Current concept and future research directions of mild cognitive impairment

Alzheimer's disease (AD) generally begins with mild memory problems which occur in an insidious manner and progresses to the development of multiple cognitive impairments. There is a ‘gray’ area between what is classified as ‘normal’ and what is classified as ‘dementia’, currently called mild cognitive impairment (MCI). In this article, a case of MCI is described, and the diagnosis, assessment, subclassification (pre‐Alzheimer type and white matter lesion type) and future therapeutic plans for MCI are reviewed.     

Polysialylated Neural Cell Adhesion is Involved in Target-induced Morphological Differentiation of Arcuate Dopaminergic Neurons

We have previously shown that the morphological and biochemical maturation of developing rat hypothalamic dopaminergic neurons is accelerated when they are cocultivated with pituitary intermediate lobe cells, one of their targets. Only two subsets of hypothalamic dopaminergic neurons (arcuate, A12, and periventricular, A14, nuclei) may project to the pars intermedia. In order to determine whether the two populations are equally responsive to coculture conditions, we microdissected the hypothalamus of 17-day-old rat fetuses in two fragments containing cell bodies from the A12 and from the A14 regions, prepared neuronal cultures from both portions and incubated them separately with intermediate lobe cells. The presence of intermediate lobe cells increased tyrosine hydroxylase levels in both dopaminergic neuron subsets, but morphological differentiation was accelerated in dopaminergic neurons originating in the arcuate nucleus only. We then investigated whether physical contact between developing arcuate neurons and their target cells was a prerequisite of the morphological effect by interposing a semipermeable membrane between cultivated neurons and intermediate lobe cells in transwell culture dishes. The morphological effect was no longer observed under transwell coculture conditions, pointing to the involvement of membrane-bound molecules. Accordingly, the stimulating effect of coculture on arcuate dopaminergic neurons was completely abolished by the removal of polysialic acid on neural cell adhesion molecules by endoneuraminidase N treatment. Thus, maturation of A12 and A14 dopaminergic neurons exhibits differential susceptibility to intermediate lobe target cells, and polysialylated-NCAM is required for the contact-dependent effect.     

单纯脑白质疏松症与皮质下动脉硬化性脑病的临床对比研究

目的探讨单纯脑白质疏松症(LA)和皮质下动脉硬化性脑病(BD)的临床表现、影像学及脑诱发电位的改变特征。方法(1)调查114例单纯脑白质疏松症患(LA组)和41例皮质下动脉硬化性脑病患(BD组)的发病危险因素和临床表现。(2)两组患均行CT检查，并按照脑白质异常程度分为3型。(3)LA组74例患，BD组35例患行MRI检查，根据T2WI显示的脑室周围高信号分为5型。(4)两组分别选择部分伴有高血压的患进行躯体感觉诱发电位(SEP)、脑干听觉诱发电位(BAEP)和视觉诱发电位(VEP)检查。结果(1)LA组患的危险因素呈多样化，无神经局灶体征，临床表现仅为轻度记忆力减退、步态不稳。CT显示脑白质异常以1型为主，占70．2％(80／114)；MRI脑白质异常也同样以1型为主，占71．6％(53／74)，均无脑室扩大。电生理学检查显示，SEP异常率为83．7％(36／43)，其中轻度60．5％，中度23．2％；BAEP异常率为62．8％(27／43)，潜伏期和峰间期延长；VEP异常率为53．5％(23／43)，各波潜伏期延长，均无波形消失。(2)BD组患危险因素以高血压为主(95．1％)，临床表现以神经局灶体征、明显认知功能障碍和卒中样发作为主。CT分型以3型多见，为73．2％(30／41)；MRI检查显示3型为54．3％(19／35)，4型45．7％(16／35)，41例患均有双侧脑室对称性扩大。电生理学检查显示，SEP异常率为96．7％(29／30)，其中轻度6．7％，中度46．7％，重度43．3％；BAEP异常率86．7％(26／30)，潜伏期和峰间期进一步延长，部分伴有Ⅲ、Ⅴ波缺失；VEP异常率为83．3％(25／30)，各波潜伏期进一步延长，部分P2单侧波形消失。结论单纯脑白质疏松症无特征性临床表现，诊断主要以影像学1型脑白质异常为依据；诱发电位表现为各波潜伏期延长，无波形完全缺失。皮质下动脉硬化性脑病的危险因素为高血压，临床有较明显的认知功能障碍，常见卒中样发作等特征，影像学检查CT显示3型脑白质异常，MRI显示3型或4型为诊断依据；诱发电位呈现各波潜伏期进一步延长并伴有部分波形完全缺失。     

Changes in central serotoninergic transmission affect clonidine analgesia in monkeys

Summary 1. The effects of changes in central serotoninergic transmission on clonidine analgesia were assessed in monkeys. The minimum electrical current required for producing jaw opening is referred to as the pain threshold. Pain was induced by electrical stimulation of tooth pulp afferents. 2. In the first series of studies, intracerebroventricular administration of clonidine (5–30 g) produced dose-dependent analgesia in monkeys. The clonidine-induced analgesia was abolished or attenuated by prior injection of the animals with p-chlorophenylalanine or 5,7-dihydroxytryptamine into the third cerebral ventricle. On the other hand, pretreatment of the animals by injecting 5-HT or its precursor 5-hydroxytryptophan into the cerebral ventricle potentiated the clonidine-induced analgesia in monkeys. 3. In the second series of experiments, administration of clonidine (1–10 g) into the diencephalic periventricular gray (of the anterior hypothalamic portion), the periaqueductal gray, or the dorsal raphe nuclei also produced dose-dependent analgesia in monkeys. The analgesia induced by clonidine injection into the diencephalic periventricular gray or the periaqueductal gray was effectively antagonized by pretreatment of the animals by injecting two 5-HT receptor antagonists (such as ketanserine and methysergide) into the diencephalic periventricular gray or the periaqueductal gray. The clonidine-induced analgesia in monkeys was not affected by pretreatment of the animals with injections of either ketanserine or methysergide into the dorsal raphe nuclei. 4. The results suggest that the functional activity of central 5-HT neurons correlate well with the analgesic sensitivity of clonidine microinjected centrally. In addition, the analgesia induced by clonidine microinjected into the diencephalic periventricular gray or the periaqueductal gray was mediated by the 5-HT receptors at the site of injection.This study was supported by grants from the National Science Council of the Republic of China and the Student Summer Fellowship of National Cheng Kung University Medical College (1986) Send offprint requests to Mao-Tsun Lin at the above address     

颅脑超声诊断新生儿脑损伤的临床价值

目的探讨颅脑超声诊断新生儿脑损伤的临床价值。方法应用颅脑超声对1 387例住院新生儿进行早期检查及随访,分析声像图表现。结果颅脑超声检查1 387例,其中正常声像图594例,异常声像图793例。结论颅脑超声对新生儿脑损伤诊断率高,并能连续监测新生儿病情变化,故可成为新生儿脑损伤早期诊断、判断其严重程度及随访的有效手段。     

Admixed phenotype of NEDD4L associated periventricular nodular heterotopia: A case report

Rationale:Periventricular nodular heterotopia-7 (PVNH7) is a neurodevelopmental disorder associated with improper neuronal migration during neurogenesis in cortex development caused by pathogenic variants in the NEDD4L gene.Patient concerns:We report the case of a polystigmatized 2-year-old boy having significant symptomatologic overlap with PVNH7, such as delayed psychomotor and mental development, seizures and infantile spasms, periventricular nodular heterotopia, polymicrogyria, cleft palate, 2 to 3 toe syndactyly, hypotonia, microretrognathia, strabismus, and absent speech and walking. The patient showed also distinct symptoms falling outside PVNH7 symptomatology, also present in the proband''s older brother, such as blue sclerae, hydronephrosis, transversal palmar crease (found also in their father), and bilateral talipes equinovarus. In addition, the patient suffered from many other symptoms.Diagnoses:The boy, his brother and their parents were subjected to whole-exome sequencing. Because of uncertainties in symptomatology and inheritance pattern, the top-down approach was hard to apply. Using the bottom-up approach, we identified a known pathogenic variant, NM_001144967.2(NEDD4L):c.2677G>A:p.Glu893Lys, in the proband''s genome that absented in any other analyzed family member, suggesting its de novo origin.Interventions and outcomes:The patient was treated with Convulex 300 mg/mL for the successful seizure control and Euthyrox 25mg for the treatment of thyroid malfunction. He also took various supplements for the metabolism support and digestion regulation. Moreover, the patient underwent the corrective surgeries of cleft palate and talipes equinovarus.Lessons:We successfully identified the causative mutation NM_001144967.2(NEDD4L):c.2677G>A:p.Glu893Lys explaining symptoms overlapping those reported for PVNH7. Symptoms shared with the brother were not explained by this variant, since he was not a carrier of the pathogenic NEDD4L variant. These are most likely not extended phenotypes of PVNH7, rather an independent clinical entity caused by a yet unidentified genetic factor in the family, highlighting thus the importance of thorough evaluation of symptomatology and genomic findings in affected and unaffected family members, when such data are available.     

Epilepsy in children with periventricular leukomalacia

Objective

We aimed to analyze the development of epilepsy in a patient group with periventricular leukomalacia followed at a tertiary pediatric neurology center.

Patients and methods

The study included 108 children aged between 2 and 8 years with radiologically proven periventricular leukomalacia who had been regularly observed at the Istanbul University, Istanbul Faculty of Medicine, Department of Pediatrics, Pediatric Neurology outpatient clinic between January 2006 and December 2011.

Results

Neonatal seizures were reported in 22 patients (20.3%), 14 of whom developed epilepsy. A significant correlation was found between neonatal seizures and prematurity and newborn asphyxia (p = 0.013 and p = 0.010, respectively). Epilepsy developed in 35 patients (32.4%), history of neonatal seizures and more severe loss of white matter, periventricular hyperintensity and corpus callosum involvement were found to be correlated with epilepsy (p = 0.001, p = 0.004, p = 0.016, and p = 0.004, respectively). The most common seizure pattern observed was generalized tonic clonic seizures (n = 13) and complex partial seizures (n = 11). Those with focal EEG findings had a significantly better neurodevelopmental and cognitive level than those with multifocal/generalized EEG findings (p = 0.024). Seizures continued with varying frequency in 14 epileptic patients (40%) despite antiepileptic treatment.

Conclusion

Almost a third of patients with periventricular leukomalacia develop epilepsy that can be intractable in substantial part. Neonatal seizures and severe MRI findings are important clues that can indicate the development of epilepsy in these patients.     

Using the Alberta Infant Motor Scale to early identify very low-birth-weight infants with cystic periventricular leukomalacia

We examined whether the Alberta Infant Motor Scale (AIMS) is able to identify very low-birth-weight (VLBW) preterm infants with cystic periventricular leukomalacia (PVL) as early as 6 months of corrected age. Longitudinal follow-up AIMS assessments were done at 6, 12, and 18 months old for 35 VLBW infants with cystic PVL (cPVL⁺), 70 VLBW infants without cystic PVL (cPVL⁻), and 76 term infants (healthy controls: HC). Corrected age was used for the preterm infants. The cPVL⁺ group had significantly lower prone, supine and sitting subscales at age 6, 12, and 18 months than the cPVL⁻ group (all p < 0.05). The cPVL⁻ group showed significantly lower supine, prone, sitting, and standing subscales than the HC group only at age 6 months. At age 6 months, the areas under the receiver operator curve used to discriminate the cPVL⁺ infants from cPVL⁻ infants were 0.82 ± 0.04 for prone, 0.93 ± 0.02 for supine, 0.83 ± 0.05 for sitting, and 0.62 ± 0.07 for standing. The AIMS may help early identify VLBW infants with cystic PVL at age 6 months old.