Neurological soft signs as trait markers of a subset of patients with obsessive-compulsive disorder with low insight and altered cognitive abilities.

Neurological soft signs (NSS) are subtle motor control impairments that include involuntary movements and abnormalities of motor coordination, sensory integration and lateralization. They engage different brain networks, including the prefrontal networks that support the higher cognitive functions that are dysfunctional in obsessive-compulsive disorder (OCD). This study investigated the relationships between the presence of NSS and patients' severity of OCD symptoms, insight, and treatment resistance in a sample of 63 patients. Treatment-resistance was assessed considering all the treatments the patients received during the course of their disease. The four dimensions of OCD defined in the dimensional obsessive-compulsive scale were considered. Links between the patients' cognitive abilities and NSS were assessed using tests targeting specifically the core components of executive functions. As expected, OCD patients displayed more NSS than individually matched control participants. In OCD patients, high NSS scores were associated with poor insight and lower cognitive abilities. Multiple regression analysis identified worse visuospatial working memory, attentional control, and verbal fluency as predictive factors of high NSS scores among cognitive functions. Unexpectedly, the patients displaying symptoms in the contamination/washing dimension displayed less NSS than the other patients. In contrast, neither the severity of OCD symptoms nor long-range treatment resistance was significantly related to patients' NSS scores. Altogether, our findings suggest that high NSS scores may be a trait marker of a subset of OCD patients with low insight and particularly altered cognitive abilities who would not express the contamination/washing dimension of the pathology.

The effects of transcranial direct-current stimulation (tDCS) on pain intensity of patients with fibromyalgia: a systematic review and meta-analysis.

INTRODUCTION: Fibromyalgia (FM) is a chronic pain condition that affects millions of people worldwide. Transcranial Direct Current Stimulation (tDCS) is a non-invasive brain stimulation technique that has shown promise as a potential treatment for FM by modulating pain perception and reducing symptoms, such as fatigue and depression. We aimed to systematically review studies that assess the effect of tDCS on pain reduction in FM patients. METHODS: Seven electronic databases (PubMed, Scopus, Embase, PsycINFO, Web of Science, Cochrane, and CINAHL Complete) were searched for records in English. Studies that measured the effect of tDCS on pain intensity in FM patients were included. The Cochrane Collaboration's tool was used to assess the quality of the included studies. A random-effect model was preferred, and statistical analysis was performed by Stata software version 17. RESULTS: Twenty studies were included for qualitative, and eleven for quantitative analysis. Out of 664 patients included in the study, 443 were in the stimulation group. The left M1 area was the most common stimulation target (n = 12), and 2 mA was the most common stimulation amplitude (n = 19). The analysis showed that active tDCS significantly reduced pain intensity in FM patients in comparison to the sham group (SMD= -1.55; 95% CI -2.10, -0.99); also, no publication bias was noted. CONCLUSION: Our systematic review highlights the potential effect of tDCS on the reduction of pain intensity in FM patients. Additionally, this current evidence could suggest that tDCS applied at an intensity of 2mA to the left M1 is the most effective strategy.

High treatment resistance is associated with lower performance in the Stroop test in patients with obsessive-compulsive disorder.

Around 50% of the patients with obsessive-compulsive disorder (OCD) are resistant to treatment, and patients with OCD show alterations in a broad range of cognitive abilities. The present study investigated the links between treatment-resistance, executive and working memory abilities, and the severity of OCD symptoms among 66 patients with OCD. The patients performed seven tests gauging their executive functions and working memory and filled in questionnaires for OCD severity and insight into their pathology. In addition, the executive and working memory abilities of a subset of these patients were compared with those of individually matched control participants. In contrast with previous studies, patients' treatment resistance was evaluated by considering the clinical outcomes of all the treatments that they received during the course of their disease. Higher treatment resistance was associated with lower performance in one particular executive test, the Stroop test, which assessed patients' ability to inhibit prepotent/automatic responses. Older age and more severe OCD symptoms were also associated with higher treatment resistance. Regardless of OCD severity, the patients displayed small to moderate deficits across most components of executive functions compared to control participants. Interestingly, patients with OCD took more time than control participants to perform speeded neuropsychological tests but never made more errors. Altogether, this study shows that the treatment-resistance of patients with OCD may be reliably quantified over the course of years and treatments using Pallanti and Quercioli's (2006) treatment resistance-related scales. The data suggest that the Stroop test could be used clinically to anticipate treatment outcomes in to-be-treated patients.

Effect of deep brain stimulation on freezing of gait in patients with Parkinson's disease: a systematic review.

BACKGROUND AND OBJECTIVES: Freezing of gait (FOG) is a disabling gait disorder in patients with Parkinson's disease (PD), characterized by recurrent episodes of halting steps. Dopaminergic drugs are common treatments for PD and FOG; however, these drugs may worsen FOG. Deep brain stimulation (DBS) is another option used to treat selected patients. The device needs to be programmed at a specific frequency, amplitude, and pulse width to achieve optimum effects for each patient. This systematic review aimed to evaluate the efficacy of DBS for FOG and its correlation with programmed parameters and the location of the electrodes in the brain. MATERIALS AND METHODS: Data for this systematic review were gathered from five online databases: Medline (via PubMed), Scopus, Embase, Web of Science, and Cochrane Library (including both Cochrane Reviews and Cochrane Trials) with a broad search strategy. We included those articles that reported clinical trials and a specific measurement for FOG. RESULTS: This review included 13 studies of DBS that targeted the subthalamic nucleus (STN), substantia nigra (SNr), or pedunculopontine nucleus (PPN). Our analysis showed that low-frequency stimulation (LFS) was superior to high-frequency stimulation (HFS) for improving FOG. In the long term, the efficacy of both LFS and HFS decreased. The effect of amplitude was variable, and this parameter needed to be adjusted for each patient. Bilateral stimulation was better than unilateral stimulation. CONCLUSION: DBS is a promising choice for the treatment of severe FOG in patients with PD. Bilateral, low-frequency stimulation combined with medical therapy is associated with better responses, especially in the first 2 years of treatment. However, individualizing the DBS parameters should be considered to optimize treatment response.

Correlation of response to subthalamic deep brain stimulation in Parkinson's disease patients with striatal dopamine transporter density on 99mtc-TRODAT-1 SPECT.

BACKGROUND: Deep brain stimulation (DBS) is a surgical approach with electrical stimulation of certain parts of the brain, which reduce Parkinson's disease (PD) symptoms. Since the loss of dopaminergic neurons in the substantia nigra is the main pathophysiology of PD, we aimed to evaluate the association of response to DBS with preoperative dopamine transporter density (DAT) and its postoperative changes in PD patients who underwent the bilateral implantation of the electrodes in the subthalamic nucleus (STN). METHOD: A prospective evaluation of Parkinson's disease patients who underwent STN-DBS for 2 years was done. 99mTc-TRODAT-1 single-photon emission computed tomography (SPECT) scan and assessment of PD using unified Parkinson's disease rating scale (UPDRS) III were performed in both pre- and post-operation states. The correlation of response to DBS after 6 months was assessed with baseline findings and postoperative changes of 99mTc-TRODAT-1 SPECT parameters. RESULTS: Compared to the preoperative state, UPDRS III scores and Levodopa equivalent daily dose (LEDD) were significantly decreased after DBS. However, in 17 patients who underwent both pre-and post-operative 99mTc-TRODAT-1 SPECT, no significant change was seen in any quantitative parameters, including right and left striatal-binding ratio (SBR) as well as striatal asymmetry index (SAI). No significant correlation was also found between the percent of UPDRS III change after DBS and values of preoperative SBRs. The percentage of LEDD reduction also showed no significant correlation with the preoperative state of 99 m-TRODAT-1 SPECT. CONCLUSION: Our results showed that the mechanism of DBS action is not accompanied by short-term compensation of DAT in basal ganglia in severely advanced PD.

Constant current or constant voltage deep brain stimulation: short answers to a long story.

PURPOSE: Recently, the feature of generating constant current output has been added to the implantable pulse generators (IPGs). The efficacy of the conventionally used constant voltage (CV) stimulation has been proved in different movement and psychiatric disorders. In this systematic review, we aimed to discuss the effect of constant current (CC) and constant voltage stimulation on patients with Parkinson's disease (PD) who had subthalamic nucleus deep brain stimulation implantation; we also compared these methods of stimulation with each other. METHODS: Using the words "Deep brain stimulation", "constant current" and "constant voltage", we developed a broad search strategy and a systematic search was conducted in PubMed, Scopus, Web of Science and Cochrane electronic bibliographic databases. Studies on the Parkinson's disease patients with subthalamic deep brain stimulation, which mentioned constant current or/and constant voltage setting stimulation were included. RESULTS: After screening of 284 articles, 10 reports were found eligible for this study. The score of unified Parkinson's disease rating scale part 3 was improved compared to the baseline, whether the stimulation was CV at baseline or CC. No significant change in non-motor outcomes was found. CONCLUSIONS: Although CC stimulation has shown a significant improvement in both motor and non-motor symptoms of PD, switching from CV to CC did not result in a significant change in the score of these items based on UPDRS. To sum up, implantation of constant current devices is safe and significantly improves motor function; it also maintains an acceptable safety profile in patients with PD.

Deep brain stimulation of the posterior subthalamic area as an alternative strategy for management of Holmes tremor: A case report and review of the literature.

Background: Holmes tremor is often refractory to medical treatment and deep brain stimulation of the ventralis intermedius nucleus of the thalamus (VIM-DBS) is the intervention of choice in controlling the tremor. Herein, we present a beneficial alternative strategy for the management of such situations, considering the posterior subthalamic area (PSA) as the target of stimulation. Case Description: We report a 57-year-old male with the right-sided tremor following a traumatic brain injury 20 years ago. He had been diagnosed with Holmes tremor that was not responsive to nonsurgical therapeutic options. When refractoriness confirmed, he became a candidate for VIM-DBS. During the operation, by performing macrostimulation with a maximum of 2 mA of amplitude, the tremor had no response to the stimulation of different tracts, and severe right hemi-body paresthesia occurred; therefore, we modified our approach and targeted the PSA, which resulted in satisfactory control of the tremor. The permanent lead was implanted into the left side PSA. At 1-year follow-up, the right side tremor was under complete control. Conclusion: Our case and other similar pieces of evidence are consistently indicating the potential regulatory effects of PSA-DBS in controlling the Holmes tremor as a feasible alternative strategy when VIM-DBS does not provide a satisfactory response. However, further studies with larger sample size are required to evaluate the long-term response and its possible long-term stimulation-related effects.

Differentiating Between Low- and High-grade Glioma Tumors Measuring Apparent Diffusion Coefficient Values in Various Regions of the Brain.

OBJECTIVES: Our study aimed to apply the apparent diffusion coefficient (ADC) values to quantify the differences between low- and high-grade glioma tumors. METHODS: We conducted a multicenter, retrospective study between September to December 2019. Magnetic resonance imaging (MRI) diffusion-weighted images (DWIs), and the pathologic findings of 56 patients with glioma tumors (low grade = 28 and high grade = 28) were assessed to measure the ADC values in the tumor center, tumor edema, boundary area between tumor with normal tissue, and inside the healthy hemisphere. These values were compared between the two groups, and cut-off values were calculated using the receiver operating characteristic curve. RESULTS: We saw significant differences between the mean ADC values measured in the tumor center and edema between high- and low-grade tumors (p< 0.005). The ADC values in the boundary area between tumors with normal tissue and inside healthy hemisphere did not significantly differ in the groups. The ADC values at tumor center and edema were higher than 1.12 × 10-3 mm2/s (sensitivity = 100% and specificity = 96.0%) and 1.15 × 10-3 mm2/s (sensitivity = 75.0% and specificity = 64.0%), respectively, could be classified as low-grade tumors. CONCLUSIONS: The ADC values from the MRI DWIs in the tumor center and edema could be used as an appropriate method for investigating the differences between low- and high-grade glioma tumors. The ADC values in the boundary area and healthy tissues had no diagnostic values in grading the glioma tumors.

Using Preimplanted Deep Brain Stimulation Electrodes for Rescue Thalamotomy in a Case of Holmes Tremor: A Case Report and Review of the Literature.

BACKGROUND: Chronic stimulation of the thalamus is a surgical option in the management of intractable Holmes tremor. Patients with deep brain stimulation (DBS) can encounter infection as a postoperative complication, necessitating explantation of the hardware. Some studies have reported on the technique and the resulting efficacy of therapeutic lesioning through implanted DBS leads before their explantation. CASE DESCRIPTION: We report the case of a patient with Holmes tremor who had stable control of symptoms with DBS of the nucleus ventralis intermedius of the thalamus (VIM) but developed localized infection over the extension at the neck, followed by gradual loss of a therapeutic effect as the neurostimulator reached the end of its service life. Three courses of systemic antibiotic therapy failed to control the infection. After careful consideration, we decided to make a rescue lesion through the implanted lead in the right VIM before explanting the complete DBS hardware. The tremor was well controlled after the rescue lesion procedure, and the effect was sustained during a 2-year follow-up period. CONCLUSION: This case and the previously discussed ones from the literature demonstrate that making a rescue lesion through the DBS lead can be the last plausible option in cases where the DBS system has to be explanted because of an infection and reimplantation is a remote possibility.

Initial Results of Bilateral Subthalamic Nucleus Stimulation for Parkinson Disease in a Newly Established Center in a Developing Country: Shiraz, Southern Iran.

OBJECTIVE: To report the establishment of a new center for deep brain stimulation (DBS) as a surgical treatment for Parkinson disease and the surgical outcomes, from 2014 to 2017 in Shiraz, Southern Iran. METHODS: A new treatment program was established in Shiraz through a multidisciplinary team in 2014. Thirty-four patients underwent implantation of subthalamic nucleus (STN) electrodes during the last 3 years. Twenty-five patients fulfilled the minimum 6-month follow-up criteria. The baseline Unified Parkinson Disease Rating Scale (UPDRS) was assessed 1 month before surgery in both off-medication and on-medication states by a movement disorder neurologist. To evaluate the outcomes, subscores of the UPDRS were assessed in all patients before surgery and at least 6 months after the operation. RESULTS: All 25 patients had advanced Parkinson disease categorized as stage 3 or 4 using the Hoehn and Yahr scale. STN DBS resulted in a dramatic improvement in motor function of most patients. A reduction in dopaminergic medication dosage (average 60% reduction) was observed. The mean improvement was 40% in UPDRS II and 67% in UPDRS III. No surgical or hardware complications were observed. Stimulation-related adverse effects, including increased falling and worsening of speech, occurred in a few patients after surgery. Most of the patients experienced weight gain after surgery. CONCLUSIONS: Bilateral STN DBS is a satisfactory and safe treatment for carefully selected patients with advanced Parkinson disease. According to the results, the procedure can be performed safely and with comparable results in developing countries around the world.

A comprehensive approach in high-grade glioma management: position statement from the Neuro-Oncology Scientific Club (NOSC), Shiraz, Iran.

Establishing a robust teamwork model in the practice of neuro-oncology requires continued interdisciplinary efforts. The Neuro-Oncology Scientific Club (NOSC) initiative is an interdisciplinary clinical forum promoting the comprehensive approach across involved disciplines in the management of central nervous system (CNS) malignancies. With its provincial founding panels and national steering board, NOSC has been operational in Iran since 2011. This initiative has pursued its mission through interval strategic meetings, tumor boards, case discussions as well as publishing neuro-oncology updates, case study periodicals, and newsletters. A provincial meeting of NOSC in Shiraz put together insights from international practice guidelines, emerging evidence, and expert opinions to draw a position statement on high-grade glioma management in adults. The present report summarizes key highlights from the above clinical forum.

Outcome after temporal lobectomy in patients with medically-refractory mesial temporal epilepsy in Iran.

BACKGROUND: Epilepsy surgery has been proved to be feasible and cost-effective in developing countries. In the current paper, we discussed the outcome of patients with mesial temporal lobe epilepsy (MTLE) and medically-refractory seizures who had surgery at our center in Shiraz, Iran. METHODS: Patients aged 18 years and older with refractory MTLE and mesial temporal sclerosis operated at Namazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran from May 2009 through December 2011 were enrolled. Presurgical evaluation included clinical history, neurological examination, 2-hour video-EEG recording, and 1.5-T MRI. All patients were submitted to standard temporal lobectomy at the side determined by MRI and video-EEG. RESULTS: Twenty-two patients (12 women and 10 men) underwent surgery between May 2009 and December 2011. All patients were followed postoperatively for at least 12 months (mean=24.8±7.7 months; minimum=12 months; maximum=36 months). At the last follow-up visit, 18 patients (81.8%) had a good outcome (15 patients [68.2%] had Engel class 1 and three others had Engel class 2). The total cost of presurgical evaluation and epilepsy surgery at our center was less than $500. CONCLUSIONS: Resources are limited for the vast majority of medically-refractory patients with epilepsy who live in the developing countries. However, it is feasible to select good surgical candidates for anterior temporal lobectomy relying on the clinical history and examination, MRI and interictal EEG. Broader application of epilepsy surgery should be encouraged in countries with limited financial resources.

Incidence of Deep Vein Thrombosis in Patients Undergoing Degenerative Spine Surgery onProphylactic Dalteparin; A Single Center Report.

OBJECTIVE: To determine the incidence of deep vein thrombosis (DVT)in patients undergoing spinal surgeries receiving prophylactic doses of Deltaparin in a single center in central Iran. METHOD: This cross-sectional study was conducted in Shariatee hospital of Isfahan during a 12-month period. We included all the patients undergoing elective spinal surgeries in our center during the study period who received prophylactic dosages of subcutaneous Dalteparin (5000unit daily) thefirst postoperative day. Those with absolute contraindications of anticoagulation therapy were not included in the study. Patients were followed for 3 months clinically and the incidence of DVT was recorded. DVT was suspected clinically and was confirmed by color Doppler sonography. RESULTS: Overall we included 120 patients with mean age of 44.8 ± 12.6years among whom there were 54 (45%) men and 66 (55%) women. Lumbar discectomy (32.9%)and laminectomy (20.2%)were the most common performed procedures. DVT was detected in 1 (0.83%) patient in postoperative period. None of the patients developed pulmonary embolism and none hemorrhagic adverse event was recorded. The patient was treated with therapeutic unfractionated heparin and was discharged with warfarin. CONCLUSION: Our results shows the efficacy of LMWH (Dalteparin) in reducing the incidence of DVT to 0.83%. These results also show the safety of Dalteparin in spine surgery because of lack of bleeding complication.

Serum Levels of Monocyte Chemoattractant Protein-1 Correlate with Poor Clinical Grades in Cerebral Aneurysms.

BACKGROUND: Ruptured cerebral aneurysms (ICAs) are the most common non-traumatic cause of subarachnoid hemorrhage (SAH) that is associated with life threatening complications such as Vasospasm, Infarction, and Hydrocephalus (HCP). The active participation of macrophage/monocyte-mediated inflammatory response in the pathogenesis of cerebral aneurysm as labeled with Monocyte Chemoattractant Protein-1 (MCP-1) is suggested. OBJECTIVE: To measure the serum level of MCP-1 in ruptured CAs in different time intervals. METHODS: We measured the serum levels of MCP-1 in SAH patients who had CAs and compared it with that of MCP-1 in two control groups: including patients with SAH without CAs, and the normal population of blood donors. We also measured the MCP-1 levels in patients with CAs one week afterward to evaluate the effect of treatment. Serum level of MCP-1 was measured by a commercial ELISA assay. RESULTS: Mean serum MCP-1 level in patients with SAH and CAs was 188.2168 Pg/ml and 331.3982 Pg/ml in the normal population. There was no statistically significant difference between serum levels of MCP-1 on the first (mean=188.2168 Pg/ml) and 7th days after SAH onset (mean=171.8450 Pg/ml) (p=0.739). Serum level of MCP-1 increased significantly as Glasgow Coma Scale decreased (p=0.078) and Hunt and Hess score increased (p=0.089). CONCLUSION: Our results did not show an increasing MCP-1 serum level in patients with aneurysmal SAH. There was a relationship between poor clinical grade and MCP-1 levels in patients with CAs. MCP-1 may be a local inflammatory marker for cerebral aneurysms without systemic manifestation.

Operationalizing Cognitive Science and Technologies' Research and Development; the "Brain and Cognition Study Group (BCSG)" Initiative from Shiraz, Iran.

Recent advances in brain and cognitive science studies have revolutionized concepts in neural dynamics, regulating mechanisms, coding systems and information processing networks which govern our function and behavior. Hidden aspects of neurological and psychiatric diseases are being understood and hopes for their treatment are emerging. Although the two comprehensive mega-projects on brain mapping are in place in the United States and Europe; the proportion of science contributed by the developing countries should not be downsized. With the granted supports from the Cognitive Sciences and Technologies Council (CSTC), Iran can take its role in research on brain and cognition further. The idea of research and development in Cognitive Sciences and Technologies (CST) is being disseminated across the country by CSTC. Towards this goal, the first Shiraz interdisciplinary meeting on CST was held on 9 January 2014 in Namazi hospital, Shiraz. CST research priorities, infrastructure development, education and promotion were among the main topics discussed during this interactive meeting. The steering committee of the first CST meeting in Shiraz decided to frame future research works within the "Brain and Cognition Study Group-Shiraz" (BCSG-Shiraz). The study group comprises scientific leaders from various allied disciplines including neuroscience, neurosurgery, neurology, psychiatry, psychology, radiology, physiology, bioengineering, biophysics, applied physics and telecommunication. As the headquarter for CST in the southern Iran, BCSG-Shiraz is determined to advocate "brain and cognition" awareness, education and research in close collaboration with CSTC. Together with CSTC, Shiraz Neuroscience Research center (SNRC) will take the initiative to cross boundaries in interdisciplinary works and multi-centric research projects within the study group.

Management of epilepsy in resource-limited areas: establishing an epilepsy surgery program in Iran.

Background Of about 40 million people with epilepsy, who live in developing countries, the majority do not receive appropriate treatment. Nonetheless, there are striking disparities among the so-called developing countries, however generally speaking, access to and availability of epilepsy management programs in developing countries are very limited and therefore, the issue of developing epilepsy centers in resource-limited settings in a large scale is very essential. The surgery for epilepsy, including temporal lobotomy, lesionectomy and corpus colostomy, for patients with medically-refractory seizures, defined as failure of adequate trials of two tolerated, appropriately chosen and using antiepileptic drug to achieve sustained freedom, from seizure has been proved to be feasible and cost-effective in developing countries. However, the success of epilepsy surgery depends upon the accurate identification of good surgical candidates based on the available resources and technologies without jeopardizing safety. In the current paper, we will share our experiences of establishing an epilepsy surgery program in Iran, despite all short-comings and limitations and try to provide some answers to those challenges, which helped us establish our program.

Outcome of decompressive craniectomy in comparison to nonsurgical treatment in patients with malignant MCA infarction.

BACKGROUND: Malignant cerebral infarction is a well-recognized disease, comprising 10-15% of all cases with cerebral infarction and causing herniation and death in 80% of cases. In this study, we compare the effects of decompressive craniectomy versus conventional medical treatment on mortality rate and functional and neurological outcome in patients with malignant MCA infarction. METHODS: We performed a prospective case-control study on 60 patients younger than 80years of age suffering malignant MCA cerebral infarction. The case group underwent decompressive craniectomy in addition to routine aggressive medical care; while the control group received routine medical treatment. Patient outcome was assessed using Glasgow outcome scale and modified Rankin scale within three months of follow-up. The data were analyzed by SPSS version 16.0 software using Chi Square, One-way ANOVA and Mann-Whitney tests. RESULTS: There were 27 male and 33 female patients with a mean age of 60.6 years (SD = 12.3). Glasgow outcome scale score averaged 2.93 in the surgical versus 1.53 in the medical group; this difference was significant (p = 0.001). Outcome in modified Rankin scale was also significantly lower in the surgical (3.27) versus medical (5.27) group (p < 0.001). Surgery could decrease the mortality rate about 47%. CONCLUSION: In this study, decompressive craniectomy could decrease mortality rate, and improve neurological and functional outcome, and decrease long-term disability in patients with malignant MCA infarction.