Subacute Horizontal Diplopia, Jaw Dystonia, and Laryngospasm.

Jaw dystonia and laryngospasm in the context of subacute brainstem dysfunction have been described in a small number of diseases, including antineuronal nuclear antibody type 2 (ANNA-2, also known as anti-Ri) paraneoplastic neurologic syndrome. Severe episodes of laryngospasms causing cyanosis are potentially fatal. Jaw dystonia can also cause eating difficulty, resulting in severe weight loss and malnutrition. In this report, we highlight the multidisciplinary management of this syndrome associated with ANNA-2/anti-Ri paraneoplastic neurologic syndrome and discuss its pathogenesis.

Objective assessment of patients with idiopathic normal pressure hydrocephalus following ventriculoperitoneal shunt placement using activity-monitoring data: pilot study.

OBJECTIVE: Idiopathic normal pressure hydrocephalus (iNPH) results in significant morbidity in the elderly with symptoms of dementia, gait instability, and urinary incontinence. In well-selected patients, ventriculoperitoneal shunt (VPS) placement often results in clinical improvement. Most postshunt assessments of patients rely on subjective scales. The goal of this study was to assess the utility of remote activity monitoring to provide objective evidence of gait improvement following VPS placement for iNPH. METHODS: Patients with iNPH were prospectively enrolled and fitted with 5 activity monitors (on the hip and bilateral thighs and ankles) that they wore for 4 days preoperatively within 30 days of surgery and for 4 days within 30 days postoperatively. Monitors collected continuous data for number of steps, cadence, body position (upright, prone, supine, and lateral decubitus), gait entropy, and the proportion of each day spent active or static. Data were retrieved from the devices and a comparison of pre- and postoperative movement assessment was performed. The gait data were also correlated with formal clinical gait assessments before and after lumbar puncture and with motion analysis laboratory testing at baseline and 1 month and 1 year after VPS placement. RESULTS: Twenty patients fulfilled the inclusion and exclusion criteria (median age 76 years). The baseline median number of daily steps was 1929, the median percentage of the day spent inactive was 70%, the median percentage of the day with a static posture was 95%, the median gait velocity was 0.49 m/sec, and the median number of steps required to turn was 8. There was objective improvement in median entropy from pre- to postoperatively, increasing from 0.6 to 0.8 (p = 0.002). There were no statistically significant differences for any of the remaining variables measured by the activity monitors when comparing the preoperative to the 1-month postoperative time point. All variables from motion analysis testing showed statistically significant differences or a trend toward significance at 1 year after VPS placement. Among the significantly correlated variables at baseline, cadence was inversely correlated with percentage of gait cycle spent in the support phase (contact with ground vs swing phase). CONCLUSIONS: This pilot study suggests that activity monitoring provides an early objective measure of improvement in gait entropy after VPS placement among patients with iNPH, although a more significant improvement was noted on the detailed clinical gait assessments. Further long-term studies are needed to determine the utility of remote monitoring for assessing gait improvement following VPS placement.

A teenager with adenoviral myocarditis mimicking hypertrophic cardiomyopathy.

A 14-year-old previously healthy female presented with chest pain and dyspnoea for 2 days in the setting of a recent upper respiratory infection. She had elevated inflammatory markers and troponin, resulting in the diagnosis of acute myocarditis. Transthoracic echocardiography demonstrated mild systolic dysfunction and a moderate pericardial effusion. Additionally, her echocardiogram showed concentric left ventricular hypertrophy raising concern for hypertrophic cardiomyopathy. She was treated with intravenous immunoglobulin. Serial echocardiograms revealed rapid resolution of her ventricular hypertrophy. Cardiac magnetic resonance confirmed the diagnosis of myocarditis.

Utility of routine surface electrophysiology to screen for functional tremor prior to surgical treatment of essential tremor.

Background: Patients with functional tremor may be clinically misdiagnosed as "medication-refractory" essential tremor (ET) and referred for surgical treatment. Electrophysiology can screen for functional tremor and avoid inappropriate surgery. Objective: To report the utility of surface electrophysiology (SEMG) to screen for functional tremor in patients referred for ET surgery. Methods: Retrospective review of consecutive ET patients referred to the Mayo Clinic DBS clinic over 1.5 years. Included subjects had a clinical diagnosis of medication-refractory ET and completed presurgical workup including routine SEMG tremor study. Results: Of 87 subjects, 9 (10%) were clinically suspected of functional tremor by the DBS neurologist. Electrophysiology confirmed functional tremor features in 7/9 and ET in the other 2/9; and newly identified 5 additional cases of functional tremor. There were 12 total confirmed cases of functional tremor: isolated in 1, and mixed functional tremor and ET in 11. Of 11 mixed patients, 6 with mild functional overlay were approved for surgery. The remaining 5 patients with moderate-severe functional overlay and the single patient with isolated functional tremor were referred to the functional tremor motor retraining program. Of these, 1 patient with mixed tremor had residual disabling organic ET after program completion and was later approved for surgery. Thus, 5/87 patients (6%) avoided unnecessary surgery. Conclusions: Functional tremor may frequently overlay "medication-refractory" ET amongst patients referred for surgery, affecting 1 of 7 patients in our quaternary referral DBS center. Electrophysiology studies are useful to routinely screen patients and prevent unnecessary surgery.

Poly (ADP-Ribose) and α-synuclein extracellular vesicles in patients with Parkinson disease: A possible biomarker of disease severity.

BACKGROUND/OBJECTIVE: Despite multiple attempts, no surrogate biomarker of Parkinson disease (PD) has been definitively identified. Alternatively, identifying a non-invasive biomarker is crucial to understanding the natural history, severity, and progression of PD and to guide future therapeutic trials. Recent work highlighted alpha synuclein-containing extracellular vesicles and Poly (ADP-ribose) polymerase (PARP-1) activity as drivers of PD pathogenesis and putative PD biomarkers. This exploratory study evaluated the role of alpha-synuclein-positive extracellular vesicles and PARP-1 activity in the plasma of PD patients as non-invasive markers of the disease's severity and progression. METHODS: We collected plasma of 57 PD patients (discovery cohort 20, replication cohort 37) and compared it with 20 unaffected individuals, 20 individuals with clinically diagnosed Alzheimer's disease, and 20 individuals with dementia with Lewy bodies. We analyzed alpha-synuclein-positive extracellular vesicles from platelet-free plasma by nanoscale flow cytometry and blood concentrations of poly ADP-ribose using sandwich ELISA kits. RESULTS: Median concentration of α-synuclein extracellular vesicles was significantly higher in PD patients compared to the other groups (Kruskal-Wallis, p < .0001). In the discovery cohort, patients with higher α-synuclein extracellular vesicles had a higher Unified Parkinson Disease Rating Scale score (UPDRS III median = 22 vs. 5, p = 0.045). Seven out of 20 patients (35%) showed detectable PAR levels, with positive patients showing significantly higher levels of α-synuclein extracellular vesicles. In the replication cohort, we did not observe a significant difference in the PAR-positive cases in relationship with UPDRS III. CONCLUSIONS: Non-invasive determination of α-synuclein-positive extracellular vesicles may provide a potential non-invasive marker of PD disease severity, and longitudinal studies are needed to evaluate the role of α-synuclein-positive extracellular vesicles as a marker of disease progression.

Treatment of Movement Disorder Emergencies in Autoimmune Encephalitis in the Neurosciences ICU.

Immune response against neuronal and glial cell surface and cytosolic antigens is an important cause of encephalitis. It may be triggered by activation of the immune system in response to an infection (para-infectious), cancer (paraneoplastic), or due to a patient's tendency toward autoimmunity. Antibodies directed toward neuronal cell surface antigens are directly pathogenic, whereas antibodies with intracellular targets may become pathogenic if the antigen is transiently exposed to the cell surface or via activation of cytotoxic T cells. Immune-mediated encephalitis is well recognized and may require intensive care due to status epilepticus, need for invasive ventilation, or dysautonomia. Patients with immune-mediated encephalitis may become critically ill and display clinically complex and challenging to treat movement disorders in over 80% of the cases (Zhang et al. in Neurocrit Care 29(2):264-272, 2018). Treatment options include immunotherapy and symptomatic agents affecting dopamine or acetylcholine neurotransmission. There has been no prior published guidance for management of these movement disorders for the intensivist. Herein, we discuss the immune-mediated encephalitis most likely to cause critical illness, clinical features and mechanisms of movement disorders and propose a management algorithm.

Camptocormia: Etiology, diagnosis, and treatment response.

BACKGROUND: We sought to determine the etiologies, diagnostic testing, and management of a retrospective cohort of patients with camptocormia evaluated at a single center. METHODS: We reviewed medical records of all adult patients evaluated at Mayo Clinic Rochester with a diagnosis of camptocormia from 2000 to 2014. Demographic and clinical data were abstracted and analyzed. RESULTS: There were 276 patients (58.0% male), with mean age at presentation of 68.6 (±12.7) years. An etiology was identified in 98.2%. The most common etiologies were idiopathic Parkinson disease (22.5%), idiopathic axial myopathy (14.1%), and degenerative joint disease without fixed deformity (13.0%). We also identified several rare causes of camptocormia. Investigations included spine imaging, needle and surface EMG, and muscle biopsy. Most patients received physical therapy and orthotic support with limited benefit. Limited improvement of camptocormia was seen where a treatable etiology was identified. CONCLUSIONS: An etiology can be identified in almost all cases of camptocormia. Most cases are due to 3 common disorders: Parkinson disease, axial myopathy, and degenerative joint disease. A diagnostic and treatment algorithm is proposed.

Routine Troponin Measurements Are Unnecessary to Exclude Asymptomatic Coronary Events in Acute Ischemic Stroke Patients.

BACKGROUND: Obtaining serum troponin levels in every patient with acute stroke is recommended in recent stroke guidelines, but there is no evidence that these contribute positively to clinical care. We sought to determine the clinical significance of measuring troponin levels in acute ischemic stroke patients. METHODS: We reviewed 398 consecutive patients with acute ischemic stroke at a large academic institution from 2010 to 2012. Troponin levels were measured as a result of protocol in place during part of the study period. The mean age was 70 years (standard deviation ±16 years) and 197 (49.5%) were men. RESULTS: Chronic kidney disease was present in 78 (19.6%), coronary artery disease in 107 (26.9%), and atrial fibrillation in 107 (26.9%). Serum troponin T was measured in 246 of 398 patients (61.8%). Troponin was elevated (>.01 ng/mL) at any point in 38 of 246 patients (15.5%) and was elevated in 28 patients at all 3 measurements (11.3% of those with troponin measured). Only 4 of 246 patients (1.6%) had a significant uptrend. Two were iatrogenic in the setting of hemodynamic augmentation using vasopressors to maintain cerebral perfusion. One case was attributed to stroke and chronic kidney disease and another case to heart failure from inflammatory fibrocalcific mitral valvular heart disease. CONCLUSIONS: Serum troponin elevation in patients with ischemic stroke is not usually caused by clinically significant acute myocardial ischemia unless iatrogenic in the setting of vasopressor administration. Serum troponin levels should be measured judicially, based on clinical context, rather than routinely in all stroke patients.