica and occulta, with respect to diagnosis and management of the disorders. We performed a neurological examination, urinary questionnaire, and urodynamic studies in 28 consecutive patients with urinary symptoms, including 16 with the cystic form (nine male and seven female patients, ages 2 to 25 years), all of whom underwent neonatal surgical management, and 12 with occult form (six men and six women, ages 7 to 32 years) diagnosed by myelography and spinal magnetic resonance imaging who did not undergo surgery. Neurological examination revealed a combination of flaccid and spastic paresis, with dominant lower motoneuron signs in the cystic form, whereas there were dominant upper motoneuron signs in the occult form. Four patients with occult spina bifida presented with urinary symptoms as the sole initial complaint. There was no correlation between neurological findings and urodynamic abnormalities. Urinary incontinence and enuresis were common at all ages, and large post-micturition residuals and vesicoureteral reflux were not uncommon, particularly in the cystic form. Bladder abnormalities in the cystic and occult forms included detrusor hyperreflexia during filling in 38% and 42%, low compliance detrusor in 81% and 67%, supersensitivity to bethanechol in two (100%) patients with the cystic form and in three of four (75%) with the occult form, and impaired bladder sensation in 25% and 8% in each form, respectively. Urethral abnormalities in cystic and occult forms included detrusor/sphincter dyssynergia in 50% and 27%, low Pure max in 56% and 17%, silent sphincter electromyographic activity in 25% and 0%, absent bulbocavernosus reflex in 87% and 56%, absent anal reflex in 100% and 57%, neurogenic motor unit potentials in one patient with cystic form studied and in two of three patients with occult form, respectively. Spina bifida cystica and occulta present with a wide spectrum of urodynamic abnormalities including upper and lower motoneuron types of bladder and urethral dysfunction. Careful uroneurological assessment and spinal magnetic resonance imaging are important for diagnosing young adult patients with spina bifida occulta because they may present with urinary symptoms as the sole initial complaint and have no other obvious neurological abnormalities.

Regional cerebral glucose utilization in rats with portacaval anastomosis.

Regional cerebral glucose utilization was measured using [2-14C]glucose in rats with an end-to-side portacaval anastomosis. The experiments were conducted in two groups of rats 4 to 8 weeks after portacaval shunting was established. One group was paralyzed and given N2O:O2 (70:30), whereas the other was conscious, unstressed, and unaware of the experiment. In both groups the rate of glucose utilization was decreased in almost all brain structures by an average of 20% after portacaval shunting. The results showed definitively that cerebral energy metabolism was reduced at a time when there were no obvious neurological abnormalities.