BMC Neurology

Published by Springer Nature

Online ISSN: 1471-2377


Table 1 Outcome variables and assesment schedule
Flowchart outlining the trial protocol.
Hydroxyethyl starch 130/0.4 and sodium chloride injection as adjunctive therapy in patients with cerebral hypoperfusion
  • Article
  • Full-text available

October 2012


105 Reads


Fang Yang





Background Both severe stenosis and completed occlusion in internal carotid artery or its distal branches have been considered the main reasons of cerebral hypoperfusion, which contributes to the washout disturbances of embolism in low perfusion territories distal to stenosis. An aggravated hypoperfusion state in certain brain region may induce ischemic stroke and further cognitive decline. However, the effective medication for cerebral hypoperfusion is largely unsettled. Methods/design By using computed tomography perfusion (CTP) imaging, the trial will evaluate the effectiveness, safety and tolerability of hydroxyethyl starch (HES) 130/0.4 for patients with extra-/intra-cranial artery stenosis and cerebral hypoperfusion. From 5 neurological inpatient wards, 300 patients will be randomly recruited for administered routine medications plus intravascular volume therapies using the equal volume of HES 130/0.4 or 0.9% sodium chloride solution. Cerebral hypoperfusion state after 7-day intervention is the primary outcome measure. The secondary outcome measures includes, impaired renal function, abnormal heart function, hematological changes, neurological dysfunctions and cerebrovascular events in peri-intervention period and/or 3-month follow-up. The sample size will allow the detection of a two-sided 5% significance level between groups in the endpoint with a power of 80%. Discussion The trial would provide important efficacy and safety data on the intravascular administration of HES 130/0.4 in patients with unilateral cerebral hypoperfusion. The effects on kidney function, heart function, coagulation, neurological function and cerebralvascular events will be assessed. Trial registration (Identifier: NCT01192581)

Table 1 Safety Blood Tests
Table 2 Visit Schedule
Protocol for a double-blind randomised placebo-controlled trial of lithium carbonate in patients with amyotrophic Lateral Sclerosis (LiCALS) [Eudract number: 2008-006891-31]

September 2011


81 Reads

Amyotrophic lateral sclerosis is a rapidly progressive neurodegenerative disorder characterised by loss of motor neurons leading to severe weakness and death from respiratory failure within 3-5 years. Riluzole prolongs survival in ALS. A published report has suggested a dramatic effect of lithium carbonate on survival. 44 patients were studied, with 16 randomly selected to take LiCO3 and riluzole and 28 allocated to take riluzole alone. In the group treated with lithium, no patients had died (i.e., 100% survival) at the end of the study (15 months from entry), compared to 71% surviving in the riluzole-only group. Although the trial can be criticised on several grounds, there is a substantial rationale from other laboratory studies that lithium is worth investigating therapeutically in amyotrophic lateral sclerosis. LiCALS is a multi-centre double-blind randomised parallel group controlled trial of the efficacy, safety, and tolerability of lithium carbonate (LiCO3) at doses to achieve stable 'therapeutic' plasma levels (0.4-0.8 mmol/L), plus standard treatment, versus matched placebo plus standard treatment, in patients with amyotrophic lateral sclerosis. The study will be based in the UK, in partnership with the MND Association and DeNDRoN (the Dementias and Neurodegnerative Diseases Clinical Research Network). 220 patients will be recruited. All patients will be on the standard treatment for ALS of riluzole 100 mg daily. The primary outcome measure will be death from any cause at 18 months defined from the date of randomisation. Secondary outcome measures will be changes in three functional rating scales, the ALS Functional Rating Scale-Revised, The EuroQOL (EQ-5D), and the Hospital Anxiety and Depression Scale.Eligible patients will have El Escorial Possible, Laboratory-supported Probable, Probable or Definite amyotrophic lateral sclerosis with disease duration between 6 months and 36 months (inclusive), vital capacity ≥ 60% of predicted within 1 month prior to randomisation and age at least18 years. Patient recruitment began in June 2009 and the last patient is expected to complete the trial protocol in November 2011. Current controlled trials ISRCTN83178718.

Hyperintense putaminal rim at 1.5 T: Prevalence in normal subjects and distinguishing features from multiple system atrophy

June 2012


207 Reads

Abstract Background Hyperintense putaminal rim (HPR) is an important magnetic resonance imaging (MRI) sign for multiple system atrophy (MSA). Recent studies have suggested that it can also be observed in normal subjects at 3 T. Whether it can be observed in normal subjects at 1.5 T is not known. This study aimed to determine whether HPR could be observed in normal subjects at 1.5 T; and if so, to establish its prevalence, the MRI characteristics, and the features which distinguish from HPR in MSA patients. Methods Axial T2-weighted images of 130 normal subjects were evaluated for the prevalence of HPR, its age and gender distribution, laterality, maximum dimension, association with hypointensity of nearby putamen, and presence of discontinuity. To distinguish from that observed in MSA, axial T2-weighted images of 6 MSA patients with predominant parkinsonism (MSA-P) and 15 MSA patients with predominant cerebellar symptoms (MSA-C) were also evaluated. The characteristics of HPR were compared between these patients and age-matched normal subjects. The mean diffusivity (MD) values of putamen were also compared. Fisher’s exact test, t-test, and one way analysis of variance were used to determine significance at corrected p

Table 1 : MRI protocol parameters in detail
Table 2 : Comparative synopsis of the 1000Plus, EPITHET and DEFUSE projects
Study Design.
Prospective study on the mismatch concept in acute stroke patients within the first 24 h after symptom onset - 1000Plus study

December 2009


440 Reads

The mismatch between diffusion weighted imaging (DWI) lesion and perfusion imaging (PI) deficit volumes has been used as a surrogate of ischemic penumbra. This pathophysiology-orientated patient selection criterion for acute stroke treatment may have the potential to replace a fixed time window. Two recent trials - DEFUSE and EPITHET - investigated the mismatch concept in a multicenter prospective approach. Both studies randomized highly selected patients (n = 74/n = 100) and therefore confirmation in a large consecutive cohort is desirable. We here present a single-center approach with a 3T MR tomograph next door to the stroke unit, serving as a bridge from the ER to the stroke unit to screen all TIA and stroke patients. Our primary hypothesis is that the prognostic value of the mismatch concept is depending on the vessel status. Primary endpoint of the study is infarct growth determined by imaging, secondary endpoints are neurological deficit on day 5-7 and functional outcome after 3 months. 1000Plus is a prospective, single centre observational study with 1200 patients to be recruited. All patients admitted to the ER with the clinical diagnosis of an acute cerebrovascular event within 24 hours after symptom onset are screened. Examinations are performed on day 1, 2 and 5-7 with neurological examination including National Institute of Health Stroke Scale (NIHSS) scoring and stroke MRI including T2*, DWI, TOF-MRA, FLAIR and PI. PI is conducted as dynamic susceptibility-enhanced contrast imaging with a fixed dosage of 5 ml 1 M Gadobutrol. For post-processing of PI, mean transit time (MTT) parametric images are determined by deconvolution of the arterial input function (AIF) which is automatically identified. Lesion volumes and mismatch are measured and calculated by using the perfusion mismatch analyzer (PMA) software from ASIST-Japan. Primary endpoint is the change of infarct size between baseline examination and day 5-7 follow up. The aim of this study is to describe the incidence of mismatch and the predictive value of PI for final lesion size and functional outcome depending on delay of imaging and vascular recanalization. It is crucial to standardize PI for future randomized clinical trials as for individual therapeutic decisions and we expect to contribute to this challenging task. NCT00715533.

Table 1 : Oxidative stress, antioxidant biomarkers and S-100B protein levels in the serum and CSF of the studied group
Table 2 : Comparison between the serum and CSF concentrations of oxidative stress, antioxidant biomarkers and S-100B protein among patients with positive and negative CSF culture for bacteria
Oxidative stress and S-100B protein in children with bacterial meningitis

October 2009


100 Reads

Bacterial meningitis is often associated with cerebral compromise which may be responsible for neurological sequelae in nearly half of the survivors. Little is known about the mechanisms of CNS involvement in bacterial meningitis. Several studies have provided substantial evidence for the key role of nitric oxide (NO) and reactive oxygen species in the complex pathophysiology of bacterial meningitis. In the present study, serum and CSF levels of NO, lipid peroxide (LPO) (mediators for oxidative stress and lipid peroxidation); total thiol, superoxide dismutase (SOD) (antioxidant mediators) and S-100B protein (mediator of astrocytes activation and injury), were investigated in children with bacterial meningitis (n = 40). Albumin ratio (CSF/serum) is a marker of blood-CSF barriers integrity, while mediator index (mediator ratio/albumin ratio) is indicative of intrathecal synthesis. Compared to normal children (n = 20), patients had lower serum albumin but higher NO, LPO, total thiol, SOD and S-100B. The ratios and indices of NO and LPO indicate blood-CSF barriers dysfunction, while the ratio of S-100B indicates intrathecal synthesis. Changes were marked among patients with positive culture and those with neurological complications. Positive correlation was found between NO index with CSF WBCs (r = 0.319, p < 0.05); CSF-LPO with CSF-protein (r = 0.423, p < 0.01); total thiol with LPO indices (r = 0.725, p < 0.0001); S-100B and Pediatric Glasow Coma Scores (0.608, p < 0.0001); CSF-LPO with CSF-S-100B (r = 0.482, p < 0.002); serum-total thiol with serum S-100B (r = 0.423, p < 0.01). This study suggests that loss of integrity of brain-CSF barriers, oxidative stress and S-100B may contribute to the severity and neurological complications of bacterial meningitis.

Table 1 Demographic data 
Table 3 Immune-mediated encephalitis 
Autoimmune causes of encephalitis syndrome in Thailand: Prospective study of 103 patients

October 2013


141 Reads

Data on encephalitis in Thailand have not been completely described. Etiologies remain largely unknown. We prospectively analyzed 103 Thai patients from 27 provinces for the causes of encephalitis using clinical, microbiological and neuroimaging indices; caseswithout a diagnosis were evaluated for autoimmune causes of encephalitis. Patients with encephalitis and/or myelitis were prospectively studied between October 2010 and August 2012. Cases associated with bacterial, rickettsial and mycobacterial diseases were excluded. Herpes viruses 1-6 and enteroviruses infection was diagnosed using PCR evaluation of CSF; dengue and JE viruses infection, by serology. The serum of test-negative patients was evaluated for the presence of autoantibodies. 103 patients were recruited. Fifty-three patients (52%) had no etiologies identified. Twenty-five patients (24%) were associated with infections. Immune encephalitis was found in 25 (24%); neuropsychiatric lupus erythematosus (4), demyelinating diseases (3), Behcet's disease (1) and the remaining had antibodies to NMDAR (5), ANNA-2 (6), Yo (2), AMPA (1), GABA (1), VGKC (1) and NMDA coexisting with ANNA-2 (1). Presenting symptoms in the autoimmune group included behavioral changes in 6/25 (versus 12/25 in infectious and 13/53 in unknown group) and as psychosis in 6/25 (versus 0/25 infectious and 2/53 unknown). Seizures were found in 6/25 autoimmune, 4/25 infectious and 19/53 unknown group. Two patients with anti-ANNA-2 and one anti-Yo had temporal lobe involvement by magnetic resonance imaging. Two immune encephalitis patients with antibodies to NMDAR and ANNA-2 had ovarian tumors. Autoantibody-associated encephalitis should be considered in the differential diagnosis and management algorithm regardless of clinical and neuroimaging features.

Table 2 Neurophysiological data of patients with GBS 
Table 3 Proportion of patients, based on the GBS score, during the follow-up 
Table 4 Possible predictor factors of a poor outcome 
Guillain-Barré Syndrome: Natural history and prognostic factors: A retrospective review of 106 cases

July 2013


716 Reads

Guillain-Barre syndrome (GBS) is characterized by acute onset and progressive course, and is usually associated with a good prognosis. However, there are forms of poor prognosis, needing ventilatory support and major deficits at discharge. With this study we try to identify the factors associated with a worse outcome. 106 cases of GBS admitted in our hospital between years 2000--2010 were reviewed. Epidemiological, clinical, therapeutical and evolutionary data were collected. At admission 45% had severe deficits, percentage which improves throughout the evolution of the illness, with full recovery or minor deficits in the 87% of patients at the first year review. Ages greater than 55 years, severity at admission (p < 0.001), injured cranial nerves (p = 0.008) and the needing of ventilator support (p = 0.003) were associated with greater sequels at the discharge and at the posterior reviews in the following months. 17% required mechanical ventilation (MV). Values < 250 L/min in the Peak Flow-test are associated with an increased likelihood of requiring MV (p < 0.001). Older age, severe deficits at onset, injured cranial nerves, requiring MV, and axonal lesion patterns in the NCS were demonstrated as poor prognostic factors. Peak Flow-test is a useful predictive factor of respiratory failure by its easy management.

PFGE and the BglII/BlnI dosage test A) Patterns of translocation between chromosome 4q35 and 10q26 KpnI units. Subtelomeric translocation changes the number of BlnI-resistant (from chromosome 4q35) and BlnI-sensitive (from chromosome 10q26) fragments. According to the number of units from chromosome 4, each individual is classified as nullsomy, monosomy, disomy, trisomy or quatrosomy. B) BglII/BlnI dosage test. Double enzyme digestion with BglII and BlnI characterizes the first KpnI unit as a 4.0-kb fragment from chromosome 4q35 or a 1.8-kb fragment from chromosome 10q26. The ratio estimated from the intensity of the two fragments are; nullsomy (N) = 0 (0/4), monosomy (M) = 0.3 (1/3), disomy (D) = 1 (2/2), trisomy (T) = 3 (3/1), and quatrosomy (Q) = infinity (4/0). C) Comparison of the dosage test with PFGE. Thirty Japanese individuals were examined using both PFGE and the dosage test. The ratio from the dosage test was consistent with the results of PFGE in all samples. D: disomy, T: trisomy E/H: EcoRI/HindIII, E/B: EcoRI/BlnI, M: Marker
Frequency of the translocation between chromosomes 4q35 and 10q26 The 4 on 10 (trisomy and quatrosomy) is more frequently observed than 10 on 4 (nullsomy and monosomy) in all populations examined, although these were similar in the Dutch population. The findings from the Dutch population were estimated from the results of PFGE [7].
Chromosome 4q;10q translocations; Comparison with different ethnic populations and FSHD patients

September 2002


273 Reads

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disorder characterized by the weakness of facial, shoulder-girdle and upper arm muscles. Most patients with FSHD have fewer numbers of tandem repeated 3.3-kb KpnI units on chromosome 4q35. Chromosome 10q26 contains highly homologous KpnI repeats, and inter-chromosomal translocation has been reported. To clarify the influence on the deletion of the repeats, we surveyed three different ethnic populations and FSHD patients using the BglII/BlnI dosage test. The frequency of translocation in 153 Japanese, 124 Korean, 114 Chinese healthy individuals and 56 Japanese 4q35-FSHD patients were 27.5%, 29.8%, 19.3%, and 32.1%, respectively. The ratio of '4 on 10' (trisomy and quatrosomy of chromosome 4) was higher than that of '10 on 4' (nullsomy and monosomy of chromosome 4) in all populations. The inter-chromosomal exchange was frequently observed in all four populations we examined, and no significant difference was observed between healthy and diseased groups.

Masked-Volume-Wise PCA and "reference Logan" illustrate similar regional differences in kinetic behavior in human brain PET study using [11C]-PIB

February 2009


66 Reads

Kinetic modeling using reference Logan is commonly used to analyze data obtained from dynamic Positron Emission Tomography (PET) studies on patients with Alzheimer's disease (AD) and healthy volunteers (HVs) using amyloid imaging agent N-methyl [11C]2-(4'-methylaminophenyl)-6-hydroxy-benzothiazole, [11C]-PIB. The aim of the present study was to explore whether results obtained using the newly introduced method, Masked Volume Wise Principal Component Analysis, MVW-PCA, were similar to the results obtained using reference Logan. MVW-PCA and reference Logan were performed on dynamic PET images obtained from four Alzheimer's disease (AD) patients on two occasions (baseline and follow-up) and on four healthy volunteers (HVs). Regions of interest (ROIs) of similar sizes were positioned in different parts of the brain in both AD patients and HVs where the difference between AD patients and HVs is largest. Signal-to-noise ratio (SNR) and discrimination power (DP) were calculated for images generated by the different methods and the results were compared both qualitatively and quantitatively. MVW-PCA generated images that illustrated similar regional binding patterns compared to reference Logan images and with slightly higher quality, enhanced contrast, improved SNR and DP, without being based on modeling assumptions. MVW-PCA also generated additional MVW-PC images by using the whole dataset, which illustrated regions with different and uncorrelated kinetic behaviors of the administered tracer. This additional information might improve the understanding of kinetic behavior of the administered tracer. MVW-PCA is a potential multivariate method that without modeling assumptions generates high quality images, which illustrated similar regional changes compared to modeling methods such as reference Logan. In addition, MVW-PCA could be used as a new technique, applicable not only on dynamic human brain studies but also on dynamic cardiac studies when using PET.

Karaszewski B, Thomas RGR, Dennis MS, Wardlaw JM. Temporal profile of body temperature in acute ischemic stroke: relation to stroke severity and outcome. BMC Neurol. 12:123

October 2012


218 Reads

Background Pyrexia after stroke (temperature ≥37.5°C) is associated with poor prognosis, but information on timing of body temperature changes and relationship to stroke severity and subtypes varies. Methods We recruited patients with acute ischemic stroke, measured stroke severity, stroke subtype and recorded four-hourly tympanic (body) temperature readings from admission to 120 hours after stroke. We sought causes of pyrexia and measured functional outcome at 90 days. We systematically summarised all relevant previous studies. Results Amongst 44 patients (21 males, mean age 72 years SD 11) with median National Institute of Health Stroke Score (NIHSS) 7 (range 0–28), 14 had total anterior circulation strokes (TACS). On admission all patients, both TACS and non-TACS, were normothermic (median 36.3°C vs 36.5°C, p=0.382 respectively) at median 4 hours (interquartile range, IQR, 2–8) after stroke; admission temperature and NIHSS were not associated (r2=0.0, p=0.353). Peak temperature, occurring at 35.5 (IQR 19.0 to 53.8) hours after stroke, was higher in TACS (37.7°C) than non-TACS (37.1°C, p<0.001) and was associated with admission NIHSS (r2=0.20, p=0.002). Poor outcome (modified Rankin Scale ≥3) at 90 days was associated with higher admission (36.6°C vs. 36.2°C p=0.031) and peak (37.4°C vs. 37.0°C, p=0.016) temperatures. Sixteen (36%) patients became pyrexial, in seven (44%) of whom we found no cause other than the stroke. Conclusions Normothermia is usual within the first 4 hours of stroke. Peak temperature occurs at 1.5 to 2 days after stroke, and is related to stroke severity/subtype and more closely associated with poor outcome than admission temperature. Temperature-outcome associations after stroke are complex, but normothermia on admission should not preclude randomisation of patients into trials of therapeutic hypothermia.

Table 1 Quality assessment results for included studies
Table 2 Characteristics of studies included in this systematic review
Table 4 Outcome measures: Cognitive tests used for two cognitive domains of memory and executive function/ processing speed
(A): Searching strategy retrieved from Ovid, (B): Flowchart of study selection.
Bolandzadeh N, Davis JC, Tam R, Handy TC, Liu-Ambrose T. The association between cognitive function and white matter lesion location in older adults: a systematic review. BMC Neurol 12: 126
Background Maintaining cognitive function is essential for healthy aging and to function autonomously within society. White matter lesions (WMLs) are associated with reduced cognitive function in older adults. However, whether their anatomical location moderates these associations is not well-established. This review systematically evaluates peer-reviewed evidence on the role of anatomical location in the association between WMLs and cognitive function. Methods In accordance with the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement, databases of EMBASE, PUBMED, MEDLINE, and CINAHL, and reference lists of selected papers were searched. We limited our search results to adults aged 60 years and older, and studies published in the English language from 2000 to 2011. Studies that investigated the association between cognitive function and WML location were included. Two independent reviewers extracted: 1) study characteristics including sample size, sample characteristic, and study design; 2) WML outcomes including WML location, WML quantification method (scoring or volume measurement), strength of the MRI magnet in Tesla, and MRI sequence used for WML detection; and 3) cognitive function outcomes including cognitive tests for two cognitive domains of memory and executive function/processing speed. Results Of the 14 studies included, seven compared the association of subcortical versus periventricular WMLs with cognitive function. Seven other studies investigated the association between WMLs in specific brain regions (e.g., frontal, parietal lobes) and cognitive function. Overall, the results show that a greater number of studies have found an association between periventricular WMLs and executive function/processing speed, than subcortical WMLs. However, whether WMLs in different brain regions have a differential effect on cognitive function remains unclear. Conclusions Evidence suggests that periventricular WMLs may have a significant negative impact on cognitive abilities of older adults. This finding may be influenced by study heterogeneity in: 1) MRI sequences, WML quantification methods, and neuropsychological batteries; 2) modifying effect of cardiovascular risk factors; and 3) quality of studies and lack of sample size calculation.

Circulating miR-30a, miR-126 and let-7b as biomarker for ischemic stroke in humans

November 2013


218 Reads

Recently, plasma miRNAs have been reported as biomarkers for various diseases. However, the knowledge on the association of plasma miRNAs with ischemic stroke is still lacking. In this study, we investigated weather plasma concentrations of miR-30a, miR-126 and let-7b may be biomarkers for ischemic stroke in humans. One hundred ninety seven patients with ischemic stroke were recruited and their blood samples were collected at 24 h, 1 week, 4 weeks, 24 weeks and 48 weeks after symptoms onset, and fifty healthy volunteers were collected as control. Levels of miRNA were quantified by quantitative real-time PCR. Relative expression level of miRNA was calculated using 2-DeltaDeltact method. The ability to distinguish the ischemic stroke group from control group was characterized by receiver operating characteristic (ROC) curve, and the area under ROC curve (AUC) was calculated. Circulating miR-30a and miR-126 levels were markedly down-regulated in all patients with ischemic stroke until 24 weeks. However, circulating let-7b was lower in patients with large-vessel atherosclerosis than healthy volunteers, whereas circulating let-7b had higher level in patients with other kinds of ischemic stroke until 24 weeks. Among all patients, circulating miRNAs levels returned to normal 48 weeks after symptom onset. Receiver operating characteristic (ROC) curve analysis showed that the areas under the curve (AUC) of plasma miR-30a were 0.91, 0.91, 0.92 and 0.93, the miR-126 were 0.92, 0.94, 0.93 and 0.92, and let-7b were 0.93, 0.92, 0.92 and 0.91 at 24 h, 1w, 4w and 24w, respectively. These data suggest that miR-30a, miR-126 and let-7b might be useful biomarkers for ischemic stroke in humans.

A novel form of human disease with a protease-sensitive prion protein and heterozygosity methionine/valine at codon 129: Case report

October 2010


234 Reads

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare neurodegenerative disorder in humans included in the group of Transmissible Spongiform Encephalopathies or prion diseases. The vast majority of sCJD cases are molecularly classified according to the abnormal prion protein (PrPSc) conformations along with polymorphism of codon 129 of the PRNP gene. Recently, a novel human disease, termed "protease-sensitive prionopathy", has been described. This disease shows a distinct clinical and neuropathological phenotype and it is associated to an abnormal prion protein more sensitive to protease digestion. We report the case of a 75-year-old-man who developed a clinical course and presented pathologic lesions compatible with sporadic Creutzfeldt-Jakob disease, and biochemical findings reminiscent of "protease-sensitive prionopathy". Neuropathological examinations revealed spongiform change mainly affecting the cerebral cortex, putamen/globus pallidus and thalamus, accompanied by mild astrocytosis and microgliosis, with slight involvement of the cerebellum. Confluent vacuoles were absent. Diffuse synaptic PrP deposits in these regions were largely removed following proteinase treatment. PrP deposition, as revealed with 3F4 and 1E4 antibodies, was markedly sensitive to pre-treatment with proteinase K. Molecular analysis of PrPSc showed an abnormal prion protein more sensitive to proteinase K digestion, with a five-band pattern of 28, 24, 21, 19, and 16 kDa, and three aglycosylated isoforms of 19, 16 and 6 kDa. This PrPSc was estimated to be 80% susceptible to digestion while the pathogenic prion protein associated with classical forms of sporadic Creutzfeldt-Jakob disease were only 2% (type VV2) and 23% (type MM1) susceptible. No mutations in the PRNP gene were found and genotype for codon 129 was heterozygous methionine/valine. A novel form of human disease with abnormal prion protein sensitive to protease and MV at codon 129 was described. Although clinical signs were compatible with sporadic Creutzfeldt-Jakob disease, the molecular subtype with the abnormal prion protein isoforms showing enhanced protease sensitivity was reminiscent of the "protease-sensitive prionopathy". It remains to be established whether the differences found between the latter and this case are due to the polymorphism at codon 129. Different degrees of proteinase K susceptibility were easily determined with the chemical polymer detection system which could help to detect proteinase-susceptible pathologic prion protein in diseases other than the classical ones.

Flow Cytometry of CD4+ IL23R+ T Cells. Expression of IL-23R subunit on the cell surface of CD4+T cells from MS patients treated with beta-interferon. (A) Results of one representative patient. (B) Percentage of IL-23R+ T cells from MS patients. Values are expressed as mean ± SEM. (C) Percentage of CD4+T cells expressing IL-23R in each MS patient treated with beta-interferon (n = 6).
Flow Cytometry of IL-12Rβ2+ CD4+ T cells from MS patients before, 24 hr and 7 d after treatment with beta-interferon. (A) Results of one representative patient. (B) Percentage of IL-12Rβ2+ T cells from MS patients shows that at 24 hours post treatment that there is an increase in this cell type that almost reaches statistical significance. Values are expressed as mean ± SEM. (C) Percentage of CD4+T cells expressing IL-12β2 in each MS patient treated with beta-interferon (n = 6).
IL-23R, IL-12Rβ2, STAT4 and phospho-STAT4 expression on CD4+T cells from MS patients treated with β-interferon. Western blot analysis of (A) IL-23R and IL-12BR2 (B) pSTAT4 and STAT4 were performed by using total proteins extracted from CD4+T cells from three patients before and after treatment with B-interferon. In each panel a polyacrylamde gel shows the results of one representative experiment. Densiometry reports the relative intensity of all three patients. GAPDH was used as the internal loading control. (Data shown are all from the same patient).
Preliminary study: Treatment with intramuscular interferon beta-1a results in increased levels of IL-12Rβ2and decreased levels of IL23RCD4T - Lymphocytes in multiple sclerosis

December 2011


114 Reads

There are a lack of biomarkers which can be used to predict clinical outcomes for multiple sclerosis (MS) patients receiving interferon beta (IFN-β). Thus the objective of this study was to characterize changes in CD4+ T-lymphocyte expression in an unbiased manner following initiation of intramuscular (IM) IFN-β-1a treatment, and then to verify those findings using marker-specific assays. Peripheral blood specimens were collected from twenty MS patients before and after treatment with intramuscular (IM) IFN-β-1a and were used for isolation of mononuclear cells (PBMCs). mRNA expression patterns of negatively-selected CD4+ T-cells from the PBMCs were analyzed using microarray gene expression technology. IL-12 and IL-23 receptor levels on PBMC-derived CD4+ T-cells were analyzed by flow cytometry. The phosphorylation status of Stat4 was measured by performing densitometry on western blots. Microarray analyses demonstrated that mRNA expression of the IL-12Rβ2 gene was uniformly up-regulated in response to IFN-β-1a treatment and was associated with an increased number of IL-12Rβ2+ CD4+ T-cells by flow cytometry in 4 of 6 patients. This finding was substantiated by demonstrating that Stat4 phosphorylation, a transcription factor for IL-12, was increased after treatment. Conversely, the number of IL-23R+ CD4+ T-cells was decreased following treatment. The IL-12 receptor shares a common subunit, the IL-12Rβ2, with the IL-23 receptor. Both of these receptors have a probable role in regulating IL-17 and TH-17 cells, important mediators of inflammation in multiple sclerosis (MS). Thus, the changes in the numbers of CD4+ T-cells expressing these receptors in response to IFN-β-1a treatment may point to an important mechanism of action for this drug, but further large scale studies are needed to confirm these preliminary observations.

Table 2 Florbetapir SUVr for selected cortical regions by diagnostic group
Table 3 Florbenazine SUVR by Clinical Diagnosis for each striatal region
Scatterplots showing a) average cortical florbetapir SUVr values for each group and b) florbenazine binding for the lowest posterior putamen region for each group. See text for description of discrimination between groups.
Pattern of scan results for florbetapir and florbenazine for subjects in the 4 diagnostic groups. The vertical line shows the florbenazine SUVr cut-off (2.12) that agrees best with expert visual interpretation. The horizontal line (SUVr = 1.1) marks the published quantitative cut-off for florbetapir. The distribution of imaging patterns (proportion of subjects in each quadrant) differed significantly between groups (chi2 = 41.7, p <0.001) In the AD, PD and HC groups, there was one dominant pattern (for example, all of the AD cases had positive florbetapir scans and negative florbenazine scans). While VMAT2 binding was low in the DLB group on average, three subjects had SUVr values above the cut-off, and no single imaging pattern was observed in a majority of DLB patient.
PET imaging of amyloid with Florbetapir F 18 and PET imaging of dopamine degeneration with F-AV-133 (florbenazine) in patients with Alzheimer’s disease and Lewy body disorders

April 2014


305 Reads

Biomarkers based on the underlying pathology of Alzheimer's disease (AD) and Dementia with Lewy Bodies (DLB) have the potential to improve diagnosis and understanding of the substrate for cognitive impairment in these disorders. The objective of this study was to compare the patterns of amyloid and dopamine PET imaging in patients with AD, DLB and Parkinson's disease (PD) using the amyloid imaging agent florbetapir F 18 and 18F-AV-133 (florbenazine), a marker for vesicular monamine type 2 transporters (VMAT2). Patients with DLB and AD, Parkinson's disease (PD) and healthy controls (HC) were recruited for this study. On separate days, subjects received intravenous injections of florbetapir, and florbenazine. Amyloid burden and VMAT2 density were assessed quantitatively and by binary clinical interpretation. Imaging results for both tracers were compared across the four individual diagnostic groups and for combined groups based on underlying pathology (AD/DLB vs. PD/HC for amyloid burden and PD/DLB vs. AD/HC for VMAT binding) and correlated with measures of cognition and parkinsonism. 11 DLB, 10 AD, 5 PD, and 5 controls participated in the study. Amyloid binding was significantly higher in the combined AD/DLB patient group (n = 21) compared to the PD/ HC groups (n = 10, mean SUVr: 1.42 vs. 1.07; p = 0.0006). VMAT2 density was significantly lower in the PD/DLB group (n = 16) compared to the AD/ HC group (n = 15; 1.83 vs. 2.97; p < 0.0001). Within the DLB group, there was a significant correlation between cognitive performance and striatal florbenazine binding (r = 0.73; p = 0.011). The results of this study show significant differences in both florbetapir and florbenazine imaging that are consistent with expected pathology. In addition, VMAT density correlated significantly with cognitive impairment in DLB patients ( identifier: NCT00857506, registered March 5, 2009).

Figure 1: Pedigree of SCA14 Family 1 at time of testing. All affected living subjects were included in the study. Intrafamilial unaffected controls included in the study are marked with C. The pedigree is slightly modified due to anonymization purposes.
Table 1 Earlier reports of cognitive function in SCA14
Figure 2: MRI from four SCA14 subjects at time of neuropsychological testing. A: Subject VI-2, disease duration 7 years; B: Subject VI-3, disease duration 10 years; C: Subject III-3, disease duration 18 years; D: Subject V-3, disease duration 25 years.
Table 2 Clinical characteristics of SCA14 subjects
Table 4 Comparison of cognitive performance between SCA14 affected subjects and intrafamilial controls
Cognition is only minimally impaired in Spinocerebellar ataxia type 14 (SCA14): A neuropsychological study of ten Norwegian subjects compared to intrafamilial controls and population norm

November 2013


309 Reads

There is an increasing awareness of the role of the cerebellum not only in motor, but also in cognitive and emotional functions. Spinocerebellar ataxia type 14 (SCA14) is an autosomal dominant hereditary ataxia characterized by a relatively pure cerebellar phenotype. Cognitive impairment has been reported in studies with phenotype descriptions of SCA14, but previous studies have been small without control groups, and no homogeneous and systematic test panel has been used. The objective of this study was to thoroughly characterize the neuropsychological profile in ten Norwegian SCA14 subjects compared to unaffected family members and population norm data. Ten SCA14 subjects and ten intrafamilial unaffected age- and education-matched controls from two Norwegian families were included. The unaffected intrafamilial controls included six first degree relatives, two second degree relatives, and two spouses. General intellectual ability, memory, visuoperceptive skills, psychomotor speed, executive functions, depression and anxiety were examined using internationally standardized tests, with minimal need for manual response to avoid motor bias. No significant cognitive deficit was found in SCA14 subjects compared to intrafamilial controls. Verbal IQ, verbal executive function and psychomotor speed tended to be reduced in affected subjects, but previously reported non-verbal executive dysfunction was not confirmed in this study. Only subtle cognitive impairment was found in SCA14 affected subjects. The current findings do not confirm earlier reports of cognitive dysfunction in SCA14, but does shows a mild impairment in specific verbal executive functions. Genotypic differences may partly account for this discrepancy, and further studies on larger materials are needed to verify the findings.

Table 2 Analysis of Western blots method and ELISA of 14-3-3 protein of CSF in 124 CJD patients and 99 patients with other neurological disorders and rapid progressive dementia
ELISA analysis of 14-3-3 protein in CSF from patients with CJD and other neurological disorders. 1-a. Receiver operating curve characteristics at different cut-off points for the 14-3-3 ELISA applied to CSF samples. 1-b. Results of the 14-3-3 ELISA analysis in CSF from patients with CJD and other forms of dementia. CJD, Creutzfeldt-Jakob disease; DAT, dementia of Alzheimer's type; CVD, cerebrovascular disorders; PD, Parkinson's disease; PSP, progressive supranuclear palsy; FTLD, frontotemporal lobular degeneration; HD, Huntington's disease; CBD, corticobasal degeneration; PCD/LEMS, paraneoplastic cerebellar disorder/Lambert-Eaton myasthenic syndrome; MELAS, mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes; MCI, mild cognitive impairment. 1-c. Comparison of CJD patients and non-prion patients.
High sensitivity of an ELISA kit for detection of the gamma-isoform of 14-3-3 proteins: Usefulness in laboratory diagnosis of human prion disease

October 2011


266 Reads

The gamma-isoform of the 14-3-3 protein (14-3-3 gamma) is expressed in neurons, and could be a specific marker for neuronal damage. This protein has been reported as a detectable biomarker, especially in the cerebrospinal fluid (CSF) of Creutzfeldt-Jakob disease (CJD) patients by Western blotting (WB) or enzyme-linked immunosorbent assays (ELISAs). Western blotting for 14-3-3 gamma is not sensitive, and the reported data are conflicting among publications. An ELISA specific for 14-3-3 gamma is not available. CJD patients (n=114 sporadic CJD patients, 7 genetic CJD, and 3 iatrogenic CJD) and 99 patients with other neurodegenerative diseases were examined in this study. The CSF samples obtained were analyzed by Western blotting for 14-3-3 gamma, and by ELISA for total tau protein. We evaluated the sensitivity and specificity of the newly developed sandwich ELISA for 14-3-3 gamma. The cut-off value of the 14-3-3 gamma ELISA was >1, 683 AU/ml; and sensitivity was 95.2%, with 72.7% specificity. This specificity was the same for the total tau protein ELISA. Seven CJD cases were negative by WB but positive using the 14-3-3 gamma ELISA, indicating that the ELISA is more sensitive. All 21 cases of early stage CJD could be diagnosed using a combination of the 14-3-3γ ELISA and diffusion weighted MR imaging (DWI-MRI). The 14-3-3 gamma ELISA was more sensitive than conventional WB, and was useful for laboratory diagnosis of CJD, similar to the ELISA for the tau protein. Using DWI-MRI and these ELISA tests on CSF, diagnosis of CJD will be possible even at early stages of the disease.

Diagnostic and classification algorithm applied to our series of clinically suspected sCJD cases.
Frequency of clinical and paraclinical data in sCJDf (light shaded bars) and non-sCJDf patients (dark shaded bars). * p < 0.05, ** p < 0.01, and *** p < 0.001. sCJDf includes both probable and definite patients.
Impact of the clinical context on the 14-3-3 test for the diagnosis of sporadic CJD

February 2006


81 Reads

The 14-3-3 test appears to be a valuable aid for the clinical diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) in selected populations. However, its usefulness in routine practice has been challenged. In this study, the influence of the clinical context on the performance of the 14-3-3 test for the diagnosis of sCJD is investigated through the analysis of a large prospective clinical series. Six hundred seventy-two Spanish patients with clinically suspected sCJD were analyzed. Clinical classification at sample reception according to the World Health Organization's (WHO) criteria (excluding the 14-3-3 test result) was used to explore the influence of the clinical context on the pre-test probabilities, and positive (PPV) and negative (NPV) predictive values of the 14-3-3 test. Predictive values of the test varied greatly according to the initial clinical classification: PPV of 98.8%, 96.5% and 45.0%, and NPV of 26.1%, 66.6% and 100% for probable sCJDi (n = 115), possible sCJDi (n = 73) and non-sCJDi (n = 484) cases, respectively. According to multivariate and Bayesian analyses, these values represent an improvement of diagnostic certainty compared to clinical data alone. In three different contexts of sCJD suspicion, the 14-3-3 assay provides useful information complementary to clinical and electroencephalographic (EEG) data. The test is most useful supporting a clinical impression, whilst it may show deceptive when it is not in agreement with clinical data.

Table 1 Clinical, biochemical and molecular features of m.14459G > A mutated patients
Neuroradiological and molecular features in our proband. A. Brain MRI showed bilateral symmetric hyperintense lesions on T2-weighted images in the head of caudate, putamen (top left), thalami (top right) and ventral mesencephalum (bottom left); these lesions were hypointense in T1-weighted images (bottom right). B. PCR-RFLP analysis of m.14459G > A mutation. The transition m.14459G > A creates a restriction site for endonuclease MaeIII in mutated amplicons obtained using a modified primer set previously described (FOR14430*-RC14710) producing two fragments of 251 and 29 base pairs (the latter is not visible on the agarose gel) while wild type molecules remain uncut. C. PCR-RFLP analysis of m.14792C > G variant. The variant m.14792C > G is recognized by restriction endonuclease HinfI which cuts mutated PCR-amplified fragments (encompassing 14400-14963 nucleotides) producing molecules of 392 and 171 base pairs. Control samples are from healthy unrelated independent subjects.
Clinical and molecular features of an infant patient affected by Leigh Disease associated to m.14459G > A mitochondrial DNA mutation: A case report

July 2011


153 Reads

Leigh Syndrome (LS) is a severe neurodegenerative disorder characterized by bilateral symmetrical necrotic lesions in the basal ganglia and brainstem. Onset is in early infancy and prognosis is poor. Causative mutations have been disclosed in mitochondrial DNA and nuclear genes affecting respiratory chain subunits and assembly factors. Here we report the clinical and molecular features of a 15-month-old female LS patient. Direct sequencing of her muscle-derived mtDNA revealed the presence of two apparently homoplasmic variants: the novel m.14792C>G and the already known m.14459G>A resulting in p.His16Asp change in cytochrome b (MT-CYB) and p.Ala72Val substitution in ND6 subunit, respectively. The m.14459G>A was heteroplasmic in the mother's blood-derived DNA. The m.14459G>A might lead to LS, complicated LS or Leber Optic Hereditary Neuropathy. A comprehensive re-evaluation of previously described 14459G>A-mutated patients does not explain this large clinical heterogeneity.

Figure 1: Clinical aspect:23-year old female patient, contusion of the hand, development of pain and attitude of contracture that was partly reduced in the 4               th             and 5               th             fingers of the left hand.
Table 1 Description of the two populations: demographic characteristics, triggering factors, initial injuries and outcome
Figure 2: Three-phase bone scintigraphy: early phase (a) and delayed phase (b) Same patient as  Staged early and delayed hyperfixation on 4th and 5th fingers suggesting CRPS stage 1.
Figure 3: Partial CRPS type 1 of the hand: proposed diagnostic flow chart.
Diagnosis of partial complex regional pain syndrome type 1 of the hand: Retrospective study of 16 cases and literature review
Background The partial form of the complex regional pain syndrome of the hand type 1 (CRPS 1), involving only 1 to 3 fingers, is a rare condition first described in 1972. The aim of the study is to define more precisely the diagnosis workup and the prognosis of this clinical entity. Methods Retrospective study of CRPS1 partial form observed during five years in a rehabilitation ward. Application of The Budapest criteria, evaluation of radiological exams, therapeutic results and vocational outcomes. Comparison with cases from literature review. Results 132 patients were hospitalized with the diagnosis of CRPS type 1 of the hand. 16 partial forms were isolated: 11 men, 5 women with a mean age of 43 years. Among these patients, 14 (88%) met The Budapest criteria and the two remaining cases were diagnosed by using the three phase bone scintigraphy. Only moderate improvement was obtained in the majority of the patients. At the maximal time of follow-up (4 to 9 years), 50% of the patients hadn’t returned to work. From the literature review, 19 cases were eligible for clinical comparisons. The main differences between our series and the literature were: more men involved, later diagnosis and worst prognosis in term of return to work. Conclusions This is the largest series of consecutive partial form of CRPS. The Budapest criteria are sufficient for the diagnosis in 88% of cases. As in complete form of CRPS1 of the hand, three phase bone scintigraphy should only be used in doubtful cases in the first six months of the illness. Partial form of CRPS1 of the hand is rare and its prevalence remains unknown. Long term prognosis (4 to 9 years) is poor in our series, 50% of patients didn’t returned to work.

Table 1 Characteristics of the study population (Continued)
Patient flow throughout the study in terms of seizure outcome. Terminal remission: seizure-freedom of at least 2 years preceding the end of follow-up. Pattern A (early and sustained seizure freedom): patients became seizure-free within 12 months of starting treatment and remained seizure-free. Pattern B (delayed and sustained seizure freedom): patients became seizure-free after 12 months of starting treatment and remained seizure-free. Pattern C (fluctuating course): patients fluctuating between periods of seizure freedom and relapse. Pattern D: patients never seizure-free for any complete year.
Kaplan-Meier curve indicating the cumulative proportion of study subjects reaching terminal remission during follow-up. Terminal remission: seizure-freedom of at least 2 years.
Kaplan-Meier curve indicating the cumulative proportion of study subjects reaching 6-month remission during follow-up according to initial response to treatment. The green line represents the patients who were seizure-free during the initial year of treatment, the yellow line the patients who experienced seizure activity and the blue line represents the total of all patients.
P64 – 1656 Clinical course and outcome of idiopathic childhood epilepsy: determinants of early and long-term prognosis

December 2013


224 Reads

Idiopathic epilepsies and epileptic syndromes predominate childhood and adolescence epilepsy. The aim of the present study was to investigate the clinical course and outcome of idiopathic childhood epilepsy and identify variables determining both early and long-term prognosis. We followed 303 children with newly diagnosed idiopathic epilepsy aged 1--14 years old, both prospectively and retrospectively. Outcome was defined at one, 2 and 4 years of follow-up, as well as at the end of the study period for all patients. Based on the data collected, patients were classified in four patterns of clinical course: "excellent", "improving", "relapsing" and "poor". Variables defined at intake and after the initial year of treatment were analyzed for their prognostic relevance towards the clinical course and outcome of the patients. The mean age at seizure onset was 6,7 years and the mean duration of follow-up was 8,3 years (range 2,0-22,0,SD 4,24). During the initial year of treatment, 70,3% of patients were seizure-free. The course of epilepsy was "excellent" in 53,1% of the subjects, "improving" in 22,8%, "relapsing" in 22,1% whereas only 6 children with idiopathic epilepsy (2%) had a "poor" clinical course exhibiting drug-resistance. After multivariate analysis, variables predictive of a poor initial response to therapy were early seizure onset, multiple seizure types and history of status epilepticus. At the end of follow-up, early response to treatment was of significant positive predictive value, while the presence of multiple seizure types and the history of migraine had a negative impact on prognosis. In the vast majority of children, the long-term prognosis of idiopathic epilepsy is favorable. More than half of the patients attain seizure freedom immediately and their clinical course is considered "excellent". About one fifth exhibit either an improving or a fluctuating course. Early seizure onset, multiple seizure types and status epilepticus are predictive of an initial poor response to treatment in children with idiopathic epilepsy. Initial non-response to treatment, multiple seizure types and history of migraine are determinants of a less favorable final outcome after long-term follow-up.

MRIs of CCMs. The echo gradient sequences of the proband (left), grandmother (middle) and the older brother (right) harbouring the Y634X mutation (III-2 in figure 3). Note the typical images of cavernous malformation and the absence of lesions in III-2, the asymptomatic carrier of the 1902insA.
Left panel, SCCP of the proband and parents of CVE10 PCR was performed with the reaction mixture supplemented with [α32P]-dCTP. Aliquots of the product were run in acrylamide gels (see Methods) and revealed by auto-radiography. Right panel, chromatogram of the 1902InsA. Traces of the sense (upper) and antisense (lower) DNA strands of the proband. The wild type and mutated nucleotide sequences and the aminoacid change are indicated over the sense strand. The sequence shows the site of the 1902insA mutation (see arrow) and the frameshift. The ambiguities are caused by the overlapping bands of the wild type and mutated strands due to the nucleotide insertion. The stop TAA triplet predicts a truncating protein with the changed phenotype Y634X.
Haplotypes and restriction fragment polymorphism (RFLP). Haplotypes were analysed using the markers surrounding CCM1 as described in Methods. The markers from top to bottom were: D7S2409, D7S1813, D7S1789, D7S646, D7S558, D7S689, D7S652 and D7S492. Exon 17 was amplified with the primers and aliquots of the PCR were digested overnight at 37°C with MseI. The fragments were separated in an 8% polyacrylamide gel containing urea and, after staining with ethidium bromide, the gel was photographed under UV. The undigested product is 297 pb long and the fragments separated from the TTAA restriction site are 158 and 139 pb. Therefore, individuals harbouring the 1902insA mutation have three fragments of 297, 158 and 139 bp. Filled symbols in the pedigree refer to patients with CCMs in the echo-gradient MRIs. Arrow indicates the proband. Stairs refer to asymptomatic carriers of the mutation. The double stair denotes the asymptomatic carrier with MRIs free of CCMs
Variable expression of cerebral cavernous malformations in carriers of a premature termination codon in exon 17 of the Krit1 gene

August 2003


59 Reads

Cerebral cavernous malformations (CCM) present as either sporadic or autosomal dominant conditions with incomplete penetrance of symptoms. Differences in genetic and environmental factors might be minimized among first-degree relatives. We therefore studied clinical expression in a family with several affected members. We studied a three-generation family with the onset of CCM as a cerebral haemorrhage in the younger (four-year-old) sibling. Identification and enumeration of CCMs were performed in T2-weighted or gradient-echo MRIs of the whole brains. Genetic analysis comprised SCCP, sequencing and restriction polymorphism of the Krit1 gene in the proband and at risk relatives. The phenotypes of cerebral cavernous malformations (CCMs) in carriers of Krit1 mutations were very variable. We identified a novel frameshift mutation caused by a 1902A insertion in exon 17 of the Krit1 gene, which leads to a premature TAA triplet and predicts the truncating phenotype Y634X. A very striking finding was the absence of both clinical symptoms and CCMs in the eldest sibling harbouring the 1902insA. Patients in this family, harbouring the same mutation, illustrate the very variable clinical and radiological expression of a Krit1 mutation. The early and critical onset in the proband contrasts with minor clinical findings in affected relatives. This consideration is important in genetic counselling.

Table 2 : relation between myasthenic crisis frequency and thymectomy
Table 6 : logistic regression model for predictors of myasthenic crisis among patients without thymoma (n = 203).
Frequency of myasthenic crisis in relation to thymectomy in generalized myasthenia gravis: A 17-year experience

October 2004


96 Reads

Myasthenic crisis is the most serious life-threatening event in generalized myasthenia gravis (MG) patients. The objective of this study was to assess the long-term impact of thymectomy on rate and severity of these attacks in Iranian patients. We reviewed the clinical records from 272 myasthenic patients diagnosed and treated in our neurology clinic during 1985 to 2002. Fifty-three patients were excluded because of unconfirmed diagnosis, ocular form of MG, contraindication to surgery, concomitant diseases and loss to follow-up. The Osserman classification was used to assess the initial severity of the disease. Frequency and severity of the attacks were compared between two groups with appropriate statistical tests according to the nature of variables. Multivariate logistic regression analysis was used to assess the predictors of myasthenic crisis in the group of patients without thymoma. 110 patients were in thymectomy group and the other 109 patients were on medical therapy. These two groups had no significant differences with respect to age at onset, gender, Osserman score in baseline and follow up period. 62 patients (28.3% of all 219 patients) had reported 89 attacks of myasthenic crisis. 20 patients of 62 (32%) were in thymectomy group and 42 (68%) were in the other group. There was significant difference between the two groups in number of patients with crisis (P = 0.001; odds ratio = 2.8 with 95% CI of 1.5 to 5.2). In addition, these attacks were more severe in group of non-thymectomized patients as the duration of ICU admission was longer and they needed more ventilatory support during their attacks. Regression model showed thymectomy and lower age at onset as two predictors of decrement in myasthenic crisis rate in non-thymomatous MG patients. It is suggested that frequency and severity of myasthenic attacks as important endpoints in evaluation of MG patients. Thymectomy seems to have a preventive role on rate and severity of these attacks.

Table 2 : Summary of 11 patients (Group B) treated with RF-DRG and evaluated by VAS.
The VAS device. Score 0/"geen": Very satisfied. Score 10/"meest": Very dissatisfied.
Questions: 1. What overall score would you give your child when considering pain, ease of care and spasticity?
2. In which domain(s) did you notice this improvement: pain, ease of care, spasticity? (See table 2)
Photomicrograph showing the position of an RF electrode a: lateral view and b: anterior- posterior view after injection of Omnipaque.
Percutaneous radiofrequency lesions adjacent to the dorsal root ganglion alleviate spasticity and pain in children with cerebral palsy: Pilot study in 17 patients

June 2010


223 Reads

Cerebral palsy (CP) may cause severe spasticity, requiring neurosurgical procedures. The most common neurosurgical procedures are continuous infusion of intrathecal baclofen and selective dorsal rhizotomy. Both are invasive and complex procedures. We hypothesized that a percutaneous radiofrequency lesion of the dorsal root ganglion (RF-DRG) could be a simple and safe alternative treatment. We undertook a pilot study to test this hypothesis. We performed an RF-DRG procedure in 17 consecutive CP patients with severe hip flexor/adductor spasms accompanied by pain or care-giving difficulties. Six children were systematically evaluated at baseline, and 1 month and 6 months after treatment by means of the Modified Ashworth Scale (MAS), Gross Motor Function Measure (GMFM) and a self-made caregiver's questionnaire. Eleven subsequent children were evaluated using a Visual Analogue Scale (VAS) for spasticity, pain and ease of care. A total of 19 RF-DRG treatments were performed in 17 patients. We found a small improvement in muscle tone measured by MAS, but no effect on the GMFM scale. Despite this, the caregivers of these six treated children unanimously stated that the quality of life of their children had indeed improved after the RF-DRG. In the subsequent 11 children we found improvements in all VAS scores, in a range comparable to the conventional treatment options. RF-DRG is a promising new treatment option for severe spasticity in CP patients, and its definitive effectiveness remains to be defined in a randomised controlled trial.

Table 1 Clinical Characteristics of the Subjects
Table 2 Clinical Charasteristics of the PD patients
Representative FMT-PET images of a healthy individual and PD patients. FMT uptake declines asymmetrically in the early stages, mostly in the posterior putamen. Left: Regions-of-interest in the putamen. H &Y, Hohen and Yahr stage.
The bar indicates the range of radioactive counts per voxel.
FMT uptake in different subregions of the striatum. Mean FMT uptake in different subregions of the striatum in normal control and PD patients (a). Comparison by side (b) shows persistant side-side asymmetry of putaminal uptake throughout the disease course. *P < 0.05, ** P < 0.01.
Decline in FMT uptake with disease duration. Scatter plots of FMT uptake against symptom duration in the putamen contralateral to the more affected limb in PD patients. Exponential decline is observed in all subregions of the putamen. Reduction of uptake is prominent at onset of the disease.
Subregional 6-[18F]fluoro-L-m-tyrosine Uptake in the Striatum in Parkinson's Disease

March 2011


183 Reads

In idiopathic Parkinson's disease (PD) the clinical features are heterogeneous and include different predominant symptoms. The aim of the present study was to determine the relationship between subregional aromatic l-amino acid decarboxylase (AADC) activity in the striatum and the cardinal motor symptoms of PD using high-resolution positron emission tomography (PET) with an AADC tracer, 6-[18F]fluoro-ʟ-m-tyrosine (FMT). We assessed 101 patients with PD and 19 healthy volunteers. PD was diagnosed based on the UK Brain Bank criteria by two experts on movement disorders. Motor symptoms were measured with the Unified Parkinson's Disease Rating Scale (UPDRS). FMT uptake in the subregions of the striatum was analyzed using semi-automated software for region-of-interest demarcation on co-registered magnetic resonance images. In all PD patients, FMT uptake was decreased in the posterior putamen regardless of predominant motor symptoms and disease duration. Smaller uptake values were found in the putamen contralateral to the side with more affected limbs. The severity of bradykinesia, rigidity, and axial symptoms was correlated with the decrease of FMT uptake in the putamen, particularly in the anterior part. No significant correlation was observed between tremors and FMT uptake. Decrease of FMT uptake in the posterior putamen appears to be most sensitive in mild PD and uptake in the anterior putamen may reflect the severity of main motor symptoms, except for tremor.

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