Reversible infantile hypoglycorrhachia: possible transient disturbance in glucose transport?

Facilitated glucose transporter isoform 1 deficiency syndrome (GLUT1 DS), caused by impaired GLUT1-mediated glucose transport into the brain, is characterized by hypoglycorrhachia. The defect in the facilitative glucose transporter isoform 1 (GLUT1) can be confirmed by functional, quantitative, and molecular analyses. Diagnostic difficulties arise when these analyses are normal and hypoglycorrhachia remains unexplained. Three infants presenting with seizures and hypoglycorrhachia at 2, 4, and 6 weeks of age, which suggests GLUT1 deficiency syndrome, are reported. The seizures responded to a ketogenic diet in Patients 1 and 3 and phenobarbitone in Patient 2. Repeated GLUT1 analyses were normal. When treatment was discontinued, all patients remained seizure-free and developed normally. Subsequent lumbar punctures showed the return to normoglycorrhachia. We conclude that these cases might represent a transient disturbance in GLUT1-mediated glucose transport. The biomolecular basis for this clinical observation remains unknown. Though no treatment is required, clinical follow-up and repeated lumbar punctures are necessary to distinguish this benign condition from the original GLUT1 deficiency syndrome.     

Sudden hemiparesis as the presenting sign in cryptococcal meningoencephalitis

A previously healthy young man presented with an acute stroke syndrome and was found to have cryptococcal organisms in the CSF. Though an initial CSF examination for an infectious etiology was negative, a second lumbar puncture was performed because of hypoglycorrhachia, which established the diagnosis. An uneventful recovery followed the administration of Amphotericin B and 5-Flucytosine. A literature search revealed only one previously reported case of cryptococcal meningoencephalitis presenting as a stroke. The need for performing a CSF examination on young patients presenting with a cerebrovascular event, and the aggressive investigation of unexplained hypoglycorrhachia are emphasized.     

Developmental outcomes and prevalence of SLC2A1 variants in young infants with hypoglycorrhachia

IntroductionThe neurodevelopmental outcomes of young infants with hypoglycorrhachia that is comparable to glucose transporter 1 deficiency syndrome (GLUT1DS), i.e. cerebrospinal fluid (CSF) glucose ≤40 mg/dL and CSF lactate <2.2 mM without causes of secondary hypoglycorrhachia are unknown. This study investigated the developmental outcomes and possibility of GLUT1DS in infants with hypoglycorrhachia, or low CSF glucose concentration.Material and methods1655 neurologically asymptomatic infants aged <4 months had CSF examinations for fever workup from 2006 to 2016. Among the infants with normal CSF cell counts and without isolated pathogens, there were hypoglycorrhachia group who had CSF glucose levels that were comparable to GLUT1DS, and age- and gender-matched non-hypoglycorrhachia group. Both groups were at a mean age of 5.9 ± 2.4 years (ranged 1–10 years) at neurodevelopmental evaluation in 2017. Mutational analysis of solute-carrier-family 2, which facilitated the glucose transporter member 1 (SLC2A1) gene was performed.ResultsAmong the 722 infants with normal CSF cell counts and without isolated pathogens, 30 (4.2%) had hypoglycorrhachia that was comparable to GLUT1DS. In the 25 infants with hypoglycorrhachia available for follow-up, 4 (16%) had abnormal outcomes, of which 3 (12%) had the history of mixed-type developmental delay before age 6 and 1 (4%) had type 1 diabetes mellitus. In the non-hypoglycorrhachia control group (n = 50), 2 patients (4%) showed abnormal outcomes, both with the history of pure speech delay. The hypoglycorrhachia group had a higher rate of the history of mixed-type of developmental delay than the control group (12% vs. 0%, P = 0.034). No SLC2A1 pathogenic variants were observed in the hypoglycorrhachia group.ConclusionHypoglycorrhachia may be a potential biomarker for neurodevelopmental delay instead of for GLUT1DS in neurologically asymptomatic young infants.     

Clinical presentation, EEG studies, and novel mutations in two cases of GLUT1 deficiency syndrome in Japan

We report the first two Japanese children diagnosed with glucose transporter type 1 (GLUT1) deficiency syndrome. Both boys had been treated under the initial diagnosis of epilepsy and were reinvestigated for previously unexplainable hypoglycorrhachia. Myoclonic seizures developed at 4 months of age in Patient #1 (7 years old), and at 2 months of age in Patient #2 (11 years old), followed by cerebellar ataxia, spastic diplegia, and mental retardation. Both patients had hypoglycorrhachia, and the symptoms were more severe in the latter. CSF and serum glucose levels determined simultaneously showed a CSF/serum glucose ratio of below 0.4 in both patients. In mildly affected Patient #1, the postprandial waking EEG showed improvement in the background activity, as compared to that recorded after overnight fasting, while no significant changes were observed in severely affected Patient #2. In both patients, the functional GLUT1 defect was confirmed by 3-O-methyl-D-glucose uptake into erythrocytes. Molecular analyses identified heterozygous novel mutations in both patients, within exons 6 and 2 of the GLUT1 gene, respectively. The ketogenic diet was refused in Patient #1, but started in Patient #2 with significant clinical benefit. Fasting CSF analysis and pre-/postprandial EEG changes in children with epileptic seizures and unexplainable neurological deterioration help in diagnosing this potentially treatable disorder.     

重型颅脑损伤术中急性脑膨出治疗体会

目的探讨影响重型颅脑损伤开颅术中急性脑膨出的原因及有效防止措施。方法回顾分析我院2009-01—2010-12收治的12例重型颅脑损伤术中急性脑膨出采取新处理方法的病例资料作为研究组,同时选择2007-01—2008-12收治的9例重型颅脑损伤术中急性脑膨出病例资料作为对照组,分析2组的疗效。结果研究组恢复较好5例,重残5例,死亡2例;对照组恢复较好1例,重残3例,死亡5例。2组比较差异有统计学意义(P<0.05)。结论重型颅脑损伤术中发生急性脑膨出,要排除迟发颅内血肿后采取控制降压、过度换气、脑室引流、切除颞叶脑组织等综合措施,能够明显提高治疗效果,降低致残率和病死率。     

Cerebral vasculitis with aneurysms caused by varicella-zoster virus infection during AIDS: a new clinicoangiographical syndrome

We describe three cases of cerebral angiopathy with aneurysms caused by a meningeal varicella-zoster virus infection occurring during AIDS. The clinical picture was rather stereotyped: severe immunocompromission due to HIV infection, ongoing multifocal cerebrovascular disease with territorial infarcts, lymphocytic meningitis with normal glucose content (two cases) or hypoglycorrhachia (one case), multifocal cerebral vasculopathy with narrowings and aneurysms, healing with or without neurological sequelae after intravenous aciclovir treatment. The diagnosis of varicella-zoster virus-induced angiopathy was ascertained by the positive specific PCR in the CSF in the three cases and by the results of the cerebromeningeal biopsy in one case. Although, varicella-zoster virus is already known as a cause of cerebral angiopathy both in the immunocompetent and the immunocompromised, these three cases are the first ever described of a particular angiopathy with narrowings and ectasias complicating AIDS. The infectious treatable cause and the risk of aggravation without treatment require early active oriented investigations in case of a patient with cerebrovascular disease occurring during HIV infection, including a CSF study with varicella-zoster PCR, to allow specific antiviral treatment. In our three cases, aciclovir intravenous treatment (30mg/kg per day) enabled VZ virus clearing from the CSF and stopped the course of the vasculopathy.     

The course of tardive dystonia in Afro Caribbean patients, a population-based study: the Curacao extrapyramidal syndromes study: VII

Tardive dystonia (TDt) is a severe side effect of long-term use of antipsychotics. Previous publications suggested that TDt persist but the results are distorted by referral bias. In a population-based nine-year follow-up study (one baseline, six follow-ups) of chronic psychiatric patients (N=194) on a Caribbean island, the course of prevalent and incident TDt was measured with the Fahn-Marsden rating scale. Of the 26 patients (mean age 53.3 yrs) with TDt at baseline, 64% recovered, 20% persisted, and in 16% the course was intermittent. The severity of baseline TDt was significantly higher in persistent cases versus those who recovered (t=3.01, P<0.008). Of the 27 incident cases (cumulative 9-year incidence: 16.1%; mean age 57.6 yrs), 80% recovered, 8% persisted, and in 12% the course was intermittent. Predominantly affected were hands, eyes (blepharospasm), neck and mouth. The natural course of TDt is better than previously suggested but severe cases tend to persist.     

Diagnostic yield of capillary compared to venous glucose in the diagnosis of hypoglycorrhachia in children: A prospective,observational study

IntroductionThe ratio of cerebrospinal fluid (CSF) glucose and blood glucose is of major relevance, conducting to the diagnosis of hypoglycorrhachia, which is a sign of neuroinfection, as well as a number of neurological diseases of genetic or neoplastic etiology. Glucose in capillary sample (glucometry) is a low cost, readily available technique, as compared to venous glucose. This study aims to compare glucometry to venous glucose in the diagnosis of hypoglycorrhachia in pediatric population.MethodsProspective cross-sectional study based on data obtained from lumbar punctures in the period from February 2017 to January 2019 in a specialized pediatric institution in Colombia.Results97 patients were analyzed, aged 1 month to 17 years old, mean 7.67 years, 52 (53.61%) were female. 26 (26.8%) were diagnosed with hypoglycorrhachia. Pearson correlation coefficient for absolute venous and capillary glucose was 0.54, and 0.55 for the ratios of CSF glucose/venous glucose and CSF glucose/glucometry, which support a linear correlation between the variables in both, absolute values and ratios. Intraclass correlation coefficient was calculated for both, the venous glucose and glucometry ratios, which was 0.52, revealing a moderate agreement among the tests. Sensitivity and specificity of CSF glucose/glucometry, as compared to gold standard are 73.1% and 60.6% respectively; whereas predictive positive value (PPV) and negative predictive value (NPV), were 40.4% and 86.0%.ConclusionGlucometry cannot replace the glucose in venous sample in the diagnosis of hypoglycorrhachia in children.     

Efficacy of methylprednisolone pulse and mild hypothermia therapies in patients with acute encephalopathy

Five patients with acute encephalopathy underwent methylprednisolone pulse (mPSL-P), hypothermia and their combination therapies (3 cases, 1 case and 1 case, respectively), with excellent outcome. Two cases with severe brain edema survived. One had severe brain damage as a sequelae. The remaining one recovered well after the combination therapy with mPSL-p and mild hypothermia, despite complete obstruction of the fourth ventricle on the first CT scan; the sequelae, hemiplegia and intelligent disturbance, was only mild. Four patients who received mPSL-P therapy within 6 hours after the onset of CNS symptoms recovered well though one was left with epilepsy. These results indicate that mPSL-P and/or hypothermia therapy will be chosen as the treatment of acute encephalopathy.     

骶骨骨折并发骶神经损伤的手术治疗

目的探讨骶骨骨折并发骶神经损伤的手术疗效。方法回顾性分析采用手术治疗的32例并发骶神经损伤的骶骨骨折患者的临床及手术资料。结果全组32例均获得随访,随访时间10～50个月,中位随访时间27个月,未见内固定松动或断裂、切口感染、骨折不愈合及双下肢明显不等长等手术并发症。20例未行骶神经减压术者中（A组）,16例神经损伤完全恢复,3例部分恢复,1例未恢复;12例行骶神经减压术者中,6例完全恢复,5例部分恢复,1例未恢复。根据Majeed评分标准,A组优8例,良8例,中3例,差1例;B组优4例,良5例,中2例,差1例。结论经皮重建钢板内固定术有利于骨折的复位和骶神经损伤的功能恢复,骶神经明显受压时需同时行骶神经减压术。     

简易运动评分与GCS对颅脑损伤伤情评价的比较

目的探讨简易运动评分(SMS)对颅脑损伤伤病情评价的可靠性。方法对72例颅脑损伤患者,分别行SMS和GCS评价并比较其伤情和不同伤情患者的预后。结果两种评价均为颅脑损伤轻型者57例,均为中重型者12例;有3例GCS评为中重型,而SMS评为轻型;SMS与GCS对伤情的评价无明显差异(P>0.05)。两种方法均评为重型者4例,3例恢复差(GOS1～3分),1例恢复良好(GOS4～5分);8例均为中型者,2例恢复差,6例良好;57例均为轻型者均恢复良好;3例GCS评为中型,而SMS评为轻型者均恢复良好。SMS与GCS分别评为颅脑损伤轻型或中型或轻型者中,预后无明显差异(P>0.05)。结论与GCS相比,SMS可作为脑损伤病情的评价方法之一,简便易行,结果可靠。     

血肿腔置水囊对防止脑出血术后再出血的临床疗效

目的探讨高血压脑出血术后应用水囊血肿腔压迫防止近期再出血的临床效果。方法选择106例适合手术治疗的高血压脑出血病人,随机分为水囊组48例,清除血肿术后血肿腔应用双腔水囊管压迫并引流,24 h后分次水囊放水,3d后拔除引流管。对照组58例,清除血肿术后硬膜下置普通引流管引流,术后2~3 d拔除引流管。术后拔管前复查头部CT,了解再出血、脑水肿等情况,2组间进行比较,治疗康复3个月后根据GOS评分进行疗效判断。结果水囊组术后继发再出血2例,恢复良好16例,中残18例,重残9例,死亡5例。对照组再出血7例,恢复良好14例,中残21例,重残11例,死亡12例。结论高血压脑出血术后血肿腔置水囊对防止术后近期再出血有可靠效果,并提高了其抢救成功率。     

眶尖综合征18例临床分析

目的探讨眶尖综合征的临床特征、病因和预后。方法回顾性总结18例眶尖综合征患者的临床资料,并结合文献进行分析。结果所有患者均出现视力减退、眼睑下垂、复视、前额头痛或眼痛等表现,但其首发症状可不同,视力下降或丧失8例,头痛、眼痛者7例,牙痛1例,鼻塞、流涕1例和眼球突出的1例。病因包括外伤6例(33%),占位5例(28%),非特异性炎症4例(22%)、感染3例(17%)。住院期间6例外伤性患者中视力、眼球活动障碍等症状有好转的5例,其中3例病情较轻者恢复更好,1例受伤较重的无好转;5例占位患者中1例蝶窦粘液囊肿患者手术后视力、眼球活动障碍等症状均有好转,其余4例诊断为眼眶腺样囊性癌或放疗后骨肉瘤患者无好转;4例非特异性炎症疾病患者治疗后2例视力、眼球活动障碍等症状较轻、病程较短的有好转,而另2例症状较重、病程较长的症状则无明显好转;3例感染性疾病者1例病程较短的症状有好转,而另2例病程较长或合并颅内感染患者无好转。结论眶尖综合征由多种病因引起,首发症状具有多样性,其预后与病因、是否及时就诊、早期诊断和早期治疗相关。     

Fungal infections of the central nervous system in HIV-negative patients: Experience from a tertiary referral center of South India

Objective:

To describe the clinical, radiological, and cerebrovascular fluid (CSF) findings and the outcome of microbiologically or histopathologically proven fungal infections of the central nervous system (CNS) in HIV-negative patients.

Methodology and Results:

We identified definite cases of CNS mycosis by screening the medical records of our institute for the period 2000–2008. The clinical and imaging details and the outcome were abstracted from the medical records and entered in a structured proforma. There were 12 patients with CNS mycosis (i.e., 2.7% of all CNS infections treated in this hospital); six (50%) had cryptococcal infection, three (25%) had mucormycosis, and two had unclassified fungal infection. Four (33%) of them had diabetes as a predisposing factor. The common presentations were meningoencephalitis (58%) and polycranial neuritis (41%). Magnetic resonance imaging revealed hydrocephalus in 41% and meningeal enhancement in 25%, as well as some unusual findings such as subdural hematoma in the bulbocervical region, carpeting lesion of the base of the skull, and enhancing lesion in the cerebellopontine angle. The CSF showed pleocytosis (66%), hypoglycorrhachia (83%), and elevated protein levels (100%). The diagnosis was confirmed by meningocortical biopsy (in three cases), paranasal sinus biopsy (in four cases), CSF culture (in three cases), India ink preparation (in four cases), or by cryptococcal polysaccharide antigen test (in three cases). Out of the ten patients for whom follow-up details were available, six patients recovered with antifungal medications (amphotericin B, 1 mg/kg/day for the minimum period of 6 weeks) and/or surgical treatment. Four patients expired (only one of them had received antifungal therapy).

Conclusions:

Most patients with CNS mycosis recover with appropriate therapy, but the diagnosis and management of these rare infections remains a challenge to clinicians.     

Rheumatoid disease with encephalopathy

A 63-year-old woman developed progressive rheumatoid disease complicated by a confusional state as well as persistent cerebrospinal fluid pleocytosis and hypoglycorrhachia. Neuropathological examination revealed extensive rheumatoid lesions in the cranial dura, falx, and choroid plexus. The choroid plexus has not been affected in any of the 16 previously reported cases of pathologically verified rheumatoid disease of the central nervous system. The findings in this patient support the observations of others regarding the role of the choroid plexus in development of CNS manifestations in systemic immune complex disease.     

结核性脑膜脑炎并发结核性脊髓神经根炎的临床特点1例报道

目的总结结核性脑膜脑炎并发结核性脊髓神经根炎病例的临床特点。方法对国内文献报道的结核性脑膜脑炎并发结核性脊髓神经根炎病例的临床资料进行回顾总结。结果患者均为中青年,首发症状为头痛、发热、脑膜刺激征等,逐渐出现截瘫、大小便障碍、传导束型感觉障碍等脊髓受累表现,脑脊液检查提示初压高,蛋白、细胞数增多,糖降低,磁共振提示颅内及脊髓病灶伴脑脊髓膜强化,抗结核药物联合激素治疗有效。结论结核性脑膜脑炎患者出现脊髓病变症状体征,需警惕并发结核性脊髓神经根炎,脑脊液结果及增强磁共振有助于诊断。     

108例新生儿缺氧缺血性脑病诊治分析

目的探讨新生儿缺氧缺血性脑病的诊治方法,降低病残率及病死率。方法对5年来收治的108例新生儿缺氧缺血性脑病患儿的临床表现、诊治过程及病因以及出院后随访情况进行分析。结果108例患儿中87例存在两种以上的病因,由唯一原因而致病者仅21例。头部影像学显示脑水肿75例,颅内出血34例,其中对90例出院患儿进行了1/2~1年的随访,48例轻度患儿临床及影像学检查均完全恢复,40例中度患儿中完全恢复28例,20例重度患儿中只有5例患儿完全康复,6例死亡,其余均有严重的后遗症且影像学多有脑出血表现。结论新生儿缺氧缺血性脑病的病因复杂,临床表现多样,疾病严重程度及诊治早晚与预后密切相关;在预防、诊断及治疗三个层面早期干预可降低此病的发生率、病残率及病死率。     

显微手术天幕缘切开在创伤性脑疝复位中的应用

目的 探讨显微手术天幕缘切开、罂粟碱明胶海棉片贴敷在重型颅脑损伤颞叶钩回疝形成患者中的应用.方法 对我科自1999年1月到2004年3月收治的92例重型颅脑损伤合并颞叶钩回疝继发脑干损伤患者,在开颅清除血肿的基础上加行显微镜下天幕缘切开、环池冲洗、罂粟碱明胶海棉贴敷.结果 GCS 3～5分30例,6～8分62例.恢复良好47例(51.0%),中残19例(20.6%),重残7例(7.6%),植物生存8例(8.7%),死亡11例(11.9%).结论 显微手术天幕缘切开、罂粟碱明胶海棉片贴敷能够彻底解除脑干受压、防治血管痉挛进而减轻由此引发的脑干继发性损伤,降低病残率和死亡率.     

Cerebrospinal fluid glucose and leukocyte responses in experimental meningitis

The fall in cerebrospinal fluid (CSF) glucose and CSF leukocyte response was studied in cats with experimental meningitis. Klebsiella pneumoniae or Streptococcus pneumoniae were injected intracisternally, and the latter organisms were incubated with CSF in vitro. When 10(6)-10(9)K. pneumoniae were incubated with 4 ml of CSF, the time time necessary for the glucose to decrease to less than 10 mg/dl ranged from 6.5 to 2.5 h, at a rate proportional to the size of the inoculum. When the same numbers of bacteria were injected intracisternally, the time ranged from 9 to 3 h, and the CSF leukocyte response did not exceed 1200 WBC/mm3. At this time, only minimal histological changes in brain and choroid plexus were seen. Twenty hours after intrathecal K. pneumoniae, large numbers of leukocytes (up to 4 X 10(4)/mm3) were recovered from the CSF. Regardless of the number of leukocytes, however, hypoglycorrhachia occurred when the CSF contained more than 10(7) bacteria/ml. At this interval, large numbers of leukocytes were seen invading the stroma of the choroid plexus, leptomeninges and perivascular spaces. When 10(8) S. pneumoniae were injected intracisternally, CSF glucose concentration decreased as rapidly as with K. pneumoniae. The spinal fluid leukocyte response to S. pneumoniae was, however, greater than that to K. pneumoniae. These results suggest that under the conditions of these studies, hypoglycorrhachia of bacterial meningitis is the result of metabolism of the bacteria with little contribution from the leukocytes.     

桥小脑角及斜坡肿瘤手术并发症的原因分析

目的探讨桥小脑角及斜坡区肿瘤手术严重并发症发生的原因。方法回顾性分析了宣武医院1998年至2004年86例该区域手术治疗患者的临床资料。结果86例患者中，术后脑干损伤3例（2例死亡），小脑肿胀导致脑疝死亡1例，瘤腔血肿2例，后组颅神经损伤19例（10d内症状减轻8例）。结论手术者预测不同肿瘤患者可能出现局部解剖关系的变化和手术中可能出现的困难，结合手术中的具体情况，运用良好的手术技巧，这一区域手术的严重并发症的发生是可以减少的。