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Highlights • COVID-19 has significant impact on PD research and education activities. • Country-specific restrictions may pose challenges to PD research and require careful adaptations. • Neurological Symptoms of COVID-19 may overlap with PD.

Research Objectives To describe the management of water homeostasis fluctuations and difficulties associated with rehabilitating a patient with post-surgical central diabetes insipidus who manifested a rare triphasic response. Design Case report. Setting Tertiary hospital. Participants 47-year-old female office worker. Interventions The patient was initially diagnosed with a left sphenoid wing meningioma and underwent elective excision. Her post-operative sodium levels fluctuated wildly, corresponding to central diabetes insipidus (DI), followed by a triphasic response comprising antidiuresis due to SIADH and subsequent DI which required longer-term desmopressin therapy. This case was notable for extreme serum sodium swings of 30mEq in a day requiring urgent reversal and titration. Main Outcome Measures Serum sodium and osmolality; Montreal Cognitive Assessment; Ambulation distance; Functional Independence Measure. Results In contrast with published reports of pituitary manipulation-induced DI, this case illustrates the possibility of brain surgery in areas remote to the pituitary to be capable of inducing the rare triphasic DI pattern. This patient developed psychiatric disturbances that may have led to inconsistent technique in self-administration of intranasal desmopressin, in addition to inappropriate polydipsia. With stabilization of her sodium fluctuations, the patient was able to continue with rehabilitation for her other deficits of diplopia, gait dysfunction, and cognition. No new neurocognitive sequelae arose from the water balance disorder and she was discharged well to independent living. Her sodium levels were stable at follow-up 1 and 3 months later, with good treatment compliance to long-term desmopressin. Conclusions Water balance disorders post-neurosurgery can be rapid and drastic, and a triphasic response of post-surgical DI can arise from seemingly-minor pituitary manipulation and even remote sphenoid meningioma excision. Post-treatment monitoring of fluid status in such patients remains crucial and physiatrists should maintain sensitivity to psychiatric disturbances and changes in mentation, if any. Author(s) Disclosures None.

Background: Diffusion tensor imaging (DTI) magnetic resonance imaging (MRI) measuring fractional anisotropy (FA) and axial diffusivity (AD) may be a useful biomarker for monitoring changes in white matter after stroke, but its associations with upper-limb motor recovery have not been well studied. We aim to describe changes in the whole-brain FA and AD in five post-stroke patients in relation to kinematic measures of elbow flexion to better understand the relationship between FA and AD changes and clinico-kinematic measures of upper limb motor recovery. Methods: We performed DTI MRI at two timepoints during the acute phase of stroke, measuring FA and AD across 48 different white matter tract regions in the brains of five hemiparetic patients with infarcts in the cortex, pons, basal ganglia, thalamus, and corona radiata. We tracked the progress of these patients using clinical Fugl-Meyer Assessments and kinematic measures of elbow flexion at the acute phase within 14 (mean: 9.4 ± 2.49) days of stroke symptom onset and at a follow-up appointment 2 weeks later (mean: 16 ± 1.54) days. Results: Changes in FA and AD in 48 brain regions occurring during stroke rehabilitation are described in relation to motor recovery. In this case series, one patient with a hemipontine infarct showed an increase in FA of the ipsilateral and contralateral corticospinal tract, whereas other patients with lesions involving the corona radiata and middle cerebral artery showed widespread decreases in perilesional FA. On the whole, FA and AD seemed to behave inversely to each other. Conclusions: This case series describes longitudinal changes in perilesional and remote FA and AD in relation to kinematic parameters of elbow flexion at the subacute post-stroke period. Although studies with larger sample sizes are needed, our findings indicate that longitudinally measured changes in DTI-based measurements of white matter microstructural integrity may aid in the prognostication of patients affected by motor stroke.

Brain stimulation, in the form of electroconvulsive therapy (ECT), has long been a gold standard treatment for depression, but today, the field of neuromodulation is rapidly changing with the advent of newer and more precise tools to alter neuroplasticity and to treat brain-based disorders. Now there are new means to induce focal seizures, as with magnetic seizure therapy (MST), or modifications to ECT. There are also surgical approaches to target brain circuits via implanted stimulators placed in the brain or on cranial nerves. Finally, there are noninvasive subconvulsive approaches for the transcranial application of either electric or magnetic fields. Collectively, these tools have transformed the face of neurotherapeutics and informed our understanding of the brain basis of complex neurobehavioral conditions.

Migraine auras are typically visual in nature but can manifest as disturbances in somatosensory, auditory, and olfactory senses. Reports of multiple sensory auras are rare in the literature, but their existence may offer novel insights into the pathogenesis of this highly common yet complex neurological condition. Here we report a case of multiple sensory auras involving somatosensory, auditory, and olfactory disturbances in a patient with migraine without visual manifestations. A 45-year-old woman with a 20-year history of migrainous headaches presented with complaints of rightsided facial and hand numbness and paraesthesia. In addition to somatosensory symptoms, she eventually presented with tinnitus, cutaneous allodynia, and phantosmia, each of which was temporally associated with episodes of headache. No abnormalities were detected on NCS, EEG, MRI, and laboratory investigations. Her symptoms were managed by prophylactic medications and acupuncture. The theories of cortical spreading depression, cortical sensitization, and thalamocortical network involvement were discussed as possible explanations for sensory auras in migraine. This case report of migraine with multiple sensory auras spanning somatosensory, auditory, and olfactory modalities offers novel insights into the pathophysiology of migrainous auras.

Introduction This study aimed to evaluate the safety and efficacy of a combination of levodopa and virtual reality (VR)-based therapy for the enhancement of upper limb recovery following acute stroke. Methods This was a pilot single-blinded case series of acute stroke patients with upper extremity hemiparesis. Patients were randomised to standard care with concomitant administration of either levodopa alone (control group) or combination therapy consisting of VR-based motivational visuomotor feedback training with levodopa neuromodulation (VR group). Main clinical outcome measures were the Fugl-Meyer Upper Extremity (FM-UE) assessment and Action Research Arm Test (ARAT). Kinematic measurements of affected upper limb movement were evaluated as a secondary measure of improvement. Results Of 42 patients screened, four patients were enrolled in each of the two groups. Two patients dropped out from the control group during the trial. Patients receiving combination therapy had clinically significant improvements in FM-UE assessment scores of 16.5 points compared to a 3.0-point improvement among control patients. Similarly, ARAT scores of VR group patients improved by 15.3 points compared to a 10.0-point improvement in the control group. Corresponding improvements were noted in kinematic measures, including hand-path ratio, demonstrating that the quality of upper limb movement improved in the VR group. Conclusion Our results suggest that VR-based therapy and pharmacotherapy may be combined for acute stroke rehabilitation. Bedside acquisition of kinematic measurements allows accurate assessment of the quality of limb movement, offering a sensitive clinical tool for quantifying motor recovery during the rehabilitation process after acute stroke.

Several stable-isotope-based peptide labeling methods have been developed to support large-scale relative quantitation, through mass spectrometry, of proteins present in two different biological samples. In one of these, trypsin-catalyzed 18O-based labeling, quantitation is typically performed at the full scan (MS) level by comparing the peak intensities of sister precursor ions corresponding to the labeled and unlabeled forms of an intact peptide as they co-elute during liquid chromatography (LC) separations. We show here that measuring relative abundance at the product ion (MS/MS) level after fragmentation provides excellent accuracy, sensitivity and signal-to-noise, while combining quantitation with global shotgun protein identification. To facilitate routine data analysis using this approach, we have developed two specialized software programs, ySelect and yRatios, which draw upon database search results for 18O-based data sets and combine fragmentation spectra peak lists to (1) accurately determine protein ratios between two samples while applying a correction for incomplete labeling and (2) tabulate these results in both intuitive summary reports and in formats amenable to systematic pathway level analysis. To validate our process, we subjected simple and complex test protein mixtures to single-step and multistep LC-MS/MS profiling experiments. Ratio distributions approached the expected means, allowing empirical derivation of confidence level cutoffs for determining statistically significant fold-changes in protein abundance. A set of stringent criteria for detecting spurious ratios based on consistency checking between unlabeled and labeled y-ion pairs was found to highlight putative false positive identifications. In summary, this toolkit facilitates comparative proteomic quantitation under conditions that are optimized for making reliable protein inferences.

Chromatin modification is an important epigenetic mechanism underlying neuroplasticity. Histone methylation and acetylation have both been shown to modulate gene expression, but the machinery responsible for mediating these changes in neurons has remained elusive. Here we identify a chromatin-modifying complex containing the histone demethylase PHF8 and the acetyltransferase TIP60 as a key regulator of the activity-induced expression of Arc, an important mediator of synaptic plasticity. Clinically, mutations in PHF8 cause X-linked mental retardation while TIP60 has been implicated in the pathogenesis of Alzheimer’s disease. Within minutes of increased synaptic activity, this dual function complex is rapidly recruited to the Arc promoter, where it specifically counteracts the transcriptionally repressive histone mark H3K9me2 to facilitate the formation of the transcriptionally permissive H3K9acS10P, thereby favoring transcriptional activation. Consequently, gain-of-function of the PHF8−TIP60 complex in primary rat hippocampal neurons has a positive effect on early activity-inducedArcgene expression, whereas interfering with the function of this complex abrogates it. A global proteomics screen revealed that the majority of common interactors of PHF8 and TIP60 were involved in mRNA processing, including PSF, an important molecule involved in neuronal gene regulation. Finally, we proceeded to show, using super-resolution microscopy, that PHF8 and TIP60 interact at the single molecule level with PSF, thereby situating this chromatin modifying complex at the crossroads of transcriptional activation. These findings point toward a mechanism by which an epigenetic pathway can regulate neuronal activity-dependent gene transcription, which has implications in the development of novel therapeutics for disorders of learning and memory.

Arc is an immediate-early gene whose genetic ablation selectively abrogates long-term memory, indicating a critical role in memory consolidation. Although Arc protein is found at synapses, it also localizes to the neuronal nucleus, where its function is less understood. Nuclear Arc forms a complex with the β-spectrin isoform βSpIVΣ5 and associates with PML bodies, sites of epigenetic regulation of gene expression. We report here a novel interaction between Arc and Tip60, a histone-acetyltransferase and subunit of a chromatin-remodelling complex, using biochemistry and super-resolution microscopy in primary rat hippocampal neurons. Arc and βSpIVΣ5 are recruited to nuclear Tip60 speckles, and the three proteins form a tight complex that localizes to nuclear perichromatin regions, sites of transcriptional activity. Neuronal activity-induced expression of Arc (1) increases endogenous nuclear Tip60 puncta, (2) recruits Tip60 to PML bodies, and (3) increases histone acetylation of Tip60 substrate H4K12, a learning-induced chromatin modification. These mechanisms point to an epigenetic role for Arc in regulating memory consolidation.