Long-Term Prophylactic Transcranial Direct Current Stimulation Ameliorates Allodynia and Improves Clinical Outcomes in Individuals With Migraine.

OBJECTIVES: Migraine is a common and substantially debilitating disorder that may associate with allodynia, a marker of central sensitization in the pain circuits. Several unmet needs, like limited adherence to drugs due to adverse events and cost-effectivity, still occur in the prophylactic treatment of migraine. Transcranial direct current stimulation (tDCS) has recently been indicated to be beneficial in individuals with migraine with and without allodynia. However, to our knowledge, there are no studies evaluating the efficacy of six-month tDCS in migraine. MATERIALS AND METHODS: This study was a randomized double-blind parallel-group sham-controlled five-month extension study after a one-month lead-in trial of tDCS in individuals with migraine. A total of 23 individuals with migraine with allodynia who completed the lead-in trial were recruited after their consent and were administered three consecutive sessions of 2-mA anodal 20-minute tDCS over the left primary motor cortex every month for an additional five months. Pain-related outcomes were determined using monthly headache diaries. Allodynia, depression, anxiety, and disability because of migraine also were assessed throughout the study. RESULTS: Improvements in allodynia levels, attack frequency, number of rescue medications, and attack duration were higher, and mostly gradual during the trial, in the active group. Migraine Disability Scale grades also were lower in the active group, whereas no between-group differences were found in depression and anxiety scores. Higher responder rates of migraine attack frequency (56.8% vs 25%), number of headache days (56% vs 16.7%), and migraine attack duration (90.9% vs 8.3%) were observed after six-month tDCS in the active group than in the sham group. CONCLUSIONS: Long-term extended tDCS is shown to be a safe, efficacious, and plausible modality for prophylactic treatment in individuals with migraine with allodynia. SIGNIFICANCE: Long-term extended tDCS can alleviate allodynia, which is an indicator of drug resistance and chronicity, and meet the goals of prophylactic treatment in individuals with migraine with allodynia.

Patient preference of device-based treatment of Parkinson's disease.

INTRODUCTION: Subthalamic nucleus deep brain stimulation (STN-DBS), continuous subcutaneous apomorphine infusion (APO), and levodopa-carbidopa intestinal gel infusion (LCIG) are treatments used to treat severe motor fluctuations and dyskinesia in patients with advanced levodopa responsive Parkinson's disease (PD), who can no longer be managed with available combinations of oral medications. This study aims to evaluate patient choice of one of three device-based treatment methods. METHODS: A total of 58 patients clinically diagnosed with PD were included in the study. Eligibility for device-based treatment of PD patients with motor symptoms despite optimal medical treatment was assessed based on Hoehn & Yahr Stages, and Unified Parkinson's Disease Rating Scale-Part III. All three device-based treatment methods were thoroughly explained with on-hand demonstrations. Preferences and reasons for choice were recorded. RESULTS: Nineteen patients were ineligible for STN-DBS due to neurological causes. A total of 23 patients preferred STN-DBS, 23 preferred APO, and only one patient preferred LCIG. Thirteen patients preferred to continue oral medical treatment, while two patients positively approached both STN-DBS and APO. CONCLUSION: The most common reason patients declined STN-DBS and LCIG was concerned about the surgical operation, while the most common reason APO was declined was its frequent administration of the injection. While STN-DBS was preferred by younger, less severe patients, APO was preferred by older patients who had a longer duration of disease.

Is Allodynia a Determinant Factor in the Effectiveness of Transcranial Direct Current Stimulation in the Prophylaxis of Migraine?

OBJECTIVES: Allodynia, the clinical marker of central sensitization, affects even simple daily living activities and increases the tendency for migraine to be more resistant to treatment and have a chronic course. Migraine that impairs quality of life can often be treated with variable pharmaceutical agents, but with various side effects. Transcranial direct current stimulation (tDCS) is a potential alternative treatment for migraine prophylaxis. MATERIALS AND METHODS: Seventy-seven patients diagnosed with migraine (48 with allodynia and 29 without allodynia) were included in the study. Randomly, 41 of the 77 patients received sham stimulation and 36 patients underwent three sessions of anodal left primary motor cortex stimulation for 2 mA, 20 min. Migraine attack characteristics (frequency, severity, and duration) and analgesic drug use were followed with headache diaries for one month after the stimulation. RESULTS: After tDCS, migraine attack frequency (p = 0.021), the number of headache days (p = 0.005), duration of attacks (p = 0.008), and symptomatic analgesic drug use (p = 0.007) decreased in patients receiving active tDCS, compared to the sham group. The therapeutic gain of tDCS was calculated as 44% (95% confidence interval [CI]: 22-60%) for headache days and 76% (95% CI: 55-86) for headache duration. Response to tDCS treatment was higher in patients without allodynia (60% vs. 24%; p = 0.028) and allodynia came out as an independent predictor of response to tDCS with logistic regression analysis. Side effects were rare and similar to the sham group. CONCLUSIONS: tDCS is a safe, efficacious, and fast method for migraine prophylaxis. However, the administration of tDCS before allodynia occurs, that is, before central sensitization develops, will provide increased responsiveness to the treatment. SIGNIFICANCE: tDCS is more effective before the development of allodynia, but it also improves the quality of life even after the development of allodynia.

Serum glial fibrillary acidic protein (GFAP)-antibody in idiopathic intracranial hypertension.

AIM: Idiopathic intracranial hypertension (IIH), a disease of obscure origin, is characterized by headache and visual disturbances due to increased intracranial pressure. Recent line of evidence has suggested involvement of inflammation in IIH pathogenesis thus bringing forward anti-glial autoimmunity as a potential contributor of IIH. Glial fibrillary acidic protein (GFAP) is a major astrocytic autoantigen associated with a specific form of meningoencephalitis. MATERIALS AND METHODS: In this study, we investigated the presence of GFAP-antibody in 65 sera (49 obtained during active disease and 16 during remission) and in 15 cerebrospinal fluid (CSF) samples of 58 consecutively recruited IIH patients using cell based assay and indirect immunohistochemistry. RESULTS: GFAP-antibody was found in active period sera of 2 IIH patients with classical symptoms and good treatment response. Two remission period sera obtained at different time points from one of these cases showed lower titers of GFAP-antibody positivity. IgG from positive samples yielded an astrocytic immunoreactivity pattern. None of the CSF samples showed GFAP-antibodies. CONCLUSIONS: These results suggest that anti-astrocyte autoimmunity might be present in a fraction of IIH patients. Exact pathogenic significance of this association needs to be further studied.

Plasma levels of inflammatory mediators in vestibular migraine.

Objectives: Vestibular migraine (VM) is an under-recognized entity with substantial burden for the individual and society. The underlying mechanism of VM and its distinction from other migraine mechanisms still remain unclear. Inflammatory pathways have been suggested to contribute to vestibular migraine. Our aim was to further investigate the possible role of inflammation in the pathophysiology of VM.Methods: We recruited 30 patients with VM diagnosed according to ICHD-3 criteria and 50 gender- and age-matched controls. Blood samples were obtained from 11 VM patients during an attack and from 13 VM patients under prophylactic treatment. Plasma levels of calcitonin gene related peptide (CGRP), neurokinin A (NKA), substance P (SP), NLRP1, NLRP3, caspase-1, IL-1ß, IL-6, TNF-α and NFκB were measured by ELISA.Results: IL-6 levels were significantly reduced in VM patients, whereas levels of other inflammation parameters were comparable to those of healthy controls. Levels of inflammatory mediators were not correlated with clinical parameters. Likewise, there were no significant differences among VM patients with and without headache attack and prophylactic treatment.Conclusion: Our results argue against involvement of systemic inflammation in the pathophysiology of VM.

Multicenter study of levodopa carbidopa intestinal gel in Parkinson's disease: the Turkish experience

Background/aim: Our purpose was to determine the efficacy of levodopa carbidopa intestinal gel (LCIG) in a series of Turkish patients with Parkinson's disease (PD). Materials and methods: We had telephone calls with 54 patients from 11 neurology centers who were on LCIG treatment, and 44 patients or their caregivers were included in an eight-item survey between September 2015 and June 2016. The reliability and validity of the survey were evaluated with intraclass correlation coefficients for every question separately. Results: Average age of the patients were 63.48 and the duration of PD was 12.79 years. Average LCIG treatment period was 15.63 months. Percentages of the patients who reported they were 'better' after LCIG treatment were as follows: 80% for time spent off, 55% for dyskinesia, 65% for tremor, 85% for gait disorder, 50% for pain, 50% for sleep disorders, 42.5% for depression, 32.5% for incontinence, and 70% for activities of daily living. Cronbach's alpha was 0.795 and the intraclass correlation coefficient was reliable for the items. Conclusion: As detected by a survey performed by telephone calls with good interrater reliability, patients with PD improve with LCIG treatment in many aspects of the disease.

Risk Factors, Biomarkers, Etiology, Outcome and Prognosis of Ischemic Stroke in Cancer Patients

Introduction: Cerebrovascular disease is the second most common complication in individuals with tumours. The aim of this study was to investigate risk factors, biomarkers, etiology and prognosis of ischemic stroke in cancer patients (ISCPs). Methods: The medical records of 619 consecutive patients who were admitted with acute ischemic stroke from January 2012 to November 2014 were retrospectively evaluated. The patients were divided into two groups (group 1, patients with an active cancer prior to the onset of ischemic stroke; group 2, patients without an active cancer history). The demographic data, risk factors, NIHSS scores, thrombocyte count, D-dimer, fibrinogen and C reactive protein (CRP) level at admission, modified Rankin Scale (mRS) scores in the follow-up period and location of lesions on DWI were recorded. The Mann-Whitney U test, chi-squared test and logistic regression was used for analyzing data, p<0.05 being considered statistically significant. Results: A total of 46 (7.4%) ISCPs were included. Hyperlipidemia was significantly lower in the ISCP group (p=0.001). Elevated thrombocyte counts, D-dimer, fibrinogen and CRP levels at admission, acute multiple ischemic lesions, other causes, mortality in hospital and worse outcome were significantly related to ISCP (p<0.05). On logistic regression analysis, follow up mRS>3, acute multiple ischemic lesions located in more than one vascular territory (AMIMCT) and other causes were significantly associated with ISCP (p<0.001). Conclusion: In our study, other causes, AMIMCT and mRS>3 were more common in the ISCP group. We consider that CCS could be more suitable for detecting other causes than TOAST. Biomarkers could be important in the ISCP group.

Intracranial hypertension related to cerebral venous thrombosis; and acute ischemic stroke with micro-infarcts associated with IgG4-related disease.

IgG4-related systemic disease (IgG4-RD) is characterized by an inflammatory reaction rich in IgG4-positive plasma cells, affecting multiple organs. This report describes a case who was diagnosed with IgG4-RD, having cerebral venous thrombosis and a subsequent acute ischemic stroke of undetermined cause. A 47-year-old woman presented with headache, visual disturbance and eyelid swelling and two years later she was admitted with acute attacks of mild left lower limb sensory-motor monoparesis. Indirect immunohistochemistry assay showed elevated level of IgG4, labeling neurons of the central nervous system, suggesting an immunological process possibly affecting vascular structures. Our experience suggests that IgG4-RD may be considered in patients with ischemic stroke and cerebral venous system involvement.

Appendectomy History is not Related to Parkinson's Disease.

BACKGROUND: It has been suggested that appendectomy may modify the emergence of Parkinson's disease (PD) by affecting the retrograde transport of α-synuclein (α-syn) from the gastrointestinal system. OBJECTIVE: To explore the possible role of appendectomy on PD. METHODS: The retrospective data of the 1625 patients (839 PD, 633 non-α-syn parkinsonism and 153 controls) were compared. Disease specific measures between PD patients with (n = 69) and without (n = 770) appendectomy were also evaluated. RESULTS: The prevalence of appendectomy was not significantly lower in the PD group (8.2%) compared to the other groups (8.4% and 7.9%, p = 0.98), and the odds of having PD against other diagnoses (OR) were not significantly different in the appendectomy group (OR = 0.99, p = 0.96). No difference was determined between PD patients with and without appendectomy with respect to the age of disease onset, disease duration and severity. Appendectomy-first symptom interval was not determined to be related with PD diagnosis (hazard ratio = 1.12, p = 0.39) and did not predict disease severity in the PD group (OR = 0.99, p = 0.54). Age of appendectomy (lower or higher than 20) also did not affect future PD diagnosis (Relative Risk = 0.9, p = 0.54) or the disease severity. CONCLUSIONS: The results of the study suggest no effect of appendectomy on the emergence and clinical manifestations of PD. The removal of the appendix is possibly not sufficient to suppress the exposure of the brain stem to α-syn via vagal retrograde transport. Further studies are needed to elucidate the role of appendix in PD.