脐带间充质干细胞在遗传性痉挛性截瘫中的应用

目的观察脐带间充质干细胞（UC-MSC）治疗遗传性痉挛性截瘫（HSP）的临床疗效及安全性。方法2010年9月及2011年4月,分别给予一HSP家系父子2人行UC-MSC鞘内注射治疗,两个疗程,每次1×106 cells/Kg,每周1次,4次为1个疗程。采用改良的Ashworth肌张力分级标准（MAS）、国际合作共济失调评分量表（ICARS）及日常生活量表（ADL）,对患者治疗前后神经功能、日常生活能力进行评定。结果第一疗程结束1个月与治疗前比较,2人MAS分级、ICARS及ADL评分均降低,两人行走站立稳定性及言语流利程度较治疗前改善;第二疗程结束后1个月与该疗程治疗前比较,2人ICARS及ADL评分降低,儿子肌张力进一步降低,父亲双上肢共济失调减轻。2人治疗后均未见明显不良反应发生。末次治疗结束后随访20个月,父、子俩分别于第二疗程治疗结束7个月及8个月后,症状继续加重。结论 UC-MSC鞘内注射治疗是安全的,可在一定时间内一定程度上减轻患者临床症状,提高患者生活质量,延缓疾病进展,但疗效不能持久。     

Uncoupling of neuroinflammation from axonal degeneration in mice lacking the myelin protein tetraspanin‐2

Deficiency of the major constituent of central nervous system (CNS) myelin, proteolipid protein (PLP), causes axonal pathology in spastic paraplegia type‐2 patients and in Plp1^null‐mice but is compatible with almost normal myelination. These observations led us to speculate that PLP's role in myelination may be partly compensated for by other tetraspan proteins. Here, we demonstrate that the abundance of the structurally related tetraspanin‐2 (TSPAN2) is highly increased in CNS myelin of Plp1^null‐mice. Unexpectedly, Tspan2^null‐mutant mice generated by homologous recombination in embryonic stem cells displayed low‐grade activation of astrocytes and microglia in white matter tracts while they were fully myelinated and showed no signs of axonal degeneration. To determine overlapping functions of TSPAN2 and PLP, Tspan2^null*Plp1^null double‐mutant mice were generated. Strikingly, the activation of astrocytes and microglia was strongly enhanced in Tspan2^null*Plp1^null double‐mutants compared with either single‐mutant, but the levels of dysmyelination and axonal degeneration were not increased. In this model, glial activation is thus unlikely to be caused by axonal pathology, and vice versa does not potentiate axonal degeneration. Our results support the concept that multiple myelin proteins have distinct roles in the long‐term preservation of a healthy CNS, rather than in myelination per se. GLIA 2013;61:1832–1847     

Hemorrhagic shock and encephalopathy syndrome in a patient with a de novo heterozygous variant in KIF1A

IntroductionKIF1A, a gene that encodes a neuron-specific motor protein, plays important roles in cargo transport along neurites. Variants in KIF1A have been described in three different disorders, and neurodegeneration and spasticity with or without cerebellar atrophy or cortical visual impairment syndrome (NESCAVS) is the severest phenotype.Case reportA 3-year-old girl was born at term with a birth weight of 2590 g. At five months of age, she visited our hospital due to developmental delay. An EEG showed multiple epileptic discharge, and a nerve conduction study showed severe axonopathy of both motor and sensory nerves. We performed exome sequencing and identified a de novo heterozygous missense variant in KIF1A (NM_001244008.1: c. 757G > A, p.E253K). At six months of age, she developed acute encephalopathy, multiple organ failure and disseminated intravascular coagulation, necessitating intensive care. Her brain CT showed severe brain edema, followed by profound brain atrophy. We diagnosed hemorrhagic shock and encephalopathy syndrome (HSES) according to the clinico-radiological features. Currently, she is bed-ridden, and requires gastrostomy because of dysphagia.ConclusionThe clinical course of our case confirmed that p.E253K is associated with severe neurological features. Severe KIF1A deficiency could cause thermoregulatory dysfunction and may increase the risk of acute encephalopathy including HSES.     

A clinical sickness score for the critically ill in Central Africa

Scoring systems provide a means for comparing results, ensuring consistent standards and evaluating changes in therapy. The APACHE II system depends partly on the results of laboratory tests which are not normally available in Central Africa. The aim of this study was to develop a scoring system based only on clinical observations. Six hundred and twenty-four consecutive admissions to the intensive care unit (ICU) were allocated a clinical sickness score (CSS) according to pulse rate, blood pressure, respiration rate, urine output, Glasgow Coma Scale, temperature and age. CSS was significantly associated with outcome, there being no significant difference between actual and predicted outcomes calculated by logistic regression analysis. There was a significant difference between mean scores for survivors and non-survivors in all diagnostic groups except diabetes. The proportional change in score from admission was also significantly associated with outcome on each subsequent day in ICU. The CSS provides an objective measure of illness severity for critically ill patients in Africa.     

Acute inflammatory demyelinating polyradiculoneuropathy following malaria

Among the neurologic complications of malaria, acute inflammatory demyelinating polyradiculoneuropathy is a rarely reported phenomenon. We describe a patient with acute inflammatory demyelinating polyradiculoneuropathy following malaria in a 26-year-old traveler to an endemic area and review the clinical features of all 23 previously reported patients. Malarial infection should be considered as a potential preceding trigger in patients residing in or travelers returning from malaria-endemic areas presenting with the clinical features of acute inflammatory demyelinating polyradiculoneuropathy in the setting of a recent or ongoing febrile illness.     

Diagnosis of coronary vasospasm by detection of postischemic regional left ventricular delayed relaxation using echocardiographic evaluation with color kinesis

BACKGROUND: Coronary vasospasm has been diagnosed by invasive provocative procedures during coronary arteriography. It would be useful to have a reliable, noninvasive, and safe diagnostic method for coronary vasospasm. Regional left ventricular (LV) diastolic dysfunction may persist without systolic dysfunction after an episode of coronary vasospasm. Color kinesis (CK) has been recently developed to facilitate the echocardiographic evaluation of regional wall motion. HYPOTHESIS: Color kinesis may be useful for diagnosis of coronary vasospasm by detection of postischemic regional LV diastolic wall motion abnormality. METHODS: Fifty-one consecutive patients with the last chest symptom within 2 weeks (4 +/- 3 days) were studied echocardiographically. Regional fractional area change during the first 30% of LV filling time in percentage of the segmental end-diastolic area change (CK diastolic index) was used to identify diastolic endocardial motion asynchrony. RESULTS: After diagnostic coronary arteriography with spasm provocation, 26 patients were diagnosed with coronary spastic angina (CSA) and the other 25 with chest pain syndrome (CPS). Regional delayed relaxation (CK-diastolic index < or = 50%) or diastolic asynchrony had been observed in at least one region in 25 (96%) patients with CSA, whereas it had been noted in 2 (8%) patients with CPS. In 17 (65%) patients with CSA, it had been detected in multiple vascular territories, suggesting multivessel spasm. The diastolic asynchrony disappeared in CSA after a month of angina-free period. CONCLUSION: Analysis of CK images allows identification of regional LV delayed relaxation or diastolic asynchrony in patients with coronary vasospasm, differentiating them from patients with chest pain syndrome (sensitivity 96%, specificity 92%).