A video-atlas of levodopa-induced dyskinesia in Parkinson's disease: terminology matters.

Dyskinesia is a common complication of long-term levodopa therapy in patients with Parkinson's disease (PD), which often worsens the quality of life. It is usually dose-dependent and emerges possibly due to pulsatile stimulation of dopamine receptors. Delineating the pattern of dyskinesia is crucial for determining the most effective therapeutic approach, a task that often presents challenges for numerous neurologists. This article comprehensively describes various patterns of dyskinesia in PD patients and features video demonstration of some of the common forms of dyskinesia. We have used a real case scenario as an example to lead the discussion on the phenomenology, distinguishing features, and management of various types of dyskinesia. A comprehensive literature search was conducted in PubMed using "dyskinesia" as a keyword. The prototype case with videos highlights the differentiating features of dyskinesia along with the treatment strategies. A wide range of descriptive rubrics have been used for certain dyskinesia which are described in detail in this article. The newer types of dyskinesia associated with continuous dopaminergic stimulation in patients with advanced PD and their implications have been described. As there are distinct ways of managing various types of dyskinesia, understanding the phenomenology and chronology of dyskinesia is vital for the optimal management of dyskinetic PD patients. We suggest that dyskinesia should be classified broadly into peak-dose dyskinesia (PDD), biphasic dyskinesia (BD), and OFF-period dystonia. The occurrence of low-dose dyskinesia and complex dyskinesia of continuous dopaminergic treatments should be known to specialists and will require additional studies.

Incidental complex repetitive discharges on needle electromyography.

INTRODUCTION/AIMS: Complex repetitive discharges (CRDs) are spontaneous electromyography (EMG) waveforms often associated with chronic neurogenic or myopathic diseases, but incidentally identified CRDs have also been described. In this study we describe the distribution and possible significance of incidentally seen CRDs in otherwise normal electrodiagnostic studies. METHODS: A retrospective chart review was performed of all patients with CRDs incidentally documented on otherwise normal electrodiagnostic studies at Mayo Clinic from January 2013 through December 2020. Each patient's clinical symptoms, referral reason, electrodiagnostic report, and imaging studies were analyzed using descriptive statistics. RESULTS: Ninety-four patients (86 females; mean age, 62 years; range, 20 to 86 years) and 107 CRDs were studied. The most common neuromuscular reasons for electrodiagnostic referrals included radiculopathy, peripheral neuropathy, and myopathy. Mean symptom duration was 43 months (range, 1 to 312 months). Eighty-five patients had a CRD identified in one muscle (range, in all patients, one to five muscles). CRDs were identified most frequently in tensor fasciae latae (n = 21), biceps brachii (n = 16), and gluteus maximus (n = 9). Of the 58 patients in whom imaging was available, 46 (79%) had abnormalities that corresponded to the myotome in which the CRDs were visualized, most commonly L5 (n = 19) and C6 (n = 12). Of these 46 patients, 28 (61%) were referred for radicular or limb pain. DISCUSSION: CRDs can be incidentally noted on otherwise normal electrodiagnostic studies, most commonly in L5 and C6 myotomes. The mechanism of CRDs in the absence of electrodiagnostic features of axon loss or remodeling is unknown.

Analysis of youtube as a source of information for peripheral neuropathy.

INTRODUCTION: YouTube is an important resource for patients. No study has evaluated the information on peripheral neuropathy disseminated by YouTube videos. In this study, our aim was to perform a systematic review of information on YouTube regarding peripheral neuropathy. METHODS: The Web site (www.youtube.com) was searched between September 19 and 21, 2014, for the terms "neuropathy," "peripheral neuropathy," "diabetic neuropathy," "neuropathy causes," and "neuropathy treatment." RESULTS: Two hundred videos met the inclusion criteria. Healthcare professionals accounted for almost half of the treatment videos (41 of 92; 44.6%), and most came from chiropractors (18 of 41; 43.9%). Alternative medicine was cited most frequently among the treatment discussions (54 of 145, 37.2%), followed by devices (38 of 145, 26.2%), and pharmacological treatments (23 of 145, 15.9%). CONCLUSIONS: Approximately half of the treatment options discussed in the videos were not evidence-based. Caution should be exercised when YouTube videos are used as a patient resource.

Exploring essential tremor: Results from a large online survey.

INTRODUCTION: Essential tremor (ET) is one of the most common movement disorders; however, many patients are misdiagnosed and do not receive effective treatment. It is important to better understand the diagnosis, symptoms and treatment patterns to improve care for those with ET. METHODS: Persons in the International Essential Tremor Foundation database were invited to complete an online survey, focusing on symptoms, diagnosis, and treatment of ET. RESULTS: The survey was emailed to 19,206 persons, with 2864 (14.9%) respondents. Mean age was 65.4 years, median age of tremor onset was 36-40 years, 61% were women, and 64% had a known family history of tremor. Forty-five percent saw multiple physicians before a diagnosis of ET with 65% being diagnosed by a neurologist. Current care is provided by a neurologist in 42%, a family physician in 26% and 28% do not see a physician for ET. Tremor was most commonly reported in the hands/arms (95%). The most commonly affected daily activities included writing, eating, drinking and carrying. Beta-blockers were the most commonly used treatment (42%); however, 33% had no benefit and 35% discontinued due to side effects. Of note, 33% had never received treatment for their tremor. CONCLUSION: This survey highlights the need for more effective treatments with greater tolerability. Increased awareness among physicians and patients in the diagnosis and treatment of ET is also warranted, with nearly half the respondents seeing multiple physicians before receiving an ET diagnosis and nearly 30% not seeing a physician and/or not receiving treatment for ET.

Clinicopathological Correlation: Dopamine and Amyloid PET Imaging with Neuropathology in Three Subjects Clinically Diagnosed with Alzheimer's Disease or Dementia with Lewy Bodies.

BACKGROUND: Imaging biomarkers have the potential to distinguish between different brain pathologies based on the type of ligand used with PET. AV-45 PET (florbetapir, Amyvid™) is selective for the neuritic plaque amyloid of Alzheimer's disease (AD), while AV-133 PET (florbenazine) is selective for VMAT2, which is a dopaminergic marker. OBJECTIVE: To report the clinical, AV-133 PET, AV-45 PET, and neuropathological findings of three clinically diagnosed dementia patients who were part of the Avid Radiopharmaceuticals AV133-B03 study as well as the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND). METHODS: Three subjects who had PET imaging with both AV-133 and AV-45 as well as a standardized neuropathological assessment were included. The final clinical, PET scan, and neuropathological diagnoses were compared. RESULTS: The clinical and neuropathological diagnoses were made blinded to PET scan results. The first subject had a clinical diagnosis of dementia with Lewy bodies (DLB); AV-133 PET showed bilateral striatal dopaminergic degeneration, and AV-45 PET was positive for amyloid. The final clinicopathological diagnosis was DLB and AD. The second subject was diagnosed clinically with probable AD; AV-45 PET was positive for amyloid, while striatal AV-133 PET was normal. The final clinicopathological diagnosis was DLB and AD. The third subject had a clinical diagnosis of DLB. Her AV-45 PET was positive for amyloid and striatal AV-133 showed dopaminergic degeneration. The final clinicopathological diagnosis was multiple system atrophy and AD. CONCLUSION: PET imaging using AV-133 for the assessment of striatal VMAT2 density may help distinguish between AD and DLB. However, some cases of DLB with less-pronounced nigrostriatal dopaminergic neuronal loss may be missed.

Levodopa-Responsive Chorea: A Review.

BACKGROUND: Chorea is one of the disabling movement disorders, and the number of drugs which can treat this disorder effectively is limited. Tetrabenazine and deutetrabenazine are the two drugs approved by the US-FDA for the treatment of chorea associated with HD. Levodopa can improve chorea in some disorders, and this review aims to provide information on the use of levodopa in chorea. METHODS: A literature search was performed in February 2019 using the following terms "levodopa chorea," "levodopa TITF-1," levodopa brain-lung-thyroid syndrome," and "levodopa Huntington's Disease." The information regarding the etiology, outcome, and dose of levodopa was collected. RESULTS: We found a total of 18 cases in the literature where the benefit was reported with levodopa. Majority of the cases were brain-thyroid-lung (BTL) syndrome (50%). Another 5 cases were HD (Huntington's Disease), one with PCH type 2 (Pontocerebellar hypoplasia type 2), one with meningovascular syphilis, and two patients with Sydenham chorea. The patients with BTL syndrome responded to a very low dose of levodopa. DISCUSSION: This review suggests that levodopa has the potential to improve chorea in BTL syndrome while its use in chorea due to other disorders requires further study. BTL syndrome due to NKX2-1 mutation responded to levodopa while we did not find any case of chorea due to ADCY-5 mutation responding to levodopa.

The Pseudodystonia of Paroxysmal Sympathetic Hyperactivity: A Reversible Post-Anoxic Complication.

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Copulatory Dyskinesia: Pathognomonic Manifestation of Tardive Dyskinesia.

Background: Copulatory or pelvic thrusting dyskinesia is a subtype of tardive dyskinesia (TD) which is caused by exposure to dopamine blocking agents. Phenomenology shown: A man exhibiting rhythmic, stereotypical pelvic thrusting movements. Educational value: Recognition of copulatory dyskinesia as a distinctive iatrogenic disorder helps prevent unnecessary investigations and guides the implementation of corrective strategies.

Chorea and Parkinsonism with Elevated Striational Antibody.

Subacute onset of a mixed movement disorder should alert the clinician to the possibility of an autoimmune or paraneoplastic cause of symptoms. Striational antibodies have been associated with myasthenia gravis but a mixed movement disorder has been rarely reported with this antibody. We report a 90-year-old female who presented with generalized chorea, blepharospasm, and parkinsonism. Extensive evaluation was done which showed an elevation in striational antibody and there was no evidence of malignancy. The patient responded dramatically to intravenous steroids. We suggest that striational antibody should be routinely tested as a part of the work-up for autoimmune or paraneo lastic movement disorder. The presence of chorea in a very elderly patient should not be dismissed as "senile chorea" and a search for treatabl etiology should always be performed.

Re-Emergent Kinetic Tremor in Parkinson's Disease.

Background: This is a case of re-emergent kinetic tremor in Parkinson's Disease (PD). Phenomenology shown: The video shows re-emergent kinetic tremor while drawing a spiral and with repeated attempts to drink water from a cup. Educational value: The kinetic tremor described by patients with PD can be a re-emergent tremor which occurs after a few repetitive movements.

DaT Scan "Abnormality" in Hyperglycemic-Hemichorea.

Background: Hyperglycemic-hemichorea is a well-established clinical entity which leads to signal changes on brain MRI. We are reporting a case of hyperglycemic-hemichorea where the DaT scan showed reduced uptake bilaterally. Case Report: A 57-year-old female was seen in the clinic for hemichorea due to hyperglycemia. Her brain magnetic resonance imaging (MRI) showed increased T1 signal intensity in bilateral lenticular nuclei and the DaT scan showed reduced uptake on both sides. Discussion: This case highlights the importance of performing a DaT scan in the correct clinical context, as an abnormality on brain MRI can lead to false-positive DaT scan results.

Long Term Response to Levodopa in Parkinson's Disease.

BACKGROUND: Levodopa is the most efficacious medication in controlling the motor symptoms of Parkinson's disease (PD). There continues to be a controversy as to whether levodopa remains effective after years of therapy. OBJECTIVE: To assess the long-term effectiveness of levodopa in PD patients. METHODS: The response to levodopa in PD patients undergoing a levodopa challenge for deep brain stimulation (DBS) surgery evaluation from June 1997 through March 2017 were evaluated. The patients were broken into four groups based on disease duration (Group I: 0- 5 years, Group II: 6- 10 years, Group III: 11- 15 years, and Group IV:≥16 years). Levodopa response was calculated based on the changes in Unified Parkinson's Disease Rating Scale (UPDRS) motor and activities of daily living (ADL) scores in the medication ON and OFF states. RESULTS: A total of 361 PD patients were included. The mean age in Group I was 59.4 years with a mean disease duration of 3.9 years (n = 29), Group II was 61 years with a mean disease duration of 8.1 years (n = 131), Group III was 64 years with a mean disease duration of 12.8 years (n = 143), and IV was 66.5 years with a mean disease duration of 18.5 years (n = 58). There was a significant improvement in UPDRS motor and ADL scores after the levodopa challenge for all groups. CONCLUSIONS: In a subgroup of PD patients who were evaluated for DBS surgery, there was a marked improvement in UPDRS motor and ADL scores which did not decrease with disease progression.

Old Drugs, New Delivery Systems in Parkinson's Disease.

Levodopa is the mainstay of treatment in Parkinson's disease (PD). As the disease progresses, variations in plasma levodopa levels lead to motor fluctuations. The common reasons behind variations in the plasma levels include delayed gastric emptying, small intestinal bacterial overgrowth, protein interaction with levodopa absorption, and limited oral bioavailability of levodopa. Efforts to find newer delivery systems for older drugs to avoid the problems associated with oral delivery of medications are continuing. This review aims to provide up-to-date information about the newer delivery options for drugs used for PD and provides a summary of infusion therapy with apomorphine, modifications to other dopamine agonists, various oral formulations of carbidopa/levodopa, inhaled levodopa, intrajejunal infusion of levodopa, and sublingual apomorphine. The advantages, dose, and adverse effects of each treatment modality are reviewed. We also discuss several drugs under investigation, such as the subcutaneous carbidopa/levodopa infusion and subcutaneous rotigotine.

Contrast Acuity With Different Colors in Parkinson's Disease.

BACKGROUND: Abnormal color vision and contrast acuity may have significant impact on daily activities. OBJECTIVE: Evaluate color visual acuity, at high and low contrast, in Parkinson's disease (PD) and controls using an iPad application. METHODS: Color visual acuity was tested with the Variable Contrast Acuity Chart (King-Devick Test LLC, Oakbrook Terrace, IL) on an iPad 2 at 40 cms using five colors (red, green, blue, yellow, and black) at low (2.5%) and high (100%) contrast. A numerical score (0-95) was assigned based on the number of correctly identified letters. RESULTS: Thirty-six PD (mean ± standard deviation age 68 ± 10 years) and 36 controls (72 ± 11.2 years) were studied. PD disease duration was 6.4 ± 4.6 years; MDS-UPDRS part II was 11.7 ± 7.0, and part III was 24.5 ± 9.9. After adjusting for age and sex, PD patients had significantly (P < 0.05) lower scores at high (100%) as well as low (2.5%) contrast for all five colors tested (red, green, blue, yellow, and black), except yellow low contrast (2.5%; P = 0.10). The largest effect size (0.88) was with yellow high contrast, and the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy using a cut-off score of 82 was 31%, 97%, 92%, 58%, and 64%, respectively. No correlation to disease duration was found. CONCLUSIONS: This iPad application may be a simple-to-use biomarker for assessing color vision in PD. Further research is needed to determine disease specificity and whether there is a role in monitoring disease progression, treatment response, and identifying prodromal PD.

Can Admission BNP Level Predict Outcome After Intravenous Thrombolysis in Acute Ischemic Stroke?

OBJECTIVE: Our study aimed to determine the prognostic value of elevated Brain Natriuretic Peptide (BNP) among patients who received intravenous thrombolysis (IVT) in acute ischemic stroke (AIS). BACKGROUND: The elevation in BNP level is correlated with infarct size, poststroke mortality, and CHADS2 score. Currently, there is a lack of validated biomarker to predict the outcome in patients with acute ischemic stroke, and there is a complex interaction amongst multiple variables. DESIGN/METHODS: A retrospective review of medical records of patients admitted to our institution with acute ischemic stroke was performed. The patients who received intravenous thrombolysis were selected for analysis and divided into 2 groups based on the level of BNP. We compared the baseline demographics, past medical history, stroke etiology, discharge disposition, and 3-month mRS between both groups. Multivariate logistic regression analysis was performed to identify the predictors of poor outcome following intravenous thrombolysis in acute ischemic stroke. RESULTS: A total of 90 patients were recruited in the study; 53 patients were found to have an elevated BNP (high BNP was defined as >100 pg/mL) level, whereas 37 had low BNP levels. Our study showed that patients with elevated BNP were more likely to have an elevation in admission and discharge NIHSS, serum creatinine, left atrial size, and blood glucose (P<0.05). Atrial fibrillation and cardioembolic strokes were seen most often in the population with elevated BNP (P<0.05). The patients with elevated BNP were less likely to be discharged home, and 3-month mRS was found to be higher, but these were not significant. On multivariate analysis, elevated BNP was not found to be an independent factor for poor outcome. CONCLUSIONS: Elevated BNP level was not found to be an independent marker of poor outcome in AIS patients following IVT.

Are Clinical Certainty Ratings Helpful in the Diagnosis of Parkinson's Disease?

BACKGROUND: Clinical diagnostic criteria for PD rely on rest tremor, bradykinesia, and rigidity. These features are non-specific and neuropathological confirmation remains the gold standard for diagnosis. This study presents data on clinical certainty ratings in autopsy-proven PD. METHODS: Subjects were assessed annually by a movement disorders specialist and assigned to a clinical certainty group for PD based on multiple clinical features before autopsy. The three groups considered for analysis are as follows: Group I 0-49% certainty, Group II 50-89% certainty, and Group III 90-100% certainty. All subjects were autopsied and had a standardized neuropathological assessment. RESULTS: 275 subjects were assigned a PD certainty at their last visit before death. Group I had 80 subjects, Group II 56 subjects, and Group III 139 subjects. The clinical features recorded in Group I, II, and III, were as follows: rest tremor, bradykinesia, rigidity, postural instability, asymmetric onset, persistent asymmetry, current response to dopaminergic treatment, motor fluctuations, and dyskinesia. Rigidity, postural instability, asymmetric onset, current response to dopaminergic treatment, motor fluctuation, and dyskinesia were more likely to be present in the group which was rated with higher certainty. The final diagnosis of PD was confirmed by neuropathological assessment in 85% of the patients in Group III as compared to 30% in Group II and 5% in Group I. CONCLUSIONS: High certainty (90-100%) had strong positive predictive value (85%) for autopsy-proven PD as compared to either lower certainty groups (0-49% and 50-89%) which had lower predictive value (5% and 30% respectively).

Post-hypoxic Myoclonus: Current Concepts, Neurophysiology, and Treatment.

BACKGROUND: Myoclonus may occur after hypoxia. In 1963, Lance and Adams described persistent myoclonus with other features after hypoxia. However, myoclonus occurring immediately after hypoxia may demonstrate different syndromic features from classic Lance-Adams syndrome (LAS). The aim of this review is to provide up-to-date information about the spectrum of myoclonus occurring after hypoxia with emphasis on neurophysiological features. METHODS: A literature search was performed on PubMed database from 1960 to 2015. The following search terms were used: "myoclonus," "post anoxic myoclonus," "post hypoxic myoclonus," and "Lance Adams syndrome." The articles describing clinical features, neurophysiology, management, and prognosis of post-hypoxic myoclonus cases were included for review. RESULTS: Several reports in the literature were separated clinically into "acute post-hypoxic myoclonus," which occurred within hours of severe hypoxia, and "chronic post-hypoxic myoclonus," which occurred with some recovery of mental status as the LAS. Acute post-hypoxic myoclonus was generalized in the setting of coma. Chronic post-hypoxic myoclonus presented as multifocal cortical action myoclonus that was significantly disabling. There was overlap of neurophysiological findings for these two syndromes but also different features. Treatment options for these two distinct clinical-neurophysiologic post-hypoxic myoclonus syndromes were approached differently. DISCUSSION: The review of clinical and neurophysiological findings suggests that myoclonus after hypoxia manifests in one or a combination of distinct syndromes: acute and/or chronic myoclonus. The mechanism of post-hypoxic myoclonus may arise either from cortical and/or subcortical structures. More research is needed to clarify mechanisms and treatment of post-hypoxic myoclonus.

Effectiveness of 3% hypertonic saline nebulization in acute bronchiolitis among Indian children: A quasi-experimental study.

OBJECTIVE: To compare the effects of 3% hypertonic saline (HS) and 0.9% normal saline with nebulized 0.9% normal saline with salbutamol in patients of acute viral bronchiolitis. MATERIALS AND METHODS: Participants were divided into three groups, that is, 3% HS group, 0.9% normal saline group and 0.9% saline with salbutamol group. Four doses at interval of 6 h were given daily until discharge. Average CS score and length of hospital stay were compared. One-way analysis of variance paired t-test and Chi-square test were utilized for statistical analysis. RESULTS: The mean ages of the patients in three groups were 6.03 ± 3.71, 5.69 ± 3.34 and 5.48 ± 3.35 respectively. The 3(rd) day CS scores for all the groups were 1.0 ± 1.1, 1.9 ± 1.1 and 3.3 ± 0.5 respectively (P = 0.000). The average length of hospital stay was 3.4 ± 1.7, 3.7 ± 1.9 and 4.9 ± 1.4 days respectively (P = 0.001). CONCLUSION: The present study concludes that 3% HS nebulization (without additional bronchodilators) is an effective and safe treatment for nonasthmatic, moderately ill patients of acute bronchiolitis. The economic benefit of this comparably priced modality of treatment can be enormous in terms of hospital costs with parents returning to work sooner.