Julieta Arena

Transient Global Amnesia

Transient global amnesia (TGA) is a clinical syndrome characterized by the sudden onset of anterograde amnesia (the inability to encode new memories), accompanied by repetitive questioning, sometimes with a retrograde component, lasting up to 24 hours, without compromise of other neurologic functions. Herein, we review current knowledge on the epidemiology, pathophysiology, clinical diagnosis, and prognosis of TGA. For this review, we conducted a literature search of PubMed, with no date limitations, using the following search terms (or combinations of them): transient global amnesia, etiology, pathophysiology, venous hypertension, migraine, magnetic resonance imaging, computed tomography, electroencephalography, prognosis, and outcome. We also reviewed the bibliography cited in the retrieved articles. Transient global amnesia is a clinical diagnosis, and recognition of its characteristic features can avoid unnecessary testing. Several pathophysiologic mechanisms have been proposed (venous insufficiency, arterial ischemia, and migrainous or epileptic phenomena), but none of them has been proved to consistently explain cases of TGA. Brain imaging may be considered and electroencephalography is recommended when episodes are brief and recurrent, but otherwise no investigations are necessary in most cases. Data on long-term prognosis are limited, but available information suggests that the relapse rate is low, the risk of stroke and seizures is not considerably increased, and cognitive outcome is generally good.

PBB3 imaging in Parkinsonian disorders: Evidence for binding to tau and other proteins

Background and Objectives: To study selective regional binding for tau pathology in vivo, using PET with [11C]PBB3 in PSP patients, and other conditions not typically associated with tauopathy.

Optimizing diagnosis in Parkinson's disease: Radionuclide imaging

Parkinsons disease (PD) and other disorders characterized by basal ganglia dysfunction are often associated with limited structural imaging changes that might assist in the clinical or research setting. Radionuclide imaging has been used to assess characteristic functional changes. Presynaptic dopaminergic dysfunction in PD can be revealed through the imaging of different steps in the process of dopamine synthesis and storage: L-aromatic amino acid decarboxylase (AADC) activity, Vesicular Monoamine Transporter type 2 (VMAT2) binding or its reuptake via the dopamine transporter (DAT). Postsynaptic dopamine dysfunction can also be studied with a variety of different tracers that primarily assess D2-like dopamine receptor availability. The function of other neurotransmitters such as norepinephrine, serotonin and acetylcholine can be imaged as well, giving important information about the underlying pathophysiologic process of PD and its complications. The imaging of metabolic activity and pathologic changes has also provided great advances in the field. Together, these techniques have allowed for a better understanding of PD, may be of aid for differentiating PD from other forms of parkinsonism and will undoubtedly be useful for the establishment of new therapeutic targets.

Bilateral Paramedian Thalamic Infarction.

Introduction:Rarely, both paramedian thalami receive arterial blood flow from a single unilateral vessel arising from the first segment of 1 posterior cerebral artery. This artery has received the name of artery of Percheron (AP). There is no consensus regarding the true prevalence of this anatomical variant. Bilateral paramedian thalamic infarcts are uncommon (0.1% to 2% of ischemic strokes). The main cause is the occlusion of the AP due to cardioembolism. Diffusion-weighted magnetic resonance imaging demonstrates the lesion in the acute setting. Materials and Methods:From September 2004 to October 2011, we identified 5 patients who had bilateral paramedian thalamic infarcts. We describe clinical findings and diagnostic imaging patterns observed in these cases and review the literature. Results:Three men and 2 women with bilateral paramedian thalamic infarction probably due to occlusion of AP are described. Mean age at presentation was 58±24 years. Magnetic resonance imaging showed the lesion in all patients. Four patients presented loss of consciousness as initial symptom. Only 1 patient evidenced mesencephalic extension of the infarct on magnetic resonance imaging, although 4 presented abnormal ocular signs. No patients received intravenous thrombolisis because of delayed diagnosis. All patients were discharged home. A 90-year-old woman recovered completely and the other 4 subjects persisted with cognitive symptoms and gaze abnormalities. Conclusions:Clinical presentation and imaging patterns described in this group of patients were similar to published data. High level of suspicion based on clinical and imaging findings is essential for early diagnosis of this rare condition. None of our patients had an early diagnosis of acute ischemic stroke and received proper thrombolytic treatment.

The effect of LRRK2 mutations on the cholinergic system in manifest and premanifest stages of Parkinson's disease: a cross-sectional PET study

BACKGROUND Markers of neuroinflammation are increased in some patients with LRRK2 Parkinsons disease compared with individuals with idiopathic Parkinsons disease, suggesting possible differences in disease pathogenesis. Previous PET studies have suggested amplified dopamine turnover and preserved serotonergic innervation in LRRK2 mutation carriers. We postulated that patients with LRRK2 mutations might show abnormalities of central cholinergic activity, even before the diagnosis of Parkinsons disease. METHODS Between June, 2009, and December, 2015, we recruited participants from four movement disorder clinics in Canada, Norway, and the USA. Patients with Parkinsons disease were diagnosed by movement disorder neurologists on the basis of the UK Parkinsons Disease Society Brain Bank criteria. LRRK2 carrier status was confirmed by bidirectional Sanger sequencing. We used the PET tracer N-11C-methyl-piperidin-4-yl propionate to scan for acetylcholinesterase activity. The primary outcome measure was rate of acetylcholinesterase hydrolysis, calculated using the striatal input method. We compared acetylcholinesterase hydrolysis rates between groups using ANCOVA, with adjustment for age based on the results of linear regression analysis. FINDINGS We recruited 14 patients with LRRK2 Parkinsons disease, 16 LRRK2 mutation carriers without Parkinsons disease, eight patients with idiopathic Parkinsons disease, and 11 healthy controls. We noted significant between-group differences in rates of acetylcholinesterase hydrolysis in cortical regions (average cortex p=0·009, default mode network-related regions p=0·006, limbic network-related regions p=0·020) and the thalamus (p=0·008). LRRK2 mutation carriers without Parkinsons disease had increased acetylcholinesterase hydrolysis rates compared with healthy controls in the cortex (average cortex, p=0·046). Patients with LRRK2 Parkinsons disease had significantly higher acetylcholinesterase activity in some cortical regions (average cortex p=0·043, default mode network-related regions p=0·021) and the thalamus (thalamus p=0·004) compared with individuals with idiopathic disease. Acetylcholinesterase hydrolysis rates in healthy controls were correlated inversely with age. INTERPRETATION LRRK2 mutations are associated with significantly increased cholinergic activity in the brain in mutation carriers without Parkinsons disease compared with healthy controls and in LRRK2 mutation carriers with Parkinsons disease compared with individuals with idiopathic disease. Changes in cholinergic activity might represent early and sustained attempts to compensate for LRRK2-related dysfunction, or alteration of acetylcholinesterase in non-neuronal cells. FUNDING Michael J Fox Foundation, National Institutes of Health, and Pacific Alzheimer Research Foundation.

Challenges in PD Patient Management After DBS: A Pragmatic Review: Challenges after Deep Brain Stimulation for Parkinson's Disease

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or internal globus pallidus (GPi) represents an effective and universally applied therapy for Parkinsons disease (PD) motor complications. However, certain procedure‐related problems and unrealistic patient expectations may detract specialists from indicating DBS more widely despite significant clinical effects.

PBB3 Imaging in Parkinsonian disorders: Evidence for binding to abnormally aggregated proteins in addition to tau proteins

Objective: The aim of this work is to evaluate clinimetric properties of a method for measuring Parkinson’s disease (PD) upper limb temporal irregularities during spiral drawing tasks.Background: B ...Basic Science Abstracts - Session Title: Parkinsons Disease: Pathophysiology: abstract no. 518

Long-Term Outcome in Patients With Transient Global Amnesia: A Population-Based Study.

Objective: To study the long‐term risk of cerebrovascular events, seizures, and cognitive impairment in patients with transient global amnesia (TGA). Patients and Methods: Data for all patients diagnosed with possible TGA in Olmsted County, Minnesota, between January 1, 1985, through December 31, 2010, were retrieved from the Rochester Epidemiology Project database. Transient global amnesia was defined clinically. End points were cerebrovascular event (stroke or transient ischemic attack), seizure, or cognitive impairment (mild cognitive impairment or dementia) during follow‐up. End points were studied using Kaplan‐Meier survival plots and log‐rank test. Results: A total of 221 patients with TGA were identified and 221 age‐ and sex‐matched controls were included in the analysis. The mean duration of follow‐up was 12 years in both groups (range, 0.07–29.93). Prevalence of vascular risk factors and history of seizures were similar between both groups. Previous migraine was more common in the TGA group (42 patients [19.1%] vs 12 patients [5.4%]; P<.001). There was no statistically significant difference between survival curves for the TGA group and the control group using time to any type of cerebrovascular event (log‐rank P=.30), time to seizures event (log‐rank P=.55), and time to cognitive impair event (log‐rank P=.88) as end points. The TGA recurrence occurred in 5.4% of patients after a median interval of 4.21 years (interquartile range, 2.82–8.44). Modified Rankin scale and death rates at last follow‐up were also similar between both groups. Conclusion: Our findings indicate that having an episode of TGA does not increase the risk of subsequent cerebrovascular events, seizures, or cognitive impairment.