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Nilotinib is a tyrosine kinase inhibitor used to treat patients with chronic myeloid leukemia (CML). This agent is also being studied in neurodegenerative disorders including Parkinson disease. Studies have shown that nilotinib may decrease the accumulation of parkin substrates and decrease the loss of dopaminergic cells. The use of nilotinib in neurologic disorders is relatively new, and little information about this use has been published. We report on a patient receiving nilotinib for CML. The patient had no previous neurologic deficits, and developed intermittent dystonic posturing of the left upper extremity and cognitive impairment after she began nilotinib treatment. The mechanisms behind this adverse effect are not clear; however, her symptoms began after nilotinib was introduced, decreased with dose reduction, stopped with its cessation, and re-emerged when the medication was restarted. To our knowledge, this is the first reported patient with neurologic symptoms secondary to nilotinib use., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2019 Justine Chan et al.)

OBJECTIVE Ventral intermediate nucleus deep brain stimulation (DBS) for essential tremor is traditionally performed with intraoperative test stimulation and conscious sedation, without general anesthesia (GA). Recently, the authors reported retrospective data on 17 patients undergoing DBS after induction of GA with standardized anatomical coordinates on T1-weighted MRI sequences used for indirect targeting. Here, they compare prospectively collected data from essential tremor patients undergoing DBS both with GA and without GA (non-GA). METHODS Clinical outcomes were prospectively collected at baseline and 3-month follow-up for patients undergoing DBS surgery performed by a single surgeon. Stereotactic, euclidean, and radial errors of lead placement were calculated. Functional (activities of daily living), quality of life (Quality of Life in Essential Tremor [QUEST] questionnaire), and tremor severity outcomes were compared between groups. RESULTS Fifty-six patients underwent surgery: 16 without GA (24 electrodes) and 40 with GA (66 electrodes). The mean baseline functional scores and QUEST summary indices were not different between groups (p = 0.91 and p = 0.59, respectively). Non-GA and GA groups did not differ significantly regarding mean postoperative percentages of functional improvement (non-GA, 47.9% vs GA, 48.1%; p = 0.96) or QUEST summary indices (non-GA, 79.9% vs GA, 74.8%; p = 0.50). Accuracy was comparable between groups (mean radial error 0.9 ± 0.3 mm for non-GA and 0.9 ± 0.4 mm for GA patients) (p = 0.75). The mean euclidean error was also similar between groups (non-GA, 1.1 ± 0.6 mm vs GA, 1.2 ± 0.5 mm; p = 0.92). No patient had an intraoperative complication, and the number of postoperative complications was not different between groups (non-GA, n = 1 vs GA, n = 10; p = 0.16). CONCLUSIONS DBS performed with the patient under GA to treat essential tremor is as safe and effective as traditional DBS surgery with intraoperative test stimulation while the patient is under conscious sedation without GA.

Background: Multiple placebo-controlled trials have assessed locally applied topical nitrate preparations in treating Raynaud's phenomenon (RP)., Objectives: The objective of this meta-analysis was to assess the effects of local topical nitrates in primary and secondary RP with respect to a combined end point integrating parameters of digital blood flow and clinical severity., Methods: A systematic review was performed using MEDLINE, Embase, and the Cochrane library. Only trials comparing locally applied topical nitrates with placebo comparators were included. Studies were appraised for bias by 2 independent reviewers., Results: A total of 7 placebo-controlled trials including 346 patients were used in the meta-analysis; 4 trials used nitroglycerin ointments, 2 used the nitroglycerin gel vehicle MQX-503, and 1 used compounded nitrite. The meta-analysis results supported a moderate-to-large treatment effect in RP (standardized mean difference [SMD] = 0.70; 95% CI, 0.35-1.05; P < .0001). Subgroup analyses showed a large treatment effect in secondary RP (SMD = 0.95; 95% CI, 0.25-1.65; P = .008) and moderate effect in primary RP (SMD = 0.45; 95% CI, 0.05-0.85; P = .03)., Limitations: Limitations include the inclusion of multiple topical nitrate preparations and integration of different outcomes assessments., Conclusion: Local topical nitrates have significant efficacy in the treatment of both primary and secondary RP., (Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: Recent studies have shown similar clinical outcomes between Parkinson disease (PD) patients treated with deep brain stimulation (DBS) under general anesthesia without microelectrode recording (MER), so-called “asleep” DBS, and historical cohorts undergoing “awake” DBS with MER guidance. However, few studies include internal controls. This study aims to compare clinical outcomes after globus pallidus internus (GPi) and subthalamic nucleus (STN) DBS using awake and asleep techniques at a single institution., Methods: PD patients undergoing awake or asleep bilateral GPi or STN DBS were prospectively monitored. The primary outcome measure was stimulation-induced change in motor function off medication 6 months postoperatively, measured using the Unified Parkinson’s Disease Rating Scale part III (UPDRS-III). Secondary outcomes included change in quality of life, measured by the 39-item Parkinson’s Disease Questionnaire (PDQ-39), change in levodopa equivalent daily dosage (LEDD), stereotactic accuracy, stimulation parameters, and adverse events., Results: Six-month outcome data were available for 133 patients treated over 45 months (78 GPi [16 awake, 62 asleep] and 55 STN [14 awake, 41 asleep]). UPDRS-III score improvement with stimulation did not differ between awake and asleep groups for GPi (awake, 20.8 points [38.5%]; asleep, 18.8 points [37.5%]; p = 0.45) or STN (awake, 21.6 points [40.3%]; asleep, 26.1 points [48.8%]; p = 0.20) targets. The percentage improvement in PDQ-39 and LEDD was similar for awake and asleep groups for both GPi (p = 0.80 and p = 0.54, respectively) and STN cohorts (p = 0.85 and p = 0.49, respectively)., Conclusions: In PD patients, bilateral GPi and STN DBS using the asleep method resulted in motor, quality-of-life, and medication reduction outcomes that were comparable to those of the awake method.

Purpose/Aim of the study: To study finger displacement in patients with Parkinson disease dementia (PDD) and in patients with Alzheimer disease (AD)., Methods: We examined 56 patients with PDD and 35 with AD. Patients were examined during their regular outpatient clinic visit. Finger displacement was measured by observers not actively involved in the study using a creative grid ruler for all PDD and AD patients. Finger displacement was examined by asking patients to point their index fingers toward the grid ruler with the nails facing upward. Patients were asked to maintain the pointing position for 15 s. After 15 s, patients were asked to close their eyes for another 15 s while maintaining the same position. A positive result was downward index finger displacement of ≥5 cm within the 15-second time window with eyes closed., Results: Of the 56 PDD patients, 53 had bilateral finger displacement of >5 cm. In comparison, of the 35 AD patients, only 1 patient had minimal displacement., Conclusions: Results of the non-invasive finger displacement test may provide insight, on an outpatient basis, of the integrity of subcortical-cortical circuits. Downward finger displacement, especially bilateral downward displacement, may signal the extensive disruption of subcortical-cortical circuits that occurs in PDD patients., Abbreviations: AChE: acetylcholinesterase; AD: Alzheimer disease; DLB: dementia with Lewy bodies; ET: essential tremor; MDS-UPDRS: Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale; MMSE: Mini-Mental State Examination; PD: Parkinson disease; PDD: Parkinson disease dementia.

Epidermolysis bullosa acquisita (EBA) is a rare, acquired subepidermal blistering disease. EBA is characterized by autoantibodies to collagen VII,which serves to link the epidermis to the dermis. The two most common presentations of EBA are classical noninflammatory EBA and bullous pemphigoid-like EBA. Diagnosis of EBA can be challenging as it sharesclinical and histopathologic features with other blistering diseases. Treatment is often recalcitrant and will often necessitate multiple therapies. We presenta case of a thirty-six-year-old Chinese man with EBA and review the literature.

We present a 38-year-old woman with local heat urticaria confirmed by heat provocation testing. Heat urticaria is a rare form of physical urticaria that istriggered by exposure to a heat source, such as hot water or sunlight. Although it is commonly localized and immediate, generalized and delayed onset forms exist. Treatment options include antihistamines and heat desensitization. A brisk, mechanical stroke elicited a linear wheal. Five minutes after exposure to hot water, she developed well-demarcated,erythematous blanching wheals that covered the distal forearm and entire hand.

Lichen planus is an inflammatory skin conditionwith characteristic histopathological findings thathas many clinical variants. Recently, there have been25 cases reported in the literature of lichen planuspigmentosus (LPPi) that preceded the developmentof frontal fibrosing alopecia (FFA), which is a variantof lichen planopilaris (LPP). We review the literatureregarding LPPi, LPP, and FFA and present a case of a40-year-old African American woman with LPPi andLPP.

Objective: Recent studies show that deep brain stimulation can be performed safely and accurately without microelectrode recording ortest stimulation but with the patient under general anesthesia. The procedure couples techniques for direct anatomical targeting on MRI with intraoperative imaging to verify stereotactic accuracy. However, few authors have examined the clinical outcomes of Parkinson's disease (PD) patients after this procedure. The purpose of this study was to evaluate PD outcomes following "asleep" deep brain stimulation in the globus pallidus internus (GPi)., Methods: The authors prospectively examined all consecutive patients with advanced PD who underwent bilateral GPi electrode placement while under general anesthesia. Intraoperative CT was used to assess lead placement accuracy. The primary outcome measure was the change in the off-medication Unified Parkinson's Disease Rating Scale motor score 6 months after surgery. Secondary outcomes included effects on the 39-Item Parkinson's Disease Questionnaire (PDQ-39) scores, on-medication motor scores, and levodopa equivalent daily dose. Lead locations, active contact sites, stimulation parameters, and adverse events were documented., Results: Thirty-five patients (24 males, 11 females) had a mean age of 61 years at lead implantation. The mean radial error off plan was 0.8 mm. Mean coordinates for the active contact were 21.4 mm lateral, 4.7 mm anterior, and 0.4 mm superior to the midcommissural point. The mean off-medication motor score improved from 48.4 at baseline to 28.9 (40.3% improvement) at 6 months (p < 0.001). The PDQ-39 scores improved (50.3 vs 42.0; p = 0.03), and the levodopa equivalent daily dose was reduced (1207 vs 1035 mg; p = 0.004). There were no significant adverse events., Conclusions: Globus pallidus internus leads placed with the patient under general anesthesia by using direct anatomical targeting resulted in significantly improved outcomes as measured by the improvement in the off-medication motor score at 6 months after surgery.

Phrynoderma is a type of follicular hyperkeratosis associated with nutritional deficiencies. It is rarely seen in developed countries, although cases have been reported in patients with severe malnutrition or malabsorption secondary to various causes. This report describes a 19-year-old patient with poorly controlled Crohn's disease and malnutrition who developed the characteristic hyperkeratotic papules and plaques on his trunk and extremities in the setting of low serum vitamin A levels. To our knowledge, there are no reports of phrynoderma associated with Crohn's disease. It is likely that our patient's low vitamin A level and subsequent phrynoderma was the result of increased Crohn's disease activity and malnutrition., (© 2013 Wiley Periodicals, Inc.)

We previously reported that patients with tremor preponderant Parkinson disease (PD) displayed upward or lateral displacement of their more tremulous finger when they pointed both their index fingers at a target and closed their eyes for 15 seconds. In this study, we examined the phenomenon in 104 PD patients: 72 patients without tremor and 32 with minimal tremor to see if the displacement is related to the disease or the tremor. Sixty-eight of the 72 patients without tremor, 94%, exhibited finger displacement suggesting the phenomenon is related to the disease. None of the 104 patients were demented: mini-mental status examination (MMSE) score 29.0 ± 0. 75. Ninety patients displayed upward displacement (56 patients) or lateral or medial displacement (34 patients). MMSE score of the 90 patients: 29.2 ± 0.74 with no score < 28. Eight patients (6 without tremor) displayed downward displacement. MMSE score of the 8 patients: 27.5 ± 0.35 with 5 having MMSE score of 27. Although not significant the results suggest that patients with downward displacement and lower MMSE score may be evolving a dementia. Upward displacement with eyes closed for 15 seconds requires an ability to "remember" the position of the finger in space and to alter tone to overcome gravity. Downward displacement implies an inability to "remember" the position of the finger in space an inability to overcome the effects of gravity. This may be more likely in patients who are evolving a dementia. Two patients, with PD-like symptoms, and specific anatomical abnormalities are also presented as they illustrate the anatomy of finger displacement.

Although, the tremor of Parkinson's disease (PD) usually, but not always, differs from essential tremor (ET), there is no simple bedside test to distinguish PD from ET. We believe we have made such an observation. We studied 50 consecutive tremor-dominant PD patients (mean age: 63.4 years; mean disease duration: 4.9 years) and 35 consecutive ET patients (mean age: 64.1 years; mean disease duration: 12.5 years). Among PD patients, 31 had a bilateral tremor and among ET patients, 29 patients had a bilateral tremor. Patients sat opposite the examiner and pointed both index fingers at the examiner's index fingers. Then they closed their eyes. Within 15 s, one or rarely both of the patient's index fingers moved, was displaced, either upward or laterally. Finger displacement occurred only with bilateral simultaneous pointing with the patient's eyes closed. All the tremor-dominant PD patients exhibited displacement of an index finger. In 46 patients, it occurred on the side of dominant tremor, in 4, it occurred bilaterally. In 31 of 35 ET patients, no displacement occurred. In 4 of 35 ET patients, it occurred unilaterally on the side of dominant tremor. Odds ratio of distinguishing PD from ET: 89.62 at 95% confidence limits (5.31-1513.4), p = 0. 0018. Sensitivity 100% (0.91-1), specificity 89% (0.72-0.96). Finger displacement can distinguish the tremor of PD from ET. The unilateral movement with eyes closed suggests the tremor of PD unlike ET may impact circuits involving the parietal and supplementary motor cortices.

Although gait and balance difficulties often occur together in Parkinson's disease (PD) patients, it is believed that they are actually two eparate symptoms. However, there are no simple tests to distinguish them. We have developed the self-administered Barrow Neurological Institute (BNI) question to distinguish between gait and balance issues in PD and it was tested in 102 consecutive PD patients. The responses were compared with those of the walking and balance question (item # 2.12) of the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS), and the MDS-UPDRS motor examination and its subsets such as gait and postural stability (PS). Fifty-five patients reported balance difficulty on the BNI question and 64 reported walking and balance difficulty on the MDS-UPDRS question. Of the patients who reported balance difficulty on the BNI question, 74.5% had a PS score ≥2 and 25.4% fell at least three times per month. Of the patients who reported walking and balance difficulty on the MDS-UPDRS question, only 59.4% had a PS score ≥2 and only 10.9% fell three or more times per month. These statistically significant results suggest that the BNI question is better able to detect balance difficulty and its associated falls in PD and can be a supplement to the MDS-UPDRS or a stand-alone question to evaluate balance difficulty and its associated falls in PD.

Background: This study investigated impaired self-awareness of motor deficits in nondemented, nondepressed Parkinson's disease (PD) patients during a defined clinical on state., Methods: Twenty-eight PD patients were examined. Patients' self-ratings and experts' ratings of patients' motor performance were compared. Patient-examiner discrepancies and level of impairment determined severity of impaired self-awareness. Motor exam assessed overall motor functioning, hemibody impairment, and 4 motor phenotypes. Neuropsychological tests were also conducted., Results: Signs of impaired self-awareness were present in 17 patients (60.7%). Higher severity of impaired self-awareness correlated significantly with higher postural-instability and gait-difficulty off scores (r = .575; P = .001), overall motor off scores (r = .569; P = .002), and higher left hemibody off scores (r = .490; P = .008). In multiple linear regression analyses, higher postural-instability and gait-difficulty off scores remained as the only significant predictor of impaired self-awareness severity., Conclusions: Postural instability and gait difficulties, disease severity, and right hemisphere dysfunction seem to contribute to impaired self-awareness., (Copyright © 2012 Movement Disorder Society.)

We describe the case of a 33-year-old woman who presented with a 2-month history of worsening head tremor. The medical evaluation led to the new diagnosis of MS and the MRI of brain demonstrated prominently active disease. Intravenous rituximab was started according to the HERMES trial, and significant improvement was noted. She has received additional rituximab dosing approximately every 6 months, and at the 2-year follow-up the tremor has not recurred. The resolution of head tremor likely resulted from the complete suppression of MS disease activity, which must have allowed restoration of normal neural circuitry. In agreement with a growing body of evidence that supports early control of MS disease activity to prevent accumulation of fixed disability, this case advocates for aggressive immunological therapy at the onset of tremor in MS patients.

Background: The increase of the growth hormone (GH) during exercise is known although the relationship of this response with other hormones, the type and intensity of the exercise, nutritional state and with the degree of training are reasons for discussion. The aim of this investigation was to study the response of the HG on a group of young adults with different degrees of training, according to the maximum consumption of oxygen (VO2 max) achieved over a short period of time., Methods: Thirty-nine healthy subjects who underwent maximum effort on the treadmill were grouped according to VO2 max reached (less than 3,000 ml/min; 3,000-4,500 ml/min and greater than 4,500 ml/min). Systolic blood pressure (SBP) and diastolic blood pressure (DBP), respiratory quotient (RQ), O2 pulse, cardiac frequency (CF) respiratory equivalence (RE), glycemia, plasma insulin (PI), C peptide, lactic acid, venous pH, plasma renin activity (PRA), plasma aldosterone, thyrotropine (TSH), triodothyronine (T3), thyroxine (T4), adrenocorticotropine (ACTH), cortisol and GH were measured basally and following achievement of VO2 max., Results: The GH was only increased in those subjects with a VO2 max higher than 3,000 ml/min with a significant positive correlation found between the GH and VO2 max and a significant negative correlation was found between the GH and lactic acid at the end of the test. The increase of glycemia at the end of the test correlated with the VO2 max. The PI and C peptide increased at the end of the test in the subjects with greater VO2 max capacity and correlated positively with the VO2 max and with the GH upon completion of the exercise., Conclusions: These results suggest that the response of the growth hormone to exercise is a function of maximum oxygen consumption although this only explains 24% of the variants of the growth hormone. Despite important hormonal and metabolic mobilization during exercise, no model of multiple regression has been found which substantially improves the association found between the growth hormone and maximum oxygen consumption.