Beginning

Through personal narrative, this chapter details the author’s experience of first becoming aware that something was not right with his body. This experience leads to visiting his primary care doctor who tells him that she is concerned about the possibility of his having Parkinson’s disease and then refers the author to a neurologist who is a movement disorder specialist. He is examined by this neurologist, who says, “What worries me is that I think you are in the early stages of Parkinson’s disease,” but who wants the author to have a brain scan that will confirm the clinical diagnosis given his young age and subtle symptoms. The author leaves his office, drives home, and informs his wife that this doctor thinks he have Parkinson’s disease. Here begins his new life as a person with Parkinson’s (PwP).

Early-Onset Parkinsonism and Early-Onset Parkinson’s Disease: A Population-Based Study (2010-2015)

Background: Early-onset Parkinson’s disease (EOPD), occurring between ages 40 and 55, carries social, societal, and personal consequences and may progress, with fewer comorbidities than typical, later-onset disease. Objective: To examine the incidence and survival of EOPD and other Parkinsonism occurring before age 55 in the population-based cohort of residents in seven Minnesota counties. Methods: A movement-disorder specialist reviewed all the medical records in a 2010–2015 Parkinsonism-incident cohort to confirm diagnosis and subtypes. Results: We identified 27 patients diagnosed at < 50 years with incident Parkinsonism 2010–15:11 (41%) cases of EOPD, 13 (48%) drug-induced Parkinsonism, and 3 (11%) other Parkinsonism and 69 incident cases of Parkinsonism < 55 years of age. Overall incidence for Parkinsonism < 50 years was 1.98/100,000 person-years, and for EOPD was 0.81/100,000 person-years. In patients < 55 years, Parkinsonism incidence was 5.05/100,000 person-years: in EOPD, 2.05/100,000 person-years. Levodopa-induced dyskinesia was present in 45%of EOPD (both < 50 years and < 55 years). Onset of cardinal motor symptoms was proximate to the diagnosis of EOPD, except for impaired postural reflexes, which occurred later in the course of EOPD. Among the 69 Parkinsonism cases < 55 years, 9 (13%; all male) were deceased (only 1 case of EOPD). Men had a higher mortality risk compared to women (p = 0.049). Conclusion: The incidence of EOPD < 50 years was 0.81/100,000 person-years (1.98 in Parkinsonism all type); prior to 55 years was 2.05/100,000 person-years (5.05 in Parkinsonism all type) with higher incidence in men than women. Men with Parkinsonism, all type, had higher mortality compared to women.

Case Report: Bupropion Reduces the [123I]FP-CIT Binding to Striatal Dopamine Transporter

The diagnosis of parkinsonian syndromes in patients with severe depression may be challenging due to overlapping clinical phenomena, especially regarding psychomotor and affective symptoms. [123I]FP-CIT-SPECT is a useful method to detect degenerative parkinsonian disorders. However, some drugs may influence the tracer binding and thus alter the result. We present a case of 56-year-old female inpatient with difficult-to-treat late-onset depression. Since the current major depressive episode (MDE) was accompanied by psychotic features including delusions and hallucinations as well as hypokinesia, stooped posture and hypomimia, underlying degenerative parkinsonism was suspected. The pathologic [123I]FP-CIT-SPECT scan under ongoing antidepressant therapy with bupropion 300 mg/die (serum level of bupropion 43 ng/ml and hydroxybupropion 2,332 ng/ml) showed reduced [123I]FP-CIT binding throughout the striatum. The scan normalized upon a wash-out phase of four half-time periods (serum level of bupropion was 0.4 ng/ml and for hydroxybupropion 80.5 ng/ml). Our report should serve as a cautionary note for use of [123I]FP-CIT in depressed patients, particularly in those treated with drugs interfering with the dopamine transporter. Furthermore, our case argues for a need of consultation of a movement disorder specialist prior to dopamine transporter imaging.

Perception of yips among professional Japanese golfers: perspectives and challenges

BackgroundYips in golf is a complex spectrum of psychological anxiety and movement disorder that affects competitive sporting performance. Existing literature is limited to several western studies and the manifestations of this problem in Japanese golfers is currently unknown.ObjectiveTo quantify self-reported perception and manifestation of yips among Japanese golfers from the professional golfers’ association (PGA).MethodsWe analyzed 1271 (of 1356) elite golfers in a cross-sectional manner. Golfers were sensitized beforehand about yips by a movement-disorder specialist. Based on a positive history for yips, participants were categorized into yips and non-yips groups. Survey questionnaire focused on demographic information, golfing habits, anxiety and musculoskeletal problems, performance deficits during golfing, changes in training and their outcomes. Statistical procedures included multiple logistic regression and network analysis to assess factors associated with yips.Results35% (N=450) of the respondents had experienced symptoms of yips in their career, their odds increasing proportionally to their golfing experience. Severity of musculoskeletal symptoms were higher in those with yips. Regardless, about 57% of all yips-golfers attributed their symptoms to psychological causes. Putting, approach and teeing shots, in that order, were highly susceptible to movement problems. Network analysis highlighted characteristic movement patterns i.e. slowing, forceful or freezing of movement for putting, approach and teeing respectively. Golfers’ self-administered strategies to relieve yips symptoms were generally inconsequential, though improvements were seen only for approach-yips.ConclusionOur findings align firmly with prior studies on yips. Though aware of the problem, most Japanese golfers were untouched by yips. Those that were affected, perceived yips to be a psychological issue despite substantial evidence pointing to a movement-disorder. While self-administered interventions for symptom relief in such golfers is satisfactory at best, it may be imperative to sensitize golfers from a movement-disorder standpoint for early identification and management of the problem.

Machine Learning–Based Automatic Rating for Cardinal Symptoms of Parkinson Disease

ObjectiveWe developed and investigated the feasibility of a machine learning–based automated rating for the 2 cardinal symptoms of Parkinson disease (PD): resting tremor and bradykinesia.MethodsUsing OpenPose, a deep learning–based human pose estimation program, we analyzed video clips for resting tremor and finger tapping of the bilateral upper limbs of 55 patients with PD (110 arms). Key motion parameters, including resting tremor amplitude and finger tapping speed, amplitude, and fatigue, were extracted to develop a machine learning–based automatic Unified Parkinson's Disease Rating Scale (UPDRS) rating using support vector machine (SVM) method. To evaluate the performance of this model, we calculated weighted κ and intraclass correlation coefficients (ICCs) between the model and the gold standard rating by a movement disorder specialist who is trained and certified by the Movement Disorder Society for UPDRS rating. These values were compared to weighted κ and ICC between a nontrained human rater and the gold standard rating.ResultsFor resting tremors, the SVM model showed a very good to excellent reliability range with the gold standard rating (κ 0.791; ICC 0.927), with both values higher than that of nontrained human rater (κ 0.662; ICC 0.861). For finger tapping, the SVM model showed a very good reliability range with the gold standard rating (κ 0.700 and ICC 0.793), which was comparable to that for nontrained human raters (κ 0.627; ICC 0.797).ConclusionMachine learning–based algorithms that automatically rate PD cardinal symptoms are feasible, with more accurate results than nontrained human ratings.Classification of EvidenceThis study provides Class II evidence that machine learning–based automated rating of resting tremor and bradykinesia in people with PD has very good reliability compared to a rating by a movement disorder specialist.

Progressive supranuclear palsy is not associated with neurogenic orthostatic hypotension

ObjectiveTo evaluate the pattern and severity of autonomic dysfunction in autopsy-confirmed progressive supranuclear palsy (PSP) compared to α-synuclein pathology.MethodsAutopsy-confirmed cases of 14 patients with PSP, 18 with multiple system atrophy (MSA), and 24 with Lewy body disease (LBD) with antemortem autonomic testing were reviewed retrospectively. All patients underwent comprehensive clinical evaluations by a movement disorder specialist, formal autonomic testing, and postmortem examinations at Mayo Clinic.ResultsThe absence of orthostatic hypotension (OH) was the strongest autonomic parameter that distinguished PSP from α-synucleinopathies (0% vs 69%, p < 0.0001). Tests of adrenergic failure, which distinguish neurogenic OH, also differentiated PSP from other groups. These included the pressure recovery time (p = 0.0008), adrenergic impairment score (p = 0.001), and magnitude of change of systolic (p = 0.0002) and diastolic (p = 0.0001) blood pressures (BPs) during upright tilt. In addition, REM sleep behavior disorder was seen less frequently (p = 0.006) in PSP (33%) compared to MSA (87%) and LBD (90%). Antemortem clinical diagnostic accuracy for these phenotypically variable disorders was 57% for PSP and 83% for α-synucleinopathies.ConclusionOur results suggest that the cardiovascular adrenergic system, which sustains BP during standing, is relatively unaffected, if not spared, in PSP. These findings increase our understanding of the clinical signature of PSP and have the potential to improve diagnostic accuracy in atypical parkinsonisms by distinguishing PSP from the α-synucleinopathies.

Electrophysiologic testing aids diagnosis and subtyping of myoclonus

ObjectiveTo determine the contribution of electrophysiologic testing in the diagnosis and anatomical classification of myoclonus.MethodsParticipants with a clinical diagnosis of myoclonus were prospectively recruited, each undergoing a videotaped clinical examination and battery of electrophysiologic tests. The diagnosis of myoclonus and its subtype was reviewed after 6 months in the context of the electrophysiologic findings and specialist review of the videotaped clinical examination.ResultsSeventy-two patients with myoclonus were recruited. Initial clinical anatomical classification included 25 patients with cortical myoclonus, 7 with subcortical myoclonus, 2 with spinal myoclonus, and 15 with functional myoclonic jerks. In 23 cases, clinical anatomical classification was not possible because of the complexity of the movement disorder. Electrophysiologic testing was completed in 66, with agreement of myoclonus in 60 (91%) and its subtype in 28 (47%) cases. Subsequent clinical review by a movement disorder specialist agreed with the electrophysiologic findings in 52 of 60; in the remaining 8, electrophysiologic testing was inconclusive.ConclusionsElectrophysiologic testing is an important additional tool in the diagnosis and anatomical classification of myoclonus, also aiding in decision-making regarding therapeutic management. Further development of testing criteria is necessary to optimize its use in clinical practice.

Are Patients with Limb and Head Tremor a Clinically Distinct Subtype of Essential Tremor?

Background:Essential tremor (ET) is the most common tremor disorder in adults. In addition to upper limbs, the tremor in ET may also involve head, jaw, voice, tongue, and trunk. Though head tremor (HT) is commonly present in patients with ET, large comparative studies of ET patients with HT (HT+) and without HT (HT−) are few.Methods:To determine whether ET with HT is a distinct clinical subtype by comparing ET patients with and without HT, a chart review of 234 consecutive patients with ET attending the neurology clinics of the National Institute of Mental Health and Neurosciences, India, was done. A movement disorder specialist confirmed the diagnosis of ET in all patients using the National Institutes of Health collaborative genetic criteria.Results:HT was present in 44.4% of the patients. Comparison between HT+ and HT− showed that the HT+ group patients: (1) were older, (2) had later onset of tremor, (3) had unimodal distribution of age at onset with a single peak in the fifth decade, (4) had more frequent voice tremor, and (5) were more likely to have mild cervical dystonia. HT was part of presenting symptoms in nearly two thirds of the ET patients and in the rest it was detected during clinical examination.Conclusions:Several demographic and clinical variables suggest that ET patients with HT have a distinct clinical phenotype.