Degeneration of corpus callosum and recovery of motor function after stroke: a multimodal magnetic resonance imaging study.

Animal models of stroke demonstrated that white matter ischemia may cause both axonal damage and myelin degradation distant from the core lesion, thereby impacting on behavior and functional outcome after stroke. We here used parameters derived from diffusion magnetic resonance imaging (MRI) to investigate the effect of focal white matter ischemia on functional reorganization within the motor system. Patients (n = 18) suffering from hand motor deficits in the subacute or chronic stage after subcortical stroke and healthy controls (n = 12) were scanned with both diffusion MRI and functional MRI while performing a motor task with the left or right hand. A laterality index was employed on activated voxels to assess functional reorganization across hemispheres. Regression analyses revealed that diffusion MRI parameters of both the ipsilesional corticospinal tract (CST) and corpus callosum (CC) predicted increased activation of the unaffected hemisphere during movements of the stroke-affected hand. Changes in diffusion MRI parameters possibly reflecting axonal damage and/or destruction of myelin sheath correlated with a stronger bilateral recruitment of motor areas and poorer motor performance. Probabilistic fiber tracking analyses revealed that the region in the CC correlating with the fMRI laterality index and motor deficits connected to sensorimotor cortex, supplementary motor area, ventral premotor cortex, superior parietal lobule, and temporoparietal junction. The results suggest that degeneration of transcallosal fibers connecting higher order sensorimotor regions constitute a relevant factor influencing cortical reorganization and motor outcome after subcortical stroke.

Simultaneous Hepatitis C Virus Genotyping and Variant Detection in Patients with Thalassemia: A Single-Center Phylogenetic Study.

BACKGROUND: Hepatitis C virus (HCV) genotype distribution is different in various regions. A variety of strategies could be used to detect HCV genotypes and subtypes. The aim of the present study was to introduce a genotyping method by an in-house protocol that could be used to determine HCV drug-resistant variants and phylogeny studies. METHODS: Samples from 91 patients with thalassemia were used for HCV genotyping by Cobas 4800 platform, and 50 cases of 1a, 1b, and 3a genotypes underwent amplification and sequencing of NS5A and NS5B by using consensus primers via conventional reverse transcription-polymerase chain reaction (RT-PCR) method. An ABI 3730xl system used for direct sequencing. Raw sequences were analyzed by popular bioinformatics software MEGA6 and CLC workbench 5. Phylogenetic construction was drawn using 1000 replicates bootstrap by the neighbor-joining method. Multiple sequence alignment (MSA) was performed for mutation detection. RESULTS: Sequencing results of 50 HCV isolates subtypes 1a (31/45), 3a (15/22) and 1b (4/8) NS5A and NS5B genes showed there were 72 NS5A and 105 NS5B mutations. Moreover, 8 resistant associated substitutions (RASs) were identified in nine thalassemia cases by multiple sequence alignment (MSA) protein analysis. The phylogenetic tree construct drew confirmed by the Cobas HCV genotyping results. CONCLUSION: The phylogenetic analysis could be a useful tool for HCV genotyping in case of determining the drug-resistant substitutions; however, it is time-consuming and needs expert analysis and interpretation. This preliminary study in Iranian patients with thalassemia introduces specific conventional RT-PCR to find RASs to direct acting antivirals (DAAs) and subtype determination at the same time.

Differential effects of high-frequency repetitive transcranial magnetic stimulation over ipsilesional primary motor cortex in cortical and subcortical middle cerebral artery stroke.

OBJECTIVE: Facilitation of cortical excitability of the ipsilesional primary motor cortex (M1) may improve dexterity of the affected hand after stroke. The effects of 10 Hz repetitive transcranial magnetic stimulation (rTMS) over ipsilesional M1 on movement kinematics and neural activity were examined in patients with subcortical or cortical stroke. METHODS: Twenty-nine patients with impaired dexterity after stroke (16 subcortical middle cerebral artery [MCA] strokes, 13 MCA strokes involving subcortical tissue and primary or secondary cortical sensorimotor areas) received 1 session of 10 Hz rTMS (5-second stimulation, 25-second break, 1,000 pulses, 80% of the resting motor threshold) applied over: 1) ipsilesional M1 and 2) vertex (control stimulation). For behavioral testing, 29 patients performed index finger and hand tapping movements with the affected and unaffected hand prior to and following each rTMS application. For functional magnetic resonance imaging, 18 patients performed index finger tapping movements with the affected and unaffected hand before and after each rTMS application. RESULTS: Ten-Hz rTMS over ipsilesional M1, but not over vertex, improved movement kinematics in 14 of 16 patients with subcortical stroke, but not in patients with additional cortical stroke. Ten-Hz rTMS slightly deteriorated dexterity of the affected hand in 7 of 13 cortical stroke patients. At a neural level, rTMS over ipsilesional M1 reduced neural activity of the contralesional M1 in 11 patients with subcortical stroke, but caused a widespread bilateral recruitment of primary and secondary motor areas in 7 patients with cortical stroke. Activity in ipsilesional M1 at baseline correlated with improvement of index finger tapping frequency induced by rTMS. INTERPRETATION: The beneficial effects of 10 Hz rTMS over ipsilesional M1 on motor function of the affected hand depend on the extension of MCA stroke. Neural activity in ipsilesional M1 may serve as a surrogate marker for the effectiveness of facilitatory rTMS.

1 Hz rTMS preconditioned by tDCS over the primary motor cortex in Parkinson's disease: effects on bradykinesia of arm and hand.

To investigate whether a period of 1 Hz repetitive transcranial magnetic stimulation (rTMS) over M1 preconditioned by tDCS improves bradykinesia of the upper limb in Parkinson's disease (PD). Fifteen patients with PD performed index finger, hand tapping and horizontal pointing movements as well as reach-to-grasp movements with either hand before (baseline conditions) and after a period of 1 Hz rTMS preconditioned by (1) sham, (2) anodal or (3) cathodal tDCS over the primary motor cortex contralateral to the more affected body side. Movement kinematics was analysed using an ultrasound-based motion analyser at baseline, immediately after and 30 min after each stimulation session. Dopaminergic medication was continued. Compared to baseline, 1 Hz rTMS significantly increased the frequency of index finger and hand tapping as well as horizontal pointing movements performed with the contralateral hand. Movement frequency increased up to 40% over 30 min after cessation of the stimulation. Preconditioning with cathodal tDCS, but not with anodal tDCS, reduced the effectiveness of 1 Hz rTMS to improve tapping and pointing movements. There was no significant increase of movement frequencies of the ipsilateral hand induced by 1 Hz rTMS preconditioned by either tDCS session. Movement kinematics of reach-to-grasp movements were not significantly influenced by either stimulation session. In PD the beneficial effects of 1 Hz rTMS over the primary motor cortex on bradykinesia of simple finger, hand and pointing movements is reduced by preconditioning with cathodal tDCS, but not with anodal tDCS. Preconditioning with tDCS is a powerful tool to modulate the behavioural effect of 1 Hz rTMS over the primary motor cortex in PD.

Non-alcoholic fatty liver disease is not independent risk factor for cardiovascular disease event: A cohort study.

BACKGROUND: There are no consistent results between previous studies for an independent association between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) events. AIM: To determine if there is an independent association between NAFLD and CVD events. METHODS: In the present study, valid outcome data of 4808 subjects were available for phase 2 of our cohort study. These subjects had been followed up for seven years from phase 1, beginning in 2009-2010 to phase 2 during 2016-2017. Simple and multiple Cox proportional models were used to determine the association between NAFLD in the primary phase of the cohort and subsequent fatal and non-fatal CVD events during follow-up. RESULTS: The incidence of non-fatal CVD events in males with NAFLD was significantly higher (P = 0.004) than in males without NAFLD. A positive association was demonstrated between NAFLD and non-fatal CVD events in males (Hazard ratio = 1.606; 95%CI: 1.166-2.212; P = 0.004) by the simple Cox proportional hazard model, but no independent association was detected between these in the multiple Cox models. CONCLUSION: No independent association was detected between NAFLD and CVD. It is likely that diabetes mellitus and age may be the principle mediators in this regard.

Arbitrary visuomotor mapping during object manipulation in Parkinson's disease.

The objective of this study is to investigate whether subjects with Parkinson's disease are able to use arbitrary color cues linked to the mass of an object to be lifted allowing for the predictive selection of appropriate grip forces. Fourteen patients with Parkinson's disease used a precision grip to lift two objects of different masses (400 and 600 g) in random order. In a "no cue" condition, a noninformative neutral visual stimulus was presented before each lift, thereby not allowing any judgement about which mass to be lifted. In a "cue" condition an arbitrary color cue provided advance information about which of the two masses patients would have to lift in the subsequent trial. Patients performed the conditions with either hand and by both on and off drugs. In the "no cue" trials patients scaled the predictive grip force output according to the perceived mass of the preceding lift. In the "cue" experiment patients scaled grip force in a predictive manner to mass based on the provided color cues. The ability of arbitrary visuomotor mapping was evident at either hand and not influenced by medication on/off. The precision of arbitrary visuomotor mapping correlated negatively with age, but not with disease duration, severity of motor disability on and off drug, severity of cognitive impairment on and off drug, or the amount of levodopa equivalent daily dosage of dopaminergic drugs. These data imply that Parkinson's disease does not preclude the ability of visuomotor mapping in the grip-lift task.

Interhemispheric transfer of predictive force control during grasping in cerebellar disorders.

When an object is repeatedly grasped and lifted, the balance between grip force (normal to the object's surface) and lift force (tangential to the object's surface) is programmed according to the mechanical object features within a few lifts. Information related to the mechanical object properties is easily transferred in between both hands, and the cerebellum may play an essential role for the integration and generalization of this information. Recently, we have shown that the transfer of weight-related information in between both hands is impaired in cerebellar degeneration (Nowak et al., Neuropsychologia, 43:20-27, 2005). Here, we investigated the role of the cerebellum for the inter-manual transfer of friction-related information. Healthy subjects and patients with either focal or generalized cerebellar disorders first repeatedly lifted an object with one hand followed by a series of lifts of the same object with the opposite hand. The experiments were performed with the object's grip surfaces covered with either silk or sandpaper. Patients and healthy subjects scaled grip force differentially to surface friction within a few lifts. However, the ability to transfer friction-related information from one hand to the other was disturbed in cerebellar patients. We interpret these data within the recent concept that the cerebellum is essential for the rapid integration and generalization of mechanical object features in between both hemispheres when handling objects in the environment.

Interhemispheric competition after stroke: brain stimulation to enhance recovery of function of the affected hand.

BACKGROUND AND PURPOSE: Within the concept of interhemispheric competition, technical modulation of the excitability of motor areas in the contralesional and ipsilesional hemisphere has been applied in an attempt to enhance recovery of hand function following stroke. This review critically summarizes the data supporting the use of novel electrophysiological concepts in the rehabilitation of hand function after stroke. SUMMARY OF REVIEW: Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are powerful tools to inhibit or facilitate cortical excitability. Modulation of cortical excitability may instantaneously induce plastic changes within the cortical network of sensorimotor areas, thereby improving motor function of the affected hand after stroke. No significant adverse effects have been noted when applying brain stimulation in stroke patients. To date, however, the clinical effects are small to moderate and short lived. Future work should elucidate whether repetitive administration of rTMS or tDCS over several days and the combination of these techniques with behavioral training (ie, physiotherapy) could result in an enhanced effectiveness. CONCLUSION: Brain stimulation is a safe and promising tool to induce plastic changes in the cortical sensorimotor network to improve motor behavior after stroke. However, several methodological issues remain to be answered to further improve the effectiveness of these new approaches.

Predictive force programming in the grip-lift task: the role of memory links between arbitrary cues and object weight.

We tested the ability of healthy participants to learn an association between arbitrary sensory cues and the weight of an object to be lifted using a precision grip between the index finger and thumb. Right-handed participants performed a series of grip-lift tasks with each hand. In a first experiment, participants lifted two objects of equal visual appearance which unexpectedly and randomly changed their weight. In two subsequent experiments, the change in object weight was indicated by cues, which were presented (i) visually or (ii) auditorily. When no cue about the weight of the object to be lifted was presented, participants programmed grip force according to the most recent lift, regardless of the hand used. In contrast, participants were able to rapidly establish an association between a particular sensory cue with a given weight and scaled grip force precisely to the actual weight thereafter, regardless of the hand used or the sensory modality of the cue. We discuss our data within the theoretical concept of internal models.

Electrical somatosensory stimulation modulates hand motor function in healthy humans.

In healthy people, electrical somatosensory stimulation modulates excitability in contralateral cortical motor areas. The question whether this is associated with a change in motor performance is still under debate. The effect of electrical somatosensory stimulation on motor performance of the hand was investigated in 14 healthy right-handed subjects. Subjects performed index finger and hand tapping movements as well as reach-to-grasp movements towards small and large cubes with each hand prior to (baseline condition) and following 2-hour electrical somatosensory stimulation (trains of 5 pulses at 10 Hz with 1 ms duration delivered at 1 Hz with an intensity on average 60 % above the individual somatosensory threshold) of the (i) right median nerve, (ii) left median nerve, (iii) right tibial nerve (control stimulation) and (iv) left tibial nerve (control stimulation) on separate occasions at least one week apart. The order of sessions was counterbalanced across subjects. Somatosensory stimulation of the median nerves, but not of the tibial nerves, reduced the frequency and velocity of index finger and hand tapping movements performed with the stimulated hand, compared to baseline. In contrast, the kinematics of reach-to-grasp movements remained unaffected by somatosensory stimulation. The data suggest that somatosensory stimulation interferes with the processing of highly automated open-loop motor output at the stimulated limb, as reflected by tapping movements, but not with the processing of closed-loop motor performance, as reflected by reach-to-grasp movements.

Relationship between elevated liver enzyme with iron overload and viral hepatitis in thalassemia major patients in Northern Iran.

OBJECTIVE: To determine the relationship between elevated liver enzymes with iron overload and viral hepatitis in thalassemic patients. METHODS: This descriptive cross-sectional study was carried out in the thalassemic ward of Tonekabon Hospital, Mazandaran, Northern Iran from 20 April to 20 September of 2006. Patients were studied with respect to age, liver enzymes, anti-hepatitis C virus (anti-HCV) antibody, and hepatitis B surface antigen (HBsAg), transferrin saturation (TSAT), and blood transfusion index (multiplication of frequency and units of transfusion). Alanine aminotransferase (ALT) > or =40 U/L was considered elevated. RESULTS: Sixty-five patients were evaluated (median age 19.51+/-8.9 years, range 4-54). Eleven patients were anti-HCV positive (16.9%). The mean serum ferritin was significantly higher in patients with ALT > or =40 (2553.08 ug/L versus 1783.7750 microg/L) (p=0.012). The mean ALT was significantly higher in patients with TSAT > or = 60% (41.26 U/L versus 28.82 U/L) (p=0.021). The relationship between ALT > or =40 and anti-HCV positivity was statistically significant. The mean ALT was 60.91 U/L in anti-HCV positive patients and 39.29 U/L in the negative group (p=0.001). The mean serum iron and transfusion index were significantly higher in anti-HCV positive versus negative patients (234.0 versus 195.4815; p=0.02), (1693.6 versus 1036.29, p=0.014). CONCLUSION: Close association between elevated ALT with iron overload, transfusion index, age, and anti-HCV positivity in thalassemic patients of Tonekabon is recommended to re-evaluate transfusion and Desferal doses and therapies other than blood transfusion.

Demonstration of Herpes Simplex Virus, Cytomegalovirus, and Epstein-Barr Virus in Colorectal Cancer.

BACKGROUND: The present study sought to investigate molecular evidence for association between the presence of herpes simplex virus (HSV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) in CRC and colorectal polyp by using the PCR method in Iran. METHODS: In this analytical case-control study, we selected 15 patients with CRC, 20 patients with colorectal polyp, and 35 patients without malignancy as controls. After DNA extraction, PCR was used to determine HSV, CMV, and EBV genome by specific primers. Statistical analysis was performed using χ2 tests. RESULTS: Our findings demonstrated that there is no direct molecular evidence to support the association between HSV, CMV, and EBV and human colorectal malignancies. CONCLUSION: The results from this study do not exclude a possible oncogenic role of these viruses in neoplastic development of colon cells.

Prevalence of colorectal adenoma in an average-risk population aged 40-50 versus 50-60 years.

According to current guidelines, screening colonoscopy begins at 50 years for the average-risk population, although there are not enough data on the incidence of precancerous lesions of individuals in the preceding decades. To evaluate the prevalence of colorectal polyps including potentially premalignant lesions in asymptomatic, average-risk individuals aged 40-49 versus 50-59 years, we offered total colonoscopy screening to individuals without any lower gastrointestinal symptoms. The primary end point was the prevalence of colorectal adenoma in two age groups. Of a total of 737 studies, 333 participants were 40-49 years old and 407 participants were 50-59 years old. The overall prevalence of adenomas was 11.2 and 16.4% in the group of 40-49 and 50-59 year olds, respectively. Advanced adenoma was more common in 50-59 year olds (1.2 vs. 2.9%). Malignancy was not reported in these groups. Furthermore, 77.5 and 68.6% of adenomas were observed in the distal colon in the groups of 40-49 year olds and 50-59 year olds, whereas in the proximal colon, 22.2 and 57.1% of adenomas in the groups of 40-49 year olds and 50-59 year olds, respectively, were advanced adenomas. In our study, male sex showed an association with adenoma. However, importantly, there was no significant association between age and colorectal adenoma. Although the prevalence of colorectal adenoma was similar in the two age groups investigated, the rate of advanced adenoma was higher in the group of individuals who were 50-59 years old, suggesting that colorectal cancer screening could be recommended at an age younger than 50 years.

Accuracy of endoscopic ultrasonography for determination of tumor invasion depth in gastric cancer.

BACKGROUND: Gastric cancer (GC) is one the common lethal cancers in Iran. Detection of GC in the early stages would assesses to improve the survival of patients. In this study, we attempt to evaluate the accuracy of EUS in detection depth of invasion of GC among Iranian Patients. MATERIALS AND METHODS: This study is a retrospective study of patients with pathologically confirmed GC. They underwent EUS before initiating the treatment. The accuracy of EUS and agreement between the two methods was evaluated by comparing pre treatment EUS finding with post operative histopathological results. RESULTS: The overall accuracy of EUS for T and N staging was 67.9% and 75.47, respectively. Underestimation and overestimation was seen in 22 (14.2%) and 40 (25.6%) respectively. The EUS was more accurate in large tumors and the tumors located in the middle and lower parts of the stomach. The EUS was more sensitive in T3 staging. The values of weighted Kappa from the T and N staging were 0.53 and 0.66, respectively. CONCLUSIONS: EUS is a useful modality for evaluating the depth of invasion of GC. The accuracy of EUS was higher if the tumor was located in the lower parts of the stomach and the size of the tumor was more than 3 cm. Therefore, judgments made upon other criteria evaluated in this study need to be reconsidered.

Prevalence of gastric precancerous lesions among chronic dyspeptic patients and related common risk factors.

Gastric cancer is one of the leading causes of cancer-related deaths worldwide. Progression of gastric cancer follows several steps from gastritis to atrophy, intestinal metaplasia, dysplasia, and finally cancer. The aim of this study was to determine the prevalence of gastric precancerous lesions and related common risk factors in a group of chronic dyspeptic patients. A total of 688 chronic dyspeptic patients older than 40 years of age were consecutively enrolled. The exclusion criteria were pregnancy, and a history of gastric cancer and gastric surgery. A questionnaire including demographic and clinical data, smoking habits, alcohol use, NSAIDs, and regular aspirin use was completed for all patients. Upper endoscopy and gastric biopsy were performed for all of the participants according to the standard protocols. Upper endoscopy was performed for all of the participants and biopsies were taken according to the biopsy protocol. The specimens were examined in a blinded manner by two expert gastrointestinal pathologists. The mean age of the participants was 57.87±9.10 years; there were 361 (52.5%) women. The prevalence of intestinal metaplasia, gastric atrophy, dysplasia, and positive Helicobacter pylori infection was 19.8, 12.8, 3.2%, and 64.5%, respectively. Age and H. pylori infection showed a significant association with pathological findings (odds ratio=3.10, 95% confidence interval: 1.91-4.72 and odds ratio=3.56, 95% confidence interval: 2.30-5.53, respectively). According to the high prevalence of precancerous lesions in patients with chronic dyspepsia who were older than 40 years of age, upper endoscopy and gastric mapping sampling for the detection of these lesions is recommended in intermediate-risk to high-risk areas.

Prevalence of colorectal polyps in a group of subjects at average-risk of colorectal cancer undergoing colonoscopic screening in Tehran, Iran between 2008 and 2013.

BACKGROUND: Colorectal cancer (CRC) is one of the prime causes of mortality around the globe, with a significantly rising incidence in the Middle East region in recent decades. Since detection of CRC in the early stages is an important issue, and also since to date there are no comprehensive epidemiologic studies depicting the Middle East region with special attention to the average risk group, further investigation is of significant necessity in this regard. AIM: Our aim was to investigate the prevalence of preneoplastic and neoplastic lesions of the colon in an average risk population. MATERIALS AND METHODS: A total of 1,208 eligible asymptomatic, average- risk adults older than 40 years of age, referred to Firuzgar Hospotal in the years 2008-2012, were enrolled. They underwent colonoscopy screening and all polypoid lesions were removed and examined by an expert gastrointestinal pathologist. The lesions were classified by size, location, numbers and pathologic findings. Size of lesions was measured objectively by endoscopists. RESULTS: The mean age of participants was 56.5±9.59 and 51.6% were male. The overall polyp detection rate was 199/1208 (16.5 %), 26 subjects having non-neoplastic polyps, including hyperplastic lesions, and 173/1208 (14.3%) having neoplastic polyps, of which 26 (2.15%) were advanced neoplasms .The prevalence of colorectal neoplasia was more common among the 50-59 age group. Advanced adenoma was more frequent among the 60-69 age group. The majority of adenomas were detected in the distal colon, but a quarter of advanced adenomas were found in the proximal colon; advance age and male gender was associated with the presence of adenoma. CONCLUSIONS: It seems that CRC screening among average-risk population might be recommended in countries such as Iran. However, sigmioidoscopy alone would miss many colorectal adenomas. Furthermore, the 50-59 age group could be considered as an appropriate target population for this purpose in Iran.

A population based study on hepatitis B virus in northern iran, amol.

BACKGROUND: Viral hepatitis is a major health problem worldwide. Change in transmission patterns of hepatitis B makes it necessary to re-evaluate its prevalence and risk factors. OBJECTIVES: We aimed to determine the prevalence of HBV infection and its related risk factors in Amol city, Northern Iran. PATIENTS AND METHODS: As a population based study, a cluster sampling approach was used and 6146 individuals from the general population of urban and rural areas of Amol, Iran, from both genders and different ages were enrolled. Inclusion criteria were willingness to participate in the study, being a lifelong resident in Amol city or its surrounding areas with Iranian nationality. Ten milliliters (10 mL) of blood was taken from each study subject and checked regarding hepatitis B markers including HbsAg, HBsAb and HBcAb using a third generation ELISA. The prevalence of HBV infections and its potential risk factors were recorded. RESULTS: The prevalence of HBsAg, HBsAb and HBcAb were estimated as 0.9%, 30.7% and 10.5%, respectively. The mean age of all participants was 43.9 (95% CI: 43.4, 44.3) in females and 55.6 in (n = 3472) males. In our study, there was a significant association between family history of hepatitis, rural residency and presence of HBsAg. There was also a positive correlation between HBcAb and family history of hepatitis, history of other types of hepatic diseases, history of tattooing, traditional phlebotomy, male gender and age. In backward logistic regression, a significant association was found between history of hepatitis in first-degree family members (OR = 13.35; 95% CI: 6.26, 28.47) and place of residence (OR = 2.32; 95% CI: 1.27, 4.22) with presence of HBsAg. There was also a positive correlation between history of hepatitis among first-degree family members (OR = 2.49; 95% CI: 1.52, 4.08), history of tattooing (OR = 2.13; 95% CI: 1.33, 3.42), history of previous hepatitis (OR = 1.87; 95% CI: 1.06, 3.28), male sex (OR = 1.36; 95% CI: 1.12, 1.66) and age (OR = 1.03; 95% CI: 1.03, 1.04) with presence of HBcAb. CONCLUSIONS: The prevalence of hepatitis B in Amol City and its surrounding areas was about one percent, a lower rate than other reports from Iran.

1Hz rTMS preconditioned by tDCS over the primary motor cortex in Parkinson's disease: absence of effect on arm lift and hand grip force control.

This study investigated whether a period of low frequency rTMS preconditioned by tDCS over the primary motor cortex modulates control of grip force in Parkinson's disease. The presented results are from the same patient cohort tested in an earlier study (Gruner et al. J Neural Transm 2010: 117: 207-216). 15 patients with Parkinson's disease (mean age: 69 ± 8 years; average disease duration: 5 ± 3 years) on dopaminergic drugs performed a grasp-lift task with either hand before (baseline) and after a period of 1Hz rTMS (90% of the resting motor threshold; 900 pulses) preconditioned by sham, anodal or cathodal tDCS (1mA, 10 min) over the primary motor cortex. We found that compared with baseline, none of the grip force parameters was significantly influenced by either stimulation session and concluded that grasping is a higher order motor skill, which cannot be modulated by tDCS preconditioned 1Hz rTMS in PD.

Arbitrary visuo-motor mapping during object manipulation in mild cognitive impairment and Alzheimer's disease: a pilot study.

Empirical evidence for an essential role of the hippocampal system in arbitrary visuo-motor mapping suggests that acquisition and retrieval of arbitrary visuo-motor mapping might be impaired in mild cognitive impairment (MCI) and Alzheimer's disease (AD). The present pilot study investigated whether MCI of amnestic type or AD impact upon the capacity to scale grip force in a predictive manner to the mass of an object to be lifted based on learned associations between arbitrary colour cues and mass. Patients with MCI (n=8) and AD (n=8) grasped and lifted two different masses (400g and 600g) in random order using a precision grip between index finger and thumb. In a "no cue" experiment, a non-informative neutral visual stimulus was presented prior to each lift, thereby disallowing any prediction about which of the two masses was going to be lifted in the next trial. In a "cue" experiment an arbitrary colour cue provided advance information about which of the two masses to be lifted. In the "no cue" condition patients scaled their grip force according to the mass of the preceding lift. In the "cue" experiment neither patients with amnestic MCI nor those with AD were able to adjust their grip force based on visuo-motor mappings with arbitrary colour cues. These preliminary data suggest that the hippocampal system plays an essential role for arbitrary visuo-motor mapping in the grip-lift task.

[18F]FLT PET for non-invasive monitoring of early response to gene therapy in experimental gliomas.

The purpose of this study was to investigate the potential of 3'-deoxy-3'-[¹8F]fluorothymidine ([¹8F]FLT) positron emission tomography (PET) to detect early treatment responses in gliomas. Human glioma cells were stably transduced with genes yielding therapeutic activity, sorted for different levels of exogenous gene expression, and implanted subcutaneously into nude mice. Multimodality imaging during prodrug therapy included (a) magnetic resonance imaging, (b) PET with 9-(4-[¹8F]fluoro-3-hydroxymethylbutyl)guanine assessing exogenous gene expression, and (c) repeat [¹8F]FLT PET assessing antiproliferative therapeutic response. All stably transduced gliomas responded to therapy with significant reduction in tumor volume and [¹8F]FLT accumulation within 3 days after initiation of therapy. The change in [¹8F]FLT uptake before and after treatment correlated to volumetrically calculated growth rates. Therapeutic efficacy as monitored by [¹8F]FLT PET correlated to levels of therapeutic gene expression measured in vivo. Thus, [¹8F]FLT PET assesses early antiproliferative effects, making it a promising radiotracer for the development of novel treatments for glioma.